Development of interleukin-27 recombinant Lactococcus lactis and its efficacy in treating psoriasis and colitis in mice.

Psoriasis and inflammatory bowel disease (IBD) are chronic immune-mediated diseases that adversely affect patients' quality of life. Interleukin (IL)-27 plays an important role in a variety of infectious diseases, autoimmune disorders, and cancers. However, its therapeutic effects in psoriasis and colitis remain underexplored. In this study, we evaluated the therapeutic potential of recombinant Lactococcus lactis (L. lactis) expressing IL-27 (pIL-27) in imiquimod-induced psoriasis and dextran sodium sulfate-induced colitis mouse models. In the psoriasis mouse model, oral administration of pIL-27 significantly reduced skin scaling, mitigated weight loss, lowered psoriasis area and severity index scores, diminished epidermal hyperplasia and inflammatory cell infiltration, and decreased inflammatory cytokine levels. In the colitis mouse model, oral administration of pIL-27 alleviated weight loss, improved disease activity index scores, prevented colon shortening, ameliorated histopathological changes, and decreased inflammatory cytokine levels. Furthermore, recombinant L. lactis expressing IL-27 could modulate the gut microbiota, increasing the amount of beneficial bacteria and reducing harmful bacteria in the intestine, thereby alleviating the progression of psoriasis and colitis. These results suggest the potential of IL-27 as a therapeutic option for treating psoriasis and IBD.

Effects of service attributes and competition on electronic word of mouth: an elaboration likelihood perspective.

The management of electronic word of mouth (eWOM) is critical in e-commerce. In this study, on the basis of the elaboration likelihood model (ELM), we constructed a model of factors influencing eWOM by dividing merchants' attributes into the central and peripheral routes, which correspond to consumers' systematic and heuristic cognitive modes respectively. We then tested the developed model by using a cross-sectional data set. The results of this study indicate that the degree of competition faced by merchants has a significant negative association with eWOM. Moreover, price level and location moderate the relationship between competition and eWOM. The services of reservation and group buying have positive associations with eWOM. This research has three main contributions. First, we explored the effect of competition on eWOM. Second, we validated the feasibility of applying the ELM to the catering industry by dividing merchant attributes into the central and peripheral routes; this approach is consistent with systematic and heuristic cognitive theories. Finally, this research provides practical suggestions for eWOM management in the catering industry.

Interpretable machine learning assisted spectroscopy for fast characterization of biomass and waste.

The combination of machine learning and infrared spectroscopy was reported as effective for fast characterization of biomass and waste (BW). However, this characterization process is lack of interpretability towards its chemical insights, leading to less satisfactory recognition for its reliability. Accordingly, this paper aimed to explore the chemical insights of the machine learning models in the fast characterization process. A novel dimensional reduction method with significant physicochemical meanings was thus proposed, where the high loading spectral peaks of BW were selected as input features. Combined with functional groups attribution of these spectral peaks, the machine learning models established based on the dimensionally reduced spectral data could be explained with clear chemical insights. The performance of classification and regression models between the proposed dimensional reduction method and principal component analysis method was compared. The influence mechanism of each functional group on the characterization results were discussed. CH deformation, CC stretch & CO stretch and ketone/aldehyde CO stretch played essential roles in C, H/ LHV and O prediction, respectively. The results of this work demonstrated the theoretical fundamentals of the machine learning and spectroscopy based BW fast characterization method.

Reduction of SLC7A11 and GPX4 Contributing to Ferroptosis in Sperm from Asthenozoospermia Individuals.

Ferroptosis is a newly defined form of regulated cell death, which is involved in various pathophysiological conditions. However, the role of ferroptosis in male infertility remains unclear. In this study, 42 asthenozoospermic and 45 normozoospermic individuals participated. To investigate the ferroptosis level in the two groups, the levels of reactive oxygen species (ROS), malondialdehyde (MDA), and iron were measured, and mitochondrial membrane potential (MMP) was detected as an indicator of mitochondrial injuries. Compared with the normozoospermic group, ROS (p < 0.05), MDA (p < 0.001), and iron (p < 0.001) of the asthenozoospermic group were significantly increased. However, the asthenozoospermia group had a decreased MMP level (p < 0.05). In addition, the expression levels of GSH-dependent peroxidase 4 (GPX4) (p < 0.001) and solute carrier family 7 member 11 (SLC7A11) (p < 0.05) were also reduced in asthenozoospermic individuals. In asthenozoospermic samples, a significantly high positive correlation was observed between GPX4 mRNA levels and progressive motility (r = 0.397, p = 0.009) and total motility (r = 0.389, p = 0.011), while a negative correlation was observed between GPX4 and iron concentration (r = - 0.276, p = 0.077). The function of ferroptosis in asthenozoospermic males has never been studied before. In our study, we concluded that GPX4 and SLC7A11 expression levels in asthenozoospermia patients were related to increased ferroptosis and impaired sperm function, revealing novel molecular insights into the complex systems involved in male infertility.

Streptococcus pneumoniae autolysin LytA inhibits ISG15 and ISGylation through decreasing bacterial DNA abnormally accumulated in the cytoplasm of macrophages.

Interferon stimulated gene 15 (ISG15) is one of the most robustly upregulated interferon stimulated genes (ISGs) and also a ubiquitin-like modifier which has been reported to play an important role in host defense against pathogens. Cytosolic nucleic acids detected by DNA sensors induce type Ⅰ interferons (IFN-Ⅰs) and ISGs in host cells. Streptococcus pneumoniae (S. pn) autolysin LytA triggers bacterial lysis and then S. pn-derived genomic DNA (hereafter referred to as S. pn-DNA) can be released and accumulates in the cytoplasm of host cells. However, it remains elusive whether LytA-mediated S. pn-DNA release is involved in ISG15 induction. Here we verified that ISG15 conjugation system can be widely activated by S. pn and cytosolic S. pn-DNA in host cells. Moreover, the phagocytosis of macrophages to the mutant strain S. pn D39 ΔlytA was enhanced when compared to S. pn D39, which in turn increased S. pn-DNA uptake into macrophages and augmented ISG15 expression. ISG15 might upregulate proinflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 1ß (IL-1ß) in macrophages and further promoted the clearance of S. pn in the absence of LytA. These results indicate that S. pn autolysis blunts ISG15 induction through preventing bacteria internalization and reducing cytosolic S. pn-DNA accumulation in macrophages, revealing a new strategy of S. pn for avoiding elimination. This study will help us to further understand the role of ISG15 during S. pn infection as well as the regulatory mechanisms of immune responses mediated by bacterial autolysis and bacterial DNA.

Implementing a cervical cancer awareness program in low- income settings in Western China: a community-based locally affordable intervention for risk reduction.

BACKGROUND: Some 60 years after introduction of the Papanicolaou smear worldwide, cervical cancer remains a burden in developing countries where >85% of world new cases and deaths occur, suggesting a failure to establish comprehensive cervical-cancer control programs. Effective interventions are available to control cervical cancer but are not all affordable in low-income settings. Disease awareness saves lives by risk-reduction as witnessed in reducing mortality of HIV/AIDS and smoking-related cancers. SUBJECTS AND METHODS: We initiated a community-based awareness program on cervical cancer in two low-income Muslim Uyghur townships in Kashi (Kashgar) Prefecture, Xinjiang, China in 2008. The education involved more than 5,000 women from two rural townships and awareness was then evaluated in 2010 and 2011, respectively, using a questionnaire with 10 basic knowledge questions on cervical cancer. Demographic information was also collected and included in an EpiData database. A 10-point scoring system was used to score the awareness. RESULTS: The effectiveness and feasibility of the program were evaluated among 4,475 women aged 19-70 years, of whom >92% lived on/ below US$1.00/day. Women without prior education showed a poor average awareness rate of 6.4% (164/2,559). A onetime education intervention, however, sharply raised the awareness rate by 4-fold to 25.5% (493/1,916). Importantly, low income and illiteracy were two reliable factors affecting awareness before or after education intervention. CONCLUSIONS: Education intervention can significantly raise the awareness of cervical cancer in low-income women. Economic development and compulsory education are two important solutions in raising general disease awareness. We propose that implementing community-based awareness programs against cervical cancer is realistic, locally affordable and sustainable in low-income countries, which may save many lives over time and, importantly, will facilitate the integration of comprehensive programs when feasible. In this context, adopting this strategy may provide one good example of how to achieve "good health at low cost".