This leads us to propose that concurrent DSBs and induction of inflammation occurring throughout life may be the underlying cause of ageing, degenerative disorders, and cancer. Finally, we discuss the prospect that agents that can inactivate/degrade cfCh may hold the key to making healthy ageing a realizable goal.Nucleic acid and genetic medicines are increasingly being developed, owing to their potential to treat a variety of intractable diseases. A comprehensive understanding of the in vivo fate of these agents is vital for the rational design, discovery, and fast and straightforward development of the drugs. In case of intravascular administration of nucleic acids and genetic medicines, interaction with blood components, especially plasma proteins, is unavoidable. However, on the flip side, such interaction can be utilized wisely to manipulate the pharmacokinetics of the agents. In other words, plasma protein binding can help in suppressing the elimination of nucleic acids from the blood stream and deliver naked oligonucleotides and gene carriers into target cells. To control the distribution of these agents in the body, the ligand conjugation method is widely applied. It is also important to understand intracellular localization. 5-aza-2'-deoxycytidine In this context, endocytosis pathway, endosomal escape, and nuclear transport should be considered and discussed. Encapsulated nucleic acids and genes must be dissociated from the carriers to exert their activity. In this review, we summarize the in vivo fate of nucleic acid and gene medicines and provide guidelines for the rational design of drugs.Global challenges posed by climate change and environmental deterioration are increasingly driving entrepreneurship with sustainable entrepreneurial intention as a key driver in predicting entrepreneurial activities. Together with experience, the environmental values of an entrepreneur are vital for sustainable entrepreneurial intention. However, the extent to which experience is a key factor to start up a sustainable enterprise is still rather unclear. To study the role of experience, we derive from the theory of planned behaviour three factors (personal attitude, social norm and self-efficacy) to examine their impact on environmental values and sustainable entrepreneurial intention. Based on a meta-analysis, the overall directions and effect intensity of the different factors in this relationship can be investigated. We develop a structural equation model to explore the mechanism behind the interaction between the different variables. We utilize information from 37 scientific articles using 40 empirical samples, 117 effect sizes and 192,015 observations. We found that environmental values are indeed positively related to a sustainable entrepreneurial intention. Furthermore, the relationship between environmental values and sustainable entrepreneurial intention is moderated by experience, as well as personal attitude, social norms and self-efficacy. In addition, environmental values are more positively related to the intention to set up a sustainable venture for entrepreneurs with low-experience compared to those entrepreneurs with high-experience. For policy makers and managers, it becomes important to stimulate environmental values to promote sustainable entrepreneurial intentions in order to stimulate the growth of sustainable enterprises. By enhancing these three factors, sustainable entrepreneurial behaviour can be facilitated by increasing entrepreneurs' sustainable intention.Despite the advancement of the healthcare system, low birth weight (LBW) remains as one of the leading causes of under-five mortality. This cross-sectional study aimed to determine the prevalence of LBW and its associated factors among 483 third trimester pregnant women recruited from six selected public health clinics in the Federal Territory of Kuala Lumpur and the state of Selangor, Malaysia. Pregnant women were interviewed for information on socio-demographic characteristics, smoking behaviour, and second-hand smoke (SHS) exposure at home and in the workplace. Information on the obstetrical history and prenatal care visits history were retrieved from the maternal medical records, while infant's birth outcomes were retrieved from infant medical records. The prevalence of LBW ( less then 2.5 kg) in infants was 10.4%, with a mean birth weight of 3.0 [standard deviation (SD) 0.4] kg. Results from the multivariable logistic regression model showed that inadequate weight gained during pregnancy [odds ratio (OR) = 2.41, 95% confidence interval (CI) = 1.18-4.90] and exposure to SHS at home (OR = 1.92, 95% CI = 1.03-3.55) were significantly associated with LBW. In conclusion, pregnant women should monitor their rate of weight gain throughout pregnancy and avoid SHS exposure at home to reduce the risk of delivering LBW infants.Resistance of tumor cells to chemoradiotherapy represents a fundamental problem in clinical oncology. The underlying mechanisms are actively debated. Here we show that blocking inflammatory cytokine receptor signaling via STAT3 re-sensitized treatment-refractory cancer cells and abolished tumor growth in a xenograft mouse model when applied together with chemoradiotherapy. STAT3 executed treatment resistance by triggering the expression of RBPJ, the key transcriptional regulator of the NOTCH pathway. The mandatory RBPJ interaction partner, NOTCH intracellular domain, was provided by tumor cell-intrinsic expression of NOTCH ligands that caused tonic NOTCH proteolysis. In fact, NOTCH inhibition phenocopied the effect of blocking STAT3 signaling. Moreover, genetic profiling of rectal cancer patients revealed the importance of the STAT3/NOTCH axis as NOTCH expression correlated with clinical outcome. Our data uncovered an unprecedented signal alliance between inflammation and cellular development that orchestrated resistance to chemoradiotherapy. Clinically, our findings allow for biomarker-driven patient stratification and offer novel treatment options.Periprosthetic joint infection (PJI) is a rare but devastating complication after total joint arthroplasty. An estimated 7-12% of patients have negative cultures despite clear clinical evidence of infection. One oft-cited reason for this occurrence is the administration of antibiotics in the weeks prior to obtaining cultures. This article reviews the influence of antibiotics on the diagnosis of PJI. Specifically, we examine the effect of prophylactic and therapeutic antibiotic administration on the diagnostic accuracy of microbiological cultures as well as serum and synovial biomarkers. We also explore the potential of molecular techniques in overcoming these limitations in patients who have received antibiotics before specimen collection and propose areas for future research.