Immune checkpoint blockade has shown significant clinical benefit in multiple cancer indications, but many patients are either refractory or become resistant to the treatment over time. HER2/neu oncogene overexpressed in invasive breast cancer patients associates with more aggressive diseases and poor prognosis. Anti-HER2 mAbs, such as trastuzumab, are currently the standard of care for HER2-overexpressing cancers, but the response rates are below 30% and patients generally suffer relapse within a year. In this study we developed a bispecific antibody (BsAb) simultaneously targeting both PD1 and HER2 in an attempt to combine HER2-targeted therapy with immune checkpoint blockade for treating HER2-positive solid tumors. The BsAb was constructed by fusing scFvs (anti-PD1) with the effector-functional Fc of an IgG (trastuzumab) via a flexible peptide linker. We showed that the BsAb bound to human HER2 and PD1 with high affinities (EC50 values were 0.2 and 0.14 nM, respectively), and exhibited potent antitumor activities in vitro and in vivo. Furthermore, we demonstrated that the BsAb exhibited both HER2 and PD1 blockade activities and was effective in killing HER2-positive tumor cells via antibody-dependent cellular cytotoxicity. In addition, the BsAb could crosslink HER2-positive tumor cells with T cells to form PD1 immunological synapses that directed tumor cell killing without the need of antigen presentation. Thus, the BsAb is a new promising approach for treating late-stage metastatic HER2-positive cancers.Accumulating evidence indicates that mitochondrial dysfunction and oxidative stress play a pivotal role in the initiation and progression of nonalcoholic fatty liver disease (NAFLD). In this study, we found that blueberry-derived exosomes-like nanoparticles (BELNs) could ameliorate oxidative stress in rotenone-induced HepG2 cells and high-fat diet (HFD)-fed C57BL/6 mice. Preincubation with BELNs decreased the level of reactive oxygen species (ROS), increased the mitochondrial membrane potential, and prevented cell apoptosis by inducing the expression of Bcl-2 and heme oxygenase-1 (HO-1) and decreasing the content of Bax in rotenone-treated HepG2 cells. We also found that preincubation with BELNs accelerated the translocation of Nrf2, an important transcription factor of antioxidative proteins, from the cytoplasm to the nucleus in rotenone-treated HepG2 cells. Moreover, administration of BELNs improved insulin resistance, ameliorated the dysfunction of hepatocytes, and regulated the expression of detoxifying/antioxidant genes by affecting the distribution of Nrf2 in the cytoplasm and nucleus of hepatocytes of HFD-fed mice. Furthermore, BELNs supplementation prevented the formation of vacuoles and attenuated the accumulation of lipid droplets by inhibiting the expression of fatty acid synthase (FAS) and acetyl-CoA carboxylase 1 (ACC1), the two key transcription factors for de novo lipogenesis in the liver of HFD-fed mice. These findings suggested that BELNs can be used for the treatment of NAFLD because of their antioxidative activity.Renal fibrosis contributes to progressive damage to renal structure and function. It is a common pathological process as chronic kidney disease develops into kidney failure, irrespective of diverse etiologies, and eventually leads to death. However, there are no effective drugs for renal fibrosis treatment at present. Lipid aggregation in the kidney and consequent lipotoxicity always accompany chronic kidney disease and fibrosis. Numerous studies have revealed that restoring the defective fatty acid oxidation in the kidney cells can mitigate renal fibrosis. Thus, it is an important strategy to reverse the dysfunctional lipid metabolism in the kidney, by targeting critical regulators of lipid metabolism. In this review, we highlight the potential “druggability” of lipid metabolism to ameliorate renal fibrosis and provide current pre-clinical evidence, exemplified by some representative druggable targets and several other metabolic regulators with anti-renal fibrosis roles. Then, we introduce the preliminary progress of noncoding RNAs as promising anti-renal fibrosis drug targets from the perspective of lipid metabolism. Finally, we discuss the prospects and deficiencies of drug targeting lipid reprogramming in the kidney.Dental caries is a largely preventable disease, yet the extraction of carious teeth is the most common reason for the hospital admission of children in England. This raises concern over the perceived failure of current preventive strategies. Despite a number of national and local preventive strategies, childhood caries remains most prevalent among the lower socioeconomic groups and ethnic minorities, especially in northern England. Often overlooked is the social and emotional impact of caries and dental treatment on the children and their families. More long-lasting can be the emotional, psychological and developmental impact on children of dental treatment and extractions under general anaesthesia, especially in unfamiliar hospital settings. GSK1265744 Yet, the number of hospital admissions for the 5-9-year-old age group continues to rise and was 26,000 in England in 2018. The aim of this paper is to review the demographic and socioeconomic factors related to hospital admission of children for dental extractions, focusing on the localities with the highest proportions of hospital admissions. It is suggested that a reappraisal of the caries-preventive strategy in those areas of England with the highest proportion of hospital admissions is now urgently needed and the case is forcefully made for targeted water fluoridation.Introduction Very little is known about the knowledge and attitudes of dental students and educators regarding environmental sustainability in dentistry (ESD), the presence of ESD in dental curricula, and barriers and enablers to embracing ESD in dental education.Methods A cross-sectional survey using piloted online questionnaires for students and educators was carried out at the Institute of Dentistry, Queen Mary University of London and at Harvard School of Dental Medicine. Data analysis included descriptive statistics and thematic analysis.Results ESD does not exist formally in the dental curricula at either institution. Despite poor knowledge, students and educators had very positive attitudes to embracing ESD in the curricula. The most noted barriers were lack of knowledge about ESD, lack of time for preparing ESD content, lack of ESD educational materials and infection control regulations. Enablers included embedding ESD in UK and US dental education standards, having institutional backing and support in terms of providing training, educational materials, capacity and incentives, as well as adopting a critical evidence-informed approach in reforming current infection control regulations.