From 1991 to 2000, amongst 23,886 full-term healthy Chinese babies delivered at our hospital, 2615 babies developed neonatal hyperbilirubinaemia. After excluding other causes of hyperbilirubinaemia and identifying the irregular antibodies, 15 cases of haemolytic disease of the newborn (HDN) due to maternal irregular antibodies were diagnosed; three cases were born in our hospital and 12 cases were referred. Amongst these 15 babies, six cases had HDN due to anti-E, three cases due to anti-E + c, three cases due to anti-D, one case due to anti-c and two cases due to 'Mi' antibodies reacting with MiIII phenotype cells (anti-Hil and anti-Mur). Although there were four cases of hydrops fetalis, only one of the patients expired. The prevalence of HDN caused by maternal irregular antibodies has been estimated to be 0.01%. Therefore, routine prenatal screening for irregular antibodies was not rational in the Chinese population in Taiwan. Anti-E and anti-E + c were the important irregular antibodies resulting in HDN. Although few cases of HDN due to anti-'Mi' have been reported, Anti-'Mi' is significant in regions with a high prevalence of the MiIII phenotype.

Precision medicine has made a significant breakthrough in the past decade. The most representative success is the molecular targeting therapy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) in non‐small‐cell lung cancer (NSCLC) with oncogenic drivers, approved by the US Food and Drug Administration (FDA) as first‐line therapeutics for substituting chemotherapy. However, the rapidly developed TKI resistance invariably leads to unsustainable treatment. For example, gefitinib is the first choice for advanced NSCLC with EGFR mutation, but most patients would soon develop secondary EGFRT790M mutation and acquire gefitinib resistance. TKI resistance is a severe emergency issue to be solved in NSCLC, but there are a few investigations of nanomedicine reported to address this pressing problem. To overcome EGFRT790M‐associated drug resistance, a novel delivery and therapeutic strategy is developed. A PD‐L1 nanobody is identified, and first used as a targeting ligand for liposomal codelivery. It is found that simvastatin/gefitinib combination nanomedicine can remodel the tumor microenvironment (e.g., neovascularization regulation, M2‐macrophage repolarization, and innate immunity), and display the effectiveness of reversing the gefitinib resistance and enhancing the EGFRT790M‐mutated NSCLC treatment outcomes. The novel simvastatin‐based nanomedicine provides a clinically translatable strategy for tackling the major problem in NSCLC treatment and demonstrates the promise of an old drug for new application.

p38 has long been known as a central mediator of protein kinase A (PKA) signaling in brown adipocytes, which positively regulate the transcription of uncoupling protein 1 (UCP-1). However, the physiological role of p38 in adipose tissues, especially the white adipose tissue (WAT), is largely unknown. Here, we show that mice lacking p38α in adipose tissues display a lean phenotype, improved metabolism, and resistance to diet-induced obesity. Surprisingly, ablation of p38α causes minimal effects on brown adipose tissue (BAT) in adult mice, as evident from undetectable changes in UCP-1 expression, mitochondrial function, body temperature (BT), and energy expenditure. In contrast, genetic ablation of p38α in adipose tissues not only markedly facilitates the browning in WAT upon cold stress but also prevents diet-induced obesity. Consistently, pharmaceutical inhibition of p38α remarkably enhances the browning of WAT and has metabolic benefits. Furthermore, our data suggest that p38α deficiency promotes white-to-beige adipocyte reprogramming in a cell-autonomous manner. Mechanistically, inhibition of p38α stimulates the UCP-1 transcription through PKA and its downstream cAMP-response element binding protein (CREB), which form a positive feedback loop that functions to reinforce the white-to-beige phenotypic switch during cold exposure. Together, our study reveals that inhibition of p38α is able to promote WAT browning and confer metabolic benefits. Our study also indicates that p38α in WAT represents an exciting pharmacological target to combat obesity and metabolic diseases.

Fluorescent imaging of β-amyloid (Aβ) is one of the most promising methods for Alzheimer's disease diagnosis. Several fluorescent probes have been reported to detect Aβ both in vitro and in vivo. However, highly sensitive and highly selective probes with low background signals are still greatly needed. Herein, we rationally designed and synthesized a PIET quenched near-infrared probe QAD-1 to detect Aβ. This probe contains BODIPY as fluorophore and tetrahydroquinoxaline as the quenching group. QAD-1 exhibited significant fluorescent switch-on after binding to soluble and insoluble Aβ species, and the probe had the benefit of low background signal to stain Aβ plaques without the need of wash-out procedures in vitro, which was specially found by the fluorescence off-on probe. QAD-1 could identify the overproduced Aβ in transgenic (APP/PSEN 1dE9) AD mice as early as 6 months old in vivo, which indicated that QAD-1 may be a potential probe for monitoring Aβ species at an early stage of AD.

Effective treatment of metastatic (stage IV) breast cancers remains a formidable challenge. To address this issue, a cell-penetrating peptide-assisted liposomal system was developed for codelivery of doxorubicin and andrographolide. This nanomedicine-based combination therapy showed the ability to inhibit the in vitro migration and invasion of 4T1 cells through the wound healing and transwell invasion assays. Furthermore, this delivery system exhibited the enhanced accumulation in the tumor tissues and deep intratumoral penetration. The synergistic effect of doxorubicin and andrographolide led to an evident inhibition of tumor growth in an orthotopic breast tumor mouse model and efficient prevention of lung metastasis. The therapeutic mechanism was associated with the anti-angiogenesis effect. In conclusion, this nanomedicine-based combination therapy provides a potential method for overcoming metastatic breast cancers.

Promoting tumor angiogenesis effectively and specifically to resolve tumor‐associated hypoperfusion holds promise for improving pancreatic cancer therapy. Herein, a doxorubicin (DOX) loaded smart liposome, MC‐T‐DOX, is constructed, that carries appropriately low‐density cilengitide, an αvβ3 integrin‐specific Arg‐Gly‐Asp (RGD)‐mimetic cyclic peptide, via a membrane type 1‐matrix metalloproteinase (MT1‐MMP) cleavable peptide. After being administered systemically in a hypoperfused pancreatic cancer mouse model at a low dose of cilengitide, the proangiogenic activity of MC‐T‐DOX is specifically “turned on” in tumor vessels through cleavage by MT1‐MMP on tumor endothelial cells to release cilengitide. This locally released cilengitide increases tumor blood perfusion, thereby improving the accumulation and distribution of MC‐T‐DOX in the tumor site. The loaded‐DOX then displays enhanced penetration and increased cellular uptake upon heat‐triggered release from MC‐T‐DOX in the tumor interstitium, contributing to the improved tumor therapy efficacy. Therefore, the strategy of combining the modulation of tumor vascular promotion with smart nanodrug delivery represents a promising approach to improving drug delivery and therapeutic efficacy in a wide range of hypoperfused tumors.

The advent of click chemistry has had a profound impact on many fields and fueled a need for reliable reactions to expand the click chemistry toolkit. However, developing new systems to fulfill the click chemistry criteria remains highly desirable yet challenging. Here, we report the development of light-induced primary amines and o-nitrobenzyl alcohols cyclization (PANAC) as a photoclick reaction via primary amines as direct click handle, to rapid and modular functionalization of diverse small molecules and native biomolecules. With intrinsic advantages of temporal control, good biocompatibility, reliable chemoselectivity, excellent efficiency, readily accessible reactants, operational simplicity and mild conditions, the PANAC photoclick is robust for direct diversification of pharmaceuticals and biorelevant molecules, lysine-specific modifications of unprotected peptides and native proteins in vitro, temporal profiling of endogenous kinases and organelle-targeted labeling in living systems. This strategy provides a versatile platform for organic synthesis, bioconjugation, medicinal chemistry, chemical biology and materials science.

Anti-'Mia' is the most common alloantibody of potential clinical significance in the Taiwanese population. The Mi.III phenotype is rare among Caucasians but has a high incidence in various Oriental populations. We describe a nulliparous woman with no history of transfusions, who had hydrops foetalis at 28 weeks gestation. Foetal haemoglobin was 4.4 g dL-1, and a positive direct antiglobulin test was positive in the foetal blood. Intrauterine intravascular transfusion was given, and the baby was discharged healthy. Anti-'Mia' was identified in the maternal serum, the cord blood serum and the eluate from red cells of the cord blood. Anti-'Mia' in the maternal serum was confirmed to be anti-Mur. The polymerase chain reaction-restriction fragment length polymorphism method confirmed that both the baby and her father had the Mi.III gene. Therefore, our report documents that anti-Mur has the potential to cause hydrops foetalis.