Metabolic communication in tumors: a new layer of immunoregulation for immune evasion

The success of cancer immunotherapy reveals the power of host immunity on killing cancer cells and the feasibility to unleash restraints of anti-tumor immunity. However, the immunosuppressive tumor microenvironment and low immunogenicity of cancer cells restrict the therapeutic efficacy of cancer immunotherapies in a small fraction of patients. Therefore deciphering the underlying mechanisms promoting the generation of an immunosuppressive tumor microenvironment is direly needed to better harness host anti-tumor immunity. Early works revealed that deregulated metabolic activities in cancer cells support unrestricted proliferation and survival by producing macromolecules. Intriguingly, recent studies uncovered that metabolic switch in immune and endothelial cells modulate cellular activities and contribute to the progression of several diseases, including cancers. Herein, we review the progress on immunometabolic regulations on fine-tuning activities of immune cells and discuss how metabolic communication between cancer and infiltrating immune cells contributes to cancer immune evasion. Moreover, we would like to discuss how we might exploit this knowledge to improve current immunotherapies and the unresolved issues in this field

Homogeneous point mutation detection by quantum dot-mediated two-color fluorescence coincidence analysis

This report describes a new genotyping method capable of detecting low-abundant point mutations in a homogeneous, separation-free format. The method is based on integration of oligonucleotide ligation with a semiconductor quantum dot (QD)-mediated two-color fluorescence coincidence detection scheme. Surface-functionalized QDs are used to capture fluorophore-labeled ligation products, forming QD-oligonucleotide nanoassemblies. The presence of such nanoassemblies and thereby the genotype of the sample is determined by detecting the simultaneous emissions of QDs and fluorophores that occurs whenever a single nanoassembly flows through the femtoliter measurement volume of a confocal fluorescence detection system. The ability of this method to detect single events enables analysis of target signals with a multiple-parameter (intensities and count rates of the digitized target signals) approach to enhance assay sensitivity and specificity. We demonstrate that this new method is capable of detecting zeptomoles of targets and achieve an allele discrimination selectivity factor >10(5)

MUC4 gene polymorphisms associate with endometriosis development and endometriosis-related infertility

<p>Abstract</p> <p>Background</p> <p>Mucin 4 (<it>MUC4</it>) plays an important role in protecting and lubricating the epithelial surface of reproductive tracts, but its role in the pathogenesis of endometriosis is largely unknown.</p> <p>Methods</p> <p>To correlate <it>MUC4 </it>polymorphism with the risk of endometriosis and endometriosis-related infertility, we performed a case-control study of 140 patients and 150 healthy women. Six unique single-nucleotide polymorphisms (SNPs) (rs882605, rs1104760, rs2688513, rs2246901, rs2258447 and rs2291652) were selected for this study. DNA fragments containing the target SNP sites were amplified by polymerase chain reaction using the TaqMan SNP Genotyping Assay System to evaluate allele frequency and distribution of genotype in <it>MUC4 </it>polymorphisms.</p> <p>Results</p> <p>Both the T/G genotype of rs882605 and the frequency of haplotype T-T (rs882605 and rs1104760) were higher in patients than in controls and were statistically significant. The frequency of the C allele at rs1104760, the C allele at rs2688513, the G allele at rs2246901 and the A allele at rs2258447 were associated with advanced stage of endometriosis. Moreover, the G allele at rs882605 was verified as a key genetic factor for infertility in patients. Protein sequence analysis indicated that amino acid substitutions by genetic variations at rs882605, rs2688513 and rs2246901 occur in the putative functional loops and the type D von Willebrand factor (VWFD) domain in the MUC4 sequence.</p> <p>Conclusions</p> <p><it>MUC4 </it>polymorphisms are associated with endometriosis development and endometriosis-related infertility in the Taiwanese population.</p

Polythiophenes comprising conjugated pendantstoward long-term air-stable inverted polymer solar cellswith high open circuit voltages

A series of polythiophenes (PTs) functionalized with bulky conjugated side chains comprising tert-butylsubstituted carbazole (tCz) as an electron donor pendant and bisbenzothiazolylvinyl (DBT) as anelectron acceptor pendant were synthesized via Stille copolymerization for polymer solar cell (PSC)applications. We use the descriptors PTtCz, PT(tCz)0.9(DBT)0.1, PT(tCz)0.64(DBT)0.36, PT(tCz)0.45(DBT)0.55,and PTDBT to identify each of these conjugated polymers, with the names denoting the compositionsof the bulky pendants. The tunable energy levels of the PTs were accomplished by incorporating bothtCz as a donor pendant and DBT as an acceptor pendant, while retaining the low-lying HOMO levels( 5.26 to 5.39 eV). Furthermore, lower bandgaps were observed for the DBT-derived PTs because ofstronger donor–p–acceptor characteristics and more efficient intramolecular charge transfer.Conventional PSCs were fabricated by spin-coating the blend of each PT and the fullerene derivative(PC71BM). The conventional PSC devices exhibited high open circuit voltages (Voc) of around 0.79–0.91 V. The power conversion efficiency (PCE) of the PSCs based on PTtCz : PC71BM (w/w ¼ 1 : 2.5)reached 2.48% with a Voc of 0.91 V, short circuit current (Jsc) of 6.58 (mA cm 2) and fill factor (FF) of41% under the illumination of AM1.5, 100 mW cm 2. Furthermore, a PTtCz/PC71BM-based inverted PSCwith ZnOx and MoO3 as an electron extraction layer and a hole extraction layer respectively was capableof retaining ca. 80% of its original efficiency after storage under ambient conditions (withoutencapsulation) for 1032 h, according to the ISOS-D-1 shelf protocol. The highly durable inverted PSCaccompanied by a large Voc value was achieved for the PT-type polymers