A Case Report of Germline Compound Heterozygous Mutations in the BRCA1 Gene of an Ovarian and Breast Cancer Patient

The germline carrier of the BRCA1 pathogenic mutation has been well proven to confer an increased risk of breast and ovarian cancer. Despite BRCA1 biallelic pathogenic mutations being extremely rare, they have been reported to be embryonically lethal or to cause Fanconi anemia (FA). Here we describe a patient who was a 48-year-old female identified with biallelic pathogenic mutations of the BRCA1 gene, with no or very subtle FA-features. She was diagnosed with ovarian cancer and breast cancer at the ages of 43 and 44 and had a strong family history of breast and gynecological cancers.     

The Role of microRNAs in Development of Colitis-Associated Colorectal Cancer

Colorectal cancer (CRC) is the third most deadly cancer worldwide, and inflammatory bowel disease (IBD) is one of the critical factors in CRC carcinogenesis. IBD is responsible for an unphysiological and sustained chronic inflammation environment favoring the transformation. MicroRNAs (miRNAs) belong to a class of highly conserved short single-stranded segments (18–25 nucleotides) non-coding RNA and have been extensively discussed in both CRC and IBD. However, the role of miRNAs in the development of colitis-associated CRC (CAC) is less clear. The aim of this review is to summarize the major upregulated (miR-18a, miR-19a, miR-21, miR-31, miR-155 and miR-214) and downregulated (miR-124, miR-193a-3p and miR-139-5p) miRNAs in CAC, and their roles in genes’ expression modulation in chronic colonic-inflammation-induced carcinogenesis, including programmed cell-death pathways. These miRNAs dysregulation could be applied for early CAC diagnosis, to predict therapy efficacy and for precision treatment.     

Spirobifluorene Dimers: Understanding How The Molecular Assemblies Drive The Electronic Properties

Spirobifluorene (SBF) is one of the most important scaffolds used in the design of organic semi-conductors (OSCs) for electronics. In recent years, among all the structures developed for these applications, SBF dimers have been highlighted due to their great potential in thermally activated delayed fluorescence and in phosphorescent organic light-emitting diodes. Attaching two SBF units generate 10 dimers, each possessing its own structural specificity, which in turn drives its electronic properties. These ten SBF dimers are gathered herein. Understanding how the molecular assembly determines the electronic properties has been one of the pillars of organic electronics. This is the goal of this article. As positional isomerism is a key tool to design OSCs, defining the design guidelines for the SBF scaffold appears of interest for the future of this building block. Herein, the importance of the two main parameters involved in the electrochemical and photophysical properties, namely the nature of the phenyl linkages and the steric congestion between the two SBF units is discussed. The combination of these two parameters drives the electronic properties but their respective weight is different as a function of the regioisomer involved or of the property considered (frontier orbitals energy level, absorption, fluorescence, phosphorescence).     

Dysprosium doped copper oxide (Cu1-xDyxO) nanoparticles enabled bifunctional electrode for overall water splitting

The production of hydrogen, a favourable alternative to an unsustainable fossil fuel remains as a significant hurdle with the pertaining challenge in the design of proficient, highly productive and sustainable electrocatalyst for both oxygen evolution reaction (OER) and hydrogen evolution reaction (HER). Herein, the dysprosium (Dy) doped copper oxide (Cu_1-xDy_xO) nanoparticles were synthesized via solution combustion technique and utilized as a non-noble metal based bi-functional electrocatalyst for overall water splitting. Due to the improved surface to volume ratio and conductivity, the optimized Cu_1-xDy_xO (x = 0.01, 0.02) electrocatalysts exhibited impressive HER and OER performance respectively in 1 M KOH delivering a current density of 10 mAcm^?2 at a potential of ?0.18 V vs RHE for HER and 1.53 V vs RHE for OER. Moreover, the Dy doped CuO electrocatalyst used as a bi-functional catalyst for overall water splitting achieved a potential of 1.56 V at a current density 10 mAcm^?2 and relatively high current density of 66 mAcm^?2 at a peak potential of 2 V. A long term stability of 24 h was achieved for a cell voltage of 2.2 V at a constant current density of 30 mAcm^?2 with only 10% of the initial current loss. This showcases the accumulative opportunity of dysprosium as a dopant in CuO nanoparticles for fabricating a highly effective and low-cost bi-functional electrocatalyst for overall water splitting.     

Development of low-loss lead-germanate glass for mid-infrared fiber optics: II. preform extrusion and fiber fabrication

For lead-germanate glass fibers, reducing the content of hydroxyl (OH) groups and the formation of metallic Pb species is essential to pave the way for their applications as low-loss mid-IR fiber optics since OH and metallic Pb species cause intense absorption and scattering loss, respectively, in the mid-IR spectral range. The first part of this study reported the optimization of the glass melting procedure to obtain low amount of OH while preventing formation of metallic Pb species in lead-germanate glass. Here, the second part of this study reports the investigation of the process conditions to fabricate low-loss lead-germanate glass fiber through further understanding of the co-effects of glass melting and heat treatment atmospheres on the formation of nano- and micron-scale metallic Pb species in both the as-produced and heat treated lead-germanate glasses. Finally, using this advance in knowledge, we successfully fabricated low-loss lead-germanate glass fibers with no presence of reduced metallic Pb particles by optimizing dehydration agent, glass melting, preform extrusion and fiber drawing conditions. The optimized fabrication conditions reduced the unstructured fiber loss by almost one order to <0.3 dB/m at 1.55 μm.     

Quantitative Proteomic Approach Reveals Altered Metabolic Pathways in Response to the Inhibition of Lysine Deacetylases in A549 Cells under Normoxia and Hypoxia

Growing evidence is showing that acetylation plays an essential role in cancer, but studies on the impact of KDAC inhibition (KDACi) on the metabolic profile are still in their infancy. Here, we analyzed, by using an iTRAQ-based quantitative proteomics approach, the changes in the proteome of KRAS-mutated non-small cell lung cancer (NSCLC) A549 cells in response to trichostatin-A (TSA) and nicotinamide (NAM) under normoxia and hypoxia. Part of this response was further validated by molecular and biochemical analyses and correlated with the proliferation rates, apoptotic cell death, and activation of ROS scavenging mechanisms in opposition to the ROS production. Despite the differences among the KDAC inhibitors, up-regulation of glycolysis, TCA cycle, oxidative phosphorylation and fatty acid synthesis emerged as a common metabolic response underlying KDACi. We also observed that some of the KDACi effects at metabolic levels are enhanced under hypoxia. Furthermore, we used a drug repositioning machine learning approach to list candidate metabolic therapeutic agents for KRAS mutated NSCLC. Together, these results allow us to better understand the metabolic regulations underlying KDACi in NSCLC, taking into account the microenvironment of tumors related to hypoxia, and bring new insights for the future rational design of new therapies.     

Airborne bacterial assemblage in a zero carbon building: A case study

Currently, there is little information pertaining to the airborne bacterial communities of green buildings. In this case study, the air bacterial community of a zero carbon building (ZCB) in Hong Kong was characterized by targeting the bacterial 16S rRNA gene. Bacteria associated with the outdoor environment dominated the indoor airborne bacterial assemblage, with a modest contribution from bacteria associated with human skin. Differences in overall community diversity, membership, and composition associated with short (day‐to‐day) and long‐term temporal properties were detected, which may have been driven by specific environmental genera and taxa. Furthermore, time‐decay relationships in community membership (based on unweighted UniFrac distances) and composition (based on weighted UniFrac distances) differed depending on the season and sampling location. A Bayesian source‐tracking approach further supported the importance of adjacent outdoor air bacterial assemblage in sourcing the ZCB indoor bioaerosol. Despite the unique building attributes, the ZCB microbial assemblage detected and its temporal characteristics were not dissimilar to that of conventional built environments investigated previously. Future controlled experiments and microbial assemblage investigations of other ZCBs will undoubtedly uncover additional knowledge related to how airborne bacteria in green buildings may be influenced by their distinctive architectural attributes.     

Potential pitfalls of smart city development: A study on parking mobile applications (apps) in Hong Kong

Smart cities are built upon information and communication technologies (ICTs) to enable a broad range of advanced services. Through a comprehensive literature review, this study identified four pitfalls brought by the pervasive application of ICT, including information insecurity, privacy leakage, information islands, and digital divide. Therefore, a questionnaire survey together with 27 interviews was conducted in Hong Kong to investigate how the public perceived these pitfalls within the context of mobile apps providing real-time parking information which form a major part of smart mobility. System insecurity and privacy leakage were found to arouse worries among the app-users while their awareness of protecting personal data was found to have room for improvement. Islands of real-time parking information occur as a result of the lack of collaboration among private carpark operators. Digital divide existed widely among the disadvantaged groups and the problem cannot be solved by mere provision of ICT facilities. Overall, technologies alone cannot make a city smart or smarter. It is the suitable way in which ICTs are used to serve all citizens that matters.     

Sulfonylguanidine Derivatives as Potential Antimelanoma Agents

Sulfonylguanidines are interesting bioactive compounds with a broad range of applications in the treatment of different pathologies. 2-Aminobenzazole-based structures are well employed in the development of new anticancer drugs. Two series of novel N-benzazol-2-yl-N′-sulfonyl guanidine derivatives were synthesized with the sulfonylguanidine in either an extra- or intracyclic frame. They were evaluated for their antiproliferative activity against malignant melanoma tumor cells, thus allowing structure-activity relationships to be defined. Additionally, NCI-60 screening was performed for the best analogue to study its efficiency against a panel of other cancer cell lines. The stability profile of this promising compound was then validated. During the synthetic process, an unexpected new deamidination of the sulfonylguanidine towards sulfonamide function was also identified.