κ-Opioid Signaling in the Lateral Hypothalamic Area Modulates Nicotine-Induced Negative Energy Balance

Several studies have reported that nicotine, the main bioactive component of tobacco, exerts a marked negative energy balance. Apart from its anorectic action, nicotine also modulates energy expenditure, by regulating brown adipose tissue (BAT) thermogenesis and white adipose tissue (WAT) browning. These effects are mainly controlled at the central level by modulation of hypothalamic neuropeptide systems and energy sensors, such as AMP-activated protein kinase (AMPK). In this study, we aimed to investigate the kappa opioid receptor (κOR)/dynorphin signaling in the modulation of nicotine’s effects on energy balance. We found that body weight loss after nicotine treatment is associated with a down-regulation of the κOR endogenous ligand dynorphin precursor and with a marked reduction in κOR signaling and the p70 S6 kinase/ribosomal protein S6 (S6K/rpS6) pathway in the lateral hypothalamic area (LHA). The inhibition of these pathways by nicotine was completely blunted in κOR deficient mice, after central pharmacological blockade of κOR, and in rodents where κOR was genetically knocked down specifically in the LHA. Moreover, κOR-mediated nicotine effects on body weight do not depend on orexin. These data unravel a new central regulatory pathway modulating nicotine’s effects on energy balance.     

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.     

Tailored-Made Polydopamine Nanoparticles to Induce Ferroptosis in Breast Cancer Cells in Combination with Chemotherapy

Ferroptosis is gaining followers as mechanism of selective killing cancer cells in a non-apoptotic manner, and novel nanosystems capable of inducing this iron-dependent death are being increasingly developed. Among them, polydopamine nanoparticles (PDA NPs) are arousing interest, since they have great capability of chelating iron. In this work, PDA NPs were loaded with Fe³⁺ at different pH values to assess the importance that the pH may have in determining their therapeutic activity and selectivity. In addition, doxorubicin was also loaded to the nanoparticles to achieve a synergist effect. The in vitro assays that were performed with the BT474 and HS5 cell lines showed that, when Fe³⁺ was adsorbed in PDA NPs at pH values close to which Fe(OH)₃ begins to be formed, these nanoparticles had greater antitumor activity and selectivity despite having chelated a smaller amount of Fe³⁺. Otherwise, it was demonstrated that Fe³⁺ could be released in the late endo/lysosomes thanks to their acidic pH and their Ca²⁺ content, and that when Fe³⁺ was co-transported with doxorubicin, the therapeutic activity of PDA NPs was enhanced. Thus, reported PDA NPs loaded with both Fe³⁺ and doxorubicin may constitute a good approach to target breast tumors.     

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.     

Analysis and optimization of DS-CDMA systems with time-limited partial response chip waveforms

Conventional direct sequence code division multiple access systems (DS-CDMA) using offset quadrature phase shift key (OQPSK) usually employ a strictly bandlimited partial response square-root raised cosine pulse as the chip waveform. They have the disadvantage of large envelope fluctuation that will incur performance degradation due to the intermodulation and bandwidth enlargement caused by post nonlinear processing. To improve the performance of DS-CDMA systems, the chip waveform and receiver should be properly selected. This paper presents a systematic performance analysis of a matched filter receiver and zero-forcing filter (ZF) receiver for DS-CDMA using a time-limited partial response chip waveform. Nevertheless the systematic performance analysis is applicable to bandlimited chip pulse as well. For the zero-forcing filters, we propose to select the frequency responses that satisfy the first Nyquist criterion. With this class of filters, we can choose the roll-off factor to minimize the total power of multiple access interference and noise power. The zero-forcing filter with proper choice of roll-off factor, referred to as optimum ZF, yields a performance better than the matched filter counterpart. The bit error rate (BER) performance of the optimum ZF with superposed quadrature amplitude modulation signal as the time pulse waveform is evaluated. It is shown that the optimum ZF provides better BER performance than conventional OQPSK and minimum shift keying, and its envelope uniformity is much better than that of OQPSK.     

Derivation of a second-order switching surface in the boundary control of buck converters

A second-order switching surface in the boundary control of buck converters is derived in this letter. The formulated switching surface can make the overall converter exhibit better steady-state and transient behaviors than the one with a first-order switching surface. The switching surface is derived by estimating the state trajectory movement after a switching action, resulting in a high state trajectory velocity along the switching surface. This phenomenon accelerates the trajectory moving toward the target operating point. The proposed control scheme has been successfully applied to a 120-W buck converter. The large-signal performance and a comparison with the first-order switching surface have been studied.