Two-stage look-up-table-based 16QAM vector millimeter-wave signal generation and reception.

We propose a two-stage look-up table (LUT) scheme for a photonic 16 quadrature-amplitude-modulation (QAM) millimeter-wave (MMW) communication system. The first-stage LUT is used at the transmitter, which can eliminate complex computational processes and adaptively adjust the precoded amplitude values to achieve optimal performance without being affected by half-wave voltage variations. We have completed a signal transmission below the hard-decision forward error correction (HD-FEC) threshold of 3.8 × 10-3 at the baud rate of 2/4 GBaud for weak turbulence and 2 GBaud for medium turbulence free-space optics (FSO) channel transmission. The second-stage LUT is used for post-compensation at the receiver as a nonlinear scheme that records the average pattern-related distortion of the channel and mitigates transmission impairment through nonlinear post-compensation. With the help of the second-stage LUT, the sensitivity of the optical receiver is improved by 0.15 dB at a baud rate of 2 GBaud for medium turbulence FSO channel transmission. As the baud rate increases to 4 GBaud, the system's bit error ratio (BER) can reach the soft-decision forward error correction (SD-FEC) threshold of 4.2 × 10-2 only after applying the second-stage LUT.

Inhibition of CREB Binding and Function with a Dual-Targeting Ligand.

CBP/p300 is a master transcriptional coactivator that regulates gene activation by interacting with multiple transcriptional activators. Dysregulation of protein-protein interactions (PPIs) between the CBP/p300 KIX domain and its activators is implicated in a number of cancers, including breast, leukemia, and colorectal cancer. However, KIX is typically considered "undruggable" because of its shallow binding surfaces lacking both significant topology and promiscuous binding profiles. We previously reported a dual-targeting peptide (MybLL-tide) that inhibits the KIX-Myb interaction with excellent specificity and potency. Here, we demonstrate a branched, second-generation analogue, CREBLL-tide, that inhibits the KIX-CREB PPI with higher potency and selectivity. Additionally, the best of these CREBLL-tide analogues shows excellent and selective antiproliferation activity in breast cancer cells. These results indicate that CREBLL-tide is an effective tool for assessing the role of KIX-activator interactions in breast cancer and expanding the dual-targeting strategy for inhibiting KIX and other coactivators that contain multiple binding surfaces.

Full-duplex transmission without an uplink light source for a millimeter-wave radio over a free-space optical system.

The radio over free-space optical (RoFSO) system is a promising alternative technique for mobile fronthaul networks such as aerial base stations where fiber link is unavailable to deploy. However, the full-duplex transmission imposes challenges on the design of the RoFSO system due to the additional structural complexity when ease-of-installation is a mandatory request. The interplay between the uplink and downlink for a simplified structure has been less investigated in related works. In this paper, we propose a full-duplex RoFSO transmission system structure in which the uplink light source is physically saved. The optical center carrier of the double-sideband (DSB) modulated signal in the downlink is extracted as the light source for the uplink, and thus the system complexity is reduced. In order to mitigate the permanence degradation of uplink transmission due to the attenuated light source, channel estimation and power pre-compensation are implemented without additional training symbols by utilizing the characteristics of the channel correlation between uplink and downlink and the information independence of optical center carrier in the DSB. The proposed channel estimation algorithm is verified theoretically and experimentally. The results show that the difference between uplink and downlink channel attenuation is -0.7dB. In case of the excessive power compensation and the resulting effects, a power control mechanism is introduced to the power pre-compensation. By using the power pre-compensation mechanism, the bit error rate (BER) can reach 1.58×10-3 and 3.8×10-3, respectively, under the channel conditions of medium turbulence and weak turbulence. Owing to the power control mechanism, the power saving rates of downlink and uplink are up to 78% and 67%.

Clinical Effect of Laparoscopic Radical Surgery Combined with Neoadjuvant Chemotherapy in Treating Cervical Cancer and Its Influence on Postoperative Complications and Adverse Reaction Rates.

BACKGROUND: Cervical cancer, the only gynecological malignancy for which a clear pathogeny has been established, has an incidence rate only second to breast cancer. OBJECTIVE: In our study, we aim to investigate the clinical effect of laparoscopic radical surgery combined with neoadjuvant chemotherapy in treating cervical cancer and its influence on postoperative complications and adverse reaction rates. METHODS: Cervical cancer patients admitted to our hospital from August 2018 to May 2020 were retrospectively analyzed as the research object and divided into the control group and the experimental group by the draw method, with 50 cases in each group. The laparoscopic radical surgery was performed on the control group, and the laparoscopic radical surgery combined with neoadjuvant chemotherapy was performed on the experimental group to compare their effective rates, adverse reaction rates, postoperative complication rates, expression levels of serum tumor necrosis factor-α (TNF-α) and soluble interleukin-2 receptor (SIL-2R) inside the body before surgery and at one week after surgery, quality of life (QLI) scores, and Mental Status Scale in Nonpsychiatric Settings (MSSNS) scores. RESULTS: Compared with the control group, the experimental group obtained significantly higher effective rate and QLI scores (P < 0.05) and significantly lower adverse reaction rates, postoperative complication rates, expression levels of serum TNF-α and SIL-2R inside the body at one week after surgery, and MSSNS scores (P < 0.05), with statistical differences; before surgery, the TNF-α and SIL-2R expression levels of the two groups were not significantly different (P > 0.05), but the levels at one week after surgery were significantly lower than those before, indicating statistical significance (P < 0.05). CONCLUSION: The clinical effect of laparoscopic radical surgery combined with neoadjuvant chemotherapy can obviously improve the effective rate of cervical cancer patients and lower the incidence rates of postoperative complications and adverse reactions.

Norstictic Acid Is a Selective Allosteric Transcriptional Regulator.

Inhibitors of transcriptional protein-protein interactions (PPIs) have high value both as tools and for therapeutic applications. The PPI network mediated by the transcriptional coactivator Med25, for example, regulates stress-response and motility pathways, and dysregulation of the PPI networks contributes to oncogenesis and metastasis. The canonical transcription factor binding sites within Med25 are large (∼900 Å2) and have little topology, and thus, they do not present an array of attractive small-molecule binding sites for inhibitor discovery. Here we demonstrate that the depsidone natural product norstictic acid functions through an alternative binding site to block Med25-transcriptional activator PPIs in vitro and in cell culture. Norstictic acid targets a binding site comprising a highly dynamic loop flanking one canonical binding surface, and in doing so, it both orthosterically and allosterically alters Med25-driven transcription in a patient-derived model of triple-negative breast cancer. These results highlight the potential of Med25 as a therapeutic target as well as the inhibitor discovery opportunities presented by structurally dynamic loops within otherwise challenging proteins.

Gibberellin JRA-003: A Selective Inhibitor of Nuclear Translocation of IKKα.

The small molecule gibberellin JRA-003 was identified as an inhibitor of the NF-kB (nuclear kappa-light-chain-enhancer of activated B cells) pathway. Here we find that JRA-003 binds to and significantly inhibits the nuclear translocation of pathway-activating kinases IKKα (IκB kinase alpha) and IKKß (IκB kinase beta). Analogs of JRA-003 were synthesized and NF-κB-inhibiting gibberellins were found to be cytotoxic in cancer-derived cell lines (HS 578T, HCC 1599, RC-K8, Sud-HL4, CA 46, and NCIH 4466). Not only was JRA-003 identified as the most potent synthetic gibberellin against cancer-derived cell lines, it displayed no cytotoxicity in cells derived from noncancerous sources (HEK 293T, HS 578BST, HS 888Lu, HS 895Sk, HUVEC). This selectivity suggests a promising approach for the development of new therapeutics.

Long non-coding RNA PCAT7 regulates ELF2 signaling through inhibition of miR-134-5p in nasopharyngeal carcinoma.

While some long noncoding RNAs (lncRNAs) might promote nasopharyngeal carcinoma (NPC) initiation and progression, the involved molecular mechanisms remain largely unclear. Here, we discovered the novel LncRNA, prostate cancer associated transcript 7 (PCAT7), which was overexpressed and associated with worse prognosis in NPC. Decreased PCAT7 expression was found to significantly suppress tumor cell proliferation in vitro, and inhibited tumor growth and reduced the expression of proliferation antigen Ki-67 in vivo. Rescue assay was performed to further confirm that PCAT7 contributed to the progression of NPC through regulating miR-134-5p/ELF2 signal pathway. These results indicated that PCAT7 might contribute to the tumor progression in NPC by functioning as a ceRNA to sponge miR-134-5p.

Effectively enhancing cytotoxic and apoptotic effects of alpha-momorcharin by integrating a heparin-binding peptide.

Alpha-momorcharin (α-MMC), a type I ribosome-inactivating protein, has attracted a great deal of attention because of its antitumor activity. However, the cytotoxicity of α-MMC is limited due to insufficient cellular internalization in cancer cells. To enhance the cytotoxicity of α-MMC, a heparin-binding domain derived from heparin-binding epidermal growth factor (named heparin-binding peptide [HBP]) was used as a cell-penetrating peptide and fused to the C-terminus of α-MMC. This novel α-MMC-HBP fusion protein was expressed and purified with a Ni2+ -resin. The N-glycosidase activity and DNase activity assay indicated that the introduction of HBP did not interfere with the intrinsic bioactivities of α-MMC. HBP was able to efficiently carry α-MMC into the tested cancer cells and significantly enhance the cytotoxic effects of α-MMC in a dose-dependent manner. This enhanced cytotoxic ability occurred due to the higher level of cell apoptosis induced by α-MMC-HBP, which was demonstrated in western blot analysis in which α-MMC-HBP triggered caspase 8, caspase 9, casapase 3, and PARP more intensely than α-MMC alone. α-MMC-HBP led to an upregulation of cleaved PARP and an increase in the Bax/Bcl-2 ratio. Our study provided a new practical way to greatly improve the antitumor activity of α-MMC, which could significantly expand the pharmaceutical applications of α-MMC.