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.

Turbulence-resistant free space optical communication via chaotic block-matching and 3D filtering.

In this paper, we propose a chaotic block-matching and three-dimensional (C-BM3D) filtering algorithm to remove the noise and enhance the security in the turbulent channel of free space optical (FSO) communication. We experimentally demonstrate the performance of C-BM3D by comparing it with chaotic non-local means filtering (C-NLM), chaotic Gaussian filtering and chaotic Median filtering based on Log-normal and Gamma-Gamma turbulence models. The results show that the peak signal-to-noise ratios (PSNRs) of C-BM3D in the weak turbulence under Log-normal and Gamma-Gamma models are up to 96.2956 and 93.2853, respectively. The C-BM3D also achieves superior image similarity in Log-normal turbulent channel, with its structural similarity index measures (SSIMs) nearly equal to 1. Additionally, the signal-to-noise ratio (SNR) of C-BM3D ranks the highest, and its bit error rate (BER) improves by at least 15 dB compared to that of the other three algorithms. The experimental results indicate that the C-BM3D can be a good candidate for the next generation of FSO communication in security and turbulence resistance.

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.

Hybrid digital-analog FSO fronthaul system with channel-adaptive insertion of analog bandwidth.

With the arrival of the 5th generation mobile network, the number of user devices is increasing exponentially, and thus it is necessary to expand the capacity of transmission systems. In order to further improve the system spectral efficiency on the basis of existing mobile fronthaul devices, we propose a hybrid digital-analog fronthaul transmission system with adaptive insertion of analog bandwidth, which can dynamically change the position of inserted analog bandwidth based on the state information of free space optical (FSO) channel. We consider the effects of atmospheric attenuation and turbulence on the FSO channel and derive an analytical expression for the maximum analog signal bandwidth that can be inserted into the first null of the digital signal spectrum to meet BER requirement of 3.8 × 10-3. Through a comprehensive simulation, it is verified that the analog bandwidth is obtained by this expression can exactly represent the lower bound of the simulation results under weak turbulence condition. The obtained results show that the maximum insertable analog bandwidth beyond the spectral null of the digital signal can reach 10% of the digital signal bandwidth, even in the FSO link with a transmission distance of 0.5 km and attenuation factor of 8 dB/km.

Secure turbulence-resistant coherent free-space optical communications via chaotic region-optimized probabilistic constellation shaping.

We propose a chaotic region-optimized probabilistic constellation shaping (CRPCS) scheme to enhance the security and the resistance to turbulence for free-space optical (FSO) communications. For this approach, a four-dimensional hyperchaotic system generates a pseudorandom sequence to rotate and encrypt the constellation. Constellation distribution of short pseudorandom sequences behaves as the law of a non-uniform character. Grouping long pseudorandom sequences and counting the characteristics of constellation distribution can realize probabilistic constellation shaping with low and fixed redundant information. We demonstrate a 56 Gbyte/s coherent FSO communication system based on log-normal and Gamma-Gamma turbulence models with a key space of 1075. The results show that the optical receiver sensitivity is improved by 0.3-1.1 dB, and the transmission distance is also improved by 3.2%-7.0% in different shaping cases.

Independent dual-single-sideband QPSK signal detection based on a single photodetector.

The two sidebands of the independent dual-single-sideband (dual-SSB) signal can carry different information to achieve higher spectral efficiency. However, the two sidebands of the independent dual-SSB vector signal are received independently. Generally, the receiver divides the signal into two channels. For each channel, we use an optical bandpass filter (OBPF) to select the left sideband (LSB) or right sideband (RSB), respectively. Then a photodetector (PD) is used for photoelectric conversion, followed by subsequent digital signal processing (DSP). To reduce the complexity and cost of the receiver, we propose a new independent dual-SSB vector signal detection scheme based on a single PD combined with conventional DSP. An electric bandpass filter (EBPF) filters out high-frequency components after photoelectric conversion, and then the signal is quadrature demodulated and processed by the DSP algorithm. The LSB and RSB are quadrature phase-shift keying (QPSK) modulated with an initial phase difference of π/4. Simulation results show that the proposed scheme performs better bit error rate (BER). For back-to-back (BTB) transmission, the BER of 2-Gbaud independent dual-SSB vector signal (1-Gbuad RSB and 1-Gbaud LSB) can reach the hard-decision forward error correction (HD-FEC) threshold of 3.8 × 10-3 when the input optical power into PD is -20 dBm. For 1-km and 2-km weak turbulence free-space optical (FSO) channel transmission, the BER of 2-Gbaud independent dual-SSB vector signal can reach the HD-FEC threshold when the input optical power into PD is -18.8 and -17 dBm, respectively. For 1-km weak turbulence FSO channel transmission, the BER of 4-, 8-, and 16-Gbuad independent dual-SSB vector signal can reach the HD-FEC threshold when the input optical power into PD is -17.8, -16, and -15 dBm, respectively.

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%.

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.

Channel prediction for intelligent FSO transmission system.

Free space optical (FSO) communication has attracted significant attention due to its high transmission rate and information security. Nevertheless, the FSO link is sensitive to various weather conditions which limit its application range. Thus, research on the FSO channel plays an important role for combatting channel fading. In the paper, we first establish a FSO transmission testbed to obtain received signal strength indication (RSSI) information of optical signal. Then we utilize an environmental chamber for indoor experiments to simulate weather changes in the real world. Finally, based on the true meteorological dataset from the official department and the RSSI dataset from the experiments, we employ expanded gated recurrent unit (GRU) neural networks to implement the FSO channel prediction. The results demonstrate that the proposed scheme can achieve the prediction of FSO channel fading with a high precision, where the absolute percentage error (APE) values lower than 6.9% account for up to ninety% of results.

Asymmetric constellation transmission for a coherent free-space optical system with spatial diversity.

Spatial diversity is widely recognized as an effective technique for free-space optical (FSO) communication to combat channel fading. Most existing works on spatial diversity in FSO systems focus on intensity modulation and direct detection, while fewer mention coherent optical detection, which excels in optical receiver responsivity. Spatial diversity enables the FSO coherent system to demodulate the signal components of in-phase (I) and quadrature (Q) separately and thus simplify the coherent detector. More importantly, due to the differential channel conditions between I and Q components, we are offered a chance to realize an asymmetric quadrature amplitude modulation (QAM) constellation that can utilize the channel capacity of both I and Q components more sufficiently. Performance results demonstrate that the simplified structure and improved spectrum efficiency can be realized in the asymmetric QAM transmission system with an acceptable bit-error-rate loss.

Virtual Network Embedding for Multi-Domain Heterogeneous Converged Optical Networks: Issues and Challenges.

The emerging 5G applications and the connectivity of billions of devices have driven the investigation of multi-domain heterogeneous converged optical networks. To support emerging applications with their diverse quality of service requirements, network slicing has been proposed as a promising technology. Network virtualization is an enabler for network slicing, where the physical network can be partitioned into different configurable slices in the multi-domain heterogeneous converged optical networks. An efficient resource allocation mechanism for multiple virtual networks in network virtualization is one of the main challenges referred as virtual network embedding (VNE). This paper is a survey on the state-of-the-art works for the VNE problem towards multi-domain heterogeneous converged optical networks, providing the discussion on future research issues and challenges. In this paper, we describe VNE in multi-domain heterogeneous converged optical networks with enabling network orchestration technologies and analyze the literature about VNE algorithms with various network considerations for each network domain. The basic VNE problem with various motivations and performance metrics for general scenarios is discussed. A VNE algorithm taxonomy is presented and discussed by classifying the major VNE algorithms into three categories according to existing literature. We analyze and compare the attributes of algorithms such as node and link embedding methods, objectives, and network architecture, which can give a selection or baseline for future work of VNE. Finally, we explore some broader perspectives in future research issues and challenges on 5G scenario, field trail deployment, and machine learning-based algorithms.

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.

Screening and analysis for potential clinical diagnostic and prognostic markers in allergic rhinitis.

PURPOSE: To identify potential clinical diagnostic and prognostic markers for allergic rhinitis (AR) by analyzing a range of inflammatory and clinical markers in a cohort of patients. METHODS: We conducted a retrospective analysis of clinical data from 493 AR patients treated at Qianjiang Central Hospital from January to March 2023. Patients were categorized based on their outcome. Inclusion and exclusion criteria were strictly applied to select the study population. Various clinical and inflammatory markers were assessed, and statistical analyses were performed to evaluate their diagnostic and prognostic utility. RESULTS: No significant differences in traditional demographic factors were found between the good and poor prognosis groups (all P > 0.05). However, significant differences were observed in several inflammatory and clinical markers: Interleukin-4 (IL-4) levels were 17.32 ± 4.21 pg/mL in the good prognosis group versus 18.56 ± 5.89 pg/mL in the poor prognosis group (t=2.562, P=0.011). Interleukin-5 (IL-5) levels were 15.65 ± 3.78 pg/mL versus 16.52 ± 4.56 pg/mL, respectively (t=2.221, P=0.027). Transforming growth factor-ß1 (TGF-ß1) levels were 39.16 ± 8.92 pg/mL versus 41.32 ± 9.67 pg/mL (t=2.513, P=0.012), and histamine levels were 11.87 ± 3.21 ng/mL versus 12.56 ± 4.03 ng/mL (t=1.991, P=0.047). Interleukin-13 (IL-13) levels were 16.32 ± 3.56 pg/mL versus 17.09 ± 4.21 pg/mL (t=2.108, P=0.036). Serum immunoglobulin E (IgE) levels were significantly different, with 164.87 ± 45.32 IU/mL in the good prognosis group compared to 198.56 ± 58.21 IU/mL in the poor prognosis group (t=6.866, P < 0.001). The composite biomarker model demonstrated high predictive value for AR prognosis with an Area Under Curve of 0.906. Individual markers such as TGF-ß1, IL-13, and serum IgE levels showed strong diagnostic potential. CONCLUSION: Our findings underscore the clinical utility of various inflammatory and clinical markers as diagnostic and prognostic indicators for AR. TGF-ß1, IL-13, and serum IgE levels, in particular, demonstrated significant diagnostic and prognostic value. An integrated approach combining multiple biomarkers could enhance the accuracy of AR diagnosis and prognosis. Further validation through prospective clinical studies and consideration of treatment interventions are recommended to clarify the clinical implications of these markers.

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.

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.

Levels, compositions, and inventory of polybrominated diphenyl ethers in sewage sludge of Guangdong Province, South China.

Polybrominated diphenyl ethers (PBDEs) were measured in sewage sludge samples collected from major wastewater treatment plants in Guangdong Province, South China. Concentrations of ∑39PBDE (all 39 compounds including tri- to hepta- PBDE congeners except for BDE-209) ranged from 3.6 to 428 ng/g dw with a mean value of 67.4 ng/g dw and a median value of 25.9 ng/g dw, and those of BDE-209 ranged from 9.9 to 5,010 ng/g dw (mean 1,024 ng/g dw and median 824 ng/g dw). The PBDE mixtures detected were mainly comprised of penta-, octa-, and deca-BDEs, with deca-BDE as the dominant constituent. The most abundant congeners, excluding BDE-209, were BDE-47, BDE-99, and BDE-183. Good correlations were found among the concentrations of BDE-47, BDE-99, BDE-100, BDE-138, and BDE-154 (r>0.8). However, poor correlations were found between the concentrations of BDE-209 and all other congeners (r<0.3). This fact suggests that most tri- to hepta-BDEs detected did not originate from decomposition of deca-BDE. The estimated annual emission of ∑allPBDEs, ∑39PBDEs, penta-BDE, octa-BDE, and deca-BDE to the Pearl River Delta environment (PRD), based on the sludge samples analyzed, amounts to 232, 20.2, 5.5, 1.7, and 212 kg per year, implicating sewage sludge as a significant source of PBDEs to the PRD environment.