Mechanism of Musashi2 affecting radiosensitivity of lung cancer by modulating DNA damage repair.

Identifying new targets for overcoming radioresistance is crucial for improving the efficacy of lung cancer radiotherapy, given that tumor cell resistance is a leading cause of treatment failure. Recent research has spotlighted the significance of Musashi2 (MSI2) in cancer biology. In this study, we first demonstrated that MSI2 plays a key function in regulating the radiosensitivity of lung cancer. The expression of MSI2 is negatively correlated with overall survival in cancer patients, and the knockdown of MSI2 inhibits tumorigenesis and increases radiosensitivity of lung cancer cells. Cellular radiosensitivity, which is closely linked to DNA damage, is influenced by MSI2 interaction with ataxia telangiectasia mutated and Rad3-related kinase (ATR) and checkpoint kinase 1 (CHK1) post-irradiation; moreover, knockdown of MSI2 inhibits the ATR-mediated DNA damage response pathway. RNA-binding motif protein 17 (RBM17), which is implicated in DNA damage repair, exhibits increased interaction with MSI2 post-irradiation. We found that knockdown of RBM17 disrupted the interaction between MSI2 and ATR post-irradiation and increased the radiosensitivity of lung cancer cells. Furthermore, we revealed the potential mechanism of MSI2 recruitment into the nucleus with the assistance of RBM17 to activate ATR to promote radioresistance. This study provides novel insights into the potential application of MSI2 as a new target in lung cancer radiotherapy.

TITAN: Combining a bidirectional forwarding graph and GCN to detect saturation attack targeted at SDN.

The decoupling of control and forwarding layers brings Software-Defined Networking (SDN) the network programmability and global control capability, but it also poses SDN security risks. The adversaries can use the forwarding and control decoupling character of SDN to forge legitimate traffic, launching saturation attacks targeted at SDN switches. These attacks can cause the overflow of switch flow tables, thus making the switch cannot forward benign network traffic. How to effectively detect saturation attack is a research hotspot. There are only a few graph-based saturation attack detection methods. Meanwhile, the current graph generation methods may take useless or misleading information to the attack detection, thus decreasing the attack detection accuracy. To solve the above problems, this paper proposes TITAN, a bidirecTional forwardIng graph-based saturaTion Attack detectioN method. TITAN defines flow forwarding rules and topology information, and designs flow statistical features. Based on these definitions, TITAN generates nodes of the bi-forwarding graph based on the flow statistics features and edges of the bi-forwarding graph based on the network traffic routing paths. In this way, each traffic flow in the network is transformed into a bi-directional forwarding graph. Then TITAN feeds the above bidirectional forwarding graph into a Graph Convolutional Network (GCN) to detect whether the flow is a saturation attack flow. The experimental results show that TITAN can effectively detect saturation attacks in SDNs with a detection accuracy of more than 97%.

Fast Response GaN Nanoscale Air Channel Diodes with Highly Stable 10 mA Output Current toward Wafer-Scale Fabrication.

Nanoscale air channel transistors (NACTs) have received significant attention due to their remarkable high-frequency performance and high switching speed, which is enabled by the ballistic transport of electrons in sub-100 nm air channels. Despite these advantages, NACTs are still limited by low currents and instability compared to solid-state devices. GaN, with its low electron affinity, strong thermal and chemical stability, and high breakdown electric field, presents an appealing candidate as a field emission material. Here, a vertical GaN nanoscale air channel diode (NACD) with a 50 nm air channel is reported, fabricated by low-cost IC-compatible manufacturing technologies on a 2-inch sapphire wafer. The device boasts a record field emission current of 11 mA at 10 V in the air and exhibits outstanding stability during cyclic, long-term, and pulsed voltage testing. Additionally, it displays fast switching characteristics and good repeatability with a response time of fewer than 10 ns. Moreover, the temperature-dependent performance of the device can guide the design of GaN NACTs for applications in extreme conditions. The research holds great promise for large current NACTs and will speed up their practical implementation.

Efficacy of the Chinese herbal medicine Jintiange capsules in the postoperative treatment of osteoporotic vertebral compression fractures: a systematic review and meta-analysis.

Background: In traditional Chinese medicine, Jintiange capsules are frequently used to treat metabolic bone diseases and strengthen bones and tendons. The main component of Jintiange capsules is bionic tiger bone powder. However, the active ingredients and proteins are derived from other animal bones, with chemical profiles similar to that of natural tiger bone. This study aimed to explore the efficacy of Jintiange capsules, a Chinese herbal medicine, in the postoperative treatment of osteoporotic vertebral compression fractures (OVCFs). Methods: In this systematic review, literature was retrieved using PubMed, the Cochrane Library, the Chinese National Knowledge Infrastructure, the Web of Science, the Wanfang Database, the Chinese Biomedical Literature Database, and the Chinese VIP Database from inception to July 2023. The primary outcome measures were the bone mineral density (BMD) and effective rate. The secondary outcome measures were the visual analog pain score (VAS), Oswestry disability index (ODI), Cobb's angle, serum osteocalcin, serum alkaline phosphatase, and adverse events. RevMan 5.4 and STATA 17.0 software were used for data analysis. Results: We enrolled randomized controlled trials (RCTs) focusing on 1,642 patients in the meta-analysis. The meta-analysis illustrated that Jintiange capsules significantly increased the BMD of the lumbar spine (p < 0.00001), femoral neck (p = 0.0005), and whole body (p = 0.01). The subgroup analysis of Jintiange capsules combination therapy showed that the BMD of the lumbar spine and whole body was significantly improved with Jintiange capsules (p < 0.00001). The test for the overall effect showed that Jintiange capsules had a significantly higher effective rate than the control groups (p = 0.003). Additionally, the overall effect test showed that Jintiange capsules decreased the VAS and ODI (p < 0.00001) and Cobb's angle (p = 0.02), and improved serum OC and ALP (p < 0.00001) compared with the controls. Furthermore, the pooled analysis of adverse reactions showed no serious impacts on the treatment of OVCFs. Conclusion: Jintiange capsules demonstrate high safety and efficacy in the treatment of OVCFs, including increasing BMD, the lift effect rate, serum OC levels, and pain relief, decreasing the ODI, serum ALP levels, and adverse events, and improving Cobb's angle. Additional research is required to validate the efficacy of Jintiange capsules for the postoperative treatment of OVCFs.Systematic review registration: https://www.crd.york.ac.uk/PROSPERO.

Zymosan-A promotes the regeneration of intestinal stem cells by upregulating ASCL2.

Intestinal stem cells (ISCs) are responsible for intestinal tissue homeostasis and are important for the regeneration of the damaged intestinal epithelia. Through the establishment of ionizing radiation (IR) induced intestinal injury model, we found that a TLR2 agonist, Zymosan-A, promoted the regeneration of ISCs in vivo and in vitro. Zymosan-A improved the survival of abdominal irradiated mice (81.82% of mice in the treated group vs. 30% of mice in the PBS group), inhibited the radiation damage of intestinal tissue, increased the survival rate of intestinal crypts and the number of ISCs after lethal IR in vivo. Through organoid experiments, we found that Zymosan-A promoted the proliferation and differentiation of ISCs after IR. Remarkably, the results of RNA sequencing and Western Blot (WB) showed that Zymosan-A reduced IR-induced intestinal injury via TLR2 signaling pathway and Wnt signaling pathway and Zymosan-A had no radioprotection on TLR2 KO mice, suggesting that Zymosan-A may play a radioprotective role by targeting TLR2. Moreover, our results revealed that Zymosan-A increased ASCL2, a transcription factor of ISCs, playing a core role in the process of Zymosan-A against IR-induced intestinal injury and likely contributing to the survival of intestinal organoids post-radiation. In conclusion, we demonstrated that Zymosan-A promotes the regeneration of ISCs by upregulating ASCL2.

Screening of miRNAs in White Blood Cell as a Radiation Biomarkers for Rapid Assessment of Acute Radiation Injury.

Accidental radiation exposure is a threat to human health that necessitates effective clinical diagnosis. Suitable biomarkers are urgently needed for early assessment of exposure dose. Existing technologies being used to assess the extent of radiation have notable limitations. As a radiation biomarker, miRNA has the advantages of simple detection and high throughput. In this study, we screened for miRNAs with dose and time dependent responses in peripheral blood leukocytes via miRNA sequencing in establishing the animal model of acute radiation injury. Four radiation-sensitive and stably expressed miRNAs were selected out in the 24 h group of leukocyte miRNAs: mmu-miR-130b-5p, mmu-miR-148b-5p, mmu-miR-184-3p, mmu-miR-26a-2-3p, and five were screened in the 48 h group of leukocyte miRNAs: mmu-miR-130b-5p, mmu-miR-423-5p, mmu-miR-676-3p, mmu-miR-150-5p, mmu-miR-342-3p.The correlation curves between their expression and irradiation dose were plotted. Then, the results were validated by RT-qPCR in mouse peripheral blood. As a result, mmu-miR-150-5p and mmu-miR-342-3p showed the highest correlation at 48h after irradiation, and mmu-miR-130b-5p showed good correlation at both 24 h and 48 h after irradiation. In a conclusion, the miRNAs that are sensitive to ionizing radiation with dose dependent effects were selected out, which have the potential of forming a rapid assessment scheme for acute radiation injury.

FG-4592 protects the intestine from irradiation-induced injury by targeting the TLR4 signaling pathway.

BACKGROUND: Severe ionizing radiation (IR)-induced intestinal injury associates with high mortality, which is a worldwide problem requiring urgent attention. In recent years, studies have found that the PHD-HIF signaling pathway may play key roles in IR-induced intestinal injury, and we found that FG-4592, the PHD inhibitor, has significant radioprotective effects on IR-induced intestinal injury. METHODS: In the presence or absence of FG-4592 treatment, the survival time, pathology, cell viability, cell apoptosis, and organoids of mice after irradiation were compared, and the mechanism was verified after transcriptome sequencing. The data were analyzed using SPSS ver. 19 software. RESULTS: Our results show that FG-4592 had significant radioprotective effects on the intestine. FG-4592 improved the survival of irradiated mice, inhibited the radiation damage of intestinal tissue, promoted the regeneration of intestinal crypts after IR and reduced the apoptosis of intestinal crypt cells. Through organoid experiments, it is found that FG-4592 promoted the proliferation and differentiation of intestinal stem cells (ISCs). Moreover, the results of RNA sequencing and Western blot showed that FG-4592 significantly upregulated the TLR4 signaling pathway, and FG-4592 had no radioprotection on TLR4 KO mice, suggesting that FG-4592 may play protective role against IR by targeting TLR4. CONCLUSION: Our work proves that FG-4592 may promote the proliferation and regeneration of ISCs through the targeted regulation of the TLR4 signaling pathway and ultimately play radioprotective roles in IR-induced injury. These results enrich the molecular mechanism of FG-4592 in protecting cells from IR-induced injury and provide new methods for the radioprotection of intestine.

Pulse repetition rate doubling in FM actively mode-locked fiber-optic parametric oscillator.

A photonic method to generate pulse trains with double repetition rate in FM actively mode-locked fiber-optic parametric oscillator (FOPO) has been proposed and experimentally demonstrated. Pulse trains can exist at either of the two extremums of phase modulation, which can be controlled by tuning an intra-cavity polarization controller (PC) before a phase modulator. Moreover, the pulse formation and spectral characteristics of the proposed FOPO are investigated. By continually rotating the intra-cavity PC, two optical pulse trains corresponding to two different mode-locked states are generated simultaneously. In the experiment, 8, 10, 12 and 14GHz pulse trains are generated using RF drive frequencies of around 4, 5, 6 and 7GHz, respectively.

Output characterization of a fiber optic parametric oscillator based on multiple four-wave mixing.

The output characteristics of a fiber optic parametric oscillator (FOPO) based on multiple four-wave mixing (multi-FWM) processes are investigated numerically and demonstrated experimentally. The theoretical model of a FOPO based on multi-FWM processes is presented. It is proved that the output signal starts to saturate when the high-order parametric products are generated in the multi-FWM processes of FOPOs. Moreover, a higher output power of the idler (i.e., the first-order parametric product) is achieved. On the other hand, the pump power is proved to be a key factor that significantly influences the output of the FOPO.

Design, synthesis, and anti-tumor activities of novel triphenylethylene-coumarin hybrids, and their interactions with Ct-DNA.

Novel triphenylethylene-coumarin hybrid derivatives containing different amounts of amino side chains were designed and synthesized in good yields under microwave radiation. The derivatives 5b-d which possessed two amino side chains (except morpholinyl) showed a broad-spectrum and good anti-proliferative activity against five tumor cells and low cytotoxicity in osteoblast. UV-vis, fluorescence, and circular dichroism (CD) spectroscopies and thermal denaturation exhibited that compounds 10 c, 5c, and 13c bearing amino side chain (except morpholinyl) on 4-phenyl had significant interactions with Ct-DNA by the intercalative mode of binding. Structure-activity relationships (SARs) analysis suggested that the amino alkyl chain would play an important role both in the compounds against tumor cells proliferation and their interactions with DNA.

Synthesis and biological activity of novel 5'-arylamino-nucleosides by microwave-assisted one-pot tandem Staudinger/aza-Wittig/reduction.

Novel pseudonucleosides with benzylamino group on 5'-position (4) were synthesized by using the microwave-assisted one-pot tandem Staudinger/aza-Wittig/reduction reaction in good yields of 55.2-71.7%. The deacetylation of 4 afforded compounds 5. HIV-1 reverse transcriptase (RT) inhibitory and antitumor activities were preliminarily evaluated with 5. The results showed that the new pseudonucleosides (5) could effectively inhibit HIV-1 RT activity, but no antitumor activity.