Supramolecular Switch for the Regulation of Antibacterial Efficacy of Near-Infrared Photosensitizer.

The global antibiotic resistance crisis has drawn attention to the development of treatment methods less prone to inducing drug resistance, such as antimicrobial photodynamic therapy (aPDT). However, there is an increasing demand for new photosensitizers capable of efficiently absorbing in the near-infrared (NIR) region, enabling antibacterial treatment in deeper sites. Additionally, advanced strategies need to be developed to avert drug resistance stemming from prolonged exposure. Herein, we have designed a conjugated oligoelectrolyte, namely TTQAd, with a donor-acceptor-donor (D-A-D) backbone, enabling the generation of reactive oxygen species (ROS) under NIR light irradiation, and cationic adamantaneammonium groups on the side chains, enabling the host-guest interaction with curcubit[7]uril (CB7). Due to the amphiphilic nature of TTQAd, it could spontaneously form nanoassemblies in aqueous solution. Upon CB7 treatment, the positive charge of the cationic adamantaneammonium group was largely shielded by CB7, leading to a further aggregation of the nanoassemblies and a reduced antibacterial efficacy of TTQAd. Subsequent treatment with competitor guests enables the release of TTQAd and restores its antibacterial effect. The reversible supramolecular switch for regulating the antibacterial effect offers the potential for the controlled release of active photosensitizers, thereby showing promise in preventing the emergence of drug-resistant bacteria.

Intelligent scoring system based on dynamic optical breast imaging for early detection of breast cancer.

Early detection of breast cancer can significantly improve patient outcomes and five-year survival in clinical screening. Dynamic optical breast imaging (DOBI) technology reflects the blood oxygen metabolism level of tumors based on the theory of tumor neovascularization, which offers a technical possibility for early detection of breast cancer. In this paper, we propose an intelligent scoring system integrating DOBI features assessment and a malignancy score grading reporting system for early detection of breast cancer. Specifically, we build six intelligent feature definition models to depict characteristics of regions of interest (ROIs) from location, space, time and context separately. Similar to the breast imaging-reporting and data system (BI-RADS), we conclude the malignancy score grading reporting system to score and evaluate ROIs as follows: Malignant (≥ 80 score), Likely Malignant (60-80 score), Intermediate (35-60 score), Likely Benign (10-35 score), and Benign (<10 score). This system eliminates the influence of subjective physician judgments on the assessment of the malignant probability of ROIs. Extensive experiments on 352 Chinese patients demonstrate the effectiveness of the proposed system compared to state-of-the-art methods.

End-Cloud Collaboration Navigation Planning Method for Unmanned Aerial Vehicles Used in Small Areas.

Unmanned aerial vehicle (UAV) collaboration has become the main means of indoor and outdoor regional search, railway patrol, and other tasks, and navigation planning is one of the key, albeit difficult, technologies. The purpose of UAV navigation planning is to plan reasonable trajectories for UAVs to avoid obstacles and reach the task area. Essentially, it is a complex optimization problem that requires the use of navigation planning algorithms to search for path-point solutions that meet the requirements under the guide of objective functions and constraints. At present, there are autonomous navigation modes of UAVs relying on airborne sensors and navigation control modes of UAVs relying on ground control stations (GCSs). However, due to the limitation of airborne processor computing power, and background command and control communication delay, a navigation planning method that takes into account accuracy and timeliness is needed. First, the navigation planning architecture of UAVs of end-cloud collaboration was designed. Then, the background cloud navigation planning algorithm of UAVs was designed based on the improved particle swarm optimization (PSO). Next, the navigation control algorithm of the UAV terminals was designed based on the multi-objective hybrid swarm intelligent optimization algorithm. Finally, the computer simulation and actual indoor-environment flight test based on small rotor UAVs were designed and conducted. The results showed that the proposed method is correct and feasible, and can improve the effectiveness and efficiency of navigation planning of UAVs.

The functions and prognostic values of chemokine and chemokine receptors in gastric cancer.

Chemokine and chemokine receptors (CCRs) play a significant role in tumor infiltration of immune cells, tumor angiogenesis and distant metastasis. In this study, we explored the importance of CCRs in gastric cancer (GC) by analyzing the datasets from TCGA database. First, we analyzed the characteristics of the CCRs mutations. Then, we screened the differentially expressed CCRs and performed GO functional annotation and KEGG pathway analyses to explore their potential biological functions. Using multivariate Cox regression analyses, we constructed a prediction model based on four-CCRs (CCL15, CCL21, CCR3 and ACKR3) signature, and we found that the risk score of the model was an independent prognostic factor of GC. Next, a nomogram was constructed to assess the prognosis of GC patients. GSEA indicated that the high-risk group was significantly enriched in immune response and immune system process. Moreover, GSVA was employed to investigate the up- and down-regulated signaling pathways in the high- and low-risk groups. The correlation between risk score and immune-cell infiltration indicated that the four-CCRs signature might play a pivotal role in GC immune microenvironment. In conclusion, we revealed the potential molecular mechanisms of CCRs in GC and constructed a prediction model which might guide personalized treatment and prognosis for GC patients.

PHF5A promotes colorectal cancerprogression by alternative splicing of TEAD2.

Dysregulated alternative splicing (AS) plays critical roles in driving cancer progression, and the underlying mechanisms remain largely unknown. Here, we demonstrated that PHF5A, a component of U2 small nuclear ribonucleoproteins, was frequently upregulated in colorectal cancer (CRC) samples and associated with poor prognosis. PHF5A promoted proliferation and metastasis of CRC cells in vitro and in vivo. Transcriptomic analysis identified PHF5A-regulated AS targets and pathways. Particularly, PHF5A induced TEAD2 exon 2 inclusion to activate YAP signaling, and interference of TEAD2-L partially reversed the PHF5A-mediated tumor progression. Pharmacological inhibition of PHF5A using pladienolide B had potent antitumor activity. Collectively, these data revealed the oncogenic role of PHF5A in CRC through regulating AS and established PHF5A as potential therapeutic target.

Intrinsically stretchable sheath-core ionic sensory fibers with well-regulated conformal and reprogrammable buckling.

Fiber-based intrinsically stretchable ionic conductors are appealing in the emerging imperceptible sensing devices with an ultrabroad working range, yet still suffer from a low strain sensitivity (gauge factor generally smaller than 3) as compared to electronic conductors. To circumvent this issue, here we report downsized superelastic sheath-core ionic sensory fibers with a fingerprint-like conformal buckling architecture. By delicately regulating the intermolecular interactions in the ionogel core and fluoroelastomer sheath as well as adjusting holding strains, the transparency and buckling density of the fiber are finely modulated. Heat to above 60 °C would further erase the formed buckles, enabling the encoded information of the fiber to be reprogrammable. Importantly, introducing conformal buckles are shown to bring about two-fold sensitivity enhancement of the sensory fibers, leading to a considerably high gauge factor of 10.1 for ionic strain sensors. Furthermore, the water droplet control ability of the buckled fibers with tunable wettability is also demonstrated, contributing to the versatility of the present sensory fibers which may gain promising applications in integrative electronics, optics, and microfluidics.

Delivery of Anti-miRNA-221 for Colorectal Carcinoma Therapy Using Modified Cord Blood Mesenchymal Stem Cells-Derived Exosomes.

Background: Exosomes, as natural intercellular information carriers, have great potential in the field of drug delivery. Many studies have focused on modifying exosome surface proteins to allow drugs to specifically target cancer cells. Methods: In this study, human cord blood mesenchymal stromal cell-derived exosomes were used in the delivery of anti-miRNA oligonucleotides so as to be specifically ingested by tumor cells to perform anti-tumor functions. Mesenchymal stem cells modified by the fusion gene iRGD-Lamp2b were constructed to separate and purify exosomes, and the anti-miRNA-221 oligonucleotide (AMO) was loaded into the exosomes by electroporation. Results: The AMO-loaded exosomes (AMO-Exos) effectively inhibited the proliferation and clonal formation of colon cancer cells in vitro, and it was further found that AMO-Exos was taken up by tumor cells through interaction with the NRP-1 protein. The results of a xenograft tumor model also showed that iRGD-modified exosomes were obviously enriched in tumor sites, exerting excellent anti-tumor efficacy. In vivo imaging showed that exosomes were mainly distributed in liver, spleen, and lung tissues. Conclusion: Our results suggest that genetically modified exosomes could be an ideal natural nanostructure for anti-miRNA oligonucleotide delivery.

Clinical Effects of Stereotactic Body Radiation Therapy Targeting the Primary Tumor of Liver-Only Oligometastatic Pancreatic Cancer.

AIM: To investigate the efficacy and safety of stereotactic body radiotherapy (SBRT) targeting the primary tumor for liver-only oligometastatic pancreatic cancer. METHODS: We compared the efficacy and safety of SBRT plus chemotherapy with chemotherapy alone in patients with liver-only oligometastatic pancreatic cancer. The populations were balanced by propensity score-weighted and propensity score-matched analyses based on baseline variables. The primary outcome was overall survival (OS). The secondary outcomes included progression free survival (PFS), local progression, metastatic progression and symptomatic local control. RESULTS: This is a retrospective study of 89 pancreatic cancer patients with liver-only oligometastasis. Overall, 34 (38.2%) and 55 (61.8%) patients received SBRT plus chemotherapy and chemotherapy alone, respectively. After propensity score matching, 1-year OS rate was 34.0% (95%CI, 17.8-65.1%) in the SBRT plus chemotherapy group and 16.5% (95%CI, 5.9-46.1%) in chemotherapy alone group (P=0.115). The 6-month PFS rate was 29.4% (95%CI, 15.4-56.1) in SBRT plus chemotherapy and 20.6% (95%CI, 8.8-48.6) in chemotherapy alone group (P=0.468), respectively. Further subgroup analysis indicated that the addition of SBRT improved OS in patients with primary tumor located in the head of pancreas (stratified HR, 0.28; 95% CI, 0.09 to 0.90) or good performance status (stratified HR, 0.24; 95% CI, 0.07 to 0.86). In terms of disease control, SBRT delayed local progression of pancreas (P=0.008), but not distant metastatic progression (P=0.56). Besides, SBRT offered significant abdominal/back pain relief (P=0.016) with acceptable toxicities. CONCLUSIONS: The addition of SBRT to chemotherapy in patients with liver-only oligometastatic pancreatic cancer improves the OS of those with primary tumor located in the head of pancreas or good performance status. In addition, it is a safe and effective method for local progression control and local symptomatic palliation in patients with metastatic pancreatic cancer.

CRISPR screen in cancer: status quo and future perspectives.

Clustered regularly interspaced short palindromic repeats (CRISPR) system offers a powerful platform for genome manipulation, including protein-coding genes, noncoding RNAs and regulatory elements. The development of CRISPR screen enables high-throughput interrogation of gene functions in diverse tumor biologies, such as tumor growth, metastasis, synthetic lethal interactions, therapeutic resistance and immunotherapy response, which are mostly performed in vitro or in transplant models. Recently, direct in vivo CRISPR screens have been developed to identify drivers of tumorigenesis in native microenvironment. Key parameters of CRISPR screen are constantly being optimized to achieve higher targeting efficiency and lower off-target effect. Here, we review the recent advances of CRISPR screen in cancer studies both in vitro and in vivo, with a particular focus on identifying cancer immunotherapy targets, and propose optimizing strategies and future perspectives for CRISPR screen.

Risk of Second Primary Malignancies Based on the Histological Subtypes of Colorectal Cancer.

Background: Previous studies have revealed an increased risk of second primary malignancies (SPMs) after colorectal cancer (CRC); however, no previous investigation has quantified differences in the risk of SPMs based on the histological subtypes of first primary CRC. Methods: Patients diagnosed with first primary CRC between 2000 and 2011 were identified from the Surveillance, Epidemiology, and End Results cancer registries. The patients were divided into three cohorts: classical adenocarcinoma (CA), mucinous adenocarcinoma (MA), and signet-ring cell carcinoma (SRCC). Standardized incidence ratios were calculated to assess the risk of SPMs among the patients. Results: Overall risk of SPMs was significantly higher among patients with three histological subtypes of CRC than in the general population. The risk of esophagus cancer was significantly increased in SRCC. The risk of small intestine, colon and rectum, and corpus uteri cancers was high in three histological subtypes, with the highest risk observed in SRCC, followed by MA. Increased risks of second stomach, uterus, urinary bladder, kidney, and thyroid cancers were only observed in CA patients, while increased risk of second renal pelvis cancer was limited to MA patients. Furthermore, the high overall risk of SPMs in CA patients persisted regardless of clinicopathological factors. After surgery combined with chemotherapy treatment, CA patients were more prone to developing second small intestine, colon and rectum cancers than those treated with surgery only. A lower second prostate cancer risk was observed in rectal CA patients treated with surgery combined with radiotherapy than in patients treated with surgery only. Conclusion: The present study revealed that the risk of developing SPMs after CRC varied based on the histological subtypes of the first primary CRC. Although the mechanisms underlying the observed patterns of SPM risk remain unknown, the study provided insights into future cancer surveillance based on the histological subtypes of CRC.

Efficient path planning for UAV formation via comprehensively improved particle swarm optimization.

Automatic generation of optimized flyable path is a key technology and challenge for autonomous unmanned aerial vehicle (UAV) formation system. Aiming to improve the rapidity and optimality of automatic path planner, this paper presents a three dimensional path planning algorithm for UAV formation based on comprehensively improved particle swarm optimization (PSO). In the proposed method, a chaos-based Logistic map is firstly adopted to improve the particle initial distribution. Then, the common used constant acceleration coefficients and maximum velocity are designed to adaptive linear-varying ones, which adjusts to the optimization process and meanwhile improves solution optimality. Besides, a mutation strategy that undesired particles are replaced by those desired ones is also proposed and the algorithm convergence speed is accelerated. Theoretically, the comprehensively improved PSO not only speeds up the convergence but also improves the solution optimality. Finally, Monte-Carlo simulation for UAV formation under terrain and threat constraints are carried out and the results illustrate the rapidity and optimality of the proposed method.

Preliminary Research on the Nonlinear Ultrasonic Detection of the Porosity of Porous Material Based on Dynamic Wavelet Fingerprint Technology.

Porosity is an important characteristic of porous material, which affects mechanical and material properties. In order to solve the problem that the large distribution range of pore size of porous materials leads to the large detection errors of porosity, the non-linear ultrasonic testing technique is applied. A graphite composite was used as the experimental object in the study. As the accuracy of porosity is directly related with feature extraction, the dynamic wavelet fingerprint (DWFP) technology was utilized to extract the feature parameter of the ultrasonic signals. The effects of the wavelet function, scale factor, and white slice ratio on the extraction of the nonlinear feature are discussed. The SEM photos were conducted using gray value to identify the aperture. The relationship between pore diameter and detection accuracy was studied. Its results show that the DWFP technology could identify the second harmonic component well, and the extracted nonlinear feature could be used for the quantitative trait of porosity. The larger the proportion of the small diameter holes and the smaller the aperture distribution range was, the smaller the error was. This preliminary research aimed to improve the nondestructive testing accuracy of porosity and it is beneficial to the application of porous material in the manufacturing field.

Long non-coding ribonucleic acid zinc finger antisense 1 promotes the progression of colonic cancer by modulating ZEB1 expression.

BACKGROUND AND AIM: Long non-coding RNA zinc finger antisense 1 (ZFAS1) is frequently amplified in hepatocellular carcinoma and promotes metastasis by increasing zinc finger E-box binding homeobox 1 (ZEB1), which can potentiate the progression of epithelial-to-mesenchymal transition (EMT). However, the expression pattern and role of ZFAS1 in colonic cancer remains unknown. The present study aimed to investigate the role of ZFAS1 and its clinical significance in colonic cancer. METHODS: Paired clinical colonic cancer tissue samples and clinicopathologic characteristics of 73 patients were analyzed. Quantitative real-time polymerase chain reaction analysis was used to evaluate expression levels of ZFAS1 in colonic cancer tissues, cell lines, and plasma. ZEB1 and EMT-related markers expression levels also were explored. Cell biology assays were used to explore the biologic consequences of ZFAS1 in regulating cell proliferation and invasion, as well as the roles in regulating EMT. RESULTS: Zinc finger antisense 1 was up-regulated in colonic cancer tissues compared with adjacent mucosa (P < 0.01), and its expression level was significantly correlated with TNM stage, vascular invasion, and lymph node metastasis (P < 0.05). ZFAS1 and ZEB1 were also increased in patients' plasma. Moreover, ZFAS1 promoted proliferation, invasion, and impeded apoptosis. Knockdown of ZFAS1 decreased expression of ZEB1 and increased the epithelial markers E-cadherin, ZO-1 while decreasing mesenchymal markers vimentin and N-cadherin. CONCLUSIONS: Long non-coding RNA ZFAS1 may function as an oncogene by modulating ZEB1 to induce EMT. Manipulation of ZFAS1 level may be a novel approach to suppress colonic cancer progression. In addition, ZFAS1 in plasma has the potential to be a diagnostic biomarker of colonic cancer.

Molecular Iodine-Mediated Difunctionalization of Alkenes with Nitriles and Thiols Leading to ß-Acetamido Sulfides.

A direct difunctionalization protocol of alkenes with nitriles and thiols toward ß-acetamido sulfide derivatives has been proposed under metal-free synthesis conditions. The present protocol provides the facile and highly efficient synthesis of various ß-acetamido sulfides in a scaled-up manner with good to excellent yields simply using inexpensive molecular iodine as a catalyst, DMSO as a mild oxidant, and readily available thiols as thiolating reagents.

Simple, green and high-yield production of single- or few-layer graphene by hydrothermal exfoliation of graphite.

Graphene is widely used as promising electronic material and devices, owing to its exceptional electronic and optoelectronic properties. Up to now, defect-free graphene has been limited to the method for controllable, reproducible and scalable mass production. A simple, green, and nontoxic approach for large-scale preparation of high quality graphene is produced by exfoliation of graphite sheets collaborated with intercalant (FeCl2) under hydrothermal conditions, the absence of defects or oxides in graphene with a yield up to 10 wt% can be a practical application and industrial process such as optical limiters, transparent conductors, and sensors. This new process could potentially be improved to give a yield of up to 35 wt% of the starting graphite mass with sediment recycling. We show with experiments and theories that exfoliation graphene is the result of a combined action by diminishing the van der Waals interactions between graphite layers and the shear force drove by the Brownian motion of H2O and FeCl2 molecules. Hydrothermal exfoliation has potential applications in the exfoliation of other layered materials (e.g. BN, MoS2) and carbon nantubes, and in the synthesis of intercalation compounds, nanoribbons, and nanoparticles, thus opening new ways of exfoliation engineering.