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Working memory is one of the essential abilities. When people have Post-Traumatic Stress Disorder (PTSD), their working memory is also impaired, mainly reflected in aspects of capacity and updating. When people directly face the disaster, it may bring serious psychological consequences and indirectly affect the injured people, leading them to suffer from PTSD. Some factors, such as personal and property safety, social support and background, and disaster mortality, can predict the incidence rate of PTSD. This paper aims to improve people's understanding of PTSD and working memory impairment and provides some insights and guidance for future research. By discussing recent studies, it can be found that PTSD patients have poor attention and task execution ability, impaired visual and auditory working memory, and insufficient capacity and updating ability of work memory. Some interventions also trained some components of working memory, which effectively alleviated the related symptoms of patients. There are relatively few relevant studies in this field, and there is a lack of sufficient evidence to prove the impact of working memory on PTSD directly. Future studies should examine this relationship with more systematic experimental designs. This review can provide some suggestions to the design of early intervention programs for at-risk populations.

There are few studies on esophageal adenosquamous carcinoma (ADSC). Our study intended to investigate the clinical and survival features of ADSC. We included esophageal cancer (EC) data from the Surveillance, Epidemiology, and End Results program database to explore clinical and survival traits. Propensity score matching (PSM), the multivariate Cox regression model, and survival curves were used in this study. A total of 137 patients with ADSC were included in our analysis. The proportion of ADSC within the EC cohort declined from 2004 to 2018. Besides, results indicated no significant difference in survival between ADSC and SCC groups (PSM-adjusted HR = 1.249, P = 0.127). However, the survival rate of the ADSC group was significantly worse than that of the ADC group (PSM-adjusted HR = 1.497, P = 0.007). For the ADSC group, combined treatment with surgery had a higher survival rate than other treatment methods (all P < 0.001). Surgical resection, radiotherapy, and chemotherapy were independent protective prognostic factors (all P < 0.05). The proportion of ADSC has been declining from 2004 to 2018. The prognosis of ADSC is not significantly different from that of SCC but is worse than that of ADC. Surgery, radiotherapy, and chemotherapy could improve the prognosis of patients. Comprehensive treatment with surgery as the main treatment is more beneficial for some patients.

In this paper, we report that the angular dispersion of the output pulses in a nonlinear process can be efficiently compensated by using a cascaded prism(s) and short hollow-core fiber (HCF) configuration. Here, the prism(s) is used to suppress the angular dispersion and transform it into spatial chirp, while the HCF is used for removing this spatial chirp and the residual angular dispersion, which can also significantly improve the beam quality. The feasibility of this novel method is numerically and experimentally investigated with the ultra-broadband idler pulses centered at 1250 nm wavelength and generated by an LBO crystal based non-collinear optical parametric amplifier. The proof-of-principle experiment shows that the angular dispersion can be effectively removed and ultra-broadband idler pulses with good spectral quality and spatial profile can be obtained. The total transmission efficiency in the experiment is around 67% and the measured M x 2 and M y 2 can reach 1.12 and 1.04, respectively. To the best of our knowledge, this is the first reported ultra-broadband angular dispersion compensation scheme combining prism(s) and HCF, which can remarkably eliminate the angular dispersion while simultaneously possesses high efficiency, good spectral and beam spatial quality.

Jingrong Yu, 1,* Cheng Fang, 2,* Ziyue Zhang, 2 Guifang Zhang, 3 Lihong Shi, 4 Jiayi Qian, 5 Jianping Xiong 6 1Department of Oncology, The Fourth Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province 330003, People’s Republic of China; 2Department of Oncology, Nanchang 334 Hospital, Nanchang, Jiangxi Province, People’s Republic of China; 3Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, People’s Republic of China; 4Department of Gynecology and Pediatrics, Nanchang 334 Hospital, Nanchang, Jiangxi Province, People’s Republic of China; 5Department of Ultrasound Electrophysiology, Nanchang 334 Hospital, Nanchang, Jiangxi Province, People’s Republic of China; 6Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province 330006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianping XiongDepartment of Oncology, The First Affiliated Hospital of Nanchang University, No. 17 Yongwai Street, Nanchang, Jiangxi Province 330006, People’s Republic of ChinaTel +86-13265847851Email jpxiong@medmail.comPurpose: The aim of this paper was to investigate H19 expression in gastric cancer (GC) and its effects on the biological behavior of gastric cancer cells (GCCs), and at exploring its potential mechanism.Methods: H19 expression in the patients’ tissues and serum was detected, and the correlation of the expression with the patients’ pathological data and survival rate was analyzed. Overexpression or inhibitory vectors of H19, microRNA-138 (miR-138) and E2F2 were constructed and transfected into GCCs to observe their effects on the cells’ proliferation, invasion and apoptosis.Results: H19 rose in GC and was higher in GC patients with a tumor size ≥ 5 cm, high stages (III+IV) and lymph node metastasis. High H19 expression was associated with the poorer survival rate of the patients, so serum H19 had a certain diagnostic value for GC. H19 knockdown could inhibit GCCs to proliferate and invade and induce their apoptosis. miR-138 can be used as the target gene of H19, and E2F2 can be negatively regulated by this miR, so miR-138 knockdown or E2F2 upregulation can weaken GCCs’ biological behavior changes that were caused by H19 knockdown.Conclusion: H19 can be used as a biological indicator for diagnosing GC and predicting patients’ poor prognosis. Additionally, it promotes GCCs to proliferate and invade through miR-138/E2F2 axis.Keywords: H19, miR-138, E2F2, gastric cancer

Gastric cancer is one of the most common digestive carcinomas throughout the world and represents high mortality. There is an urgent quest for seeking a novel and efficient antigastric cancer drug. Euphorbia fischeriana Steud had long been used as a traditional Chinese medicine for the treatment of cancer. According to the basic theory of traditional Chinese medicine, its antitumor mechanism is ‘to combat poison with poison’. However, its effective material foundation of it is still ambiguous. In our previous work, we studied the chemical constituents of E. fischeriana Steud. Jolkinolide B (JB) is an ent-abietane-type diterpenoid we isolated from it. The purpose of the present study was to investigate the antigastric effect and mechanism of JB. Results revealed that JB could suppress the proliferation of MKN45 cells in vitro and inhibit MKN45 xenograft tumor growth in nude mice in vivo. We further investigated its anticancer mechanism. On the one hand, JB caused DNA damage in gastric cancer MKN45 cells and induced the S cycle arrest by activating the ATR-CHK1-CDC25A-Cdk2 signaling pathway, On the other hand, JB induced MKN45 cells apoptosis through the mitochondrial pathway, and ultimately effectively inhibited the growth of gastric cancer cells. These results suggest that JB appears to be a promising candidate drug with antigastric cancer activity and warrants further research.

Nanostructured lipid carriers (NLC) have become a research hotspot, wherein cancer-targeting effects are enhanced and side effects of chemotherapy are overcome. Usually, accelerated blood clearance...

The object of this study was to observe and analyze the effect of glycosylated hemoglobin in treating diabetes and provide valuable guidance for clinical treatment. For this purpose, 160 patients treated in our hospital who were definitely diagnosed with diabetes after relevant examinations were classified into the study group. 160 cases with healthy physical examinations for the same period were enrolled as a reference group. Fasting blood glucose and glycosylated hemoglobin levels were measured in both groups, and inter-group comparisons were made. The detection results showed that the study group had significantly higher fasting blood glucose and glycosylated hemoglobin levels than the healthy reference group. The difference was statistically significant (p

In this paper, we report that the conversion efficiency and spectrum of femtosecond optical parametric amplification (fs-OPA) can be significantly enhanced by employing a compact cascaded femtosecond OPA (CF-OPA) scheme with the self-compensation of the temporal walk-off between two nonlinear gain media. Correspondingly, the gain related temporal contrast can also be improved. The feasibility of the CF-OPA method using three cascaded BBO crystals is numerically and experimentally analyzed. Moreover, by replacing the conventional fs-OPA with the CF-OPA and optimizing the design, the performance of a nonlinear temporal filter combining cross-polarized wave generation and fs-OPA is comprehensively improved. The experimental results demonstrate the superiority of the CF-OPA scheme, which can generate high-performance cleaned pulses at 1 kHz repetition rate with energy of 340μJ, energy fluctuation below 0.9% (RMS), spectral width of 97 nm (FWHM), Fourier-transform-limited pulse width of 12 fs and temporal contrast better than 10−12. To the best of our knowledge, this is the first reported temporal walk-off self-compensated quasi-collinear CF-OPA geometry adopting three cascaded BBO crystals, which can be easily generalized to other wavelengths or nonlinear crystals. The above nonlinear temporal filter with a CF-OPA scheme has the rarest comprehensive parameters, which can provide excellent seed pulses for PW and 10 PW class femtosecond laser systems.

To effectively inhibit the growth of breast cancer cells (MDA-MB-231 cells) by the combination method of chemotherapy and magnetic hyperthermia, we fabricated a biomimetic drug delivery (CSiFePNs) system composed of mesoporous silica nanoparticles (MSNs) containing superparamagnetic ferroferric oxide and Paclitaxel (PTX) coated with MDA-MB-231 cell membranes (CMs). In the in vitro cytotoxicity tests, the MDA-MB-231 cells incubated with CSiFePNs obtained IC50 value of 0.8 μgL−1, 3.5-fold higher than that of SiFePNs. The combination method of chemotherapy and magnetic hyperthermia can effectively inhibit the growth of MDA-MB-231 cells.

In this study, we prepared and evaluated folic acid-conjugated albumin-paclitaxel (FA-BSA-PTX) nanoparticles using a new green technique, called the high-pressure homogenisation coagulation method (HPHCM). The effect of process parameters such as BSA concentration, coagulant concentration, homogenisation time, homogenisation pressure, water/ethanol ratio, and BSA/PTX ratio was analysed to optimise nanoparticle size, albumin conversion rate, and encapsulation efficiency. BSA concentration was found to exert a great influence on albumin conversion rate and particle size. Meanwhile, the BSA/PTX ratio significantly affected the nanoparticle encapsulation efficiency. Electron microscopy showed that the freeze-dried particles mostly existed in the form of dimers and trimers with an average particle size of 300–400 nm. Infrared spectroscopy indicated that PTX was well encapsulated in BSA. Raman spectra of the synthesised nanoparticles indicated changes in the disulphide bond configuration and protein structure. In vitro drug-release analysis showed that crosslinked nanoparticles exhibited a sustained release. Furthermore, in vitro cell-uptake studies on HeLa cells showed that FA can be used as a targeting ligand for albumin carriers to enhance the active targeting effect of the nanoparticles with a high FR expression. These results suggest that HPHCM is an effective method to prepare FA-BSA-PTX drug-delivery systems.

Ru(II) complexes have attracted increasing attention as promising antitumor agents for their relatively low toxicity, high affinity to DNA molecules, and correlation with multiple targets. Meanwhile, quinolones are synthetic antibacterial agents widely used in the clinical practice. In this paper, two novel Ru(II) complexes coordinated by levofloxacin (LOFLX), [Ru(bpy)2(LOFLX)]·2ClO4 (1), and [Ru(dmbpy)2(LOFLX)]·2ClO4 (2) (bpy = 2,2′-bipyridine, dmbpy = 4,4′-dimethyl-2,2′-bipyridine) were synthesized with high efficiency under microwave irradiation and characterized by ESI-MS, 1H NMR, and 13C NMR. The binding behavior of these complexes with double-strand calf thymus DNA(CT-DNA) was investigated using spectroscopy, molecular docking, and density functional theory calculations. Results showed that 2 exhibited higher binding affinity than 1 and LOFLX. Further studies showed that 2 could induce the G2/M phase arrest of A549 cells via DNA damage. In summary, these results indicated that 2 could be developed as a potential anticancer agent in treatment of lung cancer through the induction of cell cycle arrest at G2/M phase by triggering DNA damage.

A novel design of double chirped pulse amplification laser systems implementing a combination of negatively and positively chirped pulse amplification is proposed for the first time. Without utilizing any extra dispersion compensation element, this design can sufficiently cancel out the second-, third- and especially fourth-order dispersion simultaneously, just by optimizing the parameters of the stretcher and compressor in first chirped pulse amplification stage which applies negatively chirped pulse amplification. The numerical results indicate that near Fourier-transform-limited pulse duration about 20fs can be achieved in high-peak-power femtosecond laser systems up to multi-Petawatt level. This design not only provides a feasible solution for the dispersion control in high-contrast and high-peak-power femtosecond laser systems, but also can avoid the degradation of temporal contrast induced by seed energy loss in the presence of additional dispersion compensation components.

An enzyme-responsive colon-specific delivery system was developed based on hollow mesoporous silica spheres (HMSS) to which biodegradable chitosan (CS) was attached via cleavable azo bonds (HMSS–N=N–CS). Doxorubicin (DOX) was encapsulated in a noncrystalline state in the hollow cavity and mesopores of HMSS with the high loading amount of 35.2%. In vitro drug release proved that HMSS–N=N–CS/DOX performed enzyme-responsive drug release. The grafted CS could increase the biocompatibility and stability and reduce the protein adsorption on HMSS. Gastrointestinal mucosa irritation and cell cytotoxicity results indicated the good biocompatibility of HMSS and HMSS–N=N–CS. Cellular uptake results indicated that the uptake of DOX was obviously increased after HMSS–N=N–CS/DOX was preincubated with a colonic enzyme mixture. HMSS–N=N–CS/DOX incubated with colon enzymes showed increased cytotoxicity, and its IC50 value was three times lower than that of HMSS–N=N–CS/DOX group without colon enzymes. The present work lays the foundation for subsequent research on mesoporous carriers for oral colon-specific drug delivery.

Developing cost-effective and high-performance catalysts in biomass chemistry is motivated by creating sustainable technologies dependent on inexpensive and abundant resources. The existing methods for the direct preparation of 5-methylfurfural (5-MF) from biomass-derived fructose mediated by hydrogen iodide (HI) mainly require precious metal catalysts. This research showed that low-cost tungsten carbide (WC) was capable to produce HI from iodine (I2) via liquid-phase hydrogenation, but a pivotal limitation was the poor stability under the combination effects of water and I2. To solve this problem, the bulk WC and the high dispersion supported WC were modified by hydrophobic organosilicones through simple liquid phase deposition. Both of the two superhydrophobic WC materials had better stability and their catalytic activity were comparable to the expensive palladium-carbon (Pd/C) catalyst in the preparation of 5-MF, especially the superhydrophobic high dispersion supported WC. This work highlights the potential of the low-cost WC with simple superhydrophobic modification in assisting the direct preparation of 5-MF from fructose mediated by HI, which has high significance to the sustainable development of the low-cost biomass chemical engineering.

Root system plays an essential role in water and nutrient acquisition in plants. Understanding the genetic basis of root development will be beneficial for breeding new cultivars with efficient root system to enhance resource use efficiency in maize. Here, the natural variation of 13 root and 3 shoot traits was evaluated in 297 maize inbred lines and genome-wide association mapping was conducted to identify SNPs associated with target traits. All measured traits exhibited 2.02- to 21.36-fold variations. A total of 34 quantitative trait loci (QTLs) were detected for 13 traits, and each individual QTL explained 5.7% to 15.9% of the phenotypic variance. Three pleiotropic QTLs involving five root traits were identified, SNP_2_104416607 was associated with lateral root length (LRL), root surface area (RA), root length between 0 and 0.5mm in diameter (RL005), and total root length (TRL), SNP_2_184016997 was associated with RV and RA, and SNP_4_168917747 was associated with LRL, RA and TRL. The expression levels of candidate genes in root QTLs were evaluated by RNA-seq among three long-root lines and three short-root lines. A total of five genes that showed differential expression between the long- and short-root lines were identified as promising candidate genes for the target traits. These QTLs and the potential candidate genes are important source data to understand root development and genetic improvement of root traits in maize.

The G-quadruplex (G4) DNA, which has been developed as a potential anticancer target in drug screening and design, plays a crucial role in the oncogene transcription and translation. Tanshinone IIA derivatives with a planar heterocycle structure may function as G4 stabilizers. We present an innovative case of imidazole-based tanshinone IIA derivatives (1-8) especially compound 4 that improve the selectivity and the binding affinity with G4 DNA and enhance the target tumor inhibition. Cellular and in vivo experiments indicate that the tanshinone IIA derivative 4 inhibits the growth, metastasis, and angiogenesis of triple-negative breast cancer cells possibly through the stabilization of multiple G4 DNAs (e.g., c-myc, K-ras, and VEGF) to induce DNA damage. Further investigation of the intermolecular interaction and the molecular docking indicates that tanshinone IIA derivatives have better selective binding capability to various G4 DNAs than to double-stranded DNA. These findings provide guidance in modifying the molecular structures of tanshinone IIA derivatives and reveal their potential to function as specific G4 stabilizers.

Chemotherapy drugs exerts beneficial antitumor activity before and after cancer surgery. Post-injury complications are a potential hazard after surgical tumor resection. Inflammation caused by surgical stress is known to promote the progression of post-injury complications. Recent studies have found that chemotherapy drugs can promote post-injury inflammatory response, leading to increased post-injury complications. Imidazole derivatives have effective anticancer activity. However, the impact of post-operative inflammation caused by imidazole derivatives is unclear. In this study, two novel phenanthroimidazole derivatives (L082 and L142) were synthesized and characterized. These compounds showed significant inhibitory effects on different tumor cells. The compound L082 also inhibited liver cancer in vivo. In addition, L082 played a significant role in inhibiting the accumulation of inflammatory cells and promoting the elimination of inflammatory cells at the incision, which may be related to inhibiting the production of ROS and NO in oxidative and nitric stress. These results suggest that L082 can be used as a bifunctional drug to suppress tumors and reduce post-injury inflammation complications.

Summary cGAS/STING signaling plays an essential role in sensing cytosolic DNA. cGAS activity is regulated by posttranslational modifications and binding partners. cGAS interactome largely includes mammalian or viral proteins. Whether and how bacterial proteins bind cGAS to modulate innate immunity remain elusive. Here, we found streptavidin, a secreted bacterial protein, selectively bound cGAS to promote DNA-induced cGAS activation and interferon-β production. Mechanistically, streptavidin enhanced DNA binding and cGAS phase separation, therefore facilitating cGAS activation. Using an HSV-1-infected mouse model, we found streptavidin nanoparticles facilitated HSV-1 clearance through improving innate immunity. Considering the clinical usage of streptavidin as an immune stimulant and drug delivery vehicle and its biotechnological usage for biotin-labeled protein purification and detection, our studies not only provide an example for a bacterial protein regulating cGAS activity but also suggest caution needs to be taken when using streptavidin in various applications given to its ability to induce innate immunity., Graphical Abstract, Highlights • The bacterial protein streptavidin binds cGAS to promote cGAS activation • Streptavidin enhances cGAS binding to DNA and promotes cGAS phase separation • Streptavidin nanoparticles enhance HSV-1 induced innate immunity • These findings complicate clinical and biotechnological applications of streptavidin, Immunology; Microbiology; Bacteriology

The mTOR signaling controls essential biological functions including proliferation, growth, metabolism, autophagy, ageing, and others. Hyperactivation of mTOR signaling leads to a plethora of human disorders; thus, mTOR is an attractive drug target. The discovery of mTOR signaling started from isolation of rapamycin in 1975 and cloning of TOR genes in 1993. In the past 27 years, numerous research groups have contributed significantly to advancing our understanding of mTOR signaling and mTOR biology. Notably, a variety of experimental approaches have been employed in these studies to identify key mTOR pathway members that shape up the mTOR signaling we know today. Technique development drives mTOR research, while canonical biochemical and yeast genetics lay the foundation for mTOR studies. Here in this review, we summarize major experimental approaches used in the past in delineating mTOR signaling, including biochemical immunoprecipitation approaches, genetic approaches, immunofluorescence microscopic approaches, hypothesis-driven studies, protein sequence or motif search driven approaches, and bioinformatic approaches. We hope that revisiting these distinct types of experimental approaches will provide a blueprint for major techniques driving mTOR research. More importantly, we hope that thinking and reasonings behind these experimental designs will inspire future mTOR research as well as studies of other protein kinases beyond mTOR.

The evolutionarily conserved mTOR signaling pathway plays essential roles in cell growth, proliferation, metabolism and responses to cellular stresses. Hyperactivation of the mTOR signaling is observed in virtually all solid tumors and has been an attractive drug target. In addition to changes at genetic levels, aberrant activation of the mTOR signaling is also a result from dysregulated post-translational modifications on key pathway members, such as phosphorylation that has been extensively studied. Emerging evidence also support a critical role for ubiquitin-mediated modifications in dynamically regulating the mTOR signaling pathway, while a comprehensive review for relevant studies is missing. In this review, we will summarize all characterized ubiquitination events on major mTOR signaling components, their modifying E3 ubiquitin ligases, deubiquitinases and corresponding pathophysiological functions. We will also reveal methodologies that have been used to identify E3 ligases or DUBs to facilitate the search for yet-to-be discovered ubiquitin-mediated regulatory mechanisms in mTOR signaling. We hope that our review and perspectives provide rationales and strategies to target ubiquitination for inhibiting mTOR signaling to treat human diseases.