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Yuan-yuan Wu,1 Wen-Hui Liao,1 Zong-ling Niu,1 Si-Han Zhou,1 Tian-Tian Wu,1 Zhe Li,2 Qi-Hua Zhao,1 Jing-Yuan Xu,2 Ming-jin Xie1 1School of Chemical Science and Technology, Yunnan University, Kunming, People’s Republic of China; 2Department of Chemical Biology and Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin, People’s Republic of ChinaCorrespondence: Ming-jin Xie, Email mjxie@ynu.edu.cnBackground: Gallium (III) metal-organic complexes have been shown to have the ability to inhibit tumor growth, but the poor water solubility of many of the complexes precludes further application. The use of materials with high biocompatibility as drug delivery carriers for metal-organic complexes to enhance the bioavailability of the drug is a feasible approach.Methods: Here, we modified the ligands of gallium 8-hydroxyquinolinate complex with good clinical anticancer activity by replacing the 8-hydroxyquinoline ligands with 5-bromo-8-hydroxyquinoline (HBrQ), and the resulting Ga(III) + HBrQ complex had poor water solubility. Two biocompatible materials, bovine serum albumin (BSA) and graphene oxide (GO), were used to synthesize the corresponding Ga(III) + HBrQ complex nanoparticles (NPs) BSA/Ga/HBrQ NPs and GO/Ga/HBrQ NPs in different ways to enhance the drug delivery of the metal complex.Results: Both of BSA/Ga/HBrQ NPs and GO/Ga/HBrQ NPs can maintain stable existence in different solution states. In vitro cytotoxicity test showed that two nanomedicines had excellent anti-proliferation effect on HCT116 cells, which shown higher level of intracellular ROS and apoptosis ratio than that of cisplatin and oxaliplatin. In addition, the superior emissive properties of BSA/Ga/HBrQ NPs and GO/Ga/HBrQ NPs allow their use for in vivo imaging showing highly effective therapy in HCT116 tumor-bearing mouse models.Conclusion: The use of biocompatible materials for the preparation of NPs against poorly biocompatible metal-organic complexes to construct drug delivery systems is a promising strategy that can further improve drug delivery and therapeutic efficacy.Graphical Abstract: Keywords: gallium complex, nanomedicine, anticancer, colorectal cells, drug delivery, in vivo imaging

A novel approach for the production of halogen cations through the reaction of halogens with silver ions is described.

As a promising delivery nanosystem for drug controlled-release, nanocarriers (NCs) have been investigated widely. Although various studies have concentrated on the preparation and characterization of nanoparticles (NPs), clinical applications are rarely reported, due to the unclear distribution, absorption, metabolism, toxicology processes and drug release mechanism. The clinical application of NCs is therefore still a long way off. This review describes the effects of the properties of NCs (including size, shape, surface properties, porosity, elasticity and so on) on pharmacological and toxicological behaviours

It is vital to develop general models that can be shared across subjects and sessions in the real-world deployment of electroencephalogram (EEG) emotion recognition systems. Many prior studies have exploited domain adaptation algorithms to alleviate the inter-subject and inter-session discrepancies of EEG distributions. However, these methods only aligned the global domain divergence, but overlooked the local domain divergence with respect to each emotion category. This degenerates the emotion-discriminating ability of the domain invariant features. In this paper, we argue that aligning the EEG data within the same emotion categories is important for generalizable and discriminative features. Hence, we propose the dynamic domain adaptation (DDA) algorithm where the global and local divergences are disposed by minimizing the global domain discrepancy and local subdomain discrepancy, respectively. To tackle the absence of emotion labels in the target domain, we introduce a dynamic training strategy where the model focuses on optimizing the global domain discrepancy in the early training steps, and then gradually switches to the local subdomain discrepancy. The DDA algorithm is formally implemented as an unsupervised version and a semi-supervised version for different experimental settings. Based on the coarse-to-fine alignment, our model achieves the average peak accuracy of 91.08%, 92.89% on SEED, and 81.58%, 80.82% on SEED-IV in the cross-subject and cross-session scenarios, respectively. As open science, the code is available at https://github.com/JC-Journal-Club/DDA.

Simultaneously realizing improved carrier mobility and good photoluminescence (PL) efficiency in red thermally activated delayed-fluorescence (TADF) emitters remains challenging but important. Herein, two isomeric orange-red TADF emitters

Drawing on the job demands-resources model and conservation of resources theory, this study investigates how and when the high-performance work systems (HPWS) influence proactive workforce. Using the data obtained from 204 supervisor-employee dyads in China, we developed and tested a moderated mediation model in which leader-member exchange (LMX) moderates the positive relationship between HPWS and proactive behavior via work engagement. Our results demonstrated that the association between HPWS and proactivity was fully mediated by work engagement. We also found that the indirect effect of HPWS on proactivity was significantly weaker among employees with high-quality LMX. Theoretical and practical implications, as well as directions for future research, are then discussed.

Epilepsy is a nervous system disease, and seizures are closely related to oxidative stress. Thiols, as the main antioxidant in an organism, play a key role in regulating the redox balance and defending from oxidative stress. As a result of the complexity of the brain structure, there is still a lack of suitableiin/iisitu/idetection methods of thiols to reveal the relationship between epilepsy and thiol level fluctuations. Therefore, by combining picolinate as the new recognition site for thiols, parallel synthesis, and the fluorescence rapid screening method,bDCI-Br-3/bwas developed as a rapid, highly sensitive, and selective probe to monitor thiolsiin/iivitro/iandiin/iivivo/i. It is worth noting thatbDCI-Br-3/beffectively crossed the blood-brain barrier (BBB) to reveal the negative relationship between the level of thiols and the occurrence of epilepsy and may further provide important information for the prevention and treatment of thiol-related neurological diseases.

Cervical cancer (CC) is a common malignant tumor in women. It ranks first among the malignant tumors of woman reproductive organs and is one of the most important cancers in the world. Current studies suggest that human papillomavirus (HPV) infection, especially high-risk persistent infection, is the basic cause of cervical precancerous lesions and cervical cancer. MicroRNA-21 (miR-21) plays a role similar to oncogenes in the occurrence and growth of malignant tumors and can be developed as a potential target for treating malignant tumors. Recently, the study of the mechanism of malignant invasion and metastasis has made great progress. The current consensus is that the invasion and metastasis of malignant tumors is a complicated biological process with multistep and multigene control; the process of epithelial mesenchymal transition (EMT) may be the initial event of invasion and metastasis of epithelial malignant tumors. EMT means that epithelial cells obtain the characteristics of mesenchymal cells, which has main characteristics such as the loss of epithelial cell characteristics and the achievement of mesenchymal cell features, and then induce epithelial cells to acquire the ability of migration and invasion, and participate in many physiological and pathological processes of human body, including embryogenesis, organ differentiation, tissue inflammation, and wound healing. Research has proved that miR-21 is associated with the invasion and metastasis of cervical cancer, and its specific mechanism has not been completely clear; EMT exerts a significant effect on the invasion and metastasis of epithelial malignant tumors; we speculate whether miR-21 regulates the EMT process of cervical cancer cells. ELISA and RT-PCR studied HPV-induced cervical cancer cells, and it was found that HPV may induce miR-21 to pass through the TGF β R2/hTERC pathway which promotes epithelial stromal transformation and tumor progression of cervical cancer cells.

This study sought to explore and summarize the global state of acupuncture clinical trials enrolling cancer patients included in international registries to date.All relevant trials evaluating acupuncture-related interventions for the treatment of cancer that were registered in 16 trial registries from January 1, 2001, through December 31, 2020, were identified. Subsequent publications related to these trials were additionally retrieved from the PubMed, Cochrane Library, Embase, CNKI (China National Knowledge Infrastructure), VIP (China Science and Technology Journal Database), and Wanfang databases. We compared information included in these registries regarding completed trials with any associated publications, with a focus on study design, sample size, and selective reporting, based on the registered protocol.In total, 222 eligible trials across 19 countries were identified. These trials included 17 specific cancer types and 32 symptoms. The five most common cancer types were breast cancer, head and neck cancer, colorectal cancer, lung cancer, and gastric cancer, accounting for almost half of all registered trials (48.2%). The top five symptoms included in these trials were chemotherapy-induced peripheral neuropathy (CIPN), cancer-related pain, cancer-related fatigue, chemotherapy-induced nausea and vomiting (CINV), and gastrointestinal dysfunction. The overall rate of article publication was low, with publications being associated with just 33.3% of these registered trials.This review is the first snapshot of the landscape of acupuncture clinical trials registered in international trial registries, providing a methodological basis for the management of common treatment- and disease-related side effects among cancer patients undergoing acupuncture and offering useful information that will guide future acupuncture-focused research.

Previous research has shown that T-2 toxin can damage cartilage, resulting in a disease phenotype similar to osteoarthritis. The precise molecular mechanism by which T-2 toxin causes chondrocyte injury, however, is unknown. The purpose of this study was to look into the role of YAP in T-2 toxin-induced rat chondrocyte injury. Based on research results, T-2 toxin decreased the levels of collagen II and PCNA while increasing the expression of matrix metalloproteinase MMP13. These findings supported the T-2 toxin's detrimental effect on chondrocytes. YAP's role in T-2 toxin-induced chondrocyte injury was also investigated. Total YAP and related nuclear proteins were found to decrease as the concentration of T-2 toxin increased. While PYAP expression was not significantly altered in response to T-2 toxin, the PYAP/YAP ratio decreased as the T-2 toxin concentration increased, implying that the HIPPO signaling pathway was activated. Furthermore, the YAP-specific inhibitor Verteporfin was used to investigate the role of YAP in T-2 toxin-induced chondrocyte injury. YAP inhibition increased MMP13 expression while decreasing COL2 and PCNA levels. In summary, the current study found that T-2 toxin decreased the levels of COL2 and PCNA while increasing the expression of MMP13 in chondrocytes after inhibiting YAP, providing a new insight into the mechanism of T-2 toxin-induced cartilage damage.

In the era of the Internet, artificial intelligence (AI) and other emerging technologies leading the industrial revolution, on the basis of comprehensive analysis of modern medical information services and analysis of the content of some hospital websites, from the perspective of the public, the expert scoring method is applied to establish medical information on hospital websites. Service comprehensive evaluation index system, at the same time quantification and assignment of indicators, combined with the theoretical research platform of information service quality. The comprehensive evaluation model of the medical information service function and quality of the hospital website was constructed by the comprehensive scoring method, and an empirical study was carried out. After comparing the data results of the model simulation with the actual data, it can be seen that the deviation between the actual data and the simulated data is not significant, that is, between 0.12% and 15.93%, which is within a reasonable range. Therefore, we have reason to believe that the model is an effective and reasonable use of the system dynamics method. On the basis of previous theoretical research and historical yearbook data, plus innovative theoretical assumptions, the Internet+healthcare embedded in the Internet+healthcare is constructed. The model of the traditional medical information service system can help clarify the role of Internet+health and medical information service in the overall medical information service system.

The innate immune response and inflammation contribute to hepatic steatosis and non-alcoholic fatty liver disease (NAFLD). Dectin-1 is a pathogen recognition receptor in innate immunity. In this study, we investigated the role of Dectin-1 in the pathogenesis of NAFLD. We first showed that Dectin-1 expression was significantly elevated in liver tissues of patients with NASH. NAFLD was induced in mice by feeding high fat diet (HFD) for 24 weeks. At the end of treatment, mice were sacrificed, and their blood and liver tissues were collected for analyses. We showed HFD feeding also increased liver Dectin-1 levels in mice, associated with macrophage infiltration. Either gene knockout or co-administration of a Dectin-1 antagonist laminarin (150 mg/kg twice a day, ip, from 16

Background The NAC (NAM, ATAF1/2 and CUC2) domain protein plays an important role in plant growth and development. The function of members of NAC gene family has been deeply studied in many plants. However, the evolutionary relationships and characteristics of NAC family genes in Dendrobium catenatum (D.candidum) unclear. Results In this study, we identified 33 NAC genes in D.catenatum, all contain NAM conservative domain. Subcellular localization predictions indicated that all the DcNAC proteins are localized to the nucleus. Phylogenetic analysis suggested that the DcNAC gene family could be divided into four groups. Then, the amino-acid composition, physicochemical properties, gene structure, motif, and promoter cis-acting elements were analyzed, the evolutionarily conservative gene DcNAC043 was found. Using qRT-PCR, DcNAC043 was proved to respond to drought stress induction in D.catenatum. At the same time, phloroglucinol staining proved that the expression of DcNAC043 in the plant was up-regulated, which could increase the lignin content in the plant. Conclusions We identified 33 NAC genes in D.catenatum, which supplemented the relevant information of NAC gene family in D.catenatum. At the same time, the gene function of DcNAC043 and its contribution to the response of Dendrobium to drought stress were verified. These results provide a comprehensive evolutionary history of NAC genes in D.catenatum, and insight into the biological functions of DcNAC043 genes in response to drought stress.

Current DNA base editors contain nuclease and DNA deaminase that enables deamination of cytosine (C) or adenine (A), but no method for guanine (G) or thymine (T) editing is available now. Here we developed a deaminase-free glycosylase-based guanine base editor (gGBE) with G editing ability, by fusing Cas9 nickase with engineered N-methylpurine DNA glycosylase protein (MPG). By several rounds of MPG mutagenesis via unbiased and rational screening using an intron-split EGFP reporter, we demonstrated that gGBE with engineered MPG could increase G editing efficiency by more than 1,500 folds. Furthermore, this gGBE exhibited high base editing efficiency (up to 81.2%) and high G-to-T or G-to-C (i.e., G-to-Y) conversion ratio (up to 0.95) in both cultured human cells and mouse embryos. Thus, we have provided a proof-of-concept of a new base-editing approach by endowing the engineered DNA glycosylase the capability to selectively excising a new type of substrate.

The relatively low output performance of triboelectric nanogenerator (TENG), which faces a challenge in performance improvement, limits its practical applications. Here, a high-performance TENG consisting of a silicon carbide@silicon dioxide nanowhiskers/polydimethylsiloxane (SiC@SiO2/PDMS) nanocomposite film and a superhydrophobic aluminum (Al) plate as triboelectric layers is demonstrated. The 7 wt% SiC@SiO2/PDMS TENG presents a peak voltage of 200 V and a peak current of 30 μA, which are ~ 300 and ~ 500% over that of the PDMS TENG, owing to an increase in dielectric constant and a decrease in dielectric loss of the PDMS film because of electric insulated SiC@SiO2 nanowhiskers. Furthermore, a 10 μF capacitor can be charged up to 3 V within ~ 87 s, which can be continuously operated on the electronic watch for 14 s. The work provides an effective strategy for improving output performance of TENG by adding core–shell nanowhiskers to modulate the dielectric properties of organic materials. Graphical abstract

Purpose: The purpose of this study was to conduct a matched pair analysis to assess the impact of radiotherapy (RT) on patients with malignant tracheal tumors using the Surveillance, Epidemiology, and End Results (SEER) database. Additionally, a predictive nomogram was developed for patients with malignant tracheal tumors. Methods: Propensity Score Matching (PSM) was used to minimize bias between the RT and no-RT groups. We utilized both univariate and multivariate Cox proportional hazards regression analyses to identify independent prognostic factors for patients and subgroups. We developed a novel nomogram and evaluated its results using the C-index. Results: A total of 648 patients between 1975 and 2019 were included, and 160 patients in RT were 1:1 propensity score-matched with no-RT. The independent prognostic factors for patients with tracheal malignant tumors were surgery, marital status, disease extension, pathology, and age. The independent risk factors for patients without sur-gery included RT and disease extension. The C-index confirmed that the nomogram accurately predicted the prognosis of patients with tracheal malignant tumors. Conclusions: Our findings suggest that RT may provide a survival benefit for tracheal cancer patients who did not undergo surgery. The nomogram can be a useful tool for predicting prognosis in patients with tracheal malignant tumors.

During the development of hepatocellular carcinoma (HCC), the mutual adaptation and interaction of HCC cells and the microenvironment play an important role. Benzo(a)pyrene (B[a]P) is a common environmental pollutant, which can induce the initiation of various malignant tumors, including HCC. However, the effects of B[a]P exposure on progression of HCC and the potential mechanisms remains largely uninvestigated. Here we found that, after the long-term exposure of HCC cells to low dose of B[a]P, it activated glucose-regulated protein 75 (GRP75), which then induced a modification of apoptosis-related proteome. Among them, we identified the X-linked inhibitor of apoptosis protein (XIAP) as a key downstream factor. XIAP further blocked the caspase cascade activation and promoted the acquisition of the anti-apoptosis abilities, ultimately leading to multi-drug resistance (MDR) in HCC. Furthermore, the abovementioned effects were markedly attenuated when we inhibited GRP75 by using 3,4-dihydroxycinnamic acid (caffeic acid, CaA). Collectively, our present study revealed the effects of B[a]P exposure on the progression of HCC, and identified GRP75 was a meaningful factor involved in.

Background Streptococcus mutans is a well-known oral pathogen that plays a critical role in the development of dental caries. Many studies have been directed to discover the chemical compounds present in natural products to inhibit the growth and biofilm formation activity of S. mutans. Thymus essential oils exhibit good inhibition on the growth and pathogenesis of S. mutans. However, details about the active compounds in Thymus essential oil and the inhibition mechanism still remain unclear. The aim of this study was to investigate the antimicrobial activity of 6 Thymus species (Three samples of Thymus vulgaris, two samples of Thymus zygis, and one sample of Thymus satureioides essential oils) on S. mutans, to identify the potential active components, and to reveal the underlying mechanism. Methods The composition of Thymus essential oils was analyzed by gas chromatography-mass spectrometry. And its antibacterial effect was evaluated based on the bacterial growth, acid production, biofilm formation and genetic expression of virulence factors by S. mutans. Potential active components of the Thymus essential oil were identified using molecular docking and correlation analysis. Results GC–MS analysis showed that the major components in the 6 Spain Thymus essential oils were linalool, α-terpineol, p-cymene, thymol and carvacrol. MIC and MBC analysis showed that 3 Thymus essential oils showed very sensitive antimicrobial activity, and were chosen for further analysis. The 3 Thymus essential oil exhibited a significant inhibitory effect on acid production, adherence and biofilm formation of S. mutans and the expression of virulence genes, such as brpA, gbpB, gtfB, gtfC, gtfD, vicR, spaP and relA. Correlation analysis showed that phenolic components, such as carvacrol and thymol, were positively related to DIZ value, which suggests that they are the potential antimicrobial components. Molecular docking between the Thymus essential oil components and virulence proteins also found that carvacrol and thymol exhibited strong binding affinity with functional domains of virulence genes. Conclusions Thymus essential oil showed significant inhibition against the growth and pathogenesis of S. mutans depending on their composition and concentration. And phenolic compounds, such as carvacrol and thymol, are the major active components. Thymus essential oil could be used in oral healthcare products as a potential anti-caries ingredient.

Strong-weak swirling interaction has been proved to be effective on combustion instability suppression. A linearly three-nozzle rectangular model combustor is designed to investigate the effects of strong-weak swirling interaction on emissions. Swirl number of swirlers on both sides are 0.72 and that of the middle swirlers are 0.72 and 1.02, respectively. Fuel flow rate remains constant and the equivalence ratio varies from 0.53 to 0.83 by decreasing the air flow rate. High-speed particle imaging velocimetry (HPIV) and RANS methods are applied to study the flow characteristics to reveal the reasons for reduction of pollutants. Results indicate that the "strong-weak" swirling interaction between central and outer swirlers strengthens the turbulence intensity of the swirling flow shear layers, which effectively improve mixing process between fresh premixed gas and burned high-temperature gas to promote combustion characteristics. CO emission varies from 20 to 40 ppm under different equivalence ratios in equal-strength swirl combustor. However, CO emission reduces to below 4 ppm with "strong-weak" swirling interaction. With the increase of swirl number of central swirler, NOx emission remains basically unchanged under the same equivalence ratio. The "strong-weak" swirling interaction also raises the vorticity of main recirculation zone, which strengthens the roll of high-temperature burned gas into the recirculation zone to stabilize flame combustion and widen the operating conditions. In this paper, the equal-strength swirling interaction is converted into a "strong-weak" swirling interaction by increasing the swirling number of central swirler, which helps achieve stable, high-efficiency, low-emission combustion.

Initially isolated as the dominant suppressor of the mutant epidermal growth factor receptor (ellipse), the Dachshund gene plays a key role in metazoan development regulating the Retinal Determination Gene Network. Herein, the DACH1 gene was expressed in normal prostate epithelial cells with reduced expression in human prostate cancer. DACH1 inhibited prostate cancer cellular DNA synthesis, growth in colony forming assays, and blocked contact-independent growth in soft agar assays. DACH1 inhibited androgen receptor (AR) activity, requiring a conserved DS Domain (Dachshund domain conserved with Ski/Sno) that bound NCoR/HDAC and was recruited to an androgen-responsive gene promoter. DACH1 inhibited ligand-dependent activity of AR mutations identified in patients with androgen-insensitive prostate cancer. The DS domain was sufficient for repression of the AR wild-type but failed to repress an AR acetylation site point mutant. These studies show a role for the Retinal Determination Gene Network in regulating cellular growth and signaling in prostate cancer. [Cancer Res 2009;69(8):3347–55]