Photothermally Induced Alkyl Radicals and Pyroptosis Synergistically Inhibit Breast Tumor Growth

Photothermal therapy (PTT) is an emerging local tumor ablation technique with clinical translation potential. After the NIR-II laser irradiates the tumor, the photothermal agent Hu-Kaiwen ink (Ink) converts light energy into hyperthermia and maintains the temperature at 42-45°C, thus achieving a low-temperature photothermal therapy. Alkyl radicals can kill tumor cells by overcoming the hypoxic microenvironment of the tumor. The photothermal reaction can induce the conversion of alkyl radicals from 2,2′-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH) and thus have a synergistic tumor inhibition effect. the DNA methyltransferase inhibitor decitabine (DCT) can induce pyroptosis and cause inflammation and immune response to achieve systemic immunity. In this way, a synergistic combination of photothermal, alkyl radicals and pyroptosis could be used to kill breast tumor cells. Sodium alginate (ALG) was used as a carrier to form a hydrogel structure, which can improve the stability and duration of action of the mixed drugs. The significant tumor growth inhibitory effect of composite hydrogels has been demonstrated in both in vitro and ex vivo studies

Stability enhancement method and experiment of orchard vehicle control

Study on orchard working vehicle rollover and tipping prediction is important to maintain vehicle stability control in complicated operation conditions of orchard. Existing rollover and tipping prediction models for vehicles can not directly apply to orchard working vehicle, which structure and loading are changing under operation. So it is necessary to move ahead study on orchard vehicle bodywork posture prediction and rollover and tipping prediction by theoretical analysis, mathematical modelling, real vehicle test and other methods. In this paper, firstly, we establish orchard working vehicle dynamic model, analyses variation of key parameters during vehicle instability state, and look for characteristic parameters of vehicle instability. Secondly, active safety control algorithm which based on posture detection of vehicle body is researched. Finally, control model is verified and optimized by scaled test

Novel Tet(L) Efflux Pump Variants Conferring Resistance to Tigecycline and Eravacycline in Staphylococcus Spp.

Tigecycline is regarded as one of the few important last-resort antibiotics to treat complicated skin and intra-abdominal infections. Members of the genus Staphylococcus are zoonotic pathogens and pose a serious threat to public health. Tigecycline resistance in this species appears to be a rare phenomenon, and the mechanisms underlying tigecycline resistance have not been fully elucidated. Here, we report two novel variants of the tet(L) gene in Staphylococcus spp. from swine in China, designed as tet(L)F58L and tet(L)A117V. The tet(L)F58L was located within a 18,720 bp chromosomal multidrug resistance gene cluster flanked by two copies of IS257 in Staphylococcus cohnii 11-B-312, while the tet(L)A117V was located on a 6,292 bp plasmid in S. haemolyticus 11-B-93, which could be transferred to S. aureus by electrotransformation. Cloning of each of the two tet(L) variants into S. aureus RN4220 showed 16- or 8-fold increases in the minimal inhibition concentrations (MICs), which can fully confer the resistance to tigecycline (MICs from 0.125 to 2 mg/liter) and eravacycline (MICs from 0.125 to 1 or 2 mg/liter), but no increase in the MICs of omadacycline, compared with the MICs of the recipient strain S. aureus RN4220. In the in vivo murine sepsis and in the murine pneumonia models, an increase in CFU of S. aureus 29213_pT93 carrying the tet(L)A117V was seen despite tigecycline treatment. This observation suggests that the tet(L)A117V and its associated gene product compromise the efficacy of tigecycline treatment in vivo and may lead to clinical treatment failure. Our finding, that novel Tet(L) efflux pump variants which confer tigecycline and eravacycline resistance have been identified in Staphylococcus spp., requires urgent attention. IMPORTANCE Tigecycline and eravacycline are both important last-resort broad spectrum antimicrobial agents. The presence of novel Tet(L) efflux pump variants conferring the resistance to tigecycline and eravacycline in Staphylococcus spp. and its potential transmission to S. aureus will compromise the efficacy of tigecycline and eravacycline treatment for S. aureus associated infection in vivo and may lead to clinical treatment failure

Adaptive Robust Guidance Scheme Based on the Sliding Mode Control in an Aircraft Pursuit-Evasion Problem

In this chapter, a robust guidance scheme utilizing a line-of-sight (LOS) observation is presented. Initial relative speed and distance, and error boundaries of them are estimated in accordance with the interceptor-target relative motion kinematics. A robust guidance scheme based on the sliding mode control (SMC) is developed, which requires the boundaries of the target maneuver, and inevitably has jitter phenomenon. For solving above-mentioned problems, an estimation to the target acceleration’s boundary is developed for enhancing robustness of the guidance scheme and the Lyapunov stabilization is analyzed. The proposed robust guidance scheme’s brief characteristic is to reduce the effect of relative speed and distance, to reduce the effect of target maneuverability on the guidance precision, and to strengthen the influence of line-of-sight angular velocity. The proposed scheme’s performances are validated by the simulations of different target maneuvers under two worst-case conditions

Studies on biotransformation mechanism of Fusarium sp. C39 to enhance saponin content of Paridis Rhizoma

Paridis Rhizoma is a natural medicine with strong anti-tumor and anti-inflammatory activities. Our previous research have found that Fusarium sp. C39, an endophytic fungus isolated from Dioscorea nipponica which contains the similar chemical components, significantly increased the steroidal saponins content of Paridis Rhizoma by fermentation. In this study, the inhibitory effects of fermentated Paridis Rhizoma extract (PRE) on liver cancer cells (Hepal-6), cervical cancer cells (Hela), and lung cancer cells (A549) were determined to be stronger than that of the unfermented extract. For discovering the fermentation mechanism of PRE with Fusarium sp. C39, 36 components with obviously quantitative variations were screened out by UPLC-Q/TOF-MS and 53 key genes involved in the metabolic pathways of steroidal saponins were identified by transcriptome. On the basis of comprehensively analyzing information from the metabonomics and transcriptome, it can be speculated that the increase of spirostanol saponins and nuatigenin-type saponins enhanced the inhibitory effect of fermented PRE on cancer cell proliferation. Under the action of glycosidase, glycosyltransferase, oxidoreductases, and genes involved in sterol synthesis, strain C39 achieved the synthesis of diosgenin and the alteration of configurations, sugar chain and substituent of steroidal saponins. The research suggested a microbial transformation approach to increase the resource utilization and activity of Paris polyphylla

A Mutation in the Intracellular Loop III/IV of Mosquito Sodium Channel Synergizes the Effect of Mutations in Helix IIS6 on Pyrethroid Resistance s

ABSTRACT Activation and inactivation of voltage-gated sodium channels are critical for proper electrical signaling in excitable cells

Disrupted morphological grey matter networks in early-stage Parkinson’s disease

AbstractWhile previous structural-covariance studies have an advanced understanding of brain alterations in Parkinson's disease (PD), brain–behavior relationships have not been examined at the individual level. This study investigated the topological organization of grey matter (GM) networks, their relation to disease severity, and their potential imaging diagnostic value in PD. Fifty-four early-stage PD patients and 54 healthy controls (HC) underwent structural T1-weighted magnetic resonance imaging. GM networks were constructed by estimating interregional similarity in the distributions of regional GM volume using the Kullback–Leibler divergence measure. Results were analyzed using graph theory and network-based statistics (NBS), and the relationship to disease severity was assessed. Exploratory support vector machine analyses were conducted to discriminate PD patients from HC and different motor subtypes. Compared with HC, GM networks in PD showed a higher clustering coefficient (P = 0.014) and local efficiency (P = 0.014). Locally, nodal centralities in PD were lower in postcentral gyrus and temporal-occipital regions, and higher in right superior frontal gyrus and left putamen. NBS analysis revealed decreased morphological connections in the sensorimotor and default mode networks and increased connections in the salience and frontoparietal networks in PD. Connection matrices and graph-based metrics allowed single-subject classification of PD and HC with significant accuracy of 73.1 and 72.7%, respectively, while graph-based metrics allowed single-subject classification of tremor-dominant and akinetic–rigid motor subtypes with significant accuracy of 67.0%. The topological organization of GM networks was disrupted in early-stage PD in a way that suggests greater segregation of information processing. There is potential for application to early imaging diagnosis.</jats:p