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Abstract Understanding earthquake nucleation is vital for predicting and mitigating seismic events, saving lives, and enhancing construction practices in earthquake-prone areas. Cascade triggering and preslip triggering are prevalent theories, posing challenges in differentiation based on field observations. Our study employs a novel unsupervised machine learning pipeline, integrating macroscopic- and grain-scale data from stick-slip experiments in a discrete element method (DEM) framework. Running 27 simulations, we cluster foreshocks and mainshocks separately and assess their correlation. The study supports the cascade triggering model on the macro-scale, as we did not observe any scaling between nucleation parameters and the mainshock size. On the other hand, further grain-scale analysis identifies that, separate from Coulomb stress transfer, there is an additional mechanism related to shear stress accumulation on the fault, which is likely the preslip triggering. Overall, while foreshocks may not directly influence the trend at which contact force evolves, they could prime the fault for dynamic rupture by increasing the proportion of contacts accumulating shear stresses. Our findings infer the possible coexistence of the two theorized mechanisms.

Abstract Azo switches are widely employed as essential components in light-responsive systems. Here, we develop an azo-fluorescent switch that is visible light-responsive and its light-responsive processes can be monitored using fluorescence imaging. Visible light irradiation promotes isomerization, accompanied by changes in fluorescence that enable the process to be monitored through fluorescence imaging. Furthermore, we document that the nanocavity size of liposome encapsulated nanoparticles containing azo changes in the isomerization process and show that this change enables construction of a light-responsive nanoplatform for optically controlled release of antimycotics. Also, natural light activation of nanoparticles of the switch loaded with an antimycotic agent causes death of Rhizoctonia solani. The results show that these nanoparticles can double the holding period in comparison to small molecule antimycotics. The strategy used to design the imaging-guided light-controlled nano-antimycotic release system can be applicable to protocols for controlled delivery of a wide variety of drugs.

Abstract Long‐lived luminescent materials possess wide application prospects in various areas, but their constructions still face a huge challenge, especially the achievement in solution. Manipulating aggregate is an effective method to attain intriguing luminescence, thus it is expected to build long‐lived materials in solution. In this work, a series of new gold(I) complexes were developed by employing unique carbazole and phosphine as the ligands, and these resulting systems exhibited rare long lifetimes of milliseconds in the aggregate state. It was well unveiled that these complexes emitted blue thermally activated delayed fluorescence (TADF) with the lifetimes of several microseconds in dilute solution; while orange‐red phosphorescence with much longer lifetimes of several milliseconds were achieved in the aggregate state. To our knowledge, this is the first implementation of aggregation‐induced conversion from TADF to phosphorescence. Based on their excellent luminescent properties, we successfully applied these complexes in cell imaging and inhibition of cancer cells.

Abstract The malignant energetic demands are satisfied through glycolysis, glutaminolysis and de novo synthesis of fatty acids, while the host curses with a state of catabolism and systemic inflammation. The concurrent inhibition of both, tumor anabolism and host catabolism, and their effect upon tumor growth and whole animal metabolism, have not been evaluated. We aimed to evaluate in colon cancer cells a combination of six agents directed to block the tumor anabolism (orlistat + lonidamine + DON) and the host catabolism (growth hormone + insulin + indomethacin). Treatment reduced cellular viability, clonogenic capacity and cell cycle progression. These effects were associated with decreased glycolysis and oxidative phosphorylation, leading to a quiescent energetic phenotype, and with an aberrant transcriptomic landscape showing dysregulation in multiple metabolic pathways. The in vivo evaluation revealed a significant tumor volume inhibition, without damage to normal tissues. The six-drug combination preserved lean tissue and decreased fat loss, while the energy expenditure got decreased. Finally, a reduction in gene expression associated with thermogenesis was observed. Our findings demonstrate that the simultaneous use of this six-drug combination has anticancer effects by inducing a quiescent energetic phenotype of cultured cancer cells. Besides, the treatment is well-tolerated in mice and reduces whole animal energetic expenditure and fat loss.

To develop novel 2-cyanoacrylate derivatives with potential bioactivity, a number of 2-cyanoacrylate compounds, including substituted pyrazole or 1,2,3-triazole ring, were designed, prepared, and structurally detected by 1H NMR, 13C NMR, and elemental analysis. The biological assessment displayed that some designed compounds had significant herbicidal activities against Brassica juncea, Chenopodium serotinum, Rumex acetosa, Alopecurus aequalis, Polypogon fugax, and Poa annua at a dosage of 1500 g/ha. Furthermore, some derivatives still expressed satisfactory herbicidal activities against Brassica juncea, Chenopodium serotinum, and Rumex acetosa when the dosage was lowered to 150 g/ha, especially the inhibitory effects of compounds 9a, 9d, 9f, 9i, 10a, 10b, 10e, and 10n against Brassica juncea were all over 80%, compounds 9d, 9f, 9g, 9h, 9i, 10h, 10i, 10m, 10n, and 10o possessed more than 70% inhibition rates against Chenopodium serotinum, and compound 9d indicated 70% herbicidal activity against Rumex acetosa. These results provided an important basis for further design and discovery of biologically active 2-cyanoacrylate compounds.

Superoxide dismutase (SOD) is known to be protective against oxidative stress-mediated skin dysfunction. Here we explore the potential therapeutic activities of RM191A, a novel SOD mimetic, on skin. RM191A is a water-soluble dimeric copper (Cu2+-Cu3+)-centred polyglycine coordination complex. It displays 10-fold higher superoxide quenching activity compared to SOD as well as significant antioxidant, anti-inflammatory and immunomodulatory activities through beneficial modulation of several significant inflammatory cytokines in vitro and in vivo.We tested the therapeutic potential of RM191A in a topical gel using a human skin explant model and observed that it significantly inhibits UV-induced DNA damage in the epidermis and dermis, including cyclobutane pyrimidine dimers (CPD), 8-oxo-guanine (8-oxoG) and 8-nitroguanine (8NGO). RM191A topical gel is found to be non-toxic, non-teratogenic and readily distributed in the body of mice. Moreover, it significantly accelerates excisional wound healing, reduces 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation and attenuates age-associated oxidative stress in skin, demonstrating both skin regenerative and geroprotective properties of RM191A.

The transmission principle for the horizontal drive conveyors of automobile factory,a selection method of chain of silent chain conveyor. A 25.4mm pitch silent chain conveyor applications is introduced. The chain design calculation step is expounded in detail. The chain selection is connected with the coefficient of friction of the support rail with the shaft spacing and other factors,a convenient method of design calculation for designers select chain is provided.

Background and objectives: Patients often suffer from moderate to severe pain during the early recovery period in orthopedic surgery. We investigated the impact of a single-shot preoperative peripheral nerve block (PNB) on post-anesthesia recovery parameters and interleukin (IL)-6 level during limb surgery. Materials and Methods: A prospective randomized controlled study was conducted, and patients scheduled for limb surgery were recruited. Sixty patients were randomly assigned to either the PNB group or control group, who received morphine as a primary analgesic. The peak verbal numeric rating scale (NRS) score in the post-anesthesia care unit (PACU) was evaluated as a primary outcome. We also recorded rescue analgesics requirement and wake-up time from anesthesia in the PACU. In addition, the change of plasma IL-6 level after incision was measured. Results: Fifty-two patients completed the study, 27 and 25 cases in the PNB and control group, respectively. Preemptive PNB significantly reduced peak NRS score in the PACU compared to control group. Lower rescue analgesics requirement and rapid wake-up from anesthesia were also noted in PNB group. The IL-6 concentration increased less in the PNB group at 2 h after incision. Conclusions: Preemptive PNB attenuates IL-6 expression 2 h after incision and improves pain management in the PACU. PNB was considered as an essential part of pain management in limb surgery.

Background and objectives: Flexible bronchoscopy has been widely used for diagnosis and intervention, while various drugs are used for sedation during bronchoscopy. We examined two regular standardized sedation options (with or without dexmedetomidine) regularly used in our regional hospital. The aim was to assess the efficacy and safety of dexmedetomidine on conscious sedation under bronchoscopy. Materials and Methods: A retrospective chart review was conducted from April 2017 to March 2018. All patients undergoing flexible bronchoscopy with moderate sedation were enrolled. Patients having received dexmedetomidine-propofol-fentanyl were defined as group D, and those having received midazolam-propofol-fentanyl were defined as group M. The primary outcome was a safety profile during the procedure, including the incidence of procedural interference by patient cough or movement, transient hypoxemia, and hypotension. The secondary outcome was measured by the recovery profile (awake and ambulation time). Results: Thirty-five patients in group D and thirty-three in group M were collected in this retrospective study. All patients underwent the procedure successfully. Group D showed higher safety with fewer procedural interference incidences by cough or body movement than Group M (3.3% versus 36.3%, p < 0.001) and minor respiratory adverse effects. Patients in group D showed faster recovery in a shorter ambulation time than group M (24.9 ± 9.7 versus 31.5 ± 11.9, p = 0.02). In group D, bronchoscopist satisfaction to sedation was higher than group M (p = 0.01). More transient bradycardia episodes were noted in patients receiving dexmedetomidine (p < 0.05), but all recovered without atropine intervention. Overall post-procedural adverse events and satisfaction were comparable in the two groups. Conclusions: The co-administration of dexmedetomidine met the safety and recovery demands of flexible bronchoscopy. Compared to the conventional midazolam-propofol-fentanyl regimen, the application of dexmedetomidine improved sedative effectiveness with less procedural interruptions, shorter time to ambulation and higher bronchoscopist satisfaction.

In the research field of multilevel converters, three-level NPC (neutral-point-clamped) converters, which unfortunately may cause the deviation of the neutral-point voltage of DC-link capacitors, are widely discussed. Theoretically, virtual space vector modulation (VSVM) could guarantee the balance control of the neutral-point voltage. However, there still exist some uncontrollable space vector regions. Based on VSVM, this paper proposes a varied virtual space vector modulation (VVSVM) method for three-level NPC converters. Under complete modulation conditions, this method can control the balance of the neutral-point voltage of DC-link capacitors by adjusting the duty cycle of small vectors and regulating the current generated by virtual medium vectors. Compared with commonly used VSVM methods and mixed modulation strategies, this method is simpler and more practical. The effectiveness and validity of this method are verified by simulations and experiments.

Background In chronic obstructive pulmonary disease (COPD), weakness and muscle mass loss of the quadriceps muscle has been demonstrated to predict survival and mortality rates of patients. Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK), as a member of the TNF superfamily, has recently been identified as a key regulator of skeletal muscle wasting and metabolic dysfunction. So our aim was to study the role of TWEAK during quadriceps muscle atrophy and fiber-type transformation in COPD model rats and its possible pathway. Material and Methods Forty-four healthy male adult Wistar rats were randomly divided into two groups: A normal control group (n = 16) and a COPD model group (n = 28). The COPD group was exposed to cigarette smoke for 90 d and injected with porcine pancreatic elastase on day 15, whereas the control group was injected with saline alone. Following treatment, weights of the quadriceps muscles were measured and hematoxylin and eosin staining was performed to identify structural changes in lung and quadriceps muscle tissue. Immunohistochemical staining was also conducted to determine the localization of TWEAK, nuclear factor (NF)-κB, muscle ring finger (MuRF)-1 and proliferator-activated coactivator (PGC)-1a proteins in the quadriceps muscle, and western blotting was used to assess the level of protein expression. Results Compared with controls, COPD model rats exhibited significantly lower quadriceps muscle weight (P < 0.05) accompanied by fiber atrophy and disordered fiber arrangement, a wide gap between adjacent muscle fibers, a significant reduction in nuclear number (P < 0.05) and an uneven size distribution. The proportion of fiber types was also significantly altered (P < 0.05). In addition, TWEAK expression in the quadriceps muscle of COPD model rats was significantly higher than that in control rats (P < 0.05), and was significantly associated with quadriceps atrophy and fiber-type alteration (P < 0.05). Levels of NF-κB, MuRF1 and PGC-1α expression also significantly differed between the two groups (P < 0.05). Conclusions Collectively these data suggest that increased levels of TWEAK may lead to skeletal muscle atrophy and fiber-type alteration, which in turn may be associated with activation of the ubiquitin-proteasome pathway, involving NF-κB, MuRF1 and PGC-1α as potential regulatory factors. These preliminary results in rats suggest that TWEAK may be a therapeutic target for the treatment of muscle atrophy in COPD.