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Thermally activated delayed fluorescence (TADF)-based electroluminescence (EL) devices adopting a host/guest strategy in their emitting layer (EML) are capable of realizing high efficiency. However, TADF emitters composed of donor and acceptor moieties as guests dispersed in organic host materials containing a donor and/or an acceptor are subject to donor–acceptor (D–A) interactions. In addition, electron delocalization between neighboring emitter molecules could form different species of aggregates. Here, we investigate the effects of intermolecular interacting emission species on the optoelectronic properties of sky-blue/green/red (sB/G/R) TADF emitters as guests using poly(biphenyl-Si/Ge) grafted with various donor moieties as hosts. We found the presence of guest/guest exciplex (Dg/Ag)*, host/guest exciplexes (Dh/Ag)*, and aggregates through the exploration of interactions between neighboring TADF guest molecules and between host and TADF-guest molecules. The nonradiative 3(Dh/Ag)* (ΔEST≈ 0.5 eV) could increase the internal conversion rate (kIC) and reduce delayed luminescence, and both of them could cause a decrease in PLQY. The luminescence of 3(Dh/Ag)* may have a positive or negative effect on PLQY depending on its triplet energy. As the singlet and triplet energies of (aggregate)* are lower than those of (ICT)*, energy transfer from (ICT)* to (aggregate)* could occur. The low PLQY nature of (aggregate)* means that it is more likely to cause quenching in device emission. The emissions from (Dh/Ag)* and (aggregate)* are found to have increased full width at half-maximum and lead to lower emission color purity. Such intermolecular interactions should also occur in host/guest (TADF) systems and nondoped TADF emitter systems and thus are important factors for the molecular design of the TADF emitter and/or its accompanying host for high device efficiency and emission color purity.

Tungsten (W) is a promising candidate material for the plasma-facing components in future fusion reactors. However, it has issues regarding the intrinsic brittleness as well as operational embrittlement. Tungsten fiber reinforced tungsten (Wf/W) composites overcome these issues by using extrinsic toughening mechanisms. Due to neutron irradiation and high-temperature recrystallization during fusion operation, the ductility of the fibers may degrade over a long period of service. Therefore, it is necessary to investigate the fracture behavior of Wf/W composites with brittle fibers. In the present work, the tungsten fibers were embrittled by carbonization. Subsequently, the continuous brittle Wf/W composite with yttrium oxide (Y2O3) interface was fabricated by the field-assisted sintering technology process. The microstructure of the prepared Wf/W composites was characterized. The fracture behavior and toughening mechanisms were discussed in detail based on the experimental results of 3-point bending tests and the corresponding finite element simulation. The composites show a pseudo-ductile fracture behavior. Cracks are hindered and deflected by the de-bonded fiber-matrix interface. The extrinsic toughening mechanisms of interface de-bonding, crack bridging, and fiber pull-out are active. This indicates the reinforcement concept still works even though all components in the Wf/W are brittle.

In this article, a double normalization fault diagnosis (DNFD) method is proposed to cope with open-circuit faults of permanent magnet synchronous motor drives. The proposed DNFD method consists of a current normalizer, a time-domain fault variable determinator, a time-domain to angle-domain converter, an angle normalizer, and a fault identification encoder. The affections of the variable torque can be eliminated by the current normalizer, whereas the affections of the variable speed can be eliminated by the angle normalizer, which is the main contribution of this article. To reduce the affections of the following factors, i.e., the calculation error of the time-domain to angle-domain converter, the measurement noises of current sensors, the performance of the analog-to-digital converter, the sampling frequency, and the electromagnetic interference of the system, the hysteresis comparator is employed, in which two fault thresholds are required. Compared with the conventional single normalization fault diagnosis method, the DNFD method has better robustness. The effectiveness of the proposed DNFD method is verified by the experimental results.

A chemical activation followed by a high-temperature self-healing strategy is employed to create abundant interconnected closed pores in lignin-derived hard carbon, and the mechanism of closed pore formation during carbonization is revealed.

Heart senescence is critical for cardiac function. This study aimed to characterize the role and mechanism of action of miR-30a-5p in cardiac senescence. miR-30a-5p was downregulated in aged mouse hearts and neonatal rat cardiomyocytes (NRCMs). In vivo, using a combination of echocardiography and different molecular biological approaches, we investigated the role of miR-30a-5p knockout or overexpression in natural- or D-galactose-induced heart aging in mice. In vitro, using RNA sequencing and a series of molecular biology methods, the mechanism by which miR-30a-5p regulates cardiac senescence was explored in cardiomyocytes. miR-30a-5p knockout mice showed aggravated natural- or D-galactose-induced heart aging compared to wild-type littermate mice, with significantly decreased heart function, an increased number of γH2AX-positive cells, reduced telomere length, and upregulated p21 and p53 expression. Cardiac-specific knockdown of miR-30a-5p using adeno-associated virus 9 in D-galactose-induced senescent wild-type mice resulted in effects similar to those observed in knockout mice. Notably, the overexpression of miR-30a-5p in wild-type murine hearts alleviated D-galactose-induced heart senescence by improving heart function, increasing telomere length, decreasing the number of γH2AX-positive cells, and downregulating p53 and p21 expression. This was confirmed in D-galactose-treated or naturally aged NRCMs. Mechanistically, TP53INP1 was identified as a target of miR-30a-5p by mediating the SUMOylation of TP53INP1 and its translocation from the cytoplasm to the nucleus to interact with p53. Furthermore, this study demonstrated that cardiac-specific TP53INP1 deficiency ameliorates miR-30a-5p knockout-aggravated cardiac dysfunction and heart senescence. This study identified miR-30a-5p as a crucial modulator of heart senescence and revealed that the miR-30a-5p–TP53INP1–p53 axis is essential for heart and cardiomyocyte aging.

The 1.7-mm-thick as-cast 6.5 wt.%Si steel strip was prepared by a top side-pouring twin-roll caster. The strip is subsequently warm-rolled to 0.4 mm at 700 °C. The warm-rolled sheets were cold-rolled to 0.15 mm after being annealed at various temperatures between 250 and 450 °C for 1 hour. The microstructure, microhardness, and room temperature mechanical properties, residual stress, dislocation density, ordered phases of the warm-rolled sheet and the annealed sheets were studied and analyzed. Due to the combined effect of residual stress, dislocation density, and ordered phases, the microhardness of the annealed sheets and the edge cracks of cold-rolled sheets showed a trend to decrease first and then increase with the increasing of annealing temperature. The room temperature plasticity showed a trend to increase first and then decrease. When annealing is done at 350 °C, the plasticity of the warm-rolled sheet at room temperature can be improved.

A flux switching permanent magnet (FSPM) motor is designed and optimized in this article to achieve high torque density and expanded speed regulation range from a design viewpoint of pole-changing (PC). Based on the field modulation theory, the PM field in the FSPM motor is modulated by the stator and rotor teeth, generating rich harmonics with different pole-pair numbers in the air-gap flux density. By adopting an appropriate slot pole combination, working harmonics with different slot pitch angles are obtained to establish a basis for the PC-FSPM motor. Then, different working harmonics can be used to achieve different energy conversions with different winding configurations, so the PC operation can be performed to realize the high torque and wide speed regulation range by switching the working modes. Based on the field modulation theory, the operation principle of conventional and PC-FSPM motors is analyzed and compared. Then, according to the design principle of the PC-FSPM motor, a 24/22-pole PC-FSPM motor with the E-core is designed and optimized by a multilevel optimization method. Finally, the electromagnetic performances are analyzed by finite-element analysis and the test results of the prototype have verified the feasibility of the motor.

Severe dry eye (SDE) can cause grievous damage to the ocular surface and result in vision impairment and even blindness. To investigate the fate of limbal stem cells in SDE and the underlying mechanism, the current study established an SDE rat model by removing the extraorbital and infraorbital lacrimal glands and maintaining them in a low-humidity environment. One month after the surgery, aqueous tear secretion was reduced dramatically, blood vessels invaded into the central cornea, and inflammatory cells infiltrated into the limbal stroma. The expressions of keratin 12 and paired box gene 6 were down-regulated dramatically, while those of keratin 10, small proline-rich protein 1b, and mucin 5AC were up-regulated in the corneal epithelium of the SDE rats. Cell proliferation in the limbal epithelium was up-regulated, while the stem/progenitor marker adenosine 5′-triphosphate-binding cassette member 2 and the limbal epithelial colony-forming efficiency were decreased in the SDE condition. Furthermore, the p38 mitogen-activated protein kinase signaling pathway was activated in the limbal corneal epithelium of SDE rats. The abnormal differentiation and stemness loss in the corneal epithelium could be reversed upon treatment with a p38 inhibitor in a SDE in vivomodel and in vitrohyperosmolar corneal epithelial culture conditions. These data suggest that SDE can lead to limbal stem cell dysfunction, and p38 mitogen-activated protein kinase signaling pathway activation plays an essential role in this process.

Genetic variance and functional connectivity are key for species resilience to environmental change. The tea green leafhopper Empoasca onukii has become the predominant and ubiquitous insect pest of tea in East Asia over the past decades, presenting an opportunity to explore associations between genetic variation/functional connectivity and environment. Here, we examined inter-population genetic differentiation of E. onukii, and explicitly quantified the contributions of geographic distance, environmental heterogeneity, and landscape barriers, using data from 1704 individuals from 56 locations in mainland China and offshore islands. Analyses showed a pattern of reduced gene flow and higher genetic differentiation across the mountainous region of Western China, and the islands of Taiwan and Hainan. Aside the expected influence of geographic distance and landscape barriers, climatic differences contributed more strongly to population divergence than geographic distance and landscape barriers. Additionally, population genetic diversity significantly increased with the amplitude of local temperature fluctuations. These results suggest that the spatial genetic structure of E. onukii is primarily shaped by climatic differences. The findings may explain the observed increasing outbreak frequency under climate change and suggest a potentially good adaptation and accelerating performance of E. onukii under more variable future temperatures. This situation may also apply to other arthropod pests that have become more problematic under climate change. More broadly, this study demonstrates the usefulness of molecular genetic approaches in addressing the effects of environmental heterogeneity on natural population genetic variation.

The brown planthopper (Nilaparvata lugens) is the main migratory pest in many rice growing areas in Asia. E78 is a member of the nuclear hormone receptor superfamily which plays an important role in egg development and maternal regulation of early embryogenesis. In this study, brown planthopper E78(NlE78) was cloned, and the predicted amino acid sequence showed that it contains two conserved domains: NR-LBD and DBD. qRT-PCR showed that the expression of NlE78is high in the fifth instar nymphs and the ovaries of females. After downregulation of NlE78, the rate of moulting failure (33.2%) increased significantly, and ovarian development was delayed. However, when NlE78was downregulated together with NlE93, the emergence rate increased significantly (78.79%), and ovarian development was similar to that when NlE78was downregulated but not delayed. A co-immunoprecipitation experiment showed that NlE78 interacts with NlE93, a crucial downstream transcription factor of the ecdysone signalling pathway. Cellular localization by immunofluorescence revealed that NlE78 and NlE93 are expressed in the nucleus. This study indicates that NlE78regulates ovarian development and moulting, possibly through its interaction with NlE93. This study is of great significance for the development of new pesticides and control methods based on newly discovered targets.

The graphene film with high thermal conductivity has garnered considerable attention in recent years as an ideal material for dissipating heat in high-power electronic devices. Thermal conductivity is a crucial parameter for evaluating its fundamental performance. High-precision measurement holds significant importance for understanding its basic properties, fabrication optimization, and industrial applications. However, it is difficult to simultaneously achieve efficient, accurate, and reliable measurements with existing commercial thermal conductivity testing methods. The development of a convenient, high-precision, and reliable measurement approach remains a great challenge. Here, we introduce a thermal conductivity testing methodology with superior accuracy and excellent efficiency based on an improved steady-state electric heating method, refined through the optimization of heat transfer principles, experimental operation, and data analysis, supported by finite element simulation. The accuracy of measurements is affected by four factors: heat loss calibration, sample size, device design, and data treatment. The experimental results show that the heat loss caused by heat radiation and heat convection affects the temperature distribution and the measurements of the sample, which should be strictly controlled by sample size and temperature rise. Reasonable screening and preprocessing of data are also necessary to improve measurement accuracy. Through the comparative analysis of the temperature distribution and thermal conductivity measurements of samples under different conditions, we propose feasible operational guidance and a standardized testing protocol to minimize measurement error. The measurement error is less than 3.0%, and uncertainty is reduced to 0.5%. Simulation results confirm that the response time of this method is down to milliseconds, correlating well with the experiment, which can effectively improve test efficiency. Considering the combined merits of high accuracy, repeatability, and fast response, the improved steady-state electric heating method offers useful guidance for the accurate evaluation of the thermal conductivity of materials and crucial technical support for research and application in thermal management.

It is unclear whether small plates are needed for augment fixation to provide a more stable mechanical environment in segmental fractures of the tibia treated with intramedullary nail. The purpose of this study was to investigate the efficacy of intramedullary nailing combined with locking plates in the treatment of segmental fractures of the tibia. This study included 41 patients with segmental tibia fractures between January 1, 2018 and January 1, 2023. Eighteen patients were treated with an intramedullary nail assisted by a locking plate (combination group), and 23 patients were treated with an intramedullary nail without a plate (nail group). The perioperative parameters of all patients were recorded, and clinical efficacy was evaluated during follow-up. The operation time was shorter but the incision was longer in the combination group (P < .05). The numbers of fluoroscopy procedures and the time to union were shorter in the combination group (P < .05). The rate of malunion in the nail group (4, 17.4%) was significantly greater than that in the combination group (0, 0%). At the last follow-up, no statistically significant differences in walking ability were detected. Our results suggest that a locking plate combined with an intramedullary nail for segmental tibial fractures may require a longer surgical incision, but it has significant advantages such as a shorter operative time and time to union, a shorter fluoroscopy time, and a lower rate of malunion and nonunion. Intramedullary nail fixation assisted by a locking plate is an effective method for treating segmental fractures of the tibia.

Objective: To analyze the characteristics of high-frame-rate contrast-enhanced ultrasound (H-CEUS) in solid renal tumors using qualitative and quantitative methods. Methods: Seventy-five patients who underwent preoperative conventional ultrasound (US), conventional contrast-enhanced ultrasound (C-CEUS), and H-CEUS examination of renal tumors were retrospectively analyzed, with a total of 89 renal masses. The masses were divided into the benign (30 masses) and malignant groups (59 masses) based on the results of enhanced computer tomography and pathology. The location, diameter, shape, border, calcification, and color doppler blood flow imaging (CDFI) of the lesions were observed by US, and the characteristics of the C-CEUS and H-CEUS images were qualitatively and quantitatively analyzed. The χ² test or Fisher’s exact probability method was used to compare the US image characteristics between the benign and malignant groups, and the image characteristics of C-CEUS and H-CEUS between the benign and malignant groups. Moreover, the nonparametric Mann-Whitney test was used to compare the differences in C-CEUS and H-CEUS time-intensity curve (TIC) parameters. Results: Significant differences in gender, surgical approach, echogenicity, and CDFI were observed between the malignant and benign groups (p =0.003, &lt; 0.001, &lt; 0.001, = 0003). Qualitative analysis also revealed significant differences in the mode of wash-out and fill-in direction between C-CEUS and H-CEUS in the malignant group (p= 0.041, 0.002). In addition, the homogeneity of enhancement showed significant differences between the two contrast models in the benign group (p= 0.009). Quantitative analysis indicated that the TIC parameters peak intensity (PI), deceleration time (DT) /2, area under the curve (AUC), and mean transition time (MTT) were significantly lower in the H-CEUS model compared to the C-CEUS model in both the benign and malignant groups. (all p&lt; 0.001). In contrast, ascending slope of rise curve (AS) was significantly higher in the H-CEUS model compared to the C-CEUS model in the malignant group (p= 0.048). Conclusions: In renal tumors, H-CEUS shows clearer internal enhancement of the mass and the changes in the wash-out period. The quantitative TIC parameters PI, DT/2, AUC, and MTT were lower in H-CEUS compared to C-CEUS. Both the quantitative and qualitative analyses indicated that H-CEUS better displays the characteristics of solid renal masses compared with C-CEUS.

The sequestration of 99Tc represents one of the most challenging tasks in nuclear waste decontamination. In the event of a radioactive waste leak, 99TcO4–(a main form of 99Tc) would spread into the groundwater, a scenario difficult to address with conventional anion exchange materials like resin and inorganic cationic sorbents. Herein, we present a nickel(II) metal-organic framework (MOF), TNU-143, featuring 3D four-fold interpenetrated networks. TNU-143 exhibits efficient ReO4–(a nonradioactive analogue of 99TcO4–) removal with fast anion exchange kinetics (<1 min), high sorption capacity (844 mg/g for ReO4–), and outstanding selectivity over common anions. More importantly, TNU-143 shows superior stability in alkaline solution and can remove 91.6% ReO4–from simulated alkaline high-level waste (HLW) streams with solid-liquid ratio of 40 g/L. The uptake mechanism is elucidated by the single-crystal structure of TNU-143(Re), showing that ReO4–anions are firmly coordinated to nickel cation to result in a 2D layered structures. Density functional theory (DFT) calculations confirm the transformation from TNU-143 to TNU-143(Re) is a thermodynamically favorable process. This work presents a new approach to the removal of ReO4–/99TcO4–from alkaline nulcear fuel using MOF sorbents.

Two lindenane-type sesquiterpene (LDS) trimers with unprecedented carbon skeletons, holotrichones A (1) and B (2), were obtained from the whole plant of Chloranthus holostegiusvar. trichoneurusby a ultra performance liquid chromatography-photodiode array detector-mass spectrometry (UPLC-PDA-MS)-guided isolation strategy. Compound 1represents the first LDS trimer incorporating a unique 3/5/6/6-fused framework, in which a lindenane-type monomer and the 2-methylbutyryl substituent of an LDS dimer is bridged by a six-membered ring system. Compound 2is the first hetero-trimer fused by an LDS dimer with a p-benzoquinone-meroterpenoid, featuring an unusual 3/5/6/6/3/5/6/6/6 nonacyclic system fused by the sesquiterpenoid unit and a 2-geranyl-6-methyl-2,5-cyclohexadien-1,4-dione moiety. In compound 2, the dimeric LDS moiety is equipped with a rare oxaspiro[4.5]decane system. Their structures, including absolute configurations, were established by spectroscopic methods, GIAO NMR calculations and DP4+ probability analyses, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction analysis. The plausible biogenetic pathway speculation indicated that hetero- and homo-Diels-Alder additions may dominate the formation of these highly fused polycyclic frameworks. Both compounds 1and 2induced the human acute myeloid leukemia MV-4–11 cell death viaapoptosis induction, which deserves further investigation on this new chemical class of LDS oligomers for their anti-leukemic potential.

The Global Navigation Satellite System(GNSS) has been widely used in various fields. To achieve positioning, the receiver must first lock the satellite signal. This is a complicated and expensive process that consumes a lot of resources of the receiver. For this reason, this paper proposes a new fast acquisition algorithm with High Signal-to-noise ratio(SNR) performance based on sparse fast Fourier transform(HSFFT). The algorithm first replaces the IFFT process of the traditional parallel code phase capture algorithm with inverse sparse fast Fourier transform (ISFFT) with better computing performance, and then uses linear search combined with code phase discrimination to replace the positioning loop and the estimation loop with poor noise immunity in ISFFT. Theoretical analysis and simulation results show that, compared with the existing SFFT parallel code phase capture algorithm, the calculation amount of this algorithm is reduced by 19%, and the SNR performance is improved by about 5dB. Compared with the classic FFT parallel code phase capture algorithm, the calculation amount of the algorithm in this paper is reduced by 43%, and when the capture probability is greater than 95%, the SNR performance of the two is approximately the same.

This study aimed to explore the candidate genes associated with simple steatosis (SS) using integrated bioinformatics analysis. Data in GSE89632 were used to identify differentially expressed genes (DEGs) between SS and healthy controls (HC). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis for DEGs was conducted. Protein–protein interactions (PPI) network and transcription factor (TF)-gene network were constructed, followed by pathway analysis. Drug-gene interactions were also predicted. Finally, the expression level of hub genes was verified using GSE126848 and quantitative real-time PCR (qRT-PCR). A total of 418 (139 up-regulated and 279 down-regulated) DEGs were identified between SS and HC groups. PPI analysis revealed that FOS, MYC, IL1B, and EGR1might be considered as hub genes. Pathway analysis showed that these genes were mainly involved in TNF signaling pathway. Drug-gene interaction analysis identified six gene targets (PTGS2, IL1B, MMP9, CCL2, JUN, and IL6) and 38 small molecules. Further experimental verification confirmed that the expression level of FOS, MYC, IL1B, and EGR1was significantly down-regulated in the SS samples. In conclusion, these data may provide new insights into the pathogenesis and treatment of SS. These hub genes and candidate drugs may improve the individualized diagnosis and treatment of SS.

In this paper, a novel Selective Compliance Assembly Robot Arm (SCARA) high-speed parallel manipulator that can realize three-translation and one-rotation motion is proposed, and an accurate dynamic modeling methodology is investigated. The mechanism is composed of four limbs with a double parallelogram structure and a single moving platform. The high bearing capacity and high dynamic response of the novel mechanism make it a viable alternative choice for this kind of automation equipment. The degree-of-freedom (DOF) of the mechanism is analyzed by the screw theory. At the same time, the velocity mapping model of the mechanism is established by the twist screw and the actuated Jacobian matrix. Then, the acceleration mapping model of the mechanism, including the generalized kinematic pairs, is established by reduced acceleration state, the modified Lie screw, and the acceleration Hessian matrix. On this basis, the complete dynamic model with a compact form of the mechanism is deduced by the combination of screw theory and virtual work principle, and the correctness of the developed model is verified by multibody simulation software. Finally, considering the inertial characteristics of the mechanism, the dynamic performance distribution in the reachable workspace of the mechanism is analyzed by the Joint-Reflected Inertia (JRI) index and Coefficient of Variation of joint-space Inertia (CVI) index, and some areas are selected as the task workspace using the above index to guarantee good dynamic performance.

The mortality rate for intensive care unit tuberculosis-destroyed lung (TDL) patients requiring mechanical ventilation (MV) remains high. We conducted a retrospective analysis of adult TDL patients requiring MV who were admitted to the intensive care unit of a tertiary infectious disease hospital in Chengdu, Sichuan Province, China from January 2019 to March 2023. Univariate and multivariate COX regression analyses were conducted to determine independent patient prognostic risk factors that were used to construct a predictive model of patient mortality. A total of 331 patients were included, the median age was 63.0 (50.0–71.0) years, 262 (79.2%) were males and the mortality rate was 48.64% (161/331). Training and validation data sets were obtained from 245 and 86 patients, respectively. Analysis of the training data set revealed that body mass index <18.5 kg/m2, blood urea nitrogen ≥7.14 mmol/L and septic shock were independent risk factors for increased mortality of TDL patients requiring MV. These variables were then used to construct a risk-based model for predicting patient mortality. Area under curve, sensitivity, and specificity values obtained using the model for the training data set were 0.808, 79.17%, and 68.80%, respectively, and corresponding values obtained using the validation data set were 0.876, 95.12%, and 62.22%, respectively. Concurrent correction curve and decision curve analyses confirmed the high predictive ability of the model, indicating its potential to facilitate early identification and classification-based clinical management of high-risk TDL patients requiring MV.

Liriogerphines A–D (1–4, respectively), an unprecedented class of hybrids of germacranolide-type sesquiterpenoids and aporphine-type alkaloids, were isolated from the rare medicinal plant Liriodendron chinense. Their structures were elucidated by comprehensive spectroscopic analyses combined with electronic circular dichroism calculations and X-ray crystallographic data. Biosynthetically, an aza-Michael addition reaction is proposed to be involved in the assemblies of this class of hybrids. Compound 4exhibited cytotoxicity against leukemia cells via inducing apoptosis and inhibiting Bcl-2 expression.

Intelligent confrontation has become a vital technology for future air combats. Confrontation games between a penetrating aircraft and an intercepting aircraft are essential for modern air combats. In addition, the performance indexes of both the interceptor and penetrator must be considered. Traditional methods only solve one side's guidance problem without considering the intelligence of the opponent. In this paper, an adaptive heuristic dynamic programming-based algorithm is proposed for aircraft confrontation games. This algorithm constructs a heuristic dynamic programming model for both confrontation aircraft and then updates the critical and action network parameters using the dynamic confrontation state information. Numerical simulations indicate that the proposed algorithm can optimize the guidance law for both the interceptor and penetrator and is therefore superior to traditional proportional navigation methods.

The rise of multidrug resistant (MDR) Gram-negative (GN) pathogens and the decline of available antibiotics that can effectively treat these severe infections are a major threat to modern medicine. Developing novel antibiotics against MDR GN pathogens is particularly difficult as compounds have to permeate the GN double membrane, which has very different physicochemical properties, and have to circumvent a plethora of resistance mechanisms such as multiple efflux pumps and target modifications. The bacterial type II topoisomerases DNA gyrase (GyrA2B2) and Topoisomerase IV (ParC2E2) are highly conserved targets across all bacterial species and validated in the clinic by the fluoroquinolones. Dual inhibitors targeting the ATPase domains (GyrB/ParE) of type II topoisomerases can overcome target-based fluoroquinolone resistance. However, few ATPase inhibitors are active against GN pathogens. In this study, we demonstrated a successful strategy to convert a 2-carboxamide substituted azaindole chemical scaffold with only Gram-positive (GP) activity into a novel series with also potent activity against a range of MDR GN pathogens. By systematically fine-tuning the many physicochemical properties, we identified lead compounds such as 17rwith a balanced profile showing potent GN activity, high aqueous solubility, and desirable PK features. Moreover, we showed the bactericidal efficacy of 17rusing a neutropenic mouse thigh infection model.

Plasmonics enables the manipulation of light beyond the optical diffraction limit1–4and may therefore confer advantages in applications such as photonic devices5–7, optical cloaking8,9, biochemical sensing10,11and super-resolution imaging12,13. However, the essential field-confinement capability of plasmonic devices is always accompanied by a parasitic Ohmic loss, which severely reduces their performance. Therefore, plasmonic materials (those with collective oscillations of electrons) with a lower loss than noble metals have long been sought14–16. Here we present stable sodium-based plasmonic devices with state-of-the-art performance at near-infrared wavelengths. We fabricated high-quality sodium films with electron relaxation times as long as 0.42 picoseconds using a thermo-assisted spin-coating process. A direct-waveguide experiment shows that the propagation length of surface plasmon polaritons supported at the sodium–quartz interface can reach 200 micrometres at near-infrared wavelengths. We further demonstrate a room-temperature sodium-based plasmonic nanolaser with a lasing threshold of 140 kilowatts per square centimetre, lower than values previously reported for plasmonic nanolasers at near-infrared wavelengths. These sodium-based plasmonic devices show stable performance under ambient conditions over a period of several months after packaging with epoxy. These results indicate that the performance of plasmonic devices can be greatly improved beyond that of devices using noble metals, with implications for applications in plasmonics, nanophotonics and metamaterials.

Angiogenesis plays an important role in the development of rheumatoid arthritis (RA), which increases the supply of nutrients, cytokines, and inflammatory cells to the synovial membrane. Genistein (GEN), a soy-derived isoflavone, has been validated that can effectively inhibit the angiogenesis of several tumours. We thus carried out a study in vitro to investigate the effect of GEN in vascular endothelial growth factor (VEGF) expression and angiogenesis induced by the inflammatory environment of RA.

Endothelial angiogenesis plays a vital role in recovery from chronic ischemic injuries. ZYZ-803 is a hybrid donor of hydrogen sulfide (H2S) and nitric oxide (NO). Previous studies showed that ZYZ-803 stimulated endothelial cell angiogenesis both in vitro and in vivo. In this study, we investigated whether the signal transducer and activator of transcription 3 (STAT3) and Ca2+/CaM-dependent protein kinase II (CaMKII) signaling was involved in ZYZ-803-induced angiogenesis. Treatment with ZYZ-803 (1 μM) significantly increased the phosphorylation of STAT3 (Tyr705) and CaMKII (Thr286) in human umbilical vein endothelial cells (HUVECs), these two effects had a similar time course. Pretreatment with WP1066 (STAT3 inhibitor) or KN93 (CAMKII inhibitor) blocked ZYZ-803-induced STAT3/CAMKII activation and significantly suppressed the proliferation and migration of HUVECs. In addition, pretreatment with the inhibitors significantly decreased ZYZ-803-induced tube formations along with the outgrowths of branch-like microvessels in aortic rings. In the mice with femoral artery ligation, administration of ZYZ-803 significantly increased the blood perfusion and vascular density in the hind limb, whereas co-administration of WP1066 or KN93 abrogated ZYZ-803-induced angiogenesis. By using STAT3 siRNA, we further explored the cross-talk between STAT3 and CaMKII in ZYZ-803-induced angiogenesis. We found that STAT3 knockdown suppressed ZYZ-803-induced HUVEC angiogenesis and affected CaMKII expression. ZYZ-803 treatment markedly enhanced the interaction between CaMKII and STAT3. ZYZ-803 treatment induced the nuclear translocation of STAT3. We demonstrated that both STAT3 and CaMKII functioned as positive regulators in ZYZ-803-induced endothelial angiogenesis and STAT3 was important in ZYZ-803-induced CaMKII activation, which highlights the beneficial role of ZYZ-803 in STAT3/CaMKII-related cardiovascular diseases.

The difference in the atrial organizational structure between patients with atrial fibrillation (AF) and those with sinus rhythm was investigated. In order to analyze the rationality in explaining the electrocardiogram (ECG) characteristics of AF with statistics data or tissue remodeling model, and the logical relationship between the hypothesis of pulmonary veins (PV) muscle sleeves and that of multi wavelets in mechanism of AF, we examined the expression of collagen volume fraction of type I (CVF-I) with picrosirius red staining, connexin 40 (Cx40) by immunohistochemistry, and intercalated disc (ID) using transmission electron microscope in atrial tissue. The results showed that there was significant difference in the expression of CVF-I (t=3.827, P<0.01), Cx40 (t=4.21, P<0.01), and groups of the ID that keeping the electrical transmission and atrial electrical coupling synchronization (t=15.116, P<0.001), but no significant difference was found in total IDs (t=0.611, P=0.543) between patients with AF and those with sinus rhythm. The quantitative differences in the tissue remodeling could not explain the ECG characteristics of AF. The number of normal IDs and abnormal distribution are the structural basis to trigger and maintain atrial electrical remodeling, and induce and maintain AF. Such histological reconstruction supports the hypothesis of multi wavelets and can also explain ECG features.

This study is a case–control study to explore risk and protective factors, including clinical data and bone mineral density (BMD), affecting vertebral body fragility fracture in elderly men and postmenopausal women. In addition, we investigate the effectiveness of lumbar spine BMD by quantitative computed tomography (QCT) in discriminating vertebral fragility fracture.

Background:Hepatocellular carcinoma (HCC) (about 85–90% of primary liver cancer) is particularly prevalent in China because of the high prevalence of chronic hepatitis B infection. HCC is the fourth most common malignancy and the third leading cause of tumor-related deaths in China. It poses a significant threat to the life and health of Chinese people. Summary:This guideline presents official recommendations of the National Health and Family Planning Commission of the People’s Republic of China on the surveillance, diagnosis, staging, and treatment of HCC occurring in China. The guideline was written by more than 50 experts in the field of HCC in China (including liver surgeons, medical oncologists, hepatologists, interventional radiologists, and diagnostic radiologists) on the basis of recent evidence and expert opinions, balance of benefits and harms, cost-benefit strategies, and other clinical considerations. Key Messages:The guideline presents the Chinese staging system, and recommendations regarding patients with HCC in China to ensure optimum patient outcomes.

Information on left ventricular noncompaction (LVNC) in older people is sparse. This study aimed to investigate the clinical profile of LVNC in an older cohort.

A novel flux charging method and a crucible quenching method were employed to study the mechanism of solid fluxes refining method regarding the removal of oxide inclusions (Al2O3) from molten aluminum. Electrochemical polishing method was adopted to prepare surfaces of the samples. Through experiments, the morphology of the residual solidified flux in the solidified samples as well as the wetting action of the molten flux during refining were observed for the first time. Three wetting regimes denoted by absorbing regime, engulfing regime and penetration regime correlating with the removal of oxide films (the most typical and common oxide inclusions in molten aluminum) were proposed in terms of different types and distributions of oxide films and different size ratios of the molten flux to oxide films. Particularly, from a thermodynamic point of view, for the first time, the penetration regime provided concrete evidence that the practical oxide inclusions can be wet by molten flux under ambient fluid of molten aluminum. A spreading model was proposed, according to which ingredients and size parameters of practical solid fluxes can be optimized.

Implant‐associated infection and inflammation are the main causes of implant failure, causing irreversible damage and significantly increasing clinical risks and economic losses. In this study, a 3D multifunctional architecture is constructed that consisted of hierarchical TiO2nanotubes (NTs) and electrospun polyvinylidene fluoride nanofiber layers on the surface of a titanium implant. The movement of bacteria through the nanofiber layer is facilitated by its appropriate pore sizes and electrostatic interactions to reach the NT layer where the bacteria are killed by positive charge traps. In contrast, the macrophages tend to adhere to the nanofiber layer. The mechanical interactions between the macrophages and piezoelectric nanofibers generate a self‐stimulated electric field that regulated an anti‐inflammatory phenotype. This study provides a new method for multifunctional implant materials with antibacterial, piezoelectrically self‐stimulated anti‐inflammatory, and osteointegration properties that are driven by electrical stimulation. A 3D multifunctional architecture is constructed that consisted of hierarchical titanium dioxide nanotube and electrospun polyvinylidene fluoride nanofiber layers on the surface of the titanium implants. The antibacterial, anti‐inflammatory, and osteogenic properties are remarkably enhanced both in vitro and in vivo, providing a prospective approach of the electrically driven multifunctionalization for implants.

Currently, powdered Chinese herbal medicines (CHMs) were mainly evaluated through physical property, chemical dissolution, and bioactivity independently. It could not reflect the quality comprehensively. This paper was to explore and establish a comprehensive evaluation method for powdered CHMs.

•It is able to as the balance point between the blood pressure and bleeding event.•It can reduce the bleeding amount and infusion volume and increase the cure rate of patients.•Restrictive fluid resuscitation has a promising value in the treatment of HTS, which is worthy of promotion in clinical practice.

Golgi protein 73 (GP73) is a promising biomarker of hepatocellular carcinoma (HCC). It decreases after surgical resection, and resumes upon recurrence, indicating a potential indicator for the effectiveness of the treatment. But changes of GP73 after transcatheter arterial chemoembolization (TACE) have not been reported so far. This study was to investigate the dynamic changes of GP73 in HCC patients after TACE treatment, and the possible underlying mechanisms in the cell cultures.

Introduction:Cytosolic sulfotransferases (SULTs), one of the vital enzymes of detoxication, catalyze the sulfation of native and exogenous hydrophobic molecules. Xenobiotic accumulation can induce a variety of diseases, including cancers. Sulfation facilitates the solubilization and removal of xenobiotics. However, sulfation may activate the pharmacological activities of xenobiotics.Areas covered:The purpose of this review was to correlate the sequence, structure and function of SULTs. We focused on understanding the sulfation mechanisms of SULT through its sequence variation. We selectively reviewed SULT drug substrates, explained the enzyme-catalyzed sulfation reaction and its kinetic mechanisms, and the effect of amino acid sequence variation, such as single-nucleotide polymorphism, on the enzyme function.Expert opinion:A wealth of information is available in the literature for understanding the detailed mechanisms underlying xenobiotic sulfation. We reviewed information regarding the sequence, structure and reaction mechanism of SULTs and explained how SULT activities altered. In addition to revealing the SULT kinetics, the mRNA expression of specific SULTs in tissues that revealed their distribution in tissues also affects overall SULT activities. Understanding of the structure–function relationship and the reaction mechanism of SULTs is valuable for understanding, preventing and treating diseases.

In this paper, an experiment in a quasi-static conditions was carried out on barge bow model with its cross sections simplified. The characteristics of the bow structure were studied experimentally and Finite Element Analysis (FEA) was conducted to compare with experimental results. The experiment was performed by a compression and shear testing machine and the model was axially collapsed by a rigid board. The collapse mechanisms, load-displacement curve and mean crushing strength were investigated. The study showed that basic collapse mechanism of barge bow was clarified in participates with inner diaphragms. Moreover, the accuracy of FEA to estimate mean crushing force were validated by comparing with experimental results.

Horizontal support extending loader vehicle is used in coal mine, whose main role is to play a supportive role in belt transport unit. When the support car is pulled by tractor or pushed by motor vehicle, energy consumption is high with its own excessive weight. The car lightweight design is carried out through structural designing and material changing. Lightweight design has met the requirements after analysis. Lightweight design for support vehicle is not only to achieve the purpose of energy conservation, but also make the support vehicles assembling easily and get a good effect.

Postoperative liver failure remains a life-threatening complication. Preoperative evaluation of liver function is essential in reducing the complications after hepatectomy. However, it is difficult to accurately evaluate liver function before surgery because of the limitations of the liver function tests available. Recent advances in liver function tests improved the ability to assess liver function. The present review was to analyze these methods and their advantages.

Along with the arrival of network financial information times, network accounting emerges. Accounting means have undergone through handwork accounting and computer to replace the changes of handwork accounting, database and network. Maximum share of accounting information resource can be realized by network accounting, which accelerates the accounting affairs handing, making the centralized management easier and providing with endurance to the full development for the electronic business.

PDC anchor bit has the very good rock fragmentation abilities with high penetration rate and long drilling time,which makes the drilling efficiency highly improved and the economic benefit remarkably increased.Now PDC anchor bit has been widely used in drilling field.But for the reason that it is sensitive to the formation characteristics and working conditions,it doesn’t achieve good performance in homogeneous formations such as conglomerate and interbeded sections.In order to reach the goal of enlarging the scope of PDC anchor bit application in oilfields,it is necessary to study the breakage mechanism in conglomerate formations and design the PDC anchor bit optimally.

Due to the change of car-body design, the location of exhaust systems hanger is uncertain and always fluctuates around the initial design position. So the Taguchi method is introduced to conduct exhaust systems optimal design. Firstly, the parameterization of hanger location under the grid environment was realized by combining NastranHypermesh and Isight. Then, the Taguchi robust design of the exhaust system is performed taking the hanger location as noise factors and the stiffness of hanger shock absorber as control factors. As a result, modal property and robustness of the exhaust system are improved. At last, the results of Taguchi robust design and traditional sensitivity optimization design based on the finite element method are compared, which reveals the advantage of Taguchi robust design in improving product quality.

This Delay/Disruption Tolerant Network(DTN) is a New Network Architecture for Communication in Restricted Condition with High Latency and Intermittent Connectivity.In Order to Solve the Problem that Messages can Not be Delivered Reliably because of Mobility and Limited Buffer Size of Nodes in DTN,a Probabilistic Routing Algorithm Based on Node Free Buffer-Utilization (NFBU)is Proposed.The Algorithm Sets Node Free Buffer Warning/excitation Threshold,through Warning/incentive Factor to Increase/decrease the Node Forwarding Probability,and Set up the Buffer Management Strategy,message Time to Live(TTL)value is Smaller,the Higher its Priority,at the same Time Remove the Oldest Message to get more Buffer Space.Simulations Indicate that the Algorithm Improves Delivery Ratio and Reduces Network Latencies in Different Node Free Buffer-Utilization State Compared with some other Routing Algorithms,and it is Highly Adaptable to Network.

n recent years, distributed generation has become a hot topic at home and abroad, and researchers have attached great importance to the new methods of reconfiguration in case of failure. This paper proposes to adopt improved Ant Colony System Algorithm for reconfiguration of the distributed power. Power loss and minimum load balance index as objective function, the ACS algorithms capability of avoiding being trapped in local optima can be enhanced. The algorithm can do better in global search and avoid the problem of the premature convergence. When ACS algorithm is applied to the IEEE33 node system, the simulation results show that the method can not only effectively reduce power losses, but also decrease load balancing index , thus improving the quality of power supply.