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Abstract Computational screening of single gases to replace SF6 for electrical insulation has been challenged by the difficulty in combining various mutually exclusive properties especially for dielectric performance with liquefaction and environmental properties. To reveal the inherent correlations between dielectric strength (Er), boiling point (Tb), and global warming potential (GWP) of dielectric materials, a coupled structure‐activity relationship (CSAR) model has been proposed for the first time. By means of the generic descriptors, as deduced from the electrostatic potentials, and the specific descriptors, as introduced from the respective microscopic mechanisms, the complex interdependence between Er, Tb, and GWP of the insulation gases is quantitatively characterised by the 3‐D coupling matrix. The coupling mechanism for the right balance of properties is uncovered in terms of the first‐principle descriptors. The CSAR model outperforms the previous SAR models in predicting Er, Tb, and GWP simultaneously in a self‐consistent manner. More importantly, the concept of CSAR could be extended readily to any multidimensional macroscopic properties. Novel replacement compounds have been identified tentatively to be the promising candidates to replace SF6 using the CSAR model.

Abstract With the increasing lifespan of bridges, various forms of deterioration will inevitably occur. The bridge health monitoring system enables direct monitoring of the loads (such as wind, temperature, and vehicles) experienced by the bridge during operation, as well as the corresponding vibration response of the bridge structure (including main beam deformation, tower top displacement, cable acceleration, etc.). These data provide valuable insights into the safety and durability of the bridge during its operational lifetime. However, the challenge lies in extracting meaningful information from the vast amount of collected data. This article focuses on the Fuyu Bridge as a research case and analyzes the variations in environmental factors, such as temperature, humidity, wind load, and structural vibration responses (main beam and cable), obtained from the Fuyu Bridge's structural health monitoring system. It also conducts a structural safety assessment during the operational period of the bridge. Furthermore, the research explores the relationship between environmental factors, load effects, and structural response to establish a foundation for future structural safety assessments of the Fuyu Bridge during its operational period. For instance, changes in environmental factors or load effects can be used to predict structural responses. Additionally, this study provides access to the structural health monitoring data of the Fuyu Bridge, facilitating data‐driven research for other scholars in the field.

Abstract As the wind turbine height increases, the probability of multiple upward leaders flashes within the wind farm increases. In this study, an upward lightning flash containing 21 upward positive leaders (UPLs) initiated from different wind turbines in Zhangbei Wind Farm was analysed. The average speed of the UPLs was 1.2 × 105 m/s, which mostly decreased to zero before reaching the cloud height. Only four UPLs developed to cloud height, with prolonged periods of bright light on three of them and with a minimum duration of 126 ms. A total of nine return strokes occurred on the other two dissipated leader channels, and the numbers of strokes on the two channels was six and three, respectively. The average interstroke interval for the return strokes was 10.5 ms. Most of these nine return strokes had peak currents smaller than 10 kA. The high‐speed video frames confirmed that competition does exist between the UPLs, and the range of shielding effects increases as the height of the ULs increases. The effect of fan rotation on the initiation of upward leaders and the shielding effect between the wind turbines and upward leaders are discussed.

Abstract Anxiety disorders have become one of the most severe psychiatric disorders, and the incidence is increasing every year. They impose an extraordinary personal and socioeconomic burden. Anxiety disorders are influenced by multiple complex and interacting genetic, psychological, social, and environmental factors, which contribute to disruption or imbalance in homeostasis and eventually cause pathologic anxiety. The selection of a suitable animal model is important for the exploration of disease etiology and pathophysiology, and the development of new drugs. Therefore, a more comprehensive understanding of the advantages and limitations of existing animal models of anxiety disorders is helpful to further study the underlying pathological mechanisms of the disease. This review summarizes animal models and the pathogenesis of anxiety disorders, and discusses the current research status to provide insights for further study of anxiety disorders.

Abstract Varistor coupling is recommended by International Telecommunication Union in combination wave test waveforms of surge protective devices (SPD), although the varistor coupling method and recommendation parameters for the combination wave test are not well understood. The waveform influencing characteristics introduced by varistor coupling are studied in detail in this paper. Low‐voltage varistors, with maximum operating voltages ranging from 130 to 750 V, are adopted here in the OrCAD/PSpice environment to analyze the influence of varistor coupling on the output characteristic of the combination wave generator (CWG) in test levels of 0 to 20 kV. Simulation results show that, owing to varistor coupling, the reverse oscillation phenomena will arise in the open‐circuit voltages (OCVs). Also owing to varistor coupling, compared with those generated directly by a CWG, the peak value, the front time, and the tail time for both OCV and short‐circuit current will decrease, whereas the virtual impedance will increase. Moreover, the lower the test level, or the higher the maximum operating voltage of the varistor, the more serious this effect. Experiments have also been conducted here, and our simulation results are found to match the experimental ones well. It seems that, compared with the conventional capacitor coupling, the range of the voltage of power supply networks and the levels of combination wave test by varistor coupling have to be limited to a great extent. Varistor coupling for combination wave test of SPD should be only used in special cases and special test levels where there are no strict waveform limitations.

Abstract Vapor buildup in the atmosphere and faster warming over land than over ocean are ubiquitous features of climate change. This combination is a threat to society because the associated heat stress may exceed the limit for human survival. The heat stress due to high humidity and high temperature is quantified with the wet‐bulb temperature (Tw). A common view is that the land Tw should change at the same rate as the ocean surface temperature (Ts). Using climate model data and atmospheric observations, we show that the land Tw increases 17% faster than Ts. This amplification arises from stronger downward longwave radiation (L↓) at the surface in a warmer climate, which causes moist static energy to accumulate in the atmospheric boundary layer. We also find that L↓ is a better predictor of Tw than Ts at interannual to decadal time scales. These relationships are robust across climates and across model simulations.

Abstract A simulation model composed of an interfering cable and a disturbed cable is established for studying the lightning inductive characteristics between parallel cables. Effects of the horizontal distance between cables (5–40 cm), their height difference (−6–32 cm), as well as the length of disturbed cable (1–100 m) are investigated for the cable induced voltage, which is measured at the resistive load connected between one terminal of the disturbed cable and the ground, when various lightning surge currents (8/20 μs, 5/320 μs, and 0.5 μs/100 kHz) are delivered into the interfering cable. Our findings show that an increase of horizontal distance between cables can give rise to an exponential decrease of the cable induced voltage, and that there exist linear correlations between either the height difference of two cables or the length of disturbed cable and the cable induced voltage, which reaches maximum when the cables are located at the same height and of equal length. Verification experiments for the effect of horizontal distance have also been made, and, in general, they all show a reasonable agreement with the simulations. A detailed theoretical explanation of obtained findings is provided as well.

Abstract Skin is the first barrier against external threats, and skin immune dysfunction leads to multiple diseases. Psoriasis is an inflammatory, chronic, common, immune‐related skin disease that affects more than 125 million people worldwide. RNA interference (RNAi) therapy is superior to traditional therapies, but rapid degradation and poor cell uptake are the greatest obstacles to its clinical transformation. The transdermal delivery of siRNA and controllable assembly/disassembly of nanodrug delivery systems can maximize the therapeutic effect. Tetrahedral framework nucleic acid (tFNA) is undoubtedly the best carrier for the transdermal transport of genes due to its excellent noninvasive transdermal effect and editability. The authors combine acid‐responsive tannic acid (TA), RNase H‐responsive sequences, siRNA, and tFNA into a novel transdermal RNAi drug with controllable assembly and disassembly: STT. STT has heightened resistance to enzyme, serum, and lysosomal degradation, and its size is similar to that of tFNA, enabling easy transdermal transport. After transdermal administration, STT can specifically silence nuclear factor kappa‐B (NF‐κB) p65, thereby maintaining the stability of the skin's microenvironment and reshaping normal skin immune defense. This work demonstrates the advantages of STT in RNAi therapy and the potential for future treatment of skin‐related diseases.

Abstract Aberrant expression of circular RNAs (circRNAs) has been reported to play an important biological regulatory role in gastric cancer (GC). For the purpose of silencing cancer‐related genes, a new approach for cancer treatment using nanocarriers to deliver siRNA has been proposed. In this study, abundantly expressed circMAP2K2 (hsa_circRNA_102415) is identified in GC cells. CircMAP2K2 regulates the PCBP1/GPX1 axis through proteasome‐mediated degradation, which further mediates the activation of the AKT/GSK3β/epithelial‐to‐mesenchymal transition (EMT) signaling pathway and enhances the proliferation and metastatic ability of GC cells. To establish novel GC treatment, epigallocatechin‐3‐gallate‐lysozyme (EGCG‐LYS) fibrils are synthesized, and in vitro experiments demonstrate that EGCG‐LYS has a higher siRNA delivery efficiency than Lipofectamine 2000 (lipo2000), which effectively silences the expression of circMAP2K2. Further studies show that EGCG‐LYS carrying siRNA can successfully achieve lysosome escape, which allows it to be located in the cytoplasm to achieve post‐transcriptional gene silencing. In addition, EGCG‐LYS carrying si‐circMAP2K2 has good circulating stability, excellent biosafety and antitumor ability in vivo. The EGCG‐LYS fibrils delivery system provides a new tool and approach for the treatment of GC.

Abstract We have shown previously that expression of R345W‐Fibulin‐3 induces epithelial‐mesenchymal transition (EMT) in retinal pigment epithelial (RPE) cells. The purpose of the current study was to determine if extracellular vesicles (EVs) derived from RPE cells expressing R345W‐Fibulin‐3 mutation are sufficient to induce EMT in recipient cells. ARPE‐19 cells were infected with luciferase‐tagged wild‐type (WT)‐ Fibulin‐3 or luciferase‐tagged R345W‐Fibulin‐3 (R345W) using lentiviruses. EVs were isolated from the media by ultracentrifugation or density gradient ultracentrifugation. Transmission electron microscopy and cryogenic electron microscopy were performed to study the morphology of the EVs. The size distribution of EVs were determined by nanoparticle tracking analysis (NTA). EV cargo was analysed using LC‐MS/MS based proteomics. EV‐associated transforming growth factor beta 1 (TGFβ1) protein was measured by enzyme‐linked immunosorbent assay. The capacity of EVs to stimulate RPE migration was evaluated by treating recipient cells with WT‐ or R345W‐EVs. The role of EV‐bound TGFβ was determined by pre‐incubation of EVs with a pan‐TGFβ blocking antibody or IgG control. EM imaging revealed spherical vesicles with two subpopulations of EVs: a group with diameters around 30 nm and a group with diameters over 100 nm, confirmed by NTA analysis. Pathway analysis revealed that members of the sonic hedgehog pathway were less abundant in R345W‐ EVs, while EMT drivers were enriched. Additionally, R345W‐EVs had higher concentrations of TGFβ1 compared to control. Critically, treatment with R345W‐EVs was sufficient to increase EMT marker expression, as well as cell migration in recipient cells. This EV‐increased cell migration was significantly inhibited by pre‐incubation of EVs with pan‐TGFβ‐neutralising antibody. In conclusion, the expression of R345W‐Fibulin‐3 alters the size and cargo of EVs, which are sufficient to enhance the rate of cell migration in a TGFβ dependent manner. These results suggest that EV‐bound TGFβ plays a critical role in the induction of EMT in RPE cells.

Abstract In 2019, triggered lightning was used to directly strike phase C of a 1.5 km, 10 kV double‐circuit distribution line in Guangzhou, China, with 2 flashes (13 return strokes) recorded. This paper presents the characteristics of induced voltage at the closest pole on the parallel line. The induced voltage is bipolar, which can be divided into 3 stages: negative increase stage, fast and positive transition stage and slowly returning to zero stage. The positive peak value of phase A voltage ranges from 111.4 to 228.9 kV and that of phase C voltage is from 90.1 to 200.9 kV, corresponding to lightning current from −8.9 to −29.9 kA. The positive peak value of the induced voltage is approximately 3 to 10 times the negative peak value. The negative peak, positive peak and positive 10%–10% duration time of induced voltage show a good linear relationship with the peak value of the return stroke current. There was no flashover occurred during the whole process. The result in this paper can provide data support for numerical simulation and line protection analysis.

Abstract As the height of wind turbine increases, the lightning strike accident has become a non‐negligible issue. In this paper, the lightning attachment characteristic of a 2‐MW wind turbine generator (WTG) is investigated using a model with a reduced scale of 100. The WTG model is equipped with receptors on the blades and a lightning rod on the nacelle, both serving as its external lightning protection system (LPS). The high‐voltage electrode, which delivers a lightning impulse voltage from a Marx generator, is used to simulate the final stage of downward negative lightning strikes from 29 coming‐leader positions. The experimental results indicate that lightning leaders from either front directions or side directions could be intercepted effectively by LPS, whereas the back‐direction lightning could not. Moreover, with the increase of striking distance, the capture ratio for the insulation part of blade decreases. Electric field intensity distribution simulations for the full‐scale WTG model, using conditions similar to their experimental counterparts, are conducted and compared with the lightning attachment distribution. Based on classical electro‐geometrical model, a simulative method is proposed to predict the lightning attachment distribution of WTG. Our results indicate that it is feasible with this method to produce a satisfactory approximation to the experimentally obtained lightning attachment distribution.

Abstract The operation of disconnectors in gas insulated substation (GIS) or power plant will produce very fast transient overvoltage (VFTO), which is considered to have serious harm to transformer longitudinal insulation and other high‐voltage equipment insulation. VFTO may also lead to secondary circuit failure. In this paper, the holistic modelling of 500 kV GIS step‐up substation equipment with a double circuit and long GIS busbar in a coastal power plant is established using Electromagnetic Transient Program (EMTP). The authors calculated the VFTO waveform that may be generated in different operations of the GIS substation. The authors analyze the amplitude and frequency characteristics of the VFTO waveform at lightning arresters and the entrance of transformers and find that the amplitude of VFTO at the entrance of #1 MT is less than its impulse withstand voltage. In some cases, the VFTO waveform at the entrance of #1 MT has high‐frequency content with fast attenuation. The VFTO waveform generated when operating the disconnector close to the arrester will cause the arrester to act many times and count frequently in a short time.

Abstract In 2018–2019, two types of rocket‐triggered lightning tests, that is, striking to ground and distribution line, were conducted in Guangdong, China. The main focus of this paper is to compare the waveform parameters of the return strokes (RS) from the two tests. For current, the 10%–90% risetime of RS from lightning striking to distribution line is 2.4 times higher than that striking to ground, and the differences in the other parameters are small. For close magnetic field, the RS from lightning striking to distribution line have a lower peak (30% lower after considering the peak current) and a larger risetime and half‐peak width time; besides, it is necessary to divide the front edge of the close magnetic field waveform into two parts: leader (BL) and return stroke (BRS). For close electric field, the close RS electric field peak (ERS) was less sensitive to distance than the leader electric field peak (EL). For far electric field, the differences in waveform parameters of RS from the two tests were not significant, but after considering the peak current, the normalised initial electric field peak (EP) of RS from lightning striking to distribution line was 14% lower than that striking to ground.

Abstract This paper reports the observation results of three‐phase overvoltage at the lightning strike point of a 1.5 km, 10 kV power distribution line that was struck directly by rocket triggered lightning to its phase wire C. The arrester of the direct struck phase at the lightning strike point operated in all return strokes corresponding to return stroke current from −3.3 kA to −32.9 kA. The waveform of direct struck phase includes an initial spike before negative peak, operation area of metal oxide varistor, and the final attenuation with oscillation. The overvoltage waveforms of the indirect struck phase at the lightning strike point show a small initial negative peak, rapid transition to a large positive peak, and the final negative attenuation with oscillation. The negative peak value of the indirect struck phase at lightning strike point ranged from −4.1 kV to −25.2 kV and that of the direct struck phase was between −78.1 kV and −167.8 kV. The positive peak value of indirect struck phase was between 0.2 kV and 49.8 kV. The negative peak value, zero‐crossing time and the peak‐to‐peak value of voltage all have a good linear relation with the peak value of lightning return stroke current.

Abstract Multiphase sulfur redox reactions with advanced homogeneous and heterogeneous electrochemical processes in lithium–sulfur (Li–S) batteries possess sluggish kinetics. The slow kinetics leads to significant capacity decay during charge/discharge processes. Therefore, electrocatalysts with adequate sulfur‐redox properties are required to accelerate reversible polysulfide conversion in cathodes. In this study, we have fabricated an oxygen‐modulated metal nitride cluster (C‐MoNx‐O) that has a moderate binding ability to the insoluble Li2Sx for reversible polysulfide electrocatalysis. A Li–S battery equipped with C‐MoNx‐O electrocatalyst displayed a high discharge capacity of 875 mAh g−1 at 0.5 C. The capacity decay rate of each cycle was only 0.10% after 280 cycles, which is much lower than the control groups (C‐MoOx: 0.16%; C‐MoNx: 0.21%). Kinetic studies and theoretical calculations suggest that C‐MoNx‐O electrocatalyst presents a moderate binding ability to the insoluble Li2S2 and Li2S when compared to the C‐MoOx and C‐MoNx surfaces. Thus, the C‐MoNx‐O can effectively immobilize and reversibly catalyze the solid–solid conversion of Li2S2–Li2S during charge–discharge cycling, thus promoting reaction kinetics and eliminating the shuttle effect. This study to design oxygen‐doped metal nitrides provides innovative structures and reversible solid–solid conversions to overcome the sluggish redox chemistry of polysulfides.

Abstract With the dramatic developments of renewable and environmental‐friendly electrochemical energy conversion systems, there is an urgent need to fabricate durable and efficient electrocatalysts to address the limitation of high overpotentials exceeding thermodynamic requirements to facilitate practical applications. Recently, tellurium‐based nanomaterials (Te NMs) with unique chemical, electronic, and topological properties, including Te‐derived nanostructures and transition metal tellurides (TMTs), have emerged as one of the most promising electrocatalytic materials. In the absence of comprehensive and guiding reviews, this review comprehensively summarizes the main advances in designing emerging Te NMs for electrocatalysis. First, the engineering strategies and principles of Te NMs to enhance their electrocatalytic activity and stability from the nanostructures to the catalytic atoms are discussed in detail, especially on the chemical/physical/multiplex templating strategies, heteroatom doping, vacancy/defect engineering, phase engineering, and the corresponding mechanisms and structure‐performance correlations. Then, typical applications of Te NMs in electrocatalysis are also discussed in detail. Finally, the existing key issues and main challenges of Te NMs for electrocatalysis are highlighted, and the development trend of Te NMs as electrocatalysts is expounded. This review provides new concepts to guide future directions for developing Te NMs‐based electrocatalysts, thereby promoting their future wide applications in electrochemical energy systems.

Abstract Background As a highly heterogeneous disease, lung cancer has a multitude of cellular components and patterns of gene expression which are not dependent on a single mutation or signaling pathway. Thus, using combined drugs to treat lung cancer may be a practical strategy. Methods The combined antitumor effects of HS‐10296, a third‐generation EGFR inhibitor targeting EGFR T790M mutation, with the multitargeted tyrosine kinase inhibitor (TKI) famitinib in non‐small cell lung cancer (NSCLC) were evaluated by in vitro methods such as cell proliferation, apoptosis, angiogenesis assays, and in vivo animal efficacy studies. Results Famitinib strengthened the effects of HS‐10296 on inhibiting proliferation and inducing apoptosis of NSCLC cells, possibly by synergistic inhibition of AKT and ERK phosphorylation. Meanwhile, HS‐10296 significantly potentiated the effects of famitinib on inhibiting the proliferation and migration of HUVEC, which may be through synergistic inhibition of ERK phosphorylation in HUVEC, suggesting that HS‐10296 may improve the inhibition of angiogenesis by famitinib. Moreover, combination of HS‐10296 and famitinib exerted synergistic antitumor activity in NCI‐H1975 and PC‐9 xenograft models, and this effect may be accomplished by synergistic inhibition of phosphorylation of AKT and ERK and tumor angiogenesis in tumor tissues. Conclusions Collectively, our results indicate that HS‐10296 and famitinib exhibit significant synergistic antitumor activity, suggesting that the third‐generation EGFR inhibitor combined with VEGFR inhibitor provides a promising strategy in the treatment of EGFR‐mutant NSCLC.

Abstract The authors present a statistical analysis of characteristics of magnetic fields at different distances from triggered lightning experiments on Transmission Line at Guangdong Comprehensive Observation Experiment on Lightning Discharge during the summer of 2019. The histograms and parameters of statistical distributions for the following 22 waveform characteristics are presented, including current peak, 10%–90% risetime, half‐peak width and steepness, leader magnetic field peak, return‐stroke magnetic field peak, magnetic field peak, 10%–90% risetime, half‐peak width and steepness at 15 m, 130 m and 1.55 km. The arithmetic mean of 48 return stroke current peaks is 18.3 kA and the geometric mean is 17.0 kA. The arithmetic and geometric means of the current 10%–90% risetime are 0.6 and 0.6 μs, respectively. The leader magnetic field, return‐stroke magnetic field and magnetic field peak at 18 m, 130 m and 1.55 km are shown linear relationship with current peak values. With increasing the distance(r), the magnetic field peak value decrease, combining the magnetic field characteristics reported by previous studies, the analysis of all magnetic field peaks in different distances suggest linear relationship with r −0.90. The magnetic field 10%–90% risetime shows linear relationship with ln(r) and half‐peak width did not show significant correlation with distance.

Abstract Background The feasibility of pneumothorax following low‐dose CT‐guided puncture lung biopsy in different severities of COPD has not been reported. Methods The data of the patients with pulmonary lesion who underwent low‐dose CT‐guided lung biopsy by one experienced operator in our hospital from January 1st to September 30th in 2019 were retrospectively collected. They were divided into COPD group and non‐COPD group. The risk factors, incidence and severity of pneumothorax with the severity of COPD and changes in MMRC score, treatment way and discharge time after pneumothorax were assessed. Results Two hundred and nineteen patients were retrospectively enrolled in this study with 64 in the COPD group and 155 in the non‐COPD group. The average age, MMRC score and the incidence of pneumothorax after biopsy were significantly higher in the COPD group (64.7 ± 1.27 years, 1.02 ± 0.13, 31.3%) than in the non‐COPD group (58.8 ± 1.16 years, 0.35 ± 0.06, 17.4%, P 0.05). Conclusion Although the incidence of pneumothorax after low dose CT‐guided lung biopsy is increased in COPD, there was no difference in the severity of pneumothorax amongst the different severities of COPD and it is well‐tolerated without increasing medical burden.

Abstract China lacks data demonstrating associations of cervical neoplastic lesions with CD4 T‐lymphocyte (CD4 cell) counts and antiretroviral therapy (ART) among HIV‐infected women, suggesting relevant investigations are needed. A total of 545 HIV‐infected women were enrolled in Yunnan, China, between 2011 and 2013. CD4 cell counts and ART were measured via medical records and cervical neoplastic lesions were measured by professional pathologists. Multivariable logistic models, which treated cervical intraepithelial neoplasia (CIN) 1+ and CIN2+ as outcomes, calculated adjusted odds ratio (aOR) of CD4 cell counts and ART. Subgroup analysis treating CIN1+ as the outcome was conducted by HIV infection duration (

Background Evidence of the association between serum lipid profiles and intraplaque neovascularization (IPN) is still limited. We aimed to study the value of a novel Doppler method, superb microvascular imaging, in correlating serum lipid profiles and evidence of IPN in a population with a high risk of stroke. Methods and Results A community‐based cross‐sectional study was conducted in Beijing, China. Residents (aged ≥40 years) underwent questionnaire interviews, physical examinations, and laboratory testing in 2018 and 2019. Subjects with a high risk of stroke were then selected. Standard carotid ultrasound and carotid plaque superb microvascular imaging examinations were then performed on the high–stroke‐risk participants. Logistic regression was used to evaluate the relationship between serum lipid profiles and carotid plaque IPN. Overall, a total of 250 individuals (mean age, 67.20±8.12 years; 66.4% men) met the study inclusion criteria. Superb microvascular imaging revealed carotid plaque IPN in 96 subjects (38.4%). Subjects with IPN were more likely to be current smokers (34.0% versus 46.9%, P=0.046), and their identified carotid plaques were much thicker (2.35±0.63 mm versus 2.75±0.80 mm, P=0.001). Serum lipids, including total cholesterol, non–high‐density lipoprotein cholesterol, and low‐density lipoprotein cholesterol were positively associated with the presence of IPN (4.33±1.00 mmol/L versus 4.79±1.12 mmol/L, P=0.001; 2.96±0.92 mmol/L versus 3.40±1.01 mmol/L, P=0.001; 2.18±0.76 mmol/L versus 2.46±0.80 mmol/L, P=0.005, respectively), and after adjustment for other confounders, the positive relationship remained significant. Furthermore, non–high‐density lipoprotein cholesterol (odds ratio, 2.62 [95% CI, 1.35–5.06]) was significantly associated with the presence of carotid plaque IPN even after adjusting for low‐density lipoprotein cholesterol. Conclusions Total cholesterol, non–high‐density lipoprotein cholesterol, and low‐density lipoprotein cholesterol were positively associated with the presence of carotid IPN in a Chinese high–stroke‐risk population. Further prospective studies should be conducted to better understand how much finding IPN adds to current stroke prediction tools.

Acoustic observation of laboratory simulated lightning discharge can greatly avoid the observation difficulties under natural thunderstorm environment. An acoustic observation experiment based on the impulsive current generation system and a microphone array was carried out and illustrated in this study. A quantitative study on characteristics of response sound pressure initiated from simulated lightning current was performed. The first arrived acoustic N-waves measured at different distances initiated from different discharge amplitudes were compared and analysed. The acoustic amplitude, rise time and duration time defined for N-waves and peak frequencies were found to have an obvious correlation with the discharging amplitudes of simulated lightning currents and the observing distances. The linear change of acoustic amplitude is more obvious than that of the other parameters with the changed discharging amplitude or observing distance. A certain degree of shape change of the simulated lightning current except for the amplitude may not significantly affect the response acoustic characteristics when comparing the first acoustic N-waves from 8/20 μs lightning current and another kind of impulsive current which has a wider shape and two subsequent peaks. The subsequent current peaks in short time delays were proved to successively generate acoustic N-waves independently without overlapping, which meanwhile, indicated a consistent linear relationship of amplitude and time delay between electrical and acoustic pulses.

The epithelial to mesenchymal transition (EMT) is implicated in many processes, ranging from tissue and organogenesis to cancer and metastatic spread. Understanding the key regulatory mechanisms and mediators within this process offers the opportunity to develop novel therapeutics with broad clinical applicability. To date, several components of EMT already are targeted using pharmacologic agents in fibrosis and cancer. As our knowledge of EMT continues to grow, the potential for novel therapeutics will also increase. This review focuses on the role of EMT both as a necessary part of development and a key player in disease progression, specifically the similarity in pathways used during both processes as targets for drug development. Also, the key role of the tumor microenvironment with EMT is outlined, focusing on both co-factors and cell types with the ability to modulate the progression of EMT in cancer and metastatic disease. Lastly, we discuss the current status of clinical therapies both in development and those progressed to clinical trial specifically targeting pathologic EMTs including small molecule inhibitors, non-coding RNAs, exogenous co-factors, and adjunctive therapies to current chemotherapeutics.

Bone marrow stromal cell antigen 2 (BST-2) inhibits the release of HIV-1 and other enveloped viruses from the cell surface. HIV-1 Vpu binds to BST-2 through an interaction between transmembrane domains (TMD) of the two proteins and induces the downregulation of cell surface BST-2, thereby counteracting its antiviral activity. In this study, we designed and prepared a modified peptide BST2-TM-P1, which include the sequence of BST-2 TMD, keeping its property competing with BST-2 to bind with Vpu. Biological assay results indicate BST2-TM-P1 could increase the BST-2 level at the cell surface in Vpu dependent manner and significantly inhibit the replication of HIV-1 virion. Our studies indicate that blocking the interaction of Vpu and BST-2 is an effective way to combat HIV-1 infection., (© 2014 Wiley Periodicals, Inc.)

The feasibility of articular gene therapy using insulin-like growth factor-I transgene expression in synovial tissues was assessed in vitro by transfection of synovial explant and monolayer cultures. Synovial membrane was harvested from horses and distributed for explant culture in multiwell plates or digested for monolayer culture in multiwell plates and chamber slides. Synovial monolayers were cultured for 48 h after infection with 0, 100, 200, or 500 moi adenovirus-IGF-I (AdeIGF-I) to establish an optimum dose. Explants were then either infected with AdeIGF-I or adenoviral LacZ and cultured for 8 days, treated with 100 ng/ml recombinant IGF-I as a positive control, or remained as uninfected untreated culture controls. Expression of IGF-I in explants and monolayers was assessed by in situ hybridization and quantitative polymerase chain reaction (PCR), and translation confirmed by IGF-I radioimmunoassay (RIA) and tissue immunoreaction. Effects of IGF-I on synovial function was assessed by proteoglycan and hyaluronan assay, and northern blot assessment of decorin and collagen type I expression. Significant transgene expression in synovial cells was present for all AdeIGF-I concentrations. Similarly, medium IGF-I concentrations were significantly elevated in AdeIGF-I infected synovial monolayer and explant cultures at all time points. Peak IGF-I concentration of 246 +/- 43 ng/ml developed in explant cultures on day 4; IGF-I levels in control explant groups were unchanged over baseline values. In situ hybridization and immunolocalization for IGF-I indicated focal IGF-I expression in intimal and subintimal layers of infected explants, with diffuse immunoreaction throughout infected subintimal and fibrous layers. For monolayer cultures, intracellular immunoreaction to IGF-I was markedly higher in infected cells, and was most prominent at 100 moi. Effects of IGF-I on synoviocyte cultures were evident on northern blots, which showed decreased decorin expression and elevated type I collagen production in AdeIGF-I infected monolayers. Proteoglycan concentration in the medium from explant cultures rose over the initial 4 days but was similar between treatment groups. The concentration of hyaluronan in medium from explant cultures did not differ significantly within or between treated and control groups during the 8-day study period. These data indicate that IGF-I can be successfully introduced to synovial structures by adenoviral vectors and results in effective IGF-I ligand synthesis without untoward synovial morphologic effects.

Monolayer cultures of lapine articular chondrocytes were transduced with first-generation adenoviral vectors carrying lacZ or transforming growth factor beta1 genes under the transcriptional control of the human cytomegalovirus early promoter. High concentrations of transforming growth factor beta1 were produced by chondrocytes following transfer of the transforming growth factor beta1 gene but not the lacZ gene. Transduced chondrocytes responded to the elevated endogenous production of transforming growth factor beta1 by increasing their synthesis of proteoglycan, collagen, and noncollagenous proteins in a dose-dependent fashion. The increases in collagen synthesis were not accompanied by alterations in the collagen phenotype; type-II collagen remained the predominant collagen. Transforming growth factor beta1 could not, however, rescue the collagen phenotype of cells that had undergone phenotypic modulation as a result of serial passaging. These data demonstrate that chondrocytes can be genetically manipulated to produce and respond to the potentially therapeutic cytokine transforming growth factor beta1. This technology has a number of experimental and therapeutic applications, including those related to the study and treatment of arthritis and cartilage repair.