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Abstract The large scale deployment of modern wind turbines and the yearly increase of installed capacity have drawn attention to their operation and maintenance issues. The development of highly reliable and low‐maintenance wind turbines is an urgent demand in order to achieve the low‐carbon goals, and the arrival of fault diagnosis provides assurance for its satisfactory operation and maintenance. Numerous statistical studies have pointed out that generator failures are a main cause of wind turbine system downtime. The generator, as one of the core components, converts rotating mechanical energy into electrical energy. However, the generators can hardly operate reliably towards the end of the turbine life owing to the variable‐speed conditions and harsh electromagnetic environments. This article first provides a comprehensive and up‐to‐date review of the electrical and mechanical failures of various parts (stator, rotor, air gap and bearings) of the generator. Then the fault characteristics and diagnostic processes of generators are investigated, and the principles and processes of fault diagnosis are discussed. Finally, the application of four categories of model‐based, signal‐based, knowledge‐based and hybrid approaches to wind turbine generator fault diagnosis is summarized. The comprehensive review shows that the hybrid approach is now the leading and most accurate tool for real‐time fault diagnosis for wind turbine generators. A qualitative and quantitative assessment of algorithm performance using false alarm rates is proposed. The methodology can subsequently be applied to the wind industry.

Abstract Purpose To research the therapeutic effects of 577 nm micropulse laser photocoagulation (MLP) treatment in early-stage central serous chorioretinopathy (CSCR) patients. Methods Twenty-two CSCR patients with 24 CSCR eyes were examined prior to MLP treatment. The examinations included best-corrected visual acuity (BCVA), fluorescein fundus angiography (FFA), indocyanine green angiography (ICGA), optical coherence tomography (OCT), optical coherence tomography angiography (OCTA) and microperimetry. After MLP treatment, all the subjects were reviewed at 30 days. The BCVA, macular function on microperimetry, subretinal fluid (SRF) height of the macula on OCT, and choroid vascular density (VD) of the macular area on OCTA were compared before and after MLP treatment. The correlations between SRF height and visual function, choroid VD was analyzed separately. Results BCVA and macular function significantly increased and the SRF height of the macula significantly decreased after MLP treatment. BCVA and macular function were significantly negatively correlated with SRF height. The choroid VD was significantly increased after MLP treatment, and choroid VD in the leakage site part of the macula were significantly negatively correlated with the height of the SRF. A recurrent patient who received two MLP treatments also had a negative correlation between SRF and choroid VD during the course of disease. Conclusions 577 nm MLP is safe and effective for early-stage CSCR patients, and treatment can restore macular structure and function. The increase in choroid VD of leakage site part after treatment is one of the key effects of MLP treatment for early-stage CSCR patients.

Aiming at the environmental pollution problems caused by vanadium-containing wastewater produced by mining, metallurgy, petroleum refining, and other industries, this study prepared mussel shells loaded nano-zero-valent iron composites(nZVI@CMS) by liquid-phase reduction method using pyrolyzed mussel shell powder(CMS) as the carrier. The morphology and structure of nZVI@CMS were characterized by SEM, TEM, XRD, BET, FT-IR and XPS. The adsorption performance of V(Ⅴ) on nZVI@CMS was investigated by batch adsorption experiments, and the adsorption mechanism of V(Ⅴ) on nZVI@CMS was analyzed using adsorption kinetics, adsorption isotherm, and adsorption thermodynamics. The results showed that nZVI@CMS was a loose and porous chain sphere-like structure containing a variety of oxygen-containing functional groups. The maximum adsorption of V(Ⅴ) by nZVI@CMS was 149.33 mg/g under the conditions of nZVI@CMS dosage of 0.05 g/L, initial pH=7, V(Ⅴ) concentration of 20 mg/L, solution volume of 100 mL, and temperature of 25 ℃. The adsorption of V(Ⅴ) by nZVI@CMS could be fitted by Langmuir adsorption isotherm equation and pseudo second-order reaction kinetic equation, and it was a spontaneous heat adsorption process. The main mechanisms of V(Ⅴ) removal by nZVI@CMS included adsorption, reduction, and co-precipitation. This study turned the mussel shells into treasure, and provided a new idea for the efficient treatment of V(Ⅴ) in wastewater.

Abstract Background NOD-like receptor protein 3 (NLRP3) inflammasome activation is indispensable for atherogenesis. Mitophagy has emerged as a potential strategy to counteract NLRP3 inflammasome activation triggered by impaired mitochondria. Our previous research has indicated that dihydromyricetin, a natural flavonoid, can mitigate NLRP3-mediated endothelial inflammation, suggesting its potential to treat atherosclerosis. However, the precise underlying mechanisms remain elusive. This study sought to investigate whether dihydromyricetin modulates endothelial mitophagy and inhibits NLRP3 inflammasome activation to alleviate atherogenesis, along with the specific mechanisms involved. Methods Apolipoprotein E-deficient mice on a high-fat diet were administered daily oral gavages of dihydromyricetin for 14 weeks. Blood samples were procured to determine the serum lipid profiles and quantify proinflammatory cytokine concentrations. Aortas were harvested to evaluate atherosclerotic plaque formation and NLRP3 inflammasome activation. Concurrently, in human umbilical vein endothelial cells, Western blotting, flow cytometry, and quantitative real-time PCR were employed to elucidate the mechanistic role of mitophagy in the modulation of NLRP3 inflammasome activation by dihydromyricetin. Results Dihydromyricetin administration significantly attenuated NLRP3 inflammasome activation and vascular inflammation in mice on a high-fat diet, thereby exerting a pronounced inhibitory effect on atherogenesis. Both in vivo and in vitro, dihydromyricetin treatment markedly enhanced mitophagy. This enhancement in mitophagy ameliorated the mitochondrial damage instigated by saturated fatty acids, thereby inhibiting the activation and nuclear translocation of NF-κB. Consequently, concomitant reductions in the transcript levels of NLRP3 and interleukin-1β (IL-1β), alongside decreased activation of NLRP3 inflammasome and IL-1β secretion, were discerned. Notably, the inhibitory effects of dihydromyricetin on the activation of NF-κB and subsequently the NLRP3 inflammasome were determined to be, at least in part, contingent upon its capacity to promote mitophagy. Conclusion This study suggested that dihydromyricetin may function as a modulator to promote mitophagy, which in turn mitigates NF-κB activity and subsequent NLRP3 inflammasome activation, thereby conferring protection against atherosclerosis.

Aiming at the problems of siltation promotion and siltation return in the beach area of Hangzhou Bay, a numerical calculation model of hydrodynamic and scour and siltation in the south bank of Ningbo Bay was constructed, and the reliability of the short-term scour and siltation numerical calculation model was verified by combining with the field measured scour and siltation data, so as to obtain the natural siltation situation in this area under a longer time scale in the future. Meanwhile, the siltation promotion scheme was selected by comparing with artificial embankment construction. The research results show that the restoration effect of natural silt beach under the action of excavation diversion is remarkable, and the construction of barrier has a significant effect on the retention and sedimentation of sediment in the trench. After the construction of the barrier with a height of -2.22m, the average thickness of sediment promotion in the low-lying area reaches 0.22m, and the elevation of seabed in the low-lying area can reach about 2.5m. Therefore, it is particularly effective for the sediment deposition in low-lying areas in the high sediment content sea area to adopt the method of natural diversion and separation embankment.

In planetary surfaces, oblique impact events are commonplace, and their study holds significant importance for understanding planetary impact processes and aiding in the design of landers and impactors. Current research predominantly focuses on simplified models to study the force and motion under vertical impact craters in terms of scale and impact loading. For oblique impacts, investigations have primarily concentrated on the final crater shape. However, the specific influence of impact load motion on particle bed movement and the precise impact angle’s effect on the ultimate crater shape during the impact process remain unclear. In this study, we used a custom-built oblique impact experimental setup to analyze changes in the velocity field of the particle bed and the horizontal movement of the impact load. Using quasi-static region to assess ellipticity, we aimed to reveal the state of particle movement during oblique impacts and explore the impact of impact angles and energies on crater formation. The results indicate that under large impact angles, the obliquely acquired kinetic energy is minimal, leading to a predominant static point source movement of the particle bed. At higher energy levels, the impact load primarily excavates downward, resulting in the formation of circular impact craters. These findings underscore the sensitivity of particle bed motion to impact angles, making it a crucial metric for assessing the impact of oblique angles on final crater morphology.

Objective To investigate the needs and feedback from clinical medical students on the diversified teaching mode adopted by the Department of Endocrinology in Peking Union Medical College Hospital. Methods Questionnaires were distributed to the medicine students who were in clinical rotation in Peking Union Medical College, and the teaching status and teaching effect was investigated. Results A total of 95 valid questionnaires were received. The attending physicians and the teaching resident physicians performed well in the daily teaching activities. The medical students believed that outpatient training was necessary in addition to ward rotations. After the rotation in the endocrinology department, the self-evaluated score of mastery of endocrinology knowledge had been significantly improved, especially in those who rotated in outpatient clinic, suggesting that outpatient teaching was of great significance. In addition, the establishment of a self-learning platform including clinical cases and videos in endocrinology could be used as an important supplementary means for clinical teaching. Conclusions Outpatient training improves learning outcomes of medical students, so must be kept and further strengthened in the future. Building a database of typical clinical cases and teaching videos can improve the training quality.

Objective On December 18, 2023, an MS 6.2 earthquake occurred in Jishishan County, Gansu Province, China. Coseismic geological hazards induced by the earthquake crucially threatened the safety of personnel and property. Existing research is mainly concentrated in the vicinity of active faults and the concentrated distribution area of hidden danger points. Moreover, no special susceptibility assessment studies have been carried out on coseismic geological hazards in the administrative area of Jishishan County, making it challenging to meet the needs of the county's post-disaster recovery and reconstruction planning. Hence, the development laws of coseismic geological hazards must be summarized and analyzed crucially, and county susceptibility must be analyzed in time to support post-earthquake recovery and reconstruction. Methods The development characteristics of coseismic geological hazards are analyzed and summarized through emergency investigations, field surveys, and result analysis. Using the newly added and exacerbated coseismic hazard points identified during post-earthquake investigations as analysis samples, influencing factors were selected using the Pearson correlation coefficient and random forest Gini coefficient analysis methods. Then, a machine learning-random forest model was applied to assess the susceptibility of coseismic geological hazards in Jishishan County. Results In analyzing the development characteristics of coseismic geological hazards, we identified 134 instances of increased and exacerbated hazards in Jishishan County. Overall, the degree of development of these hazards was relatively low, with primarily small-scale occurrences. These hazards were categorized into three main types and eight sub-categories: ① Collapse (including cut slope loess collapse, high loess collapse, and high rock collapse); ② Landslide (encompassing loess landslide, secondary sand/mudstone landslide, and potential landslide); and ③ Debris flow (comprising gully debris flow and slope debris flow). In terms of factor selection, 15 influencing factors were screened. Regarding the susceptibility assessment results, the AUC value of the susceptibility assessment results of coseismic geological hazards in most Jishishan counties was 0.961, and the results showed that the areas of extremely high susceptibility accounted for approximately 8.67 %, mainly distributed in Hulinjia, Xuhujia, Liugoujia, and other townships. The statistical results of the proportion of susceptibility zones in 17 townships in Jishishan County showed that the top three townships with the largest proportions of extremely high-susceptibility areas are Hulinjia (24.67%), Xuhujia (21.24%), and Biezang (20.94%). Conclusion (1) Most coseismic geological hazards in Jishishan are distributed in the loess hilly area, with few occurrences in the Jishishan area and the right bank terrace of the Yellow River. (2) The influence of elevation and peak ground acceleration (PGA) on hazard occurrence is notably greater than that of other factors, playing a predominant role in developing coseismic geological hazards. (3) Utilizing the random forest model, the susceptibility assessment of coseismic geological hazards in Jishishan County demonstrates high accuracy, with hidden danger points clustered in highly susceptible areas. This alignment between susceptibility assessment results and the spatial distribution of hidden dangers underscores the reliability of the assessment outcomes. Significance In addition to identifying existing hidden danger points, this study offers predictive insights into slope deformation and potential landslides significantly affected by seismic cracking. The assessment results exhibit high accuracy and reliability, offering valuable geological safety support for post-disaster recovery and reconstruction planning in the county.

Aims To explore the sensitive components of full-field electroretinography (ERG) as indicators of retina function at the onset of acute ischaemic central retinal vein occlusion (CRVO).Methods 11 patients (11 eyes) with ischaemic CRVO and 32 patients (32 eyes) with non-ischaemic CRVO who presented with first-episode unilateral CRVO within 1 month of symptom onset and with no previous intervention were examined by the International Society for Clinical Electrophysiology of Vision standard ERG.Results A significant amplitude decline and peak time delay in light-adapted (LA) 3 ERG and LA 30 Hz flicker ERG (p

[Objective] In the rapidly evolving landscape of digital technology, cloud computing is widely utilized in various industries including metro systems. To ensure passenger travel safety and achieve real-time acquisition and efficient analysis of large-scale passenger flow data, it is necessary to propose an elastic cluster cloud platform tailored for passenger flow analysis scenarios. [Method] The core functional requirements of the above platform are analyzed, and the architecture of it is proposed, highlighting the platform unique capabilities. Two deployment plans for the elastic cluster cloud platform are put forward for metro systems at different stages of development, and the pros and cons of each deployment plan are analyzed. Taking Shanghai Metro as example, the investment costs of the deployment plans are compared based on capability requirements. The alignment between the architecture of the elastic cluster cloud platform and the characteristics of metro passenger flow analysis business is also examined. [Result & Conclusion] Metro passenger flow analysis scenarios exhibit characteristics such as multi-system concurrency, high real-time requirements, and large data volume. The elastic cluster cloud platform can meet various demands of passenger flow analysis business.

Abstract Background The essential roles of platelets in thrombosis have been well recognized. Unexpectedly, thrombosis is prevalent during thrombocytopenia induced by cytotoxicity of biological, physical and chemical origins, which could be suffered by military personnel and civilians during chemical, biological, radioactive, and nuclear events. Especially, thrombosis is considered a major cause of mortality from radiation injury-induced thrombocytopenia, while the underlying pathogenic mechanism remains elusive. Methods A mouse model of radiation injury-induced thrombocytopenia was built by exposing mice to a sublethal dose of ionizing radiation (IR). The phenotypic and functional changes of platelets and megakaryocytes (MKs) were determined by a comprehensive set of in vitro and in vivo assays, including flow cytometry, flow chamber, histopathology, Western blotting, and chromatin immunoprecipitation, in combination with transcriptomic analysis. The molecular mechanism was investigated both in vitro and in vivo, and was consolidated using MK-specific knockout mice. The translational potential was evaluated using a human MK cell line and several pharmacological inhibitors. Results In contrast to primitive MKs, mature MKs (mMKs) are intrinsically programmed to be apoptosis-resistant through reprogramming the Bcl-xL-BAX/BAK axis. Interestingly, mMKs undergo minority mitochondrial outer membrane permeabilization (MOMP) post IR, resulting in the activation of the cyclic GMP-AMP synthase-stimulator of IFN genes (cGAS-STING) pathway via the release of mitochondrial DNA. The subsequent interferon-β (IFN-β) response in mMKs upregulates a GTPase guanylate-binding protein 2 (GBP2) to produce large and hyperreactive platelets that favor thrombosis. Further, we unmask that autophagy restrains minority MOMP in mMKs post IR. Conclusions Our study identifies that megakaryocytic mitochondria-cGAS/STING-IFN-β-GBP2 axis serves as a fundamental checkpoint that instructs the size and function of platelets upon radiation injury and can be harnessed to treat platelet pathologies.

Fermented soybeans are popular among many for their rich soy sauce-like aroma. However, the precise composition of this aroma remains elusive, with key aroma compounds unidentified. In this study, we screened the candidate genes ilvA and serA in BJ3-2 based on previous multi-omics data, and we constructed three mutant strains, BJ3-2-ΔserA, BJ3-2-ΔilvA, and BJ3-2-ΔserAΔilvA, using homologous recombination to fermented soybeans with varying intensities of soy sauce-like aroma. Our objective was to analyze samples that exhibited different aroma intensities resulting from the fermented soybeans of BJ3-2 and its mutant strains, thereby exploring the key flavor compounds influencing soy sauce-like aroma as well analyzing the effects of ilvA and serA on soy sauce-like aroma. We employed quantitative descriptive sensory analysis (QDA), gas chromatography–olfactometry–mass spectrometry (GC-O-MS), relative odor activity value analysis (rOAV), principal component analysis (PCA), orthogonal partial least squares-discriminant analysis (OPLS-DA), and partial least squares regression analysis (PLSR). QDA revealed the predominant soy sauce-like aroma profile of roasted and smoky aromas. GC-MS detected 99 volatile components, predominantly pyrazines and ketones, across the four samples, each showing varying concentrations. Based on rOAV (>1) and GC-O, 12 compounds emerged as primary contributors to soy sauce-like aroma. PCA and OPLS-DA were instrumental in discerning aroma differences among the samples, identifying five compounds with VIP > 1 as key marker compounds influencing soy sauce-like aroma intensity levels. Differential analyses of key aroma compounds indicated that the mutant strains of ilvA and serA affected soy sauce-like aroma mainly by affecting pyrazines. PLSR analysis indicated that roasted and smoky aromas were the two most important sensory attributes of soy sauce-like aroma, with pyrazines associated with roasted aroma and guaiacol associated with smoky aroma. In addition, substances positively correlated with the intensity of soy sauce-like aroma were verified by additional experiments. This study enhances our understanding of the characteristic flavor compounds in soy sauce-like aroma ferments, provides new perspectives for analyzing the molecular mechanisms of soy sauce-like aroma formation, and provides a theoretical framework for the targeted enhancement of soy sauce-like aroma in various foods.

Precipitation is particularly important for the earth's climate system. Understanding the structural characteristics, microphysical processes and drop size distribution (DSD) of precipitation is very important for quantitative precipitation estimation with radar and improving microphysical parameter schemes of numerical weather prediction models. With the launch of the Second Tibet Plateau Scientific Expedition and Research(STEPS), Chinese Academy of Meteorological Sciences has deployed Ka-band cloud radar (KaCR), X-band dual polarization phased array radar (X-PAR), disdrometer, micro rain radar (MRR) and other detection equipment in Mêdog, filling the gap of cloud and precipitation observation in this area and provides data basis for studying the physical characteristics of clouds and precipitation. Mêdog is located at Yarlung Zangbo Grand Canyon, the entrance of the water vapor channel in southeastern Tibet. Influenced by the warm and humid airflow brought by the Indian Ocean monsoon, the precipitation of Mêdog during the monsoon period exceeds 60% of the annual precipitation. MRR is a low-cost, miniaturized vertical directional Doppler rain radar that can more accurately analyze the vertical structural changes of precipitation. Based on observation of the rain gauge, MRR and disdrometer set up at Mêdog National Climate Observatory from 1 June to 30 September in 2021, the consistency of different instruments is studied. The observed rainfall is classified into convective, stratiform and shallow precipitation types, and the average vertical distribution characteristics of different precipitation types are studied from the aspects of raindrop size distribution, falling speed, rain rate, liquid water content and radar reflectivity. The results show that the measurement of rain gauge, MRR and distrometer are highly consistent. The correlation coefficient of daily rainfall is above 0.89, and the highest correlation coefficient between MRR and rain gauge is 0.96. However, MRR overestimates weak precipitation and underestimate strong precipitation. There are significant differences in the vertical structure of different precipitation types during the monsoon period of Mêdog. Values of each microphysical quantity of convective precipitation are larger. The collision and growth process of raindrop is significant during the falling process below 3 km height, and the raindrop number concentration increases rapidly. There is significant updraft at a height of 1-2 km. The echo intensity of stratiform cloud precipitation is weak below the height of the melting layer. The radar reflectivity, rain rate and liquid water content increase with altitude decrease, the falling speed of raindrops remains basically stable in the vertical direction. The concentration of medium-sized raindrops remains constant with height, and the evaporation, fragmentation, and coalescence processes are in a relatively balance. Values of each microphysical quantity of shallow precipitation are relatively small but vary significantly with height and show negative slops in the vertical direction. The shallow precipitation is dominated by the collision process of raindrops.

Adrenal insufficiency is a disease characterized by insufficient secretion of adrenocortical hormones, usually treated with glucocorticoid replacement therapy. The routine drugs have two forms-short-acting and long-acting. The shorter one should be taken 2-3 times a day resulting hormone level of patients fluctuating greatly within a day. Although long-acting drugs reduce the frequency of administration, it is easy to lead to excessive replacement, resulting in adverse effects on metabolism. New alternative treatments for adult patients have emerged, including modified-release hydrocortisone and hydrocortisone subcutaneous infusion pumps. In this review, we briefly introduce these new therapies, emphasizing the pharmacodynamics and pharmacokinetics of the replacement, the effects on metabolism and drug safety, aiming at contributing to the future clinical practice.

Objective To explore the influence of a contracted endodontic access cavity on the risk of canal transportation in the danger zone of the mesial root canal of mandibular first molars (MFMs) using a one-curve preparation system, and to provide an experimental basis for the clinical selection of a better pulp approach. Methods Twenty MFMs extracted for severe periodontal disease that met the inclusion criteria, including intact coronal roots, mesial roots with two separate root canals, mesiobuccal canal (MB) and mesiolingual canal (ML), and a curvature of 0° to 20°, were selected. Subsequently, these MFMs were randomly divided into two groups based on the endodontic access design, including the traditional endodontic access cavity (TEC) group and the contracted endodontic access cavity (CEC) group. In the TEC group, the pulp chamber roof of the tooth was completely removed, while in the CEC group, the pulp chamber roof and peri-cervical dentin were preserved as much as possible. Then, the One Curve single file was adopted to conduct root canal preparation. Next, cone beam computed tomography (CBCT) was performed on extracted teeth before and after preparation, and the measurement sections were located at 0-7.0 mm below the root bifurcation of the mesial root canal at 1 mm intervals. The minimum wall thickness on the mesial and distal aspect of the root canal was measured in each section. Results ① Prepreparation CT measurements of 20 MFMs showed that the danger zone in the range 0-4 mm under root bifurcation, a mean thickness of 1.18 mm on the mesial aspect of the MB root canal and 1.08 mm on the distal aspect. The mean thickness of the ML root canal was 1.28 mm on the mesial aspect and 1.07 mm on the distal aspect. ② Compared with that of the traditional endodontic access cavity, no significant difference in the decrease of wall thickness was observed in the danger zone of mesial root canal of MFMs in the contracted endodontic access cavity (t = 1.319，P = 0.19). ③ In the mesiobuccal canal, compared with the apical transportation of the traditional endodontic access cavity, which tends to be more mesial side, the apical transportation of contracted endodontic access cavity tends to the distal side. In the mesiolingual canal, both apical transportation groups tended to be on the distal side. Conclusion When using the One Curve file, compared with traditional endodontic access, the contracted endodontic access cavity based on the minimally invasive concept does not increase the risk that the mesial root canal of mandibular first molars is transported.

Abstract Background Human epidermal growth factor receptor 2 (HER2) targeted therapy combined with endocrine therapy has been recommended as an alternative treatment strategy for patients with hormone receptor (HR)-positive, HER2-positive metastatic breast cancer (MBC). This study aimed to evaluate the role of pyrotinib, an oral pan-HER irreversible tyrosine kinase inhibitor, in combination with letrozole for patients with HR-positive, HER2-positive MBC. Methods In this multi-center, phase II trial, HR-positive and HER2-positive MBC patients who were not previously treated for metastasis disease were enrolled. Patients received daily oral pyrotinib 400 mg and letrozole 2.5 mg until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was the clinical benefit rate (CBR) assessed by an investigator according to the Response Evaluation Criteria in Solid Tumors version 1.1. Results From November 2019 to December 2021, 53 patients were enrolled and received pyrotinib plus letrozole. As of August 2022, the median follow-up duration was 11.6 months (95% confidence interval [CI], 8.7–14.0 months). The CBR was 71.7% (95% CI, 57.7–83.2%), and the objective response rate was 64.2% (95% CI, 49.8–76.9%). The median progression-free survival was 13.7 months (95% CI, 10.7–18.7 months). The most common treatment-related adverse event of grade 3 or higher was diarrhea (18.9%). No treatment-related deaths were reported, and one patient experienced treatment discontinuation due to adverse event. Conclusions Our preliminary results suggested that pyrotinib plus letrozole is feasible for the first-line treatment of patients with HR-positive and HER2-positive MBC, with manageable toxicities. Trial registration ClinicalTrials.gov, NCT04407988.

Direct solid diffusion bonding of Ti2AlNb alloy was carried out, and the effect of pressure on the microstructure and mechanical properties of the bonded joints was studied. Scanning electron microscopy was used to analyze the microstructure of the welded joint under different pressures. The tensile property of the joints with different pressures was tested and the variation trend of the tensile property with pressure was analyzed. The results show that with the increase of pressure, the deformation within the sample surface layer increased, and the dynamic recovery and recrystallization occurred in the deformed area at high temperature, which promotes the closing of voids on the bonding interface and the rise of well-bonded areas. A diffusion bonded joint of Ti2AlNb alloy can be divided into three parts：recrystallization zone, deformation zone and base metal. The recrystallization zone is mainly composed of equiaxed B2 phase and α2 phase. With the increase of pressure, the width of the recrystallization zone becomes wider obviously, and the strength of the bonded joint increases first and then decreases. When the welding parameters are 960 ℃-60 MPa-120 min, the welded joint had the best performance, and its tensile strength is 972 MPa, reaching 98% of the base metal. An excessive pressure coarsened the recrystallization grains, and cracks appeared at the interface of the recrystallized zone and the deformation zone, which deteriorated the performance of the bonded joint.

For the problem that the abnormal circulation of bipolar double twelve-pulse ultra high voltage direct current (UHVDC) line permanent grounding fault can not be effectively isolated, an optimized scheme for suppressing the abnormal fault circulation is proposed. Firstly, the influencing factors of abnormal circulating current value for DC line permanent grounding fault are analyzed. Secondly, combined with the existing removal strategies of DC line fault in China, the causes of abnormal circulation are analyzed, which are caused by restarting the high-end valve group with communication condition, unsuccessful restart with communication condition or without communication condition after DC line grounding fault happens. Then, a circulating current suppression scheme for DC line permanent ground fault based on pole isolation and blocking after shifting phase 90° strategy is proposed accordingly. Finally, the simulation model is established through real time digital system (RTDS) to verify the effectiveness of the improved scheme. The results show that the scheme proposed in this paper can effectively solve the abnormal circulation problem of DC line permanent grounding fault under different working conditions.

Abstract In order to realize the automation, standardization, and informatization of clinical laboratory work, this research topic develops and accomplishes a set of laboratory information systems (LISs). According to the design methods of software engineering, we first understand user’s demand and the current work situation of clinical laboratory and establish the system case model using Unified Modeling Language (UML) modeling technique. During the system design period, we explain the key technology theories, network structure, system security policy and the connection scheme with hospital information system (HIS). During the system function design period, the system was designed with 6 modules, they are daily inspection work, inquire and statistics, quality control, data dictionary, system configuration, and other tools. Through establishing database model, we accomplish the system database structure design. After the system design, we perform system implementation and test, to show the interface of system implementation and test plan accordingly. The development and application of LIS360 laboratory information management system can greatly improve the management level of laboratory and promote the standardization, modernization, and science of laboratory management. This system has solved the traditional mode of sending test report sheet manually for many years in the laboratory and won valuable time for clinicians to know the patient's condition in time.

As the navigation design capacity of the Three Gorges‒Gezhouba cascade hub has been gradually saturated and the volume of transiting cargo has increased rapidly in the past two decades, it is necessary to adopt advanced information technologies to improve the navigation capacity and promote the high-quality navigation of the Three Gorges. This study aims to investigate the technical system and its engineering application for the high-quality navigation of the Three Gorges‒Gezhouba cascade project, and involves the aspects of current situation analysis, technical system construction, implementation results, existing bottlenecks, and follow-up development measures. The study reviews the research status of cascade hubs in China and abroad and explores the major factors affecting the high-quality navigation of the Three Gorges, namely navigation equipment, traffic organization, safety assurance, environmental improvement, and environmental-friendly maintenance. The technical system is also built. The innovative development and practice of the Three Gorges‒Gezhouba cascade hub over the past 20 years are summarized from the aspects of intelligent operation, navigation organization, safety assurance, channel capacity, and green navigation. Moreover, the medium- and long-term suggestions are proposed for the intelligent and green navigation of the Gorges‒Gezhouba cascade hub focusing on the major bottlenecks.The improvement in the intelligent operation level and efficiency of the Three Gorges‒Gezhouba cascade hub can provide a key technical reference for the high-quality navigation construction of large-scale inland river cascade hubs in China.

With the development of information and control technology, fully automatic operation system (FAO) has been widely adopted in the construction of new subway lines. Since the main line operating vehicles under FAO mode do not have driver posts, the dispatchers at the control center need to monitor the running status of all trains on the line in real time to ensure the correct operation of the trains. According to the characteristics of FAO mode , this paper designs a train dispatching system based on big data architecture. The system collects status data of train subsystems and processes and analyzes them based on big data framework,which realizes real-time status monitoring of vehicles on the whole line; and provides human-computer interaction interface for remote control, which meets the requirements of metro operation dispatcher for vehicle running status monitoring. The system has been verified by the third party security assessment, and its stability and availability meet the FAO line operation requirements.

Dynamic communication within adipose tissue depends on highly vascularized structural characteristics to maintain systemic metabolic homoeostasis. Recently, it has been noted that adipose endothelial cells (AdECs) act as essential bridges for biological information transmission between adipose-resident cells. Hence, paracrine regulators that mediate crosstalk between AdECs and adipose stromal cells were summarized. We also highlight the importance of AdECs to maintain adipocytes metabolic homoeostasis by regulating insulin sensitivity, lipid turnover and plasticity. The differential regulation of AdECs in adipose plasticity often depends on vascular density and metabolic states. Although choosing pro-angiogenic or anti-angiogenic therapies for obesity is still a matter of debate in clinical settings, the growing numbers of drugs have been confirmed to play an anti-obesity effect by affecting vascularization. Pharmacologic angiogenesis intervention has great potential as therapeutic strategies for obesity.

Background: Cholangiocarcinoma (CCA) is a highly lethal and aggressive epithelial tumor of the hepatobiliary system. A poor prognosis, propensity for relapse, low chance of cure and survival are some of its hallmarks. Pemigatinib, the first targeted treatment for CCA in the United States, has been demonstrated to have a significant response rate and encouraging survival data in early-phase trials. The adverse events (AEs) of pemigatinib must also be determined.Objective: To understand more deeply the safety of pemigatinib in the real world through data-mining of the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS).Methods: Disproportionality analysis was employed in a retrospective pharmacovigilance investigation to identify the AEs linked to pemigatinib use as signals. Data were collected between 1 January 2020 to 30 June 2022. Four data-mining methods (proportional reporting odds ratio; proportional reporting ratio; Bayesian confidence propagation neural networks of information components; empirical Bayes geometric means) were used to calculate disproportionality.Results: A total of 203 cases using pemigatinib as the prime-suspect medication were found in our search, which involved 99 preferred terms (PTs). Thirteen signals of pemigatinib-induced AEs in seven System Organ Classes were detected after confirming the four algorithms simultaneously. Nephrolithiasis was an unexpected significant AE not listed on the drug label found in our data-mining. Comparison of the differences between pemigatinib and platinum drugs in terms of 33 PTs revealed that 13 PTs also met the criteria of the four algorithms. Ten of these PTs were identical to those compared with all other drugs, in which (excluding a reduction in phosphorus in blood) other PT signal values were higher than those of all other drugs tested. However, comparison of the differences between pemigatinib and infigratinib in terms of the 33 PTs revealed no significant signals in each algorithm method.Conclusion: Some significant signals were detected between pemigatinib use and AEs. PTs with apparently strong signals and PTs not mentioned in the label should be taken seriously.

An increasing share of fluctuating and intermittent renewable energy sources can cause over-currents (OCs) in the power system. The heat generated during OCs increases the junction temperature of semiconductor devices and could even lead to thermal runaway if thermal limits are reached. In order to keep the junction temperature within the thermal limit of the semiconductor, the power module structure with heat-absorbing material below the chip is investigated through COMSOL Multiphysics simulations. The upper limits of the junction temperature for Silicon (Si) and Silicon Carbide (SiC) are assumed to be 175 and 250 ∘C, respectively. The heat-absorbing materials considered for analysis are a copper block and a copper block with phase change materials (PCMs). Two times, three times, and four times of OCs would be discussed for durations of a few hundred milliseconds and seconds. This article also discusses the thermal performance of a copper block and a copper block with PCMs. PCMs used for Si and SiC are LM108 and Lithium, respectively. It is concluded that the copper block just below the semiconductor chip would enable OC capability in Si and SiC devices and would be more convenient to manufacture as compared to the copper block with PCM.

Accurately determining the stress state in deep shale reservoirs is the key to the efficient development of shale gas and other unconventional energy sources. An effective method to increase the evaluation and calculation accuracy of in-situ stress parameters in a deep shale reservoir is to combine different methods to obtain different stress information, such as obtaining the minimum horizontal principal stress based on the in-situ stress measurement, predicting the magnitudes of horizontal stress difference and the horizontal principal stresses by establishing the stress profile based on the rheological model, and estimating the direction of the maximum horizontal principal stress by the wellbore failure imaging logging. We applied this research idea to Well SZ1 in Hanzhong, Shaanxi Province. The minimum horizontal principal stress obtained by hydraulic fracturing ranged from 32 to 41 MPa; Then, the variation laws of rock rheological parameters with the depth were determined by the rock mechanical parameters obtained from cross-dipole acoustic logging data. And combined with the burial history of the reservoir and the strain rate of the crust, the stress profile of Well SZ1 was established. The results show that the magnitude of horizontal stress difference in the depth range of 1950~2025 m in the Niutitang Formation is between 10~15 MPa, and ranges of the minimum and maximum principal stresses are 28~41 MPa and 47~49 MPa, respectively. The predicted horizontal minimum principal stress values are in good agreement with the measured results. Based on the in situ stress measurement and predicted stress profiles, Well SZ1 is characterized by normal faulting (Sv > SH > Sh)or a combination of normal and strike-slip faulting regimes (Sv≈SH > Sh).The horizontal stress difference decreases with the increase of the gamma value, indicating that the stress profile has a good corresponding relationship with the formation lithology. Based on the distribution characteristics of borehole-induced tensile fractures recorded by imaging logging, the direction of the maximum horizontal principal stress in Well SZ1 is ~N74°W, which is consistent with the direction of the regional tectonic stress field. This study provides an important basis for accurately understanding the in-situ stress state of the target layer of Well SZ1, as well as the later horizontal well layout and fracturing control.

Abstract A simple method is proposed here to improve the gap loss concentration problem of a nanocrystalline core in an LCL filter inductor for high switching frequency converters using SiC devices. This alloy‐gapped inductor design aims to reach two primary goals. First, to reduce the concentrated gap loss in a nanocrystalline core. Second, decrease the maximum temperature around the gap region and lead to more even temperature distribution. A finite element (FE) power loss and thermal models, validated by experiment, have been created to evaluate the proposed design. Based on the FE model results, the eddy current loss on the surfaces, which used to have the most severe gap loss is reduced by either 70% or 40% for the two commonly used winding placements. The total eddy current loss can be reduced by 29% and 27% for those two winding placements. In addition, FEA thermal model indicates that the hotspot temperature can be significantly decreased, and the nanocrystalline core can achieve a more uniform temperature distribution by this design, which can be a potential downsize method for the nanocrystalline core inductor.

Under the stress of the global change, rocky desertification has become a serious environmental problem in the Karst Mountain area. At present, few remote sensing monitoring research works on rocky desertification based on feature space model have been conducted and reported. In this study, the Albedo-LST feature space remote sensing monitoring index based on point-point model has been proposed, and subsequently the spatio–temporal evolution pattern and driving mechanism of rocky desertification in Dafang district from 1986 to 2019 were analyzed. The results show that: (1) The point-point Albedo-LST feature space model of rocky desertification has good applicability with the overall accuracy of 90.79%; (2) From 1986 to 2019, the rocky desertification in Dafang district first showed an increasing trend (1986–2005) and then a decreasing trend (2005–2019); (3) The comprehensive evolution frequency of rocky desertification during 2001–2005 was the largest with 7.51% a−1, which was related to the implementation of the Grain for Green Project; (4) The single factor with the largest contribution rates to rocky desertification are land use type, landform, and temperature. The interactive factors with the largest explanatory power are temperature ∩ land use type and landform ∩ land use type. The research results can provide decision support for the prevention and control of rocky desertification in Southwest China.

To effectively identify the key material parameters of different zones of concrete face rockfill dams and improve the efficiency of parameter optimization, a global sensitivity analysis method of parameters based on sparse polynomial chaotic expansion (sPCE) is proposed in this paper. The latin hypercube sampling method is used to select multiple groups of material parameters, and then finite element method is used to calculate the displacement of dam characteristic nodes in dam body. On this basis, the displacement is expanded by sPCE, and the polynomial basis function is reconstructed by orthogonal matching pursuit to improve the construction and analysis efficiency of the proxy model. According to the chaos coefficients, Sobol’ indices are calculated to evaluate the influence of the material parameters and their interaction on different displacements of the dam. The results show that the sPCE model can accurately simulate dam displacement and its statistical characteristics with a relatively small sample size. The sensitivity of the same parameter has spatial variability, and under the influence of parameter levels and spatial distribution of different materials, the parameter sensitivity ranking of different zones has certain differences. The proposed method provides a new reference to sensitivity analysis and uncertainty analysis for practical engineering.

mRNA methylation modification, including N6-methyladenosine (m6A), N5-methylcytidine (m5C) and N1-methyladenosine (m1A), etc., represents more than 60% of all mRNA modifications and varies distribution on mRNA. “Writers” “erasers” “readers” participate in the dynamic and reversible biological process of mRNA methylation modification, which can lead to tumor, virus infection, metabolism diseases, heart or nervous system diseases, etc. when abnormalities occur in a certain link. At present, there are many methylation modification detection technologies, among which the most popular one is high-throughput sequencing.

Exercise is reported to play a crucial role in skeletal muscle performance. However, the underlying mechanism is still unknown. Thus, we investigated the effect of high-intensity aerobic exercise on skeletal muscle performance. In this study, the male C57BL/6J mice were accepted by high-intensity aerobic exercise for 8 weeks to establish an exercise model. It was observed that high-intensity aerobic exercise markedly affected the expression of genes in skeletal muscle. Moreover, high-intensity aerobic exercise significantly improved skeletal muscle grip strength and serum testosterone levels. HE staining showed that the cross-sectional area (CSA) of the skeletal muscle was successfully increased after 8 weeks of high-intensity aerobic exercise. Additionally, we found that high-intensity aerobic exercise changed gut microbiota structure by altering the abundance of Akkermansia, Allobaculum, and Lactobacillus, which might be related to testosterone production. However, the beneficial effects disappeared after the elimination of the gut microbiota and recovered after fecal microbiota transplantation (FMT) experiments for 1 week. These results indicated that the beneficial effects of high-intensity aerobic exercise on skeletal muscle were partly dependent on the gut microbiota. Our results suggested that long-term high loading intensity of aerobic exercise could improve skeletal muscle performance, which was probably due to the gut microbiota-testosterone axis.

Background: Since lobaplatin (LBP) has been approved to treat metastatic breast cancer in China, this study aimed to evaluate the safety and efficacy of LBP-based chemotherapy in clinical practice. Methods: This trial was a prospective, open-label, multicenter phase IV clinical trial that enrolled patients with unresectable locally advanced or recurrent/metastatic breast cancer from 34 sites between July 2013 and March 2017. Patients were treated with LBP monotherapy or in combination for four to six cycles. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Results: A total of 1179 patients were analyzed; 59 (5.0%) were treated with LBP alone, 134 (11.4%) with LBP plus paclitaxel, 263 (22.3%) with LBP plus docetaxel, 237 (20.1%) with LBP plus gemcitabine, 403 (34.2%) with LBP plus vinorelbine, and 83 (7.0%) with other LBP-based regimens. The overall incidence of adverse events (AEs) was 95.2%, and 57.9% of patients had grade >3 AEs. The most common grade >3 AEs were neutropenia (43.9%), leukopenia (39.4%), anemia (17.8%), and thrombopenia (17.7%). LBP monotherapy showed the lowest incidence of grade >3 AEs (39.0%), followed by LBP plus docetaxel (52.9%), LBP plus paclitaxel (59.0%), LBP plus vinorelbine (62.5%), and LBP plus gemcitabine (62.9%). The ORR and DCR were 36.8 and 77.0%, respectively. The median PFS was 5.5 months (95% confidence interval: 5.2–5.9). Conclusion: LBP-based chemotherapy shows favorable efficacy in patients with advanced breast cancer, with manageable safety profile. Trial registration: This trial was registered with ChiCTR.org.cn, ChiCTR-ONC-13003471.

Active fractions and constituents with antioxidant and lipid-lowering activities were investigated using bio-assay-guided isolation and identification. The data showed that the antioxidant fraction of A. cepa was AC50%, the main constituents of which were quercetin and isoquercitrin, by way of both ultra-high performance liquid chromatography–mass spectrometry (UPLC-MS) and bio-assay-guided purification and elucidation. Similarly, the lipid-lowering active fraction of A. cepa was AC30% with the main constituents of 3,4-dihydroxybenzoic acid and quercetin 3,4′-O-diglucoside. Also, bio-assay-guided isolation led to the isolation and identification of five known compounds with a purity of more than 98%, and quercetin was both the best free radical scavenger and lipid-lowering constituent. Moreover, the mechanism of the lipid-lowering effect of AC30% might be its reduction in mRNA expression levels of sterol regulatory element binding protein 2 (SREBP2) and FAS gene in lipid synthesis. Otherwise, reducing the mRNA expression level of lipid synthesis genes, including SREBP1, SREBP2, fatty acid synthetase (FASN), β-Hydroxy β-methylglutaryl-CoA (HMGCR), stearoyl CoA desaturase 1 (SCD1), and increasing the mRNA expression level of lipid decomposition gene, such as carnitine palmitoyl transferease-1 (CPT1), might be involved in the lipid-lowering activity of quercetin. This study suggested that Allium cepa might be used to prevent and treat oxidative stress and dislipidemia-related disorders, including NAFLD.

Abstract Hypertension (HTN) and osteoarthritis (OA) are frequent in middle-aged and elderly people, and the co-occurrence of these two diseases is common. However, the pathogenesis of the multimorbidity of both diseases and the relation with sleep quality, hyperlipemia, and hyperglycemia is unclear. We conducted a cross-sectional study to make sense of the multimorbidity of HTN and OA and the relation with sleep quality, hyperlipemia, and hyperglycemia. The relation between sleep quality and OA and its joint effect with hyperlipemia or hyperglycemia was evaluated with logistic regression models. The additive interaction was assessed with the relative excess risk due to interaction (REEI), the attributable proportion (AP), and the synergy index (S). According to this research in a remote rural area, approximately 34.2% of HTN patients are accompanied with OA and 49.1% are suffering poor sleep. Both hyperlipemia/hyperglycemia and sleep quality were related to OA prevalence with crude ORs of 1.43 (95% CI 1.014–2.029) and 1.89 (95% CI 1.411–2.519, P

Objective: In order to accurately and quickly discriminate cigarettes. Methods: After collecting the near-infrared spectra of different brands and reducing the interference factors through the spectral preprocessing method, the spectral pretreatment method, the population number of firefly algorithm （FA） and the number of iterations on the correct rate of cigarette classification were investigated by using firefly algorithm to optimize support vector machine （SVM） parameters. Results: The standard normal variable transformation （SNV） combined with the first derivative method （1D） was used for near-infrared spectroscopy preprocessing. Under the condition that the number of firefly populations was 20 and the number of iterations was 20, optimized support vector parameters could achieve better recognition. As a result, the classification accuracy rate of the training set was 100%, and the classification accuracy rate of the test set was between 96.67% and 100.00%. Conclusion: It shows that using near-infrared spectroscopy technology combined with FA algorithm to optimize SVM can achieve accurate identification of cigarette brands.

BackgroundAcquired immunodeficiency syndrome (AIDS) is a global pandemic caused by human immunodeficiency virus (HIV), which is transmitted through human behaviors, such as sexual intercourse, intravenous drug injection, and blood transfusion. Rare studies have focused on the evaluation of the effects of culture, society, and HIV-related policies in adjusting people's HIV-related behaviors, i.e., ways of HIV transmission.MethodsBy taking the new HIV infections in Hubei Province each year from 1995 to 2020 as the sample, our study used the Hierarchical Age-Period-Cohort (HAPC) model to analyze the effects of age, period, and cohort on the trends of ways of HIV transmission.ResultsFrom 1995 to 2020, the number of new HIV infections in Hubei presented a general upward trend. A total of 34,636 HIV infections were reported during this period. According to the statistics of the new HIV infections in Hubei Province between 1995 and 2020, there is a negative correlation between age (−0.099, p < 0.001), squared age (−0.002, p < 0.001), and the rate of blood transmission. While there is a positive correlation between age (0.143, p < 0.001), squared age (0.002, p < 0.001), and the rate of HIV infection through sexual transmission. The significant period and cohort effects on ways of HIV transmission were also observed in the Chinese population.ConclusionSexual and blood transmission are the two main ways of HIV infection in China and Hubei. The trend of blood transmission is in accordance with the wave of blood trade in the early 1990s in China. The trend of sexual transmission indicates an increasing need to promote safer sexual behavior among the older population and later generations and design more tailored, innovative, and diverse HIV prevention strategies, especially for the high-risk groups.

An amendment to this paper has been published and can be accessed via the original article.

Abstract Background Fatty liver is a high incidence of perinatal disease in dairy cows caused by negative energy balance, which seriously threatens the postpartum health and milk production. It has been reported that lysine acetylation plays an important role in substance and energy metabolism. Predictably, most metabolic processes in the liver, as a vital metabolic organ, are subjected to acetylation. Comparative acetylome study were used to quantify the hepatic tissues from the severe fatty liver group and normal group. Combined with bioinformatics analysis, this study provides new insights for the role of acetylation modification in fatty liver disease of dairy cows. Results We identified 1841 differential acetylation sites on 665 proteins. Among of them, 1072 sites on 393 proteins were quantified. Functional enrichment analysis shows that higher acetylated proteins are significantly enriched in energy metabolic pathways, while lower acetylated proteins are significantly enriched in pathways related to immune response, such as drug metabolism and cancer. Among significantly acetylated proteins, many mitochondrial proteins were identified to be interacting with multiple proteins and involving in lipid metabolism. Furthermore, this study identified potential important proteins, such as HADHA, ACAT1, and EHHADH, which may be important regulatory factors through modification of acetylation in the development of fatty liver disease in dairy cows and possible therapeutic targets for NAFLD in human beings. Conclusion This study provided a comprehensive acetylome profile of fatty liver of dairy cows, and revealed important biological pathways associated with protein acetylation occurred in mitochondria, which were involved in the regulation of the pathogenesis of fatty liver disease. Furthermore, potential important proteins, such as HADHA, ACAT1, EHHADH, were predicted to be essential regulators during the pathogenesis of fatty liver disease. The work would contribute to the understanding the pathogenesis of NAFLD, and inspire in the development of new therapeutic strategies for NAFLD.