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Abstract Leveraging its ability to handle large and complex datasets, artificial intelligence can uncover subtle patterns and correlations that human observation may overlook. This is particularly valuable for understanding the intricate dynamics of spinal surgery and its multifaceted impacts on patient prognosis. This review aims to delineate the role of artificial intelligence in spinal surgery. A search of the PubMed database from 1992 to 2023 was conducted using relevant English publications related to the application of artificial intelligence in spinal surgery. The search strategy involved a combination of the following keywords: "Artificial neural network," "deep learning," "artificial intelligence," "spinal," "musculoskeletal," "lumbar," "vertebra," "disc," "cervical," "cord," "stenosis," "procedure," "operation," "surgery," "preoperative," "postoperative," and "operative." A total of 1,182 articles were retrieved. After a careful evaluation of abstracts, 90 articles were found to meet the inclusion criteria for this review. Our review highlights various applications of artificial neural networks in spinal disease management, including (1) assessing surgical indications, (2) assisting in surgical procedures, (3) preoperatively predicting surgical outcomes, and (4) estimating the occurrence of various surgical complications and adverse events. By utilizing these technologies, surgical outcomes can be improved, ultimately enhancing the quality of life for patients.

Objective To investigate the use of anti‐osteoporotic agents and refracture incidence in patients with osteoporotic vertebral compression fracture (OVCF) following percutaneous vertebral augmentation (PVA) and to evaluate the real‐world treatment of patients using denosumab following PVA. This study aims to provide spine surgeons with empirical insights derived from real‐world scenarios to enhance the management of bone health in OVCF patients. Methods This retrospective cohort study was based on data from the MarketScan and Optum databases from the USA. Female patients aged 55–90 years who underwent PVA for OVCF between January 2013 and March 2020 were included and followed up from the day after surgery. Patients who received at least one dose of denosumab were included in the denosumab cohort and were further divided into the on‐treatment and off‐treatment groups according to whether they received a second dose of denosumab, with follow‐up beginning on the index day (225 days after the first denosumab dose). In this study, the off‐treatment group was considered as the control group. Refracture incidence after PVA, the proportion of patients using anti‐osteoporotic agents in the total study population, and refracture incidence after the index day in the denosumab cohort were analyzed. Results A total of 13,451 and 21,420 patients from the MarketScan and Optum databases, respectively, were included. In the denosumab cohort, the cumulative incidence of clinical osteoporotic fractures within 3 years after the index day was significantly lower in the on‐treatment group than in the off‐treatment group (MarketScan database: 23.0% vs 39.0%, p = 0.002; Optum database: 28.2% vs 40.0%, p = 0.023). The cumulative incidence of clinical vertebral fractures was also lower in the on‐treatment group than in the off‐treatment group, with a significant difference in the MarketScan database (14.4% vs 25.5%, p = 0.002) and a numerical difference was found in the Optum database (20.2% vs 27.5%, p = 0.084).The proportion of patients using anti‐osteoporotic agents was low at 6 months postoperatively, with only approximately 7% using denosumab and 13%–15% taking oral bisphosphonates. Conclusion Postmenopausal women have a high refracture rate and a low proportion of anti‐osteoporotic drug use after PVA. Continued denosumab treatment after PVA is associated with a lower risk of osteoporotic and clinical vertebral fractures. Therefore, denosumab may be a treatment option for patients with osteoporosis after PVA.

Three new rare-earth high-entropy oxides with compositions of (Y1/7La1/7Nd1/7Sm1/7Gd1/7Yb1/7Lu1/7)2O3 (7HEO), (Y1/8La1/8Nd1/8Sm1/8Gd1/8Yb1/8Lu1/8Ce1/8)2O3 (8HEO) and (Y1/10La1/10Nd1/10Sm1/10Gd1/10Yb1/10Lu1/10Ce1/10Zr1/10Hf1/10)2O3 (10HEO) were prepared using a solid-state reaction method combined with conventional sintering at 1600 °C for 10 h 7HEO has a monoclinic structure. The addition of Ce into 7HEO not only leads to the phase transformation from monoclinic to bixbyite structure, but also contributes to the grain refinement. When the three elements of Ce, Zr and Hf are added into 7HEO, a second fluorite-structured phase forms and further promotes the grain refinement. 10HEO and 8HEO have a higher thermal conductivity compared with 7HEO in 25–600 °C. When the temperature reaches 900 °C, the thermal conductivity of 8HEO is lower than that of 7HEO. The addition of Ce or Ce/Zr/Hf into 7HEO causes the weakening of the bond strength and the increase of the bond length of cation-O2- in the samples, which in turn increases the thermal expansion coefficient. Moreover, 7HEO possesses a better oxygen barrier property compared with 8HEO and 10HEO. The hardness and Young's modulus of 7HEO are lower than those of 8HEO and 10HEO.

Abstract Obesity is accompanied by multiple known health risks and increased morbidity, and obese men display reduced reproductive health. However, the impact of obesity on the testes at the molecular levels remain inadequately explored. This is partially attributed to the lack of monitoring tools for tracking alterations within cell clusters in testes associated with obesity. Here, we utilized single-cell RNA sequencing to analyze over 70,000 cells from testes of obese and lean mice, and to study changes related to obesity in non-spermatogenic cells and spermatogenesis. The Testicular Library encompasses all non-spermatogenic cells and spermatogenic cells spanning from spermatogonia to spermatozoa, which will significantly aid in characterizing alterations in cellular niches and the testicular microenvironment during high-fat diet (HFD)-induced obesity. This comprehensive dataset is indispensable for studying how HFD disrupts cell-cell communication networks within the testis and impacts alterations in the testicular microenvironment that regulate spermatogenesis. Being the inaugural dataset of single-cell RNA-seq in the testes of diet-induced obese (DIO) mice, this holds the potential to offer innovative insights and directions in the realm of single-cell transcriptomics concerning male reproductive injury associated with HFD.

Commercial districts, as the epicenters of urban commerce and economic activity, largely reflect an area’s prosperity through their customer flow. However, previous research, which often relied on statistical and survey data, has typically not captured the full scope of customer flow dynamics throughout urban commercial districts and has not adequately measured the specific impacts of business district locations and their surrounding communities on customer flow. To bridge these gaps, this study utilizes multidimensional big geo-data resources, including mobile phone signaling data, Points of Interest (POI) data, and transportation network data, to uncover the underlying factors that influence customer flow within urban commercial districts. The findings suggest that several factors—the size of the commercial district, the diversity of business formats, the convenience of parking, the working and residential population in surrounding communities, and the proximity to urban centers—significantly influence the customer flow. Consumers show a preference for larger-scale, centrally-located commercial districts that offer convenient parking options, while a homogenized and uncharacteristic business format may reduce a commercial district’s appeal. Furthermore, the study reveals that industrial parks and mixed-use complexes within the 15-minute living circle surrounding the commercial district have a stronger attraction to customer flow than residential neighborhoods do. The insights from this research not only guide the strategic placement of new commercial centers but also provide a robust framework for enhancing the layout of urban commercial spaces and for the revitalization and advancement of established commercial districts.

Abstract The intensification of global heat wave events is seriously affecting residents' emotional health. Based on social media big data, our research explored the spatial pattern of residents' sentiments during heat waves (SDHW). Besides, their association with urban functional areas (UFAs) was analyzed using the Apriori algorithm of association rule mining. It was found that SDHW in Beijing were characterized by obvious spatial clustering, with hot spots predominately dispersed in urban areas and far suburbs, and cold spots mainly clustered in near suburbs. As for the associations with urban function areas, green space and park areas had significant effects on the positive sentiment in the study area, while a higher percentage of industrial areas had a greater impact on negative SDHW. When it comes to combined UFAs, our results revealed that the green space and park area combined with other functional areas was more closely related to positive SDHW, indicating the significance of promoting positive sentiment. Subdistricts with a lower percentage of residential and traffic areas may have a more negative sentiment. There were two main combined UFAs that have greater impacts on SDHW: the combination of residential and industrial areas, and the combination of residential and public areas. This study contributes to the understanding of improving community planning and governance when heat waves increase, building healthy cities, and enhancing urban emergency management.

Background Osteonecrosis of the femoral head (ONFH) is a refractory orthopedic disease with a high disability rate. Long-term administration of steroids is the most common pathogenic factor for non-traumatic ONFH. Early diagnosis of steroid-induced osteonecrosis of the femoral head (SONFH) is difficult and mainly depends on imaging.Objectives The objectives of this review were to examine the pathological mechanisms of SONFH, summarize related markers of SONFH, and identify areas for future studies.Methods We reviewed studies on pathological mechanisms and related markers of SONFH and discussed the relationship between them, as well as clinical applications and the outlook of potential markers.Results The pathological mechanisms of SONFH included decreased osteogenesis, lipid accumulation, increased intraosseous pressure, and microcirculation disruption. Differential proteomics and genomics play crucial roles in the occurrence, progression, and outcome of SONFH, providing novel insights into SONFH. Additionally, the biological functions of mesenchymal stem cells (MSCs) and exosomes (Exos) in SONFH have attracted increasing attention.Conclusions The pathological mechanisms of SONFH are complex. The related markers mentioned in the current review can predict the occurrence and progression of SONFH, which will help provide effective early clinical prevention and treatment strategies for SONFH.

Abstract The general strategy for n‐type organic thermoelectric is to blend n‐type conjugated polymer hosts with small molecule dopants. In this work, all‐polymer n‐type thermoelectric is reported by dissolving a novel n‐type conjugated polymer and a polymer dopant, poly(ethyleneimine) (PEI), in alcohol solution, followed by spin‐coating to give polymer host/polymer dopant blend film. To this end, an alcohol‐soluble n‐type conjugated polymer is developed by attaching polar and branched oligo (ethylene glycol) (OEG) side chains to a cyano‐substituted poly(thiophene‐alt‐co‐thiazole) main chain. The main chain results in the n‐type property and the OEG side chain leads to the solubility in hexafluorineisopropanol (HFIP). In the polymer host/polymer dopant blend film, the Coulombic interaction between the dopant counterions and the negatively charged polymer chains is reduced and the ordered stacking of the polymer host is preserved. As a result, the polymer host/polymer dopant blend exhibits the power factor of 36.9 µW m−1 K−1, which is one time higher than that of the control polymer host/small molecule dopant blend. Moreover, the polymer host/polymer dopant blend shows much better thermal stability than the control polymer host/small molecule dopant blend. This research demonstrates the high performance and excellent stability of all‐polymer n‐type thermoelectric.

The aboveground biomass (AGB) is closely linked to the carbon cycle in grassland ecosystems worldwide. Accurately quantifying AGB variations is thus essential for assessing grassland carbon sequestration and its feedback on climate change. Although many studies have investigated grassland AGB, they are limited to local areas and few research efforts have been attempted to estimate AGB at large scales with the constraint of in situ quadrat harvested AGB. In this study, we used multi-source satellite remote sensing data from 2000 to 2021 and abundant harvest quadrats data to explore AGB estimation methods and then analyze the spatiotemporal patterns of AGB for various grassland types across China’s three ecoregions. The results indicate that: (1) The temporal resolution improvement of remote sensing data results in a higher correlation between satellite remotely sensed NDVI and in situ AGB. Therefore, the MODIS MCD43A4 dataset with higher temporal resolution has a better fit with the harvesting AGB data. (2) Compared to the statistical methods, the machine learning algorithms exhibit high accuracy in estimating grassland AGB. Among them, the random forest (RF) model performs the most robustly, with the highest R2 of 0.83 (explaining 83 % of the variation of the harvesting AGB), and the lowest RMSE of 43.84 gm−2. (3) The multi-year average annual maximum grassland AGB decreases from the southeast to the northwest, with the temperate steppe region having the highest, followed by the alpine vegetation region and the temperate desert region. (4) While approximately 61.94 % of grassland pixels show an increasing trend in average annual maximum AGB from 2000 to 2021, significant (P

Background: Symptomatic Tarlov cysts are extremely rare, and there is no consensus on the optimal treatment for this condition. Here, we encountered a patient with a symptomatic giant sacral Tarlov cyst and reviewed the relevant literature.Case descriptionA 55-year-old male patient was diagnosed with a large sacral canal cyst based on an MRI examination four years ago. Due to mild symptoms, the patient received conservative treatment. In 2023, the patient's symptoms worsened, significantly affecting daily activities. It was suspected that the symptoms were related to the cyst. Subsequently, the patient underwent laminectomy and microsurgical excision of the cyst. Postoperatively, the patient experienced an improvement in symptoms. We conducted a review of the surgical approach used for this patient and explored alternative treatment methods proposed in the literature for similar conditions. Conclusions: We achieved favorable outcomes by performing microsurgical excision of symptomatic giant Tarlov cysts in a 55-year-old patient. Additionally, we reviewed relevant literature regarding Tarlov cysts. The treatment approaches for this condition vary, and conservative, interventional, or surgical treatments have all shown efficacy. Therefore, it is crucial to choose an appropriate treatment plan based on the patient's specific circumstances.

Abstract Purpose We aimed to explore the relationship between bone mineral density (BMD), bone metabolism markers, and blood lipid-related indicators, body mass index (BMI) in elderly individuals. Methods A retrospective analysis was conducted on 710 patients. Patients’ gender, age, height, weight, bone density values, T-scores, bone metabolism markers (including serum N-terminal propeptide of type I collagen (s-PINP), serum C-terminal telopeptide of type I collagen (s-CTX) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and lipid-related indicators (including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) and Castelli index 1 (TC/HDL-C index) and Castelli index 2 (LDL-C/HDL-C index) were recorded. Correlations between variables were analyzed, and patients were grouped according to gender and T-score for intergroup comparisons. Results HDL-C negatively correlates with BMD and s-CTX. TG, Castelli index, and BMI positively correlate with BMD. BMI negatively correlates with s-PINP. 1,25(OH)2D3 negatively correlates with TC, LDL-C, and Castelli index. LDL-C positively correlates with BMD in males, and TC negatively correlates with s-PINP. In females, HDL-C negatively correlates with BMD, and s-CTX positively correlates with Castelli index. 1,25(OH)2D3 negatively correlates with TC, LDL-C, and Castelli index. TG and Castelli index were higher in normal bone mass group, while HDL-C is higher in the osteoporosis group. TG and BMI positively predicted bone mass density, while HDL-C negatively predicted bone mass density. Conclusions HDL-C may have a predictive role in osteoporosis, particularly in women. The likelihood of osteoporosis is lower in individuals with high BMI or hyperlipidemia. Some lipid metabolism markers can be used to predict osteoporosis, and further research is needed.

Abstract Background To date, few reports have evaluated the long-term outcome of percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fractures (OVCFs) and the factors influencing the long-term outcome of this procedure are uncertain. Methods A total of 91 patients underwent PKP for thoracolumbar OVCFs from June 2012 to December 2012. Pain Visual Analogue Scores (VAS) and Oswestry Disability Index (ODI) were recorded preoperatively and after 10-year follow-up. Factors that may affect surgical outcome, such as gender, age, height, weight, hypertension, diabetes, cause of injury, fracture segment, length of hospitalization, history of previous spinal surgery, preoperative bone mineral density (BMD), preoperative VAS and ODI scores, length of surgery, bone cement dosage, postoperative standardized anti-osteoporosis treatment, and other new vertebral fractures, were analyzed by multiple linear regression with VAS and ODI scores at the last follow-up. The correlation factors affecting the efficacy were analyzed. Results The preoperative and final follow-up pain VAS was 7.9 ± 1.1 and 2.2 ± 1.1. ODI scores were 30.4 ± 4.2 and 10.7 ± 2.6. The difference was statistically significant (P 0.05). Conclusion The long-term outcome after PKP is satisfactory. Age, gender, cause of injury, and standardized postoperative anti-osteoporosis treatment may be factors affecting the long-term outcome.

Abstract The senescence-associated secretory phenotype (SASP) is a generic term for the secretion of cytokines, such as pro-inflammatory factors and proteases. It is a crucial feature of senescent cells. SASP factors induce tissue remodeling and immune cell recruitment. Previous studies have focused on the beneficial role of SASP during embryonic development, wound healing, tissue healing in general, immunoregulation properties, and cancer. However, some recent studies have identified several negative effects of SASP on fracture healing. Senolytics is a drug that selectively eliminates senescent cells. Senolytics can inhibit the function of senescent cells and SASP, which has been found to have positive effects on a variety of aging-related diseases. At the same time, recent data suggest that removing senescent cells may promote fracture healing. Here, we reviewed the latest research progress about SASP and illustrated the inflammatory response and the influence of SASP on fracture healing. This review aims to understand the role of SASP in fracture healing, aiming to provide an important clinical prevention and treatment strategy for fracture. Clinical trials of some senolytics agents are underway and are expected to clarify the effectiveness of their targeted therapy in the clinic in the future. Meanwhile, the adverse effects of this treatment method still need further study.

PurposeMinimally invasive therapies (MIT) have gained popularity due to their capacity to reduce trauma, enhance aesthetic outcomes, and shorten recovery periods. This article explores patients’ perceptions and preferences regarding MIT for varicose veins (VVs) while analyzing associated influencing factors to provide a better understanding.Patients and methodsA cross-sectional survey at Zhejiang Rongjun Hospital was performed from January 2022 to June 2023, involving 305 participants with VVs. The questionnaire assessed patient demographics, VVs severity, prior treatment experiences, and treatment preferences. Statistical analyses, including chi-square and Kruskal-Wallis tests, were conducted to explore the correlations between patient characteristics, treatment preferences, and factors influencing these choices.ResultsNearly half of the participants (44.3%) lacked information on any surgical options, whereas a slight majority (55.7%) possessed familiarity with at least one treatment modality, and only 9.8% knew of all six treatment methods presented. Patient surveys discerned that the majority (68.5%) declared an inadequate grasp of treatment methodologies to articulate a treatment preference. Among the 96 patients who made a treatment choice, 24.0% opted for traditional surgery, while 76.0% chose MIT and a higher preference for MIT among male patients compared to female patients (p = 0.006). The patients preferred treatment options for VVs significantly affected by vascular surgeon recommendations and the number of follow-up visits (r = 0.129, p = 0.024; r = 0.122, p = 0.033).ConclusionThe study highlights limited awareness of MIT among Chinese patients with VVs. The insights emphasize the influential role of vascular surgeons’ recommendations and suggest a growing predilection for less invasive treatments due to their advantages in recovery and aesthetics. Provider-patient communication, including education about available treatments and shared decision-making, is essential to align treatment plans with patient expectations and improve outcomes.

BackgroundA serious consequence of diabetes is diabetic nephropathy (DN), which is commonly treated by statins. Studies evaluating the effects of statin medication have yielded inconsistent results regarding the potential association with diabetic nephropathy. To manage diabetic nephropathy’s onset and improve the quality of life of patients, it is imperative to gain a comprehensive understanding of its contributing factors.Data and methodsOur study was conducted using the National Health and Nutrition Examination Survey (NHANES) as well as weighted multivariate logistic regression models to determine the odds ratio (OR) and 95% confidence intervals (95%CI) for diabetic nephropathy. We conducted stratified analyses to examine the impact of statins and the duration of their usage on diabetic nephropathy in different subgroups. A nomogram model and the receiver operating characteristic (ROC) curve were also developed to predict DN risk.ResultsStatin use significantly increased the incidence of DN (OR=1.405, 95%CI (1.199,1.647), p

Aiming at the problems of rolling torque and yaw torque of zigzag UAV, a multi-objective optimization method based on hybrid airfoil parameterization was proposed. The optimization model was established by combining the non dominated sorting genetic algorithm (NSGA-Ⅱ) with hybrid airfoil parameterization, SCDM flow field modeling, fluent meshing and fluent solution flow field calculation. Then an automatic optimization process based on Isight platform was developed to realize the aerodynamic optimization design of zigzag UAV. The results show that the optimization platform based on hybrid airfoil parameterization increases the search space of airfoil optimization, achieves the optimization of multi-objective predetermined values, reduces the roll torque and yaw torque of Z-shaped UAV to the greatest extent, and improves its overall aerodynamic performance. The proposed method can eliminate the moment of UAV with limited wingspan, which provides a technical reference for solving the roll and yaw problems of asymmetric UAV.

This paper addresses the problem of target tracking and circumnavigation control for a bearing-only multi-Unmanned Aerial Vehicle (UAV) system. First, using the bearing measurements, an adaptive algorithm in the form of a Proportional Integral (PI) controller is developed to estimate the target state. Subsequently, a distributed circumnavigation control protocol is established to evenly encircle the target. Then, we use the local information from each UAV in the network to calculate the relative position of the target, and further enhance the accuracy of estimation and circumnavigation algorithms by employing a Kalman filter. Finally, numerical simulation experiments are conducted to validate the effectiveness of the proposed tracking control algorithm.

With the support of big data mining techniques, utilizing social media data containing location information and rich semantic text information can construct large-scale daily activity OD flows for urban populations, providing new data resources and research perspectives for studying urban spatiotemporal structures. This paper employs the ST-DBSCAN algorithm to identify the residential locations of Weibo users in four communities and then uses the BERT model for activity-type classification of Weibo texts. Combined with the TF-IDF method, the results are analyzed from three aspects: temporal features, spatial features, and semantic features. The research findings indicate: ① Spatially, residents’ daily activities are mainly centered around their residential locations, but there are significant differences in the radius and direction of activity among residents of different communities; ② In the temporal dimension, the activity intensities of residents from different communities exhibit uniformity during different time periods on weekdays and weekends; ③ Based on semantic analysis, the differences in activities and venue choices among residents of different communities are deeply influenced by the comprehensive characteristics of the communities. This study explores methods for OD information mining based on social media data, which is of great significance for expanding the mining methods of residents’ spatiotemporal behavior characteristics and enriching research on the configuration of public service facilities based on community residents’ activity spaces and facility demands.

Abstract Objectives This study aimed to evaluate the clinical efficacy and safety of percutaneous endoscopic interlaminar discectomy (PEID) for treating highly downward-migrated disc herniation. Methods We conducted a retrospective study on 39 patients with highly downward-migrated disc herniation who underwent PEID treatment between January 2015 and October 2020. The clinical outcomes, including the preoperative and postoperative visual analogue scale (VAS) for the back and leg, Oswestry Disability Index (ODI), and MacNab criteria for surgical success, were evaluated and compared to thirty-seven patients treated with posterior lumbar interbody fusion (PLIF). Results The mean operation time of PEID was 93.00(77.00,110.00) min, while that of PLIF was 169.00(157.00,183.00) min. Continued improvement in both PEID and PLIF was observed in the VAS and ODI scores immediately after the surgery to the last follow‐up. The VAS and ODI scores of PEID one week after surgery were significantly different from those of PLIF. One patient with recurrent lumbar disc herniation in the same segment improved after undergoing repeat PEID, two patients had dura tears, and conservative treatment helped relieve the symptoms. The overall percentage of patients with good to excellent results of PELD according to the modified MacNab criteria was 97.43%, while that of PLIF was 94.60%. Conclusions PEID has reliable efficacy and safety for treating highly downward-migrated disc herniation. And the long-term efficacy of PEID is comparable to PLIF. No severe complications occurred after surgery, and most patients’ symptoms were relieved.

IntroductionCOVID-19, being a new type of infectious disease, holds significant implications for scientific prevention and control to understand its spatiotemporal transmission process. This study examines the diverse spatial patterns of COVID-19 within Wuhan by analyzing early case data alongside urban infrastructure information.MethodsThrough co-location analysis, we assess both local and global spatial risks linked to the epidemic. In addition, we use the Geodetector, identifying facilities displaying unique spatial risk characteristics, revealing factors contributing to heightened risk.ResultsOur findings unveil a noticeable spatial distribution of COVID-19 in the city, notably influenced by road networks and functional zones. Higher risk levels are observed in the central city compared to its outskirts. Specific facilities such as parking, residence, ATM, bank, entertainment, and hospital consistently exhibit connections with COVID-19 case sites. Conversely, facilities like subway station, dessert restaurant, and movie theater display a stronger association with case sites as distance increases, hinting at their potential as outbreak focal points.DiscussionDespite our success in containing the recent COVID-19 outbreak, uncertainties persist regarding its origin and initial spread. Some experts caution that with increased human activity, similar outbreaks might become more frequent. This research provides a comprehensive analytical framework centered on urban facilities, contributing quantitatively to understanding their impact on the spatial risks linked with COVID-19 outbreaks. It enriches our understanding of the interconnectedness between urban facility distribution and transportation flow, affirming and refining the distance decay law governing infectious disease risks. Furthermore, the study offers practical guidance for post-epidemic urban planning, promoting the development of safer urban environments resilient to epidemics. It equips government bodies with a reliable quantitative analysis method for more accurately predicting and assessing infectious disease risks. In conclusion, this study furnishes both theoretical and empirical support for tailoring distinct strategies to prevent and control COVID-19 epidemics.

Abstract Thrombocytopenia is a major complication in a subset of patients with multiple myeloma (MM). However, little is known about its development and significance during MM. Here, we show thrombocytopenia is linked to poor prognosis in MM. In addition, we identify serine, which is released from MM cells into the bone marrow microenvironment, as a key metabolic factor that suppresses megakaryopoiesis and thrombopoiesis. The impact of excessive serine on thrombocytopenia is mainly mediated through the suppression of megakaryocyte (MK) differentiation. Extrinsic serine is transported into MKs through SLC38A1 and downregulates SVIL via SAM-mediated tri-methylation of H3K9, ultimately leading to the impairment of megakaryopoiesis. Inhibition of serine utilization or treatment with TPO enhances megakaryopoiesis and thrombopoiesis and suppresses MM progression. Together, we identify serine as a key metabolic regulator of thrombocytopenia, unveil molecular mechanisms governing MM progression, and provide potential therapeutic strategies for treating MM patients by targeting thrombocytopenia.

Intervertebral disc degeneration (IVDD) is a worldwide disease that causes low back pain and reduces quality of life. Biotherapeutic strategies based on tissue engineering alternatives, such as intervertebral disc scaffolds, supplemented by drug-targeted therapy have brought new hope for IVDD. In this study, to explore the role and mechanism of MnO2/GelMA composite hydrogels in alleviating IVDD, we prepared composite hydrogels with MnO2 and methacrylate gelatin (GelMA) and characterized them using compression testing and transmission electron microscopy (TEM). Annulus fibrosus cells (AFCs) were cultured in the composite hydrogels to verify biocompatibility by live/dead and cytoskeleton staining. Cell viability assays and a reactive oxygen species (ROS) probe were used to analyze the protective effect of the composite hydrogels under oxidative damage. To explore the mechanism of improving the microenvironment, we detected the expression levels of antioxidant and autophagy-related genes and proteins by qPCR and Western blotting. We found that the MnO2/GelMA composite hydrogels exhibited excellent biocompatibility and a porous structure, which promoted cell proliferation. The addition of MnO2 nanoparticles to GelMA cleared ROS in AFCs and induced the expression of antioxidant and cellular autophagy through the common SIRT1/NRF2 pathway. Therefore, the MnO2/GelMA composite hydrogels, which can improve the disc microenvironment through scavenging intracellular ROS and resisting oxidative damage, have great application prospects in the treatment of IVDD.

Abstract The flat torque‐angle characteristic of torque motor plays a decisive role in the control quality of electro‐hydraulic servo and proportional valve. To solve the issue that the current wet‐type torque motor for two‐dimensional (2D) valve does not have flat torque‐angle characteristic, a method for adjusting the flat torque‐angle characteristic of torque motor for 2D valve based on magnetic saturation of tooth tip is proposed. Taking the current limited angle torque motor with rectangular tooth (TM‐R) as an application example, the rectangular teeth on the stator are replaced by sharp teeth to form a novel torque motor with sharp tooth (TM‐S), and the flat torque‐angle characteristic can be obtained by constructing magnetic saturation of tooth tip. The variation trends of magnetic permeance in each magnetic saturation region of the tooth tip are analyzed. The torque‐angle characteristics of TM‐S and TM‐R under different control currents are compared. Prototypes of TM‐S and TM‐R with optimized parameters are designed and manufactured, and special experimental benches are built for static and dynamic test. Experimental results are basically consistent with the theoretical analysis. The comparative study shows that the torque‐angle characteristic of TM‐R is a downward curve, while the torque‐angle characteristic of TM‐S is an approximate flat curve. The research validates the effectiveness of the proposed method, which can both realize the flat torque‐angle characteristic and improve the dynamic response of torque motor. Finally, the proposed method can be further applied to other rotary and direct‐acting electro‐mechanical converter (EMC) with multi‐tooth structure.

Proven by publications, long non-coding RNAs (lncRNAs) play critical roles in the development of clear cell renal cell carcinoma (ccRCC). Although lncRNA LINC00565 has been implicated in the progression of various cancers, its biological effects on ccRCC remain unknown. This study aimed to investigate the biological functions of LINC00565, as well as its potential mechanism in ccRCC. Here, the expression data of mature microRNAs (miRNAs) (normal: 71, tumor: 545), messenger RNAs (mRNAs), and lncRNAs (normal: 72, tumor: 539) of ccRCC were acquired from The Cancer Genome Atlas (TCGA) database and subjected to differential expression analysis. Quantitative reverse transcriptase polymerase chain reaction analyzed the expression levels of LINC00565, miR-532-3p, and ADAM19 mRNA. TCGA database, dual-luciferase report detection, and Argonaute 2 RNA immunoprecipitation were utilized to confirm the relationships between LINC00565 and miR-532-3p and between miR-532-3p and ADAM19, respectively. The progression of ccRCC cells was determined via CCK-8, colony formation, scratch healing, and transwell assays. Western blot was applied to detect the protein levels of epithelial-mesenchymal transition markers and ADAM19. We herein suggested that LINC00565 was prominently upregulated in ccRCC tissues and cells. Knockdown of LINC00565 repressed cell progression. We further predicted and validated miR-532-3p as a target of LINC00565, and miR-532-3p could target ADAM19. Knockdown of LINC00565 resulted in ADAM19 level downregulation in ccRCC cells and suppressed miR-532-3p could restore ADAM19 level. Thus, the three RNAs constructed a ceRNA network. Overexpressed ADAM19 could eliminate the anticancer effects caused by knocking down LINC00565 on ccRCC cells. In conclusion, LINC00565 upregulated ADAM19 via absorbing miR-532-3p, thereby facilitating the progression of ccRCC cells.

Abstract The manufacturing of spiral groove structure of two-dimensional valve (2D valve) feedback mechanism has shortcomings of both high cost and time-consuming. This paper presents a novel configuration of rotary electro-mechanical converter with negative feedback mechanism (REMC-NFM) in order to replace the feedback mechanism of spiral groove and thus reduce cost of valve manufacturing. In order to rapidly and quantitative evaluate the driving and feedback performance of the REMC-NFM, an analytical model taking leakage flux, edge effect and permeability nonlinearity into account is formulated based on the equivalent magnetic circuit approach. Then the model is properly simplified in order to obtain the optimal pitch angle. FEM simulation is used to study the influence of crucial parameters on the performance of REMC-NFM. A prototype of REMC-NFM is designed and machined, and an exclusive experimental platform is built. The torque-angle characteristics, torque-displacement characteristics, and magnetic flux density in the working air gap with different excitation currents are measured. The experimental results are in good agreement with the analytical and FEM simulated results, which verifies the correctness of the analytical model. For torque-angle characteristics, the overall torque increases with both current and rotation angle, which reaches about 0.48 N·m with 1.5 A and 1.5°. While for torque-displacement characteristics, the overall torque increases with current yet decrease with armature displacement due to the negative feedback mechanism, which is about 0.16 N·m with 1.5 A and 0.8 mm. Besides, experimental results of conventional torque motor are compared with counterparts of REMC-NFM in order to validate the simplified model. The research indicates that the REMC-NFM can be potentially used as the electro-mechanical converter for 2D valves in civil servo areas.

Abstract ECD is considered to have rapid progression and poor prognosis. Studies have shown that vemurafenib is effective for ECD patients with orbital involvement, but not for ECD with multiple organs. The refinement of treatment approaches and the increased awareness of ECD have led to a dramatic improvement in prognosis.

The bone tumour microenvironment plays an essential role in multiple myeloma (MM) development. Here, the authors show that bone collagen degradation provides glycine to support MM progression through glutathione and purine synthesis.

This paper aims to design a novel AFCM-SMOTENC-APRIORI model to mine the default feature attributes of small enterprises. It can overcome the problem that the data characteristics of “small defaulting small enterprises and large non-defaulting small enterprises” make it difficult to mine the defaulting feature attributes of existing small enterprises. We used 1,231 small enterprise credit data from a city commercial bank in China to make an empirical analysis. We found that 23 feature attributes are strongly associated with default and 87% of the association rules are the same between the extended data and the original data mining. It shows that the data mining results with SMOTE-NC are highly consistent with the results of the original data mining, and the model is robust and reliable. It can be used as a reference for the credit risk identification of small enterprises in commercial banks.

BackgroundLumbar disc herniation (LDH) linked with posterior ring apophysis separation (PRAS) is a rare and distinct subset of disc herniation. Few studies have evaluated the clinical efficacy of percutaneous endoscopic lumbar discectomy (PELD), which is a procedure used to treat LDH linked with PRAS.ObjectivesTo evaluate the clinical efficacy and safety of PELD in the treatment of LDH linked with PRAS.MethodsPatients who met inclusion criteria (n = 67; 40 males and 27 females) underwent PELD. General and operation-related information and perioperative complications of the patients were recorded. Clinical efficacy was measured using the Visual Analog Scale (VAS) and Oswestry Disability Index (ODI) during the follow-up period.ResultsThe mean operation time was 118.04 ± 19.31 min and the mean blood loss was 22.84 ± 15.89 ml. The VAS and ODI scores continued to improve immediately after the surgery to the last follow-up. Four patients experienced postoperative complications i.e., herniation recurrences. The conditions of the patients with the complications improved after treatment.ConclusionsPELD has reliable efficacy and safety in the treatment of LDH linked with PRAS.

As a hydro-mechanical servo system, the whole performance of the two-dimensional proportional valve with magnetic coupling (2D-MC-PV) highly depend on certain structural parameters. To tradeoff good static/dynamic characteristics, good working stability and low leakage pilot stage, a multi-objective optimization is inevitable for preliminary design stage. Therefore, this paper proposes a multi-objective optimization method based on AMESim and Matlab/Simulink co-simulation model, which optimizes key structural parameters by adjusting weight coefficients (balancing static, dynamic, and pilot leakage performance). Considering that magnetic coupling (MC) is the key component for 2D-MC-PV to realize spool position feedback and translational motion conversion, the analytical equation of MC is derived based on the Coulomb’s law and the law of equivalent magnetic charge, and the Monte Carlo method is used to calculate. Finally, the prototype of 2D-MC-PV is designed and manufactured, and a special experimental platform is built to test the static/dynamic characteristics. The experimental results show that 2D-MC-PV has good working stability: under working pressure of 20 MPa, the maximum no-load flow rate is 108.8 L/min with the hysteresis of 3.36%, and the amplitude and phase frequency width is 27.8 and 36.6 Hz. It shows that the multi-objective optimization method proposed in this paper can be used as an optimization method for 2D-MC-PV.

Introduction Natural cycle (NC) and hormone replacement treatment (HT) are frequently used endometrial preparation protocols prior to frozen-thawed embryo transfer in ovulatory women. It is not clear which protocol results in a higher live birth rate. It has been suggested that there is an increased risk in maternal and perinatal morbidity following HT protocol due to the lack of corpus luteum. The objective of this trial is to compare the clinical outcomes of NC and HT protocols in frozen embryo transfer.Methods and analysis COMPETE is an open-label, single-centre, randomised controlled trial targeting to recruit 888 women, with 444 women each in two arms (1:1 treatment ratio). Women undergoing in vitro fertilisation scheduled for a frozen embryo transfer and have a regular menstrual cycle are eligible. Exclusion criteria include ovulation disorders and intrauterine adhesions. The primary outcome is live birth resulting from the first frozen embryo transfer after randomisation. Secondary outcomes include biochemical pregnancy, clinical pregnancy, multiple pregnancy, ongoing pregnancy, miscarriage, endometrial thickness, cycle cancellation, gestational diabetes mellitus, hypertensive disorders of pregnancy, antepartum haemorrhage, preterm birth, birth weight, large for gestational age, congenital anomaly and perinatal mortality. The data analysis will be following the intention-to-treat principle.Ethics and dissemination This study has been approved by the Institutional Review Board of Northwest women’s and children’s hospital (2020008). Written informed consent will be obtained from each participant before randomisation. The results of the trial will be presented via publications.Trial registration number ChiCTR2000040640.

BackgroundThe data about the clinical features and outcomes of Chinese patients with follicular lymphoma (FL) are limited. Here, we conducted a retrospective study to explore the initial treatment strategies and clinical outcomes of Chinese patients with FL in the real world.MethodThis study included FL patients who were newly diagnosed in Tianjin Medical University Cancer Institute and Hospital from March 2002 to August 2020.ResultsA total of 926 FL patients were enrolled. The median age was 54 years old, and the majority of the Chinese FL patients had advanced-stage disease and Eastern Cooperative Oncology Group(ECOG)

The aim of this paper is to focus on a fuzzy metric called Deng’s metric in [0,1]-topology. Firstly, we will extend the domain of this metric function from M0×M0 to M×M, where M0 and M are defined as the sets of all special fuzzy points and all standard fuzzy points, respectively. Secondly, we will further extend this metric to the completely distributive lattice LX and, based on this extension result, we will compare this metric with the other two fuzzy metrics: Erceg’s metric and Yang-Shi’s metric, and then reveal some of its interesting properties, particularly including its quotient space. Thirdly, we will investigate the relationship between Deng’s metric and Yang-Shi’s metric and prove that a Deng’s metric must be a Yang-Shi’s metric on IX, and consequently an Erceg’s metric. Finally, we will show that a Deng’s metric on IX must be Q−C1, and Deng’s metric topology and its uniform structure are Erceg’s metric topology and Hutton’s uniform structure, respectively.

The aim of this paper is to focus on the metrization question in L-fuzzy sets. Firstly, we put forward an L-quasi (pseudo)-metric on the completely distributive lattice LX by comparing some existing lattice-valued metrics with the classical metric and show a series of its related properties. Secondly, we present two topologies: ψp and ζp, generated by an L-quasi-metric p with different spherical mappings, and prove ψp=ζp′ if p is further an L-pseudo-metric on LX. Thirdly, we characterize an equivalent form of L-pseudo-metric in terms of a class of mapping clusters and acquire several satisfactory results. Finally, based on this kind of L-metric, we assert that, on LX, a Yang–Shi metric topology is Q−CI, but an Erceg metric topology is not always so.

Thermoelectric (TE) materials based on conjugated polymers have received much attention due to their great advantages of solution processibility, light weight, flexibility, and low thermal conductivity. These advantages make them potential candidates for large-area, low-cost and low-power TE applications. Both efficient p-type and n-type conjugated polymers with high and comparable thermoelectric performance are required for practical TE applications. However, due to the inefficient n-doping efficiency and unstable electron transport of most n-type conjugated polymers, the TE performance of n-type polymers is much poorer than that of their p-type counterparts, impeding the development of polymer TE materials. Great efforts have been made to address the low n-doping efficiency and TE performance of n-type polymers, including the chemical modification of traditional n-type polymers, the design of new n-type conjugated polymers, and the development of more efficient n-dopants, as well as doping engineering. Nowadays, the TE performance of n-type polymers has been greatly improved, indicating a bright future for polymer TE materials. In this review, we summarize the recent progress made on n-type polymer TE materials, mainly focusing on the structure-performance relationships based on promising n-type polymers for TE applications. This review aims to provide some guidelines for future material design.

Diffuse large B-cell lymphoma (DLBCL) is a biologically and clinically heterogeneous disease that requires personalized clinical treatment. To assign patients into different risk categories, cytogenetic abnormalities and genetic mutations have been widely applied to the prognostic stratification of DLBCL. Increasing evidence has demonstrated that deregulated epigenetic modifications and long noncoding RNAs (lncRNAs) contribute to the initiation and progression of DLBCL. However, specific lncRNAs that affect epigenetic regulation and their value in predicting prognosis and therapy response remain uncertain. Here, 2,025 epigenetic-related genes were selected, and 9 lncRNAs (PRKCQ-AS1, C22orf34, HCP5, AC007389.3, APTR, SNHG19, ELFN1-AS1, LINC00487, and LINC00877) were tested and validated to establish an lncRNA-regulating epigenetic event signature (ELncSig). ELncSig, which was established based on independent lymphoma datasets, could distinguish different survival outcomes. Functional characterization of ELncSig showed that it could be an indicator of the immune microenvironment and is correlated with distinctive mutational characteristics. Univariate and multivariate analyses showed that ELncSig was independent of traditional prognostic factors. The novel immune-related ELncSig exhibits promising clinical prognostic value for DLBCL.

The role of N6-methyladenosine (m6A) modification in tumor microenvironment has rarely been explored in follicular lymphoma (FL). To examine the role of m6A modification in biological behavior, especially the immune landscape of FL, we utilized the Gene Expression Omnibus database to determine the expression signatures of m6A-regulators by unsupervised clustering, and then condense into a risk score, which was validated in an external cohort from the Tianjin Medical University Cancer Institute and Hospital. Finally, 16 m6A-regulators in 351 FL patients were evaluated and two m6A clusters were identified, characterized by differences in prognosis and biological behaviors. The m6A score was further developed based on 20-genes to quantify the m6A-regulator expression signature in each patient with FL. The low m6A score was associated with inferior prognosis of patients, with a median survival time of 8.84 (95% confidence interval [CI]: 7.251-10.429) years, which was remarkably shorter than that of patients with high m6A scores (15.73 years, 95% CI: 11.729-19.731; p

Objective: The immunoscore, which is used to quantify immune infiltrates, has greater relative prognostic value than tumor, node, and metastasis (TNM) stage and might serve as a new system for classification of colorectal cancer. However, a comparable immunoscore for predicting lung adenocarcinoma (LUAD) prognosis is currently lacking. Methods: We analyzed the expression of 18 immune features by immunohistochemistry in 171 specimens. The relationship of immune marker expression and clinicopathologic factors to the overall survival (OS) was analyzed with the Kaplan-Meier method. A nomogram was developed by using the optimal features selected by least absolute shrinkage and selection operator (LASSO) regression in the training cohort (n = 111) and evaluated in the validation cohort (n = 60). Results: The indicators integrated in the nomogram were TNM stage, neuron-specific enolase, carcino-embryonic antigen, CD8center of tumor (CT), CD8invasive margin (IM), FoxP3CT, and CD45ROCT. The calibration curve showed prominent agreement between the observed 2- and 5-year OS and that predicted by the nomogram. To simplify the nomogram, we developed a new immune-serum scoring system (I-SSS) based on the points awarded for each factor in the nomogram. Our I-SSS was able to stratify same-stage patients into different risk subgroups. The combination of I-SSS and TNM stage had better prognostic value than the TNM stage alone. Conclusions: Our new I-SSS can accurately and individually predict LUAD prognosis and may be used to supplement prognostication based on the TNM stage.

A comprehensive understanding of the relationship between public transportation supply and demand is crucial for the construction and sustainable development of urban transportation. Due to the spatial and networked nature of public transportation, revealing the spatial configuration and structural disparities between public transportation supply and demand networks (TSN and TDN) can provide significant insights into complex urban systems. In this study, we explored the spatial configuration and structural disparities between TSN and TDN in the complex urban environment of Beijing. By constructing subdistrict-scale TSN and TDN using urban public transportation operation data and mobile phone data, we analyzed the spatial characteristics and structural disparities of these networks from various dimensions, including global indicators, three centralities, and community structure, and measured the current public transportation supply and demand matching pattern in Beijing. Our findings revealed strong structural and geographic heterogeneities of TSN and TDN, with significant traffic supply–demand mismatch being observed in urban areas within the Sixth Ring Road. Moreover, based on the percentage results of supply–demand matching patterns, we identified that the current public transportation supply–demand balance in Beijing is approximately 64%, with around 18% of both excess and shortage of traffic supply. These results provide valuable insights into the structure and functioning of public transportation supply–demand networks for policymakers and urban planners; these can be used to facilitate the development of a sustainable urban transportation system.

Generally, airplane upsets in flight are considered a precursor to loss of control in flight (LOC-I) accidents, and unfortunately LOC-I is classified as the leading cause of fatal accidents. To further explore the risk factors, causal relationships, and coupling mechanism of airplane upsets, this study proposed a risk analysis model integrating the Interpretative Structural Modeling (ISM) and Bayesian Network (BN). Seventeen key risk factors leading to airplane upsets were identified through the analysis of typical accident cases and the literature. The ISM approach was used to construct the multi-level interpretative structural model of airplane upsets, which could reveal the causal relationship among various risk factors and risk propagation paths. Then, taking 286 accident/incident investigation data as training samples, a data-driven BN model was established using machine learning for dependency intensity assessment and inference analysis. The results reveal that the interaction among risk factors of fatal accidents caused by airplane upsets is more significant than that of non-fatal accidents/incidents. Risk factors such as pilot-induced oscillations/airplane-pilot coupling and non-adherence to Standard Operating Procedures (SOPs)/neglect of cross-validation have a significant effect on airplane upsets in flight among seventeen risk factors. Moreover, this study also identifies the most likely set of risk factors that lead to fatal accidents caused by airplane upsets. The research results have an important theoretical significance and application value for preventing airplane upsets risk.

Evolution of accretion disk and corona during outbursts in black hole binary systems is still unclear. Here, the authors show spectral analysis of MAXI J1820+070 and propose a scenario of a dynamical corona to explain the evolution of the reflection fraction observed by Insight-HXMT.

BackgroundTo compare the efficacy and safety of pembrolizumab combined with neoadjuvant chemotherapy (neoCT) versus neoadjuvant chemoradiotherapy (neoCRT) followed by surgery for locally advanced resectable oesophageal squamous cell carcinoma (ESCC).MethodsThis study is a multicentre, prospective, randomized-controlled, phase III clinical study. Eligible ESCC (staging: cT1N2M0 or cT2-3N0-2M0 (stage II/III, high-risk lesions in T2N0M0)) patients will be randomly assigned to either the experimental group (pembrolizumab with neoCT, n = 228) or the control group (neoCRT, n = 114) at a ratio of 2:1. Within 4–6 weeks after preoperative therapy, the McKeown procedure will be performed. Patients in the experimental group will also receive pembrolizumab alone as adjuvant therapy after surgery until 1 year or until the radiographically confirmed PD or other condition indicated for premature termination is observed. The primary endpoint is event-free survival (EFS). The secondary endpoints are 1-, 3-, and 5-year overall survival (OS) and disease-free survival (DFS), short-term outcomes, and quality of life.DiscussionThis is the first prospectively randomized controlled trial designed to compare pembrolizumab plus chemotherapy and chemoradiotherapy as neoadjuvant therapy for resectable ESCC. According to our hypothesis, preoperative pembrolizumab combined with chemotherapy will result in a better tumour response and prolong the survival of patients, with acceptable toxicity. This study started in December 2021, and the enrolment time is estimated to be 2 years.Trial RegistrationThis prospective study has been registered at ClinicalTrials.gov (NCT04807673), March 2021.

Abstract It has been previously shown that (never in mitosis gene A)‐related kinase 2 (NEK2) is upregulated in multiple myeloma (MM) and contributes to drug resistance. However, the mechanisms behind this upregulation remain poorly understood. In this study, it is found that amplification of NEK2 and hypermethylation of distal CpG islands in its promoter correlate strongly with increased NEK2 expression. Patients with NEK2 amplification have a poor rate of survival and often exhibit TP53 deletion, which is an independent prognostic factor in MM. This combination of TP53 knockout and NEK2 overexpression induces asymmetric mitosis, proliferation, drug resistance, and tumorigenic behaviors in MM in vitro and in vivo. In contrast, delivery of wild type p53 and suppression of NEK2 in TP53−/− MM cell lines inhibit tumor formation and enhance the effect of Bortezomib against MM. It is also discovered that inactivating p53 elevates NEK2 expression genetically by inducing NEK2 amplification, transcriptionally by increased activity of cell cycle‐related genes like E2F8 and epigenetically by upregulating DNA methyltransferases. Dual defects of TP53 and NEK2 may define patients with the poorest outcomes in MM with p53 inactivation, and NEK2 may serve as a novel therapeutic target in aggressive MM with p53 abnormalities.

Abstract The torque–angle characteristics of electric–mechanical converters are important determinants of the quality of electrohydraulic proportional control systems. It is far more difficult for a rotary electric–mechanical converter (REMC) to obtain flat torque–angle characteristics than traditional proportional solenoid, greatly influencing the promotion and application of rotary valves for electrohydraulic proportional control systems. A simple and feasible regulation method for the torque–angle characteristics of REMCs based on a hybrid air gap is proposed. The regulation is performed by paralleling an additional axial air gap with the original radial air gap to obtain a flat torque–angle characteristic and increase output torque. For comparison, prototypes of REMCs based on hybrid and radial air gaps were manufactured, and a special test rig was built. The torque–angle characteristics under different excitation currents and step responses were studied by magnetic circuit analysis, finite element simulation, and experimental research. The experimental results were consistent with the theoretical analysis. It was shown that REMCs based on a hybrid air gap can obtain a flat torque–angle characteristic with further optimizing of key structural parameters and also increase output torque. This regulation method provides a new approach for the design of proportional rotary electromechanical converters.

NEK2 is associated with drug resistance in multiple cancers. Our previous studies indicated that high NEK2 confers inferior survival in multiple myeloma (MM); thus, a better understanding of the mechanisms by which NEK2 induces drug resistance in MM is required. In this study, we discovered that NEK2 enhances MM cell autophagy, and a combination of autophagy inhibitor chloroquine (CQ) and chemotherapeutic bortezomib (BTZ) significantly prevents NEK2‐induced drug resistance in MM cells. Interestingly, NEK2 was found to bind and stabilize Beclin‐1 protein but did not affect its mRNA expression and phosphorylation. Moreover, autophagy enhanced by NEK2 was significantly prevented by knockdown of Beclin‐1 in MM cells, suggesting that Beclin‐1 mediates NEK2‐induced autophagy. Further studies demonstrated that Beclin‐1 ubiquitination is decreased through NEK2 interaction with USP7. Importantly, knockdown of Beclin‐1 sensitized NEK2‐overexpressing MM cells to BTZ in vitro and in vivo. In conclusion, we identify a novel mechanism whereby autophagy is activated by the complex of NEK2/USP7/Beclin‐1 in MM cells. Targeting the autophagy signaling pathway may provide a promising therapeutic strategy to overcome NEK2‐induced drug resistance in MM.

Consider the problem of clustering objects with temporally changing multivariate variables, for instance, in the classification of cities with several changing socioeconomic indices in geographical research. If the changing multivariate can be recorded simultaneously as a multivariate time series, in which the length of each subseries is equal and the subseries can be correlated, the problem is transformed into a multivariate time series clustering problem. The available methods consider the correlations between distinct time series but overlook the shape of each time series, which causes multivariate time series with similar correlations and opposite shapes to be clustered into the same class. To overcome this problem, this paper proposes a two-phase multivariate time series clustering algorithm that considers both correlation and shape. In Phase I, the discrete wavelet transform is applied to capture the wavelet variances and the correlation coefficients between each pair of variables to realize the initial clustering of multivariate time series, where time series with a similar correlation but opposite shape may be assigned to the same cluster. In Phase II, multivariate time series are clustered based on shape via the symbolic aggregate approximation (SAX) method. In this phase, time series with similar correlations but opposite morphologies are differentiated. The method is evaluated using multivariate time series of incoming and outgoing passenger volumes from Beijing IC card data; these volume data were collected between March 4, 2013 and March 17, 2013. Based on the silhouette coefficient, our approach outperforms two popular multivariate time series clustering methods: a wavelet-based method and the SAX method.