Search

Abstract CSF1R is a receptor tyrosine kinase responsible for the growth/survival/polarization of macrophages and overexpressed in some AML patients. We hypothesized that a novel multi-kinase inhibitor (TKi), narazaciclib (HX301/ON123300), with high potency against CSF1R (IC50 ~ 0.285 nM), would have anti-AML effects. We tested this by confirming HX301’s high potency against CSF1R (IC50 ~ 0.285 nM), as well as other kinases, e.g. FLT3 (IC50 of ~ 19.77 nM) and CDK6 (0.53 nM). An in vitro proliferation assay showed that narazaciclib has a high growth inhibitory effect in cell cultures where CSF1R or mutant FLT3-ITD variants that may be proliferation drivers, including primary macrophages (IC50 of 72.5 nM) and a subset of AML lines (IC50

In 2019 as a national key research program, the Development and Effectiveness Evaluation of an Innovative Health Management Model – Internet plus Medical Alliance-based Co-prevention and Co-management on Cardio-cerebrovascular Diseases was initiated in several regions including Shanghai and Guangzhou municipality and Xinjiang Uygur Autonomous Region. The ROCCIPI framework refers to a way of identifying and analyzing fundamental causes of problems in health policy through interrelated thinking patterns of seven elements: rule, opportunity, capacity, communication, interest, process and ideology. The framework could provide an evidence-based strategic approach to solve health policy problems. In this article, we try to identify and analyze the progress and problems in the implementation of the innovative health management at 21 comprehensive demonstration regions in China based on the ROCCIPI framework. Specific suggestions are also presented for promoting the comprehensive disease prevention and management project.

Study region: The Qinghai Lake basin on the Qinghai-Tibetan Plateau. Study focus: The abrupt rise of the water level of the Qinghai Lake after 2004 has garnered significant attention. Combining remote sensing and observed data, this study estimated the long-term variations in the water area and volume of the lake. In order to explore the factors contributing to the fluctuation in water level, the study developed annual and inter-annual water budgets for two time intervals: 1960 to 2004 and 2004 to 2020. Additionally, a hydrological model was implemented in the Buha River Basin, to gain further insight into the increased runoff and the impact of frozen soil. New hydrological insights for the region: The study found that the rise in lake level since 2004 was primarily driven by increased runoff, followed by increased precipitation, and decreased evaporation. Furthermore, water budgets were established for the freezing period (November to March of the next year) and the thawing period (April to October), respectively. The results revealed that the contribution of surface runoff during the thawing period was significantly larger at 68.20 % compared to 15.64 % during the freezing period, which is consistent to the conclusions of model simulation suggested. These findings suggest that the degradation of frozen soil in the Qinghai Lake Basin was a significant factor positively influencing surface runoff, with its impact intensifying after 2004.

Cymbaria daurica L. is a well-known traditional Mongolian medicine, which has been used to treat diabetes-related conditions characterized by persistent thirst and hunger, copious urination, and weight loss. We aimed to investigate the protective effects of C. daurica extracts and phenylethanoid glycosides including verbascoside and isoacteoside on INS-1 cells. We discovered phenylethanoid glycosides from n-butanol extract with large content through extraction and separation. We continue to study the protective effects of phenylethanoid glycosides including verbascoside and isoacteoside on INS-1 cells. INS-1 cells were treated with C. daurica, cell viability assay, RNA-seq technology, superoxide dismutase activity and malonaldehyde content, quantitative real time-PCR and Western blot analysis were used to study the protective effects of C. daurica. Cell viability assay resulted that n-butanol extract and verbascoside, isoacteoside showed protective effects of C. daurica. According to the RNA-seq technology to identify the differentially expressed genes in INS-1 cells, the pathway of gene enrich the protective effect of C. daurica on oxidative stress. SOD activity and the content of MDA indicated that C. daurica could enhance the antioxidant capacity of INS-1 cells. Further investigation indicated C. daurica alleviate oxidative stress by inhibiting INS-1 cell apoptosis. C. daurica may play an anti-diabetic role by inhibiting islet cell apoptosis.

Snow plays a crucial role in the global water and energy cycles, and its melting process can have a series of impacts on hydrological or climatic systems. Accurately capturing the timing of snowmelt runoff is essential for the utilization of snow resources and the early warning of snow-related disasters. A synthetic aperture radar (SAR) offers an effective means for capturing snowmelt runoff onset dates (RODs) over large areas, but its accuracy under different land cover types remains unclear. This study focuses on the Sierra Nevada Mountains and surrounding areas in the western United States. Using a total of 3117 Sentinel-1 images from 2017 to 2023, we extracted the annual ROD based on the Google Earth Engine (GEE) platform. The satellite extraction results were validated using the ROD derived from the snow water equivalent (SWE) data from 125 stations within the study area. The mean absolute errors (MAEs) for the four land cover types—tree cover, shrubland, grassland, and bare land—are 24, 18, 18, and 16 d, respectively. It indicates that vegetation significantly influences the accuracy of the ROD captured from Sentinel-1 data. Furthermore, we analyze the variation trends in the ROD from 2017 to 2023. The average ROD captured by the stations shows an advancing trend under different land cover types, while that derived from Sentinel-1 data only exhibits an advancing trend in bare land areas. It indicates that vegetation leads to a delayed trend in the ROD captured by using Sentinel-1 data, opposite to the results from the stations. Meanwhile, the variation trends of the average ROD captured by both methods are not significant (p > 0.05) due to the impact of the extreme snowfall in 2023. Finally, we analyze the influence of the SWE on RODs under different land cover types. A significant correlation (p < 0.05) is observed between the SWE and ROD captured from both stations and Sentinel-1 data. An increase in the SWE causes a delay in the ROD, with a greater delay rate in vegetated areas. These findings will provide vital reference for the accurate acquisition of the ROD and water resources management in the study area.

Abstract Sulfonyl and sulfonimidoyl fluorides are versatile substrates in organic synthesis and medicinal chemistry. However, they have been exclusively used as S(VI)+ electrophiles for defluorinative ligations. Converting sulfonyl and sulfonimidoyl fluorides to S(VI) radicals is challenging and underexplored due to the strong bond dissociation energy of SVI−F and high reduction potentials, but once achieved would enable dramatically expanded synthetic utility and downstream applications. In this report, we disclose a general platform to address this issue through cooperative organosuperbase activation and photoredox catalysis. Vinyl sulfones and sulfoximines are obtained with excellent E selectivity under mild conditions by coupling reactions with alkenes. The synthetic utility of this method in the preparation of functional polymers and dyes is also demonstrated.

Abstract Objectives To evaluate the outcomes of bronchial artery embolization (BAE) for the treatment of massive hemoptysis in patients with pulmonary tuberculosis and identify risk factors that influence recurrence. Methods A total of 81 patients with massive hemoptysis who underwent BAE between January 2014 and December 2017 were retrospectively reviewed. All of the patients had either a history of pulmonary tuberculosis or a current diagnosis of pulmonary tuberculosis. Follow‐up ranged from 18 to 66 months. Results Hemoptysis was stopped or markedly decreased, with subsequent clinical improvement in 73 patients, while 11 patients experienced recurrence during the follow‐up period. Systemic‐pulmonary shunts and clinical failure showed a statistically significant correlation with the recurrence rate. The cumulative non‐recurrence rate was 95.3% for 3 months and 81.9% for more than 24 months. Complications were common (12.5%), but self‐limiting. Conclusions BAE is a safe and effective treatment option for the control of massive hemoptysis in pulmonary tuberculosis patients. Systemic‐pulmonary shunts and clinical failure are the risk factors for recurrence.

AIM: To compare the efficacy of 25-gauge(25G)vitrectomy combined with intraocular lens transciliary sulcus scleral suture fixation and sutureless scleral tunnel interlamellar fixation in the treatment of complete lens dislocation.METHODS: Retrospective case-control study. A total of 40 patients(40 eyes)diagnosed with complete lens luxation in the vitreous cavity in our hospital from May 2015 to September 2021 were selected, among which 21 eyes(suture group)underwent 25G vitrectomy combined with intraocular lens fixation via ciliary sulci scleral suture, and 19 eyes(sutureless group)underwent 25G vitrectomy combined with interlamellar scleral tunnel fixation of intraocular lens. The patients in both groups were followed up until 3mo after surgery to observe the operative time, best corrected visual acuity(BCVA), corneal endothelial cell count(CECC), central corneal thickness(CCT)and postoperative complications.RESULTS: The operation time was significantly shorter in the sutureless group than in the suture group(31.79±6.01min vs. 45.38±8.04min, P0.05).CONCLUSION: 25G vitrectomy combined with intraocular lens sutureless scleral tunnel interlamellar fixation in the treatment of complete lens luxation has shorter operation time, faster postoperative visual acuity improvement and fewer postoperative complications.

Nitrogen oxides (NOx) have long been the focus of air pollution control. Examining the spatial and driving characteristics of NOx emissions at the urban scale and from the supply-chain perspective is critical. Using the inventory method and the environmentally extended input–output analysis, energy-related NOx emissions of 90 cities in eastern China were calculated, and the spatial patterns and driving sectors of urban emissions were analyzed from both production- and consumption-based perspectives. The results show that the production-based emissions of eastern Chinese cities are substantially affected by their industrial structure and are higher in the north and lower in the south. The cities with higher consumption-based emissions are mainly those with large populations and relatively developed economies. Production-based NOx emissions per unit gross domestic product (GDP) are higher in the north and lower in the south, and emissions per unit area are generally higher in coastal areas and lower in inland areas. The emission intensities of 5 selected major urban agglomerations differ, due to the influences of industrial structure and population density. The consumption-based NOx emissions per capita are mainly affected by urban affluence and consumption patterns. The sectors that contribute most to the production-based emissions per unit GDP are mainly “mining and processing”, “petroleum, chemical and non-metallic mineral products”, “metal products”, “production and supply of electricity, natural gas and water” and “transportation, storage, and postal services”, while the sector that contributes most to the consumption-based emissions per capita is the construction industry. Emission reduction strategies are proposed for both consumption-oriented and production-oriented cities.

As a newly emerging organ transplantation technique, islet transplantation has shown the advantages of minimal trauma and high safety since it was first carried out. The proposal of the Edmonton protocol, which has been widely applied, was a breakthrough in this method. However, direct contact between islets and portal vein blood will cause a robust innate immune response leading to massive apoptosis of the graft, and macrophages play an essential role in the innate immune response. Therefore, therapeutic strategies targeting macrophages in the innate immune response have become a popular research topic in recent years. This paper will summarize and analyze recent research on strategies for regulating innate immunity, primarily focusing on macrophages, in the field of islet transplantation, including drug therapy, optimization of islet preparation process, islet engineering and Mesenchymal stem cells cotransplantation. We also expounded the heterogeneity, plasticity and activation mechanism of macrophages in islet transplantation, providing a theoretical basis for further research.

Vegetable production in Subtropical China is distinguished by excessive nitrogen (N) fertilization, frequent irrigation, and multiple crop rotations in a single year. The aforementioned variables are closely related to soil nitrous oxide (N2O) and methane (CH4) emissions. Hence, we conducted a field trial to measure N2O and CH4 emissions using static chamber–gas chromatograph. Four treatments were used: control (CK) with no fertilizer, 100% chemical N fertilization (CN), the conventional 30% chicken manure N plus 70%CN (CMN + CN), and 30% chicken manure biochar N plus 70%CN (CMBN + CN). The annual cumulative N2O emissions reached 12.4, 63.5, 111.8, and 44.1 kg N2O-N ha−1 for the CK, CN, CMN + CN, and CMBN + CN treatments, respectively. Compared to the CN and CMN + CN treatments, the CMBN + CN treatment reduced N2O emissions by 35.9%–65.7%, while it simultaneously increased the total vegetable yield by 16.1% compared to the CN treatment. Seven seasons mean N2O emission factors are 1.3% for CN, 3.8% for CMN + CN, and 0.9% for CMBN + CN. The CH4 emission was negligible, ranging from 0.07 kg CH4-C ha−1 for the CK treatment to 0.8 kg CH4-C ha−1 for the CN treatment. N2O emissions peaked under the conditions of an interior chamber temperature of around 31.9 °C and the water-filled pore space (WFPS) of the soil being approximately 60%. Future climate change will intensify, triggering higher N2O emissions from subtropical vegetable fields. CMB can be one of the best substitutes for direct chicken manure application as a soil supplement because it has a beneficial effect on improving vegetable yield and reducing N2O emissions in Subtropical China.

IntroductionNitrogen (N) plays a significant role in food systems, but only a fraction of N is effectively utilized and the rest is lost to the environment and negatively affects the ecosystem. So far, there has been relatively little research on N flow associated with the food production and consumption of production-oriented cities in developing countries.MethodsIn this study, we present a comprehensive analysis of N flow in the food production and consumption system of Changchun in China between 1991 and 2014, and define three types of nitrogen use efficiency (NUE) and compare them.Results(1) Total new N input into the food system in Changchun increased by 63.75% (240.8 to 394.3 Gg N yr−1) during the study period, mainly attributable to the high volume of food exports(total output from 47.63 to 72.51 Gg N yr−1). (2) Changchun typically exhibited lower apparent NUE and virtual NUE of the food system, while its actual NUE was typically higher, compared to food-importing cities. (3) The consumption of crop food witnessed a decrease from 24.2 Gg N in 1991 to 18.7 Gg N in 2014, whereas the consumption of animal food showed an upward trend from 2.5 Gg N to 7.7 Gg N. Both urban and rural residents consumed less grain food but more fruits and meat. (4) The total N loss has increased from 131.3 Gg N in 1991 to 266.6 Gg N in 2014. The crop production caused 58.1% of the total N loss in 2014, and the atmospheric loss accounted for 40.2% of the total.ConclusionThe study has revealed the distinctive features, fluctuations, and underlying drivers of N flow in the food-exporting city, setting it apart from food-importing city. These findings provide a valuable point of reference for the implementation of customized and diversified nitrogen management strategies in these specific urban areas.

Objective To investigate the incidence and risk factors of postoperative respiratory complications (PRCs) in children with early‐onset scoliosis (EOS) following posterior spine deformity surgery (PSDS) based on growth‐friendly techniques, so as to help improve the safety of surgery. Methods A retrospective study of children with EOS admitted for PSDS based on growth‐friendly techniques from October 2013 to October 2018 was reviewed at a single center. There were 73 children (30 boys, 43 girls) who fulfilled the criteria in this research. The mean age of the patients was 7 ± 6.2 years. Patients were divided into the groups with and without PRCs. Variables that might affect the PRCs during the perioperative period, including general factors, radiographic factors, laboratory factors and surgical factors, were analyzed using univariate analysis to evaluate the potential risk factors. The variables that were significantly different were further analyzed by binary logistic regression analysis to identify the independent factors of PRCs. Results All the 73 children included 42 idiopathic scoliosis (57.5%), 12 congenital scoliosis (16.4%), 10 syndromic scoliosis (13.7%) and nine neuromuscular scoliosis (12.3%). PRCs were detected in 16 children (21.9%) with nine different PRCs. The total frequency of detected PRCs was 54, including pleural effusion (25.9%), postoperative pneumonia (20.4%), hypoxemia (18.5%), atelectasis (14.8%), prolonged intubation with mechanical positive pressure ventilatory support (PIMPPVS) (7.4%), bronchospasm (3.7%), reintubation (3.7%), delayed extubation (3.7%) and pneumothorax (1.9%). Results of univariate testing demonstrated that the following six variables were statistically different (P

Nephrolithiasis is a complicated disease affected by various environmental and genetic factors. Crystal-cell adhesion is a critical initiation process during kidney stone formation. However, genes regulated by environmental and genetic factors in this process remain unclear. In the present study, we integrated the gene expression profile data and the whole-exome sequencing data of patients with calcium stones, and found that ATP1A1 might be a key susceptibility gene involved in calcium stone formation. The study showed that the T-allele of rs11540947 in the 5′-untranslated region of ATP1A1 was associated with a higher risk of nephrolithiasis and lower activity of a promoter of ATP1A1. Calcium oxalate crystal deposition decreased ATP1A1 expression in vitro and in vivo and was accompanied by the activation of the ATP1A1/Src/ROS/p38/JNK/NF-κB signaling pathway. However, the overexpression of ATP1A1 or treatment with pNaKtide, a specific inhibitor of the ATP1A1/Src complex, inhibited the ATP1A1/Src signal system and alleviated oxidative stress, inflammatory responses, apoptosis, crystal-cell adhesion, and stone formation. Moreover, the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine reversed ATP1A1 down-regulation induced by crystal deposition. In conclusion, this is the first study to show that ATP1A1, a gene modulated by environmental factors and genetic variations, plays an important role in renal crystal formation, suggesting that ATP1A1 may be a potential therapeutic target for treating calcium stones.

Introduction and Objectives: Tenofovir Alafenamide (TAF) is a preferred treatment in the most recent EASL and AASLD HBV Guidelines, especially in patients with risk factors for TDF-associated renal and bone effects. In 2 identically-designed double-blind (DB), randomized (2:1), Phase 3 studies (HBeAg-negative patients [N = 425] and HBeAg-positive patients [N = 873]), TAF demonstrated antiviral efficacy non-inferior to that of TDF with superior renal and bone safety. After completing three years of DB treatment, all patients were eligible to receive open-label (OL) TAF through Year eight. Here we present study results for Year five. Materials and Methods: Efficacy was assessed by serial virologic, biochemical, and serologic assessments, while safety data included changes in renal function and changes in hip and spine bone mineral density. Resistance testing and phenotyping were performed annually through Year 5. Results: Of 1298 randomized and treated patients, 1157 (89%; 775 TAF; 382 TDF) entered OL, at year 5, 999 (77%; 675 TAF, 136 TDFTAF OL 3y, 188 TDF-TAF OL 2y) patients remained on treatment. High rates of virologic control were achieved and maintained in patients receiving TAF throughout and for TDF patients who switched to TAF at Weeks 96 or 144. Rates of ALT normalization and serologic responses were also comparable among groups. Eight patients are undergoing phenotypic testing to assess resistance. Adverse events (AEs) leading to discontinuation were low and similar among groups. Renal and bone outcomes were improved following the switch to OL TAF from TDF. Conclusions: After five years of treatment, virologic suppression rates remained high, and TAF was safe and well tolerated, with improved renal and bone safety in patients switching from TDF.

The main objective of the black-start in a terminal distribution network is restoring the regional distribution network in a blackout. Aiming at the problem that there are multiple optimization objectives in the process of black start, a black start model with comprehensive consideration is established, considering the minimum switching operation cost, maximum recovery efficiency and priority start of important load. Then, the constraints of voltage and frequency stability of the distribution network in black-start are put forward. Aiming at the problem that heuristic algorithm such as binary particle swarm optimization cannot get the global optimal solution, a black-start method based on pruning algorithm is proposed, which has higher efficiency than traditional algorithm as well as the ability to search the global optimal method. Finally, the efficiency of the above method is verified in the terminal distribution network of a coastal mountain county.

Abstract Background Pubic symphysis diastasis (PSD) hinders the connection between bilateral ischia and pubic bones, resulting in instability of the anterior pelvic ring. PSD exceeding 25 mm is considered disruptions of the symphyseal and unilateral/bilateral anterior sacroiliac ligaments and require surgical intervention. The correct choice of fixation devices is of great significance to treat PSD. This study aimed to evaluate the construct stability and implant performance of seven fixation methods to treat PSD using finite element analysis. Methods The intact skeleton-ligament pelvic models were set as the control group. PSD models were simulated by removing relevant ligaments. To enhance the stability of the posterior pelvic ring, a cannulated screw was applied in the PSD models. Next, seven anterior fixation devices were installed on the PSD models according to standard surgical procedures, including single plates (single-Plate group), single plates with trans-symphyseal cross-screws (single-crsPlate group), dual plates (dual-Plate group), single cannulated screws, dual crossed cannulated screws (dual-canScrew group), subcutaneous plates (sub-Plate group), and subcutaneous pedicle screw-rod devices (sub-PedRod group). Compression and torsion were applied to all models. The construct stiffness, symphyseal relative micromotions, and von Mises stress performance were recorded and analyzed. Results The construct stiffness decreased dramatically under PSD conditions. The dual-canScrew (154.3 ± 9.3 N/mm), sub-Plate (147.1 ± 10.2 N/mm), and sub-PedRod (133.8 ± 8.0 N/mm) groups showed better ability to restore intact stability than the other groups (p

Mycoplasma gallisepticum (MG) is recognized as a principal causative agent of avian chronic respiratory disease, inflicting substantial economic losses upon the poultry industry. However, the extensive use of conventional antibiotics has resulted in the emergence of drug resistance and various challenges in their clinical application. Consequently, there is an urgent need to identify effective therapeutic agents for the prevention and treatment of mycoplasma-induced respiratory disease in avian species. AMP-activated protein kinase (AMPK) holds significant importance as a regulator of cellular energy metabolism and possesses the capacity to exert an anti-inflammatory effect by virtue of its downstream protein, SIRT1. This pathway has shown promise in counteracting the inflammatory responses triggered by pathogenic infections, thus providing a novel target for studying infectious inflammation. Quercetin possesses anti-inflammatory activity and has garnered attention as a potential alternative to antibiotics. However, there exists a gap in knowledge concerning the impact of this activation on MG-induced inflammatory damage. To address this knowledge gap, we employed AlphaFold2 prediction, molecular docking, and kinetic simulation methods to perform a systematic analysis. As expected, we found that both quercetin and the AMPK activator AICAR activate the chicken AMPKγ1 subunit in a similar manner, which was further validated at the cellular level. Our project aims to unravel the underlying mechanisms of quercetin’s action as an agonist of AMPK against the inflammatory damage induced by MG infection. Accordingly, we evaluated the effects of quercetin on the prevention and treatment of air sac injury, lung morphology, immunohistochemistry, AMPK/SIRT1/NF-κB pathway activity, and inflammatory factors in MG-infected chickens. The results confirmed that quercetin effectively inhibits the secretion of pro-inflammatory cytokines such as IL-1β, TNF-α, and IL-6, leading to improved respiratory inflammation injury. Furthermore, quercetin was shown to enhance the levels of phosphorylated AMPK and SIRT1 while reducing the levels of phosphorylated P65 and pro-inflammatory factors. In conclusion, our study identifies the AMPK cascade signaling pathway as a novel cellular mediator responsible for quercetin’s ability to counter MG-induced inflammatory damage. This finding highlights the potential significance of this pathway as an important target for anti-inflammatory drug research in the context of avian respiratory diseases.

Improving yield in potato production with minimal environmental impact is of great significance for China’s potato staple food policy. Previous research has been limited by the absence of regional-scale parameters to evaluate the environmental costs of regional potato production. To address this gap, we utilized the input–output analysis method to offer a thorough estimation of nitrogen (N), phosphorus (P), and potassium (K) inputs and outputs in the potato production stage at a regional scale, leveraging a meta-analysis dataset from plenty of the literature. On this basis, we calculated the virtual N, P, and K factors (VNFs, VPFs, and VKFs) for different potato production regions, under both conventional and optimal management practices. China’s potato production suffered from excessive N and P inputs, while K inputs remained insufficient. Significant spatial heterogeneities were observed for the VNFs, VPFs, and VKFs across different potato production regions. Northeast China and northwest China emerged as the most suitable potato cultivation regions because they demonstrated high potato yields with relatively low inputs and, consequently, lower VNFs and VPFs. Southwest China was the most vital region where targeted efforts could lead to reducing VNF and VPF, thus significantly mitigating environmental N and P losses. In addition to reducing fertilizer inputs, site-specific and whole optimization measures are proposed to lower the environmental costs and promote the sustainable development of potato production.

Abstract The charge transport and accumulation in oil–paper can cause the insulation degradation. So far, the most widely used model to simulate space charge transport and accumulation is the bipolar charge transport (BCT) model, which can well simulate the space charge dynamics. However, there are two shortcomings in the algorithms for solving the BCT model. One is that there is almost no use of vectorisation technology, which may increase the complexity of the algorithm, the other is the usage of fixed step size which might bring extra computation cost. In view of this, an adaptive time‐stepping transient upstream finite element method (FEM) is developed to solve the BCT model considering trapping/detrapping, as well as the recombination phenomenon under DC condition in this article. Then, a vectorisation technology is used in the method to optimise the algorithm. Moreover, the adaptive time‐stepping method is introduced in simulation to reduce computation time and calculation amount. Simulation results are obtained by programing and later presented, which are basically consistent with the corresponding experimental results. Therefore, the proposed method is expected to promote the optimization design of the oil–paper insulation system.

Abstract Background Circulating tumor DNA (ctDNA) has potential as a specific, noninvasive, and cost‐effective new biomarker for patients with lung cancer. This study aimed to determine whether plasma ctDNA can be used to predict treatment outcomes in patients with lung cancer. Methods Pre‐ and in‐treatment blood samples were collected from 14 patients with lung cancer receiving chemotherapy. Based on next‐generation sequencing technology, we constructed a unique molecular identifier (UMI) library and performed targeted deep sequencing of 72 genes (15 000×). We used dVAF to evaluate the change level and trend of variant allele frequency (VAF). Results We identified MUC16, KMT2D, AMER1, and NTRK1 as the most‐frequently mutated genes in ctDNA associated with lung cancer. Furthermore, we showed that the change trend of dVAF in patients with lung cancer undergoing chemotherapy was closely related to the changes in both tumor volume and tumor biomarkers, including CEA, CA125, NSE, and CK (Cytokeratin). Moreover, the ctDNA analysis revealed disease progression of SCLC patients earlier than did computed tomography. Conclusions The dynamic detection of plasma ctDNA VAF has the potential value as a biomarker for evaluating the efficacy of chemotherapy in patients with SCLC and advanced NSCLC, and may predict the progression of lung cancer patients earlier than radiography.

The continuous improvement of the Chinese people’s lifestyle and consumption level and the promotion of healthful and reasonable diets have created a greater demand for fruit production. There is an urgent to determine how to meet the increasing demand for fruit, with lower inputs and environmental costs, because the Chinese fruit production has excessive agricultural input and relatively high environmental burden of greenhouse gas (GHG) emissions. This study conducted a meta-analysis of the experimental results of 307 conventional management measures and 333 optimized management measures. We found that by taking appropriate optimization measures such as N reduction, coupling of water and fertilizer and increasing organic carbon, has not only the fruit yield increased by 16.1% (5 Mg ha−1 year−1) but also the GHG emissions of the entire orchard system have also been drastically reduced by 65.4%. Net GHG balance has decreased from 11.3 ± 0.3 to 3.9 ± 0.3 Mg of CO2 equivalent (CO2e) ha−1 year−1, and GHG intensity per unit product has decreased from 3.6 ± 0.1 to 1.1 ± 0.1 kg of CO2e kg−1. The main sources of total GHG emissions are from upstream production and transportation, due to N fertilizer application, mechanical irrigation energy, and N-fertilizer-induced soil N2O emissions. Our results highlight that the Chinese fruit production system has a large room to reduce GHG emissions by applying the mentioned optimization measures in above, and our findings will provide some guidance for agricultural carbon peak.

Abstract Background Lung cancer has the highest mortality rate among malignant tumors, with non‐small cell lung cancer (NSCLC) being the most common type. As the main component of the human microflora, the intestinal flora interacts with the human body to affect immunity, metabolism, and the formation of diseases. Methods Forty‐five patients with advanced NSCLC who received platinum‐containing dual‐drug chemotherapy were enrolled in a prospective exploratory cohort study. The intestinal flora was dynamically collected at baseline and after two chemotherapy cycles. Next‐generation sequencing and metagenomics were then used to analyze the species and function of the intestinal flora at all levels. Results Significant differences in the intestinal flora of patients with NSCLC were found according to sex and age. At the family level, the abundances of Streptococcaceae, Lactobacillaceae, and Leuconostocaceae after platinum‐containing dual‐drug chemotherapy were significantly higher compared to those before chemotherapy. At the family level, patients with chemotherapy‐induced gastrointestinal reactions had a significantly higher abundance of Leuconostocaceae than those without gastrointestinal responses. Meanwhile, patients with gastrointestinal reactions had higher metabolism, human diseases, cellular processes, and environmental information processing than those who did not. At the genus level, responders had higher abundances of Bacteroides compared to nonresponders. Moreover, nonresponders had higher levels of the six major metabolic pathways compared to responders. Conclusions The intestinal flora of Chinese patients with advanced NSCLC differed according to sex and age. Moreover, significant differences in the intestinal flora were noted after chemotherapy, which could be associated with chemotherapy‐induced gastrointestinal reactions and the efficacy of chemotherapy.

Presently, the grid-connected scale from photovoltaic (PV) system is getting higher among renewable power generations. However, the PV output power can be affected by different meteorological conditions due to PV randomness and volatility. Accordingly, reasonable generation plans can be well arranged using accurate PV power prediction among various types of energy sources, thus reducing the effect of PV system on the grid. To resolve this problem, a PV output power prediction model, namely IMWOASVM, is proposed based on the combination of improved whale optimization algorithm (IMWOA) and support vector machine (SVM). The IMWOA is used to optimize the kernel function parameter and penalty coefficient in SVM. The optimal parameter and coefficient values can then be input to SVM for enhancing the PV prediction. The performance results verify that the coefficient of determination using the IMWOA model can reach beyond 99% in both sunny and cloudy days. Simultaneously, the mean absolute errors on sunny and cloudy days are 0.0251 and 0.0705, respectively. The root mean square errors in sunny and cloudy days are 2.17% and 1.03%, respectively. The results confirm that the proposed model effectively increases the accuracy of the PV output power prediction and is superior to existing methods.

Given that the traditional adsorption material is difficult to be recycled, the efficient and easy-to-recyclable magnetic biomass activated carbon was prepared by impregnation-calcination process with coconut shell as raw material. The obtained materials were characterized by XRD, SEM and specific surface area analysis etc. The effect of the mass ratio of metal salt and coconut shell on the adsorption performance of methylene blue was studied. The results show that when the mass ratio of metal salt to coconut shell is 1∶2, the magnetic activated carbon has mesoporous structure with a larger specific surface area and a larger adsorption capacity for methylene blue. The adsorption efficiency can still reach more than 90% after repeatedly used for 7 times. The material can be separated from the solution by the external magnetic field, and it is easy to be recycled.

Background and Objective: This study aims to find the key immune genes and mechanisms of low bone mineral density (LBMD) in ankylosing spondylitis (AS) patients.Methods: AS and LBMD datasets were downloaded from the GEO database, and differential expression gene analysis was performed to obtain DEGs. Immune-related genes (IRGs) were obtained from ImmPort. Overlapping DEGs and IRGs got I-DEGs. Pearson coefficients were used to calculate DEGs and IRGs correlations in the AS and LBMD datasets. Louvain community discovery was used to cluster the co-expression network to get gene modules. The module most related to the immune module was defined as the key module. Metascape was used for enrichment analysis of key modules. Further, I-DEGs with the same trend in AS and LBMD were considered key I-DEGs. Multiple machine learning methods were used to construct diagnostic models based on key I-DEGs. IID database was used to find the context of I-DEGs, especially in the skeletal system. Gene–biological process and gene-pathway networks were constructed based on key I-DEGs. In addition, immune infiltration was analyzed on the AS dataset using the CIBERSORT algorithm.Results: A total of 19 genes were identified I-DEGs, of which IFNAR1, PIK3CG, PTGER2, TNF, and CCL3 were considered the key I-DEGs. These key I-DEGs had a good relationship with the hub genes of key modules. Multiple machine learning showed that key I-DEGs, as a signature, had an excellent diagnostic performance in both AS and LBMD, and the SVM model had the highest AUC value. Key I-DEGs were closely linked through bridge genes, especially in the skeletal system. Pathway analysis showed that PIK3CG, IFNAR1, CCL3, and TNF participated in NETs formation through pathways such as the MAPK signaling pathway. Immune infiltration analysis showed neutrophils had the most significant differences between case and control groups and a good correlation with key I-DEG.Conclusion: The key I-DEGs, TNF, CCL3, PIK3CG, PTGER2, and IFNAR1, can be utilized as biomarkers to determine the risk of LBMD in AS patients. They may affect neutrophil infiltration and NETs formation to influence the bone remodeling process in AS.

BackgroundBone metastases (BM) from malignant tumors could disrupt the balance between osteoclasts and osteoblasts and affect bone homeostasis. Malignant breast cancer (BC) is rare in male patients, and co-occurrence of BM is even rarer. Given its low incidence, there is limited research evaluating risk and prognosis. Despite the widespread application of nomograms to predict uncommon malignancies, no studies have constructed predictive models focusing on the diagnosis and prognosis of male breast cancer with bone metastases (MBCBM).MethodsThis study selected all male breast cancer patients (MBC) between 2010 and 2019 in the Surveillance, Epidemiology, and End Results (SEER) database. We used simple and multivariate Logistic regression analyses to identify independent risk factors for BM in MBC patients. Then simple and multivariate Cox regression analyses were employed to determine the independent prognostic factors for overall survival (OS) and cancer-specific survival (CSS) in MBCBM patients. We established and validated three new nomograms based on these independent factors.ResultA total of 4187 MBC patients were included, with 191 (4.56%) having bone metastases at the time of diagnosis. The independent risk factors of BM in MBC patients included age, tumor size, marital status, T stage, and N stage. In MBCBM patients, independent prognostic factors for OS and CSS were both age, T stage, ER status, PR status, and surgery. The concordance index (C-index), the area under the curve (AUC) of the receiver operating characteristic curve (ROC), the calibration curve, and the decision curve analysis (DCA) confirmed that these three nomograms could accurately predict the diagnosis and prognosis of MBCBM patients with excellent discrimination and clinical utility superior to the TNM staging system. We then established two prognostic-based risk stratification systems and three visualized dynamic nomograms that could be applied in clinical practice.ConclusionIn conclusion, this study aimed to establish and validate an accurate novel nomogram to objectively predict the diagnosis and prognosis of MBCBM patients. On this basis, prognostic-based risk stratification systems and visualized dynamic nomograms were constructed to facilitate doctors and patients to quantify individual BM risk probability and survival probability to assist in personalized risk assessment and clinical decision-making.

Background: 5-Aza-2′-deoxycytidine (5-Aza-CdR) is a demethylating agent that has various biological effects related to DNA methylation. DNA methylation plays important roles in learning and memory. We have reported that 5-Aza-CdR improved the performance of mice in the water maze and step-down tests. Some behaviours have been well recognized to be mediated by neurogenesis in the hippocampus. The Notch signalling pathway plays a key role in adult hippocampal neurogenesis. In this study, we examined whether 5-Aza-CdR (DNA methyltransferase inhibitor) affects neurogenesis and Notch1 expression. Methods: The learning and memory behaviour of mice was evaluated by a conditioned avoidance learning 24 h after 5-Aza-CdR treatment. The mRNA and protein expression levels of Notch1 and HES1 were measured by real-time PCR and Western blotting. The 5-bromo-2′-deoxyuridine (BrdU)-positive cells and the expression of Notch1 in the hippocampal DG were observed through laser confocal microscopy. To further clarify whether 5-Aza-CdR affects behaviour through neurogenesis, the expression level of Notch1, cell viability and cell cycle were analysed using the HT22 cell line. Results: The behaviour in conditioned avoidance learning was improved, while neurogenesis and the Notch1 pathway were increased in the hippocampus of mice that were injected with 5-Aza-CdR. In vitro experiments showed that 5-Aza-CdR increased the expression of the Notch1 pathway and upregulated S-phase in the cell cycle and cell viability. Conclusions: Our results suggest that the effect of 5-Aza-CdR on behaviour may be related to an increase in neurogenesis with upregulation of the Notch1 pathway in the hippocampus.

The key to image depth estimation is to accurately find corresponding points between the left and right images. A binocular camera can directly estimate the depth of the left and right image range, which completely avoids the requirement of target recognition accuracy in a monocular depth estimation. However, it is difficult for binocular stereo matching to accurately segment objects and find matching points in the ill-posed areas (weak texture, deformation, object edge, etc.) of the left and right images. In the semantic segmentation task, atrous convolution is used to solve the contradiction between the receptive field and the segmentation accuracy. This research focused on balancing the impact of holes on the segmentation task. In addition, in order to solve the issue where matching points in the ill-posed regions of left and right images are affected by noise, we used a 3D convolution to aggregate the cost volume to obtain better accuracy. However, the 3D convolution method is prone to mismatching in ill-posed areas of the image. To tackle the problems above, we proposed a dense grouping atrous convolution spatial pyramid pooling (DenseGASPP) method. The feature of the DenseGASPP method is that there is a dense connection between the group atrous convolutions to fully integrate feature information. This method can expand the receptive field and balance the effect of holes on the segmentation task. Moreover, we introduced multi-scale cost aggregation into our method, which uses the repeated exchange of information between cost volumes of different scales to obtain rich contextual information and reduce the mismatching of the network. To evaluate the performance of our method, we conducted several groups of typical algorithm experiments on the scene flow and KITTI 2015 standard datasets. From the results, our model achieves better performance, reducing the EPE from 1.09 to 0.67, which improves the mismatching ability of binocular depth estimation algorithm in ill-posed regions.

Abstract Circular RNAs (circRNAs) have been reported to play crucial roles in the progression of various cancers, including colorectal cancer (CRC). SP1 (Sp1 transcription factor) is a well-recognized oncogene in CRC and is deemed to trigger the Wnt/β-catenin pathway. The present study was designed to investigate the role of circRNAs which shared the same pre-mRNA with SP1 in CRC cells. We identified that hsa_circ_0026628 (circ_0026628), a circular RNA that originated from SP1 pre-mRNA, was upregulated in CRC cells. Sanger sequencing and agarose gel electrophoresis verified the circular characteristic of circ_0026628. Functional assays including CCK-8, colony formation, transwell, immunofluorescence staining, and sphere formation assay revealed the function of circ_0026628. RNA pull-down and mass spectrometry disclosed the proteins interacting with circ_0026628. Mechanistic assays including RIP, RNA pull-down, CoIP, ChIP, and luciferase reporter assays demonstrated the interplays between molecules. The results depicted that circ_0026628 functioned as a contributor to CRC cell proliferation, migration, EMT, and stemness. Mechanistically, circ_0026628 served as the endogenous sponge of miR-346 and FUS to elevate SP1 expression at the post-transcriptional level, thus strengthening the interaction between SP1 and β-catenin to activate the Wnt/β-catenin pathway. In turn, the downstream gene of Wnt/β-catenin signaling, SOX2 (SRY-box transcription factor 2), transcriptionally activated SP1 and therefore boosted circ_0026628 level. On the whole, SOX2-induced circ_0026628 sponged miR-346 and recruited FUS protein to augment SP1, triggering the downstream Wnt/β-catenin pathway to facilitate CRC progression.

BackgroundPrevious prediction models of osteosarcoma have not focused on survival in patients undergoing surgery, nor have they distinguished and compared prognostic differences among amputation, radical and local resection. This study aimed to establish and validate the first reliable prognostic nomogram to accurately predict overall survival (OS) after surgical resection in patients with osteosarcoma. On this basis, we constructed a risk stratification system and a web-based nomogram.MethodsWe enrolled all patients with primary osteosarcoma who underwent surgery between 2004 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database. In patients with primary osteosarcoma after surgical resection, univariate and multivariate cox proportional hazards regression analyses were utilized to identify independent prognostic factors and construct a novel nomogram for the 1-, 3-, and 5-year OS. Then the nomogram's predictive performance and clinical utility were evaluated by the concordance index (C-index), receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA).ResultThis study recruited 1,396 patients in all, with 837 serving as the training set (60%) and 559 as the validation set (40%). After COX regression analysis, we identified seven independent prognostic factors to develop the nomogram, including age, primary site, histological type, disease stage, AJCC stage, tumor size, and surgical method. The C-index indicated that this nomogram is considerably more accurate than the AJCC stage in predicting OS [Training set (HR: 0.741, 95% CI: 0.726–0.755) vs. (HR: 0.632, 95% CI: 0.619–0.645); Validation set (HR: 0.735, 95% CI: 0.718–0.753) vs. (HR: 0.635, 95% CI: 0.619–0.652)]. Moreover, the area under ROC curves, the calibration curves, and DCA demonstrated that this nomogram was significantly superior to the AJCC stage, with better predictive performance and more net clinical benefits.ConclusionThis study highlighted that radical surgery was the first choice for patients with primary osteosarcoma since it provided the best survival prognosis. We have established and validated a novel nomogram that could objectively predict the overall survival of patients with primary osteosarcoma after surgical resection. Furthermore, a risk stratification system and a web-based nomogram could be applied in clinical practice to assist in therapeutic decision-making.

Due to the lack of appropriate experimental methods for imaging the evolution of the microstructure of materials at the growth conditions, our understanding of the physical behavior of crystal growth and defect formation during the vapor deposition growth of SiC crystals is still rather limited. In the present work, the vapor deposition growth of SiC crystal on a 4H-SiC substrate has been investigated by the molecular dynamics (MD) computer simulation method. Three different lattice planes of 4H-SiC ((0001), (112-0) and (1-100)) were selected as the surface of the substrate, and three different temperatures for substrate (2200 K, 2300 K and 2400 K) were used in growth simulations. The characteristics of the formation of different polytypes of SiC and dislocations in the grown crystals were examined. The results show that the SiC crystals were grown by a subsurface nucleation and growth mode in the vapor deposition process. For substrates with (0001) plane as the surface, the 3C-SiC single crystal was obtained in the deposited thin film. For substrates with (112-0) or (1-100) plane as the surface, the 4H-SiC single crystal was obtained instead. The temperature of the substrate was found to have a significant effect on the dislocation density generated in the grown crystals. The mechanism for the formation of Frank partial dislocations during the growth of SiC crystals has been analyzed, for which the importance of the diffusivity of atoms on the surface layer in growth has been highlighted, and it gives a good explanation of the temperature effect on dislocation formation in the grown crystals. These results can be helpful for experimental vapor deposition growth of SiC single crystals and epitaxial layers of high quality.

Improving the digital economy and environmental governance efficiency are important methods for current high-quality economic development. Based on the panel data of 11 cities in Zhejiang, on the eastern coast of China, fine particulate matter smaller than a 2.5 μm (PM2.5) environmental efficiency (PMEE) was measured by the undesirable output Slack-Based Measure-Data Envelopment Analysis (SBM-DEA) model. The fixed effect regression model, the divergences in the difference model and other empirical methods were obtained to test the driving mechanism of social-economic factors on the PMEE. The results showed that: (1) the concentration of PM2.5 was continually decreasing, and environmental quality experienced a continuous improvement in Zhejiang province in the observation period, although cities such as Hangzhou, Jiaxing and Shaoxing have relatively severe PM2.5 pollution. (2) The total average value of PMEE in Zhejiang was 0.6430 over the observation period, while there was still a lot of room for improvement when compared to the production frontier. Additionally, PMEE in each city showed a fluctuating growth trend. Cities with a higher PMEE were mainly Zhoushan, Hangzhou and Ningbo. (3) The level of the digital economy had a positive role in promoting the PMEE, which was statistically significant. The level of pollution control and technological innovation also had a significantly positive effect. However, the ratio of the industrial output value to the gross domestic product (GDP) presented a negative effect on the PMEE. In the future, it is suggested that the development of the urban digital economy should be accelerated in an all-around way to improve the efficiency of government pollution control and to improve the technical efficiency of PM2.5 via innovative technological progress.

Hyperlipidemia is a risk factor for the development of fatty liver and cardiovascular diseases such as atherosclerosis and coronary heart disease, and hence, cholesterol-lowering drugs are considered important and effective in preventing cardiovascular diseases. Thus, researchers in the field of new drug development are endeavoring to identify new types of cholesterol-lowering drugs. 3β-hydroxysterol-Δ(24)-reductase (DHCR24) catalyzes the conversion of desmosterol to cholesterol, which is the last step in the cholesterol biosynthesis pathway. We speculated that blocking the catalytic activity of DHCR24 could be a novel therapeutic strategy for treating hyperlipidemia. In the present study, by virtually screening the DrugBank database and performing molecular dynamics simulation analysis, we selected four potential DHCR24 inhibitor candidates: irbesartan, risperidone, tolvaptan, and conivaptan. All four candidates showed significant cholesterol-lowering activity in HepG2 cells. The experimental mouse model of hyperlipidemia demonstrated that all four candidates improved high blood lipid levels and fat vacuolation in the livers of mice fed with a high-fat diet. In addition, Western blot analysis results suggested that irbesartan reduced cholesterol levels by downregulating the expression of the low-density lipoprotein receptor. Finally, the immune complex activity assay confirmed the inhibitory effect of irbesartan on the enzymatic activity of DHCR24 with its half-maximal inhibitory concentration (IC50) value of 602 nM. Thus, to the best of our knowledge, this is the first study to report that blocking the enzymatic activity of DHCR24 via competitive inhibition is a potential strategy for developing new cholesterol-lowering drugs against hyperlipidemia or multiple cancers. Furthermore, considering that irbesartan is currently used to treat hypertension combined with type 2 diabetes, we believe that irbesartan should be a suitable choice for patients with both hypertension and hyperlipidemia.

Abstract Colorectal cancer (CRC) is a fatal disease ranking the third among the commonplace cancer types around the world. It is extremely significant to exploit effective treatments against CRC. FAM225A was proved to influence cell progression and forecast unfavorable prognosis in nasopharyngeal carcinoma. The role and function mechanism of FAM225A are still unclear in CRC. In this research, FAM225A was discovered presenting much higher expression in CRC tissues and cell lines. In addition, depleting FAM225A was capable of inhibiting cell proliferation, migration, and epithelial‐to‐mesenchymal transition (EMT) progress, and enhancing cell apoptosis ability. Furthermore, miR‐613 exerted important effects as a mediator between FAM225A and NOTCH3. NOTCH3 was negatively correlated with miR‐613, whereas was positively associated with FAM225A. Via competitively binding with miR‐613, FAM225A positively regulated NOTCH3 expression. FAM225A facilitated CRC occurrence and development through positively regulating NOTCH3 expression by binding with miR‐613. In a word, FAM225A/miR‐613/NOTCH3 axis may play a tumor‐facilitator in CRC cell progression. These data manifested the pivotal effect of FAM225A/miR‐613/NOTCH3 pathway in CRC cell proliferation, apoptosis, and migration process. The findings may provide some theoretical basis and different perspective for CRC treatment.

Abstract Background The treatment effect of dapoxetine in real-world practice is not well established. This study was to investigate the factors influencing efficacy of dapoxetine for the treatment of Premature ejaculation (PE) in the real-world setting. Methods Altogether 154 patients were followed up between Jan 2015 and Dec 2015. The clinical global impression of change (CGIC), premature ejaculation profile (PEP), the estimated intravaginal ejaculation latency time (eIELT) and estimated number of intravaginal thrusts before ejaculation (NITBE) were collected. The clinical characteristics of patients with CGIC = 0 and CGIC≥1 were compared. Results After 4 weeks treatment, an obvious improvement compared with the baseline was found regarding mean eIELT (2.4 ± 1.6 min vs 1.0 ± 0.7 min, P

Single pixel imaging (SPI) combined with compressed sensing techniques can provide solutions for special optical imaging to avoid array detectors and raster scanning. However, the imaging speed should be further improved for real-time SPI and the challenge is to reduce the sampling time and post-processing time. This paper proposes a deep compressive and super-fast single pixel imaging protocol based on reordering Hadamard basis patterns and Fourier domain regularization inversion (FDRI) algorithm. Two reordered Hadamard basis patterns in terms of the improvement in the compressing ratio and reconstruction quality are proposed and compared to other methods. The deterministic Hadamard basis are reordered through their total variation (TV) in ascending order and total wavelet transformed coefficients (TW) in ascending order to have the best performance. Numerical simulation shows that this protocol can reconstruct a 128 × 128 pixels natural image at the sampling ratio of 5% with the peak-signal-to-noise ratio (PSNR) of 25.56 dB in 0.00039s. Terahertz near-field imaging experiment also verifies the proposed protocol. The inherent advantage and mechanism of reordering approaches are discussed and then revealed by comparing the coherent area generated by these reordered patterns. The TV order and TW order Hadamard basis patterns can be deterministically described mathematically and easily constructed. Meanwhile, it results in a significant improvement both in the compression ratio and image reconstruction quality. Finally, the realization this protocol in real SPI system in the future will bring the real-time SPI closer to practical applications.

Due to the complexity of high-squint synthetic aperture radar (SAR) mounted on maneuvering platforms, the traditional geometric model and imaging algorithms cannot be directly applied in the diving or climbing stage for the existence of vertical velocity. Aiming at this issue, an equivalent geometric model of maneuvering high-squint-mode SAR is constructed, and a modified wavenumber-domain imaging algorithm combined with the proposed equivalent range model is proposed in this article. First, the disadvantages of the conventional range model are analyzed in detail and an equivalent range model is proposed to describe the motion characteristic of squint SAR in maneuvering mode, which maintains the azimuth-shift invariance along the flight direction in the new slant range plane. Then, to achieve the requirement of maneuvering SAR real-time processing, a modified wavenumber-domain imaging algorithm with a high usage of the spectrum by axis rotation for high-squint SAR data is proposed. Further, since the equivalent model may introduce the severe distortion in the imaging plane, a novel geometric correction method based on inverse projection is performed to obtain the ground imagery with a little distortion. Finally, simulation and real-data processing results validate the superiority of the proposed algorithm.

Study region: The Qinghai Lake Basin, Qinghai-Tibetan Plateau. The Qinghai Lake is the largest inland saltwater lake in China. Study focus: Significant increase in runoff into the Qinghai Lake has been reported; however, the relationship between frozen soil changes and runoff remains poorly understood. This study investigated the temporal and spatial variations in frozen soil and associate effects on streamflow and soil moisture in the study region by a distributed eco-hydrological model. New hydrological insights: The results illustrate that the coverage of permafrost decreased by about 13% from 1971 to 2015, and permafrost degradation mainly occurred in the elevation interval of 3600–4200 m. The maximum frozen depth averaged in the seasonally frozen ground significantly decreased by 0.06 m/10a, while the active layer thickness averaged in the permafrost enhanced by 0.02 m/10a. Permafrost degradation caused enhanced soil liquid water storage and an increase in freezing season runoff. The increase in runoff in the thawing season was dominated by changes in precipitation. The results suggest that frozen soil degradation altered the seasonal flow regime, leading to lags in the monthly runoff peak, and it increased the base flow and reduced the thawing season runoff. This offset of the competing impacts of frozen soil changes in different seasons led to a negative effect on annual runoff. This study provides new understandings of cryospheric hydrological responses to climate change.

Intermetallic compounds (IMC) are found in the dual-layer composite, such as Si/Cu composite in multilayer semiconductor structures, and are often ignored in simulations that aim to predict the mechanical properties. The interface model of Si/Cu composites with different thickness of IMC layer is first established by molecular dynamics simulation. Then this study analyzed the elastoplastic behavior and adhesion behavior of the Si/Cu interface and the effect of IMC on the fracture properties. The simulation results demonstrate that the Si/Cu interface fails in a quasi-brittle fracture mode. The crack propagates along the interface between Si and the IMC layer. An apparent dislocation emission and large plastic deformation are found exclusively in the Cu layer. The thickness of the IMC layer increased from 2 to 10 Å, and the critical strain energy release rate increased from 14.48 J/m2 to 19.76 J/m2, while the equivalent modulus is not increase monotonically. Therefore, the IMC is of high significance for predicting the mechanical properties of the dual-layer composite.

Based on China’s potato staple food policy, we chose potatoes as a study case to analyze the following indicators—the virtual new nitrogen factor (VNNF), the virtual new phosphorus factor (VNPF), the virtual irrigation-water (IW) factor (VIWF), the virtual total water (IW + precipitation) factor (VTWF), and the virtual greenhouse gas (GHG) emission factor (VCF) of the potatoes consumed by households in the six potato cultivation regions—by reviewing 220 publications from 2000 to 2020. The results showed that the VNNF ranged between 17.8 ± 7.8 and 30.1 ± 17.0 kg N kg−1 N in the consumed potato, the VNPF ranged between 8.4 ± 5.0 and 18.8 ± 11.3 kg P kg−1 P in the consumed potato, the VIWF ranged between 0.3 ± 1.0 and 1.8 ± 1.4 m3 IW kg−1 for the consumed standard yield (except in the three mainly rainfed potato regions), the VTWF ranged between 4.8 ± 2.2 and 9.3 ± 3.7 m3 total water kg−1 for the consumed standard yield, and the VCF ranged between 3.4 ± 1.5 and 5.9 ± 2.4 kg CO2 equivalent kg−1 for the consumed standard yield, under the conventional practice in the six potato cultivation regions. The normalization score results indicate that the northeast, northwest, southwest, and south of China are relatively more suitable regions in which to plant potatoes, based on the VNNF, VNPF, VIWF or VTWF, and VCF indicators.

To reduce carbon dioxide emissions, wind power generation is receiving more attention. The conversion of wind energy into electricity requires frequent use of insulated-gate bipolar transistors (IGBTs). Therefore, it is important to improve their reliability. This study proposed a method to predict the junction temperature of IGBTs, which helps to improve their reliability. Limited by the bad working environment, the physical temperature measurement method proposed by previous research is difficult to apply. Therefore, a junction temperature prediction method based on an extreme learning machine optimized by an improved honey badger algorithm was proposed in this study. First, the data of junction temperature were obtained by the electro-heat coupling model method. Then, the accuracy of the proposed method was verified with the data. The results show that the average absolute error of the proposed method is 0.0303 °C, which is 10.62%, 11.14%, 91.67%, and 95.54% lower than that of the extreme learning machine optimized by a honey badger algorithm, extreme learning machine optimized by a seagull optimization algorithm, extreme learning machine, and back propagation neural network model. Therefore, compared with other models, the proposed method in this paper has higher prediction accuracy.

This paper evaluates the mechanical properties of amorphous silicon carbon nitride (a-SiCxNy) films with different atomic ratios via molecular dynamics simulation. The Si-C-N ternary amorphous model is constructed using ReaxFF potential and melt-quenching method. The results demonstrate that the density range of constructed model spans a wide range of densities (2.247–2.831 g/cm3). The short- and medium-range order of the constructed a-SiCxNy structures show a good correlation with the experimental observations. Based on the structural feasibility, the elastoplastic performance is analyzed. There is significant ductility during the uniaxial tension process of a-SiCxNy, except for Si(CN2)2. The calculated elastic modulus ranges from 206.80 GPa to 393.58 GPa, close to the experimental values of coating films. In addition, the elastic modulus of a-SiCxNy does not change monotonically with the carbon or silicon content but is related to the atomic ratio. This article provides an understanding of the chemical composition dependence of the mechanical properties of amorphous compounds at the molecular level.

Soil organic carbon (SOC) plays a crucial role in controlling the nitrate-dependent Fe(II) oxidation (NDFO) process, especially for saline-alkaline soils. The effects of straw returning combined with Nitrogen (N) fertilizer application on soil NO3−-N content, Fe(II) form and nirK genes in saline-alkaline soil were studied in a five-year field experiment to explore the regulatory mechanism of SOC on NDFO process. Six treatments were designed with two factors (1) three straw returning rates (C0, C1 and C2, which was 0, 4500 and 9000 kg C ha−1, respectively) and (2) two N fertilization rates (N1 and N2, which was 255 and 400 kg N ha−1, respectively). Under both N levels, compared with C0 and C2 rates, NO3−-N content was increased by 65% and 50% in C1 rate, respectively. NirK genes were decreased with straw returning, in which they were 42.9–58.8% lower in C1 and C2 treatments than that in C0 treatment, respectively. In the N1C1 treatment, the increase of SOC reduced the denitrification by converting aqueous Fe(II) (Fe(II)aq) into Fe(II)-OM complexes and reducing the abundance of nirK genes. Overall, appropriate straw returning (C1) under optimal N fertilization rate (N1) could reduce N loss by decreasing the NDFO process in saline-alkaline paddy soils.

Ship detection and management in coastal regions are challenging tasks due to the complex appearances of ships and the background. For further applications in the context of fisheries monitoring and vessel traffic services, a single-channel synthetic aperture radar (SAR) is mounted on a number of maneuvering and inexpensive rotor platforms, which are utilized according to the consideration of flexible observation, cost savings, weight, and space constraints. In this paper, a hierarchical scheme of ship detection, ship imaging, and classification is proposed. It mainly includes three parts. First, a mixture statistical model of semi-parametric K-lognormal distribution based on adaptive background windows with a constant false alarm rate (CFAR) is proposed for ship prescreening in SAR imagery. Then, the discrimination stage, combined with ship imaging via the difference between the true ship targets and the false ones in the aspects of micro-Doppler motion properties, is performed. Finally, the simulation and field data processing results are presented to validate the proposed scheme.

The influence of microbiota on host health and disease has attracted adequate attention, and gut microbiota components and microbiota-derived metabolites affect host immune homeostasis locally and systematically. Some studies have found that gut dysbiosis, disturbance of the structure and function of the gut microbiome, disrupts pulmonary immune homeostasis, thus leading to increased disease susceptibility; the gut-lung axis is the primary cross-talk for this communication. Gut dysbiosis is involved in carcinogenesis and the progression of lung cancer through genotoxicity, systemic inflammation, and defective immunosurveillance. In addition, the gut microbiome harbors the potential to be a novel biomarker for predicting sensitivity and adverse reactions to immunotherapy in patients with lung cancer. Probiotics and fecal microbiota transplantation (FMT) can enhance the efficacy and depress the toxicity of immune checkpoint inhibitors by regulating the gut microbiota. Although current studies have found that gut microbiota closely participates in the development and immunotherapy of lung cancer, the mechanisms require further investigation. Therefore, this review aims to discuss the underlying mechanisms of gut microbiota influencing carcinogenesis and immunotherapy in lung cancer and to provide new strategies for governing gut microbiota to enhance the prevention and treatment of lung cancer.

Cardiovascular disease is the main cause of death worldwide, and traditional cardiovascular risk factors cannot fully explain the occurrence of the disease. In recent years, the relationship between gut microbiota and its metabolites and cardiovascular disease has been a hot study topic. The changes in gut microbiota and its metabolites are related to the occurrence and development of atherosclerosis, myocardial infarction, heart failure, and hypertension. The mechanisms by which gut microbiota and its metabolites influence cardiovascular disease have been reported, although not comprehensively. Additionally, following ingestion, flavonoids are decomposed into phenolic acids that are more easily absorbed by the body after being processed by enzymes produced by intestinal microorganisms, which increases flavonoid bioavailability and activity, consequently affecting the onset of cardiovascular disease. However, flavonoids can also inhibit the growth of harmful microorganisms, promote the proliferation of beneficial microorganisms, and maintain the balance of gut microbiota. Hence, it is important to study the relationship between gut microbiota and flavonoids to elucidate the protective effects of flavonoids in cardiovascular diseases. This article will review the role and mechanism of gut microbiota and its metabolites in the occurrence and development of atherosclerosis, myocardial infarction, heart failure, and hypertension. It also discusses the potential value of flavonoids in the prevention and treatment of cardiovascular disease following their transformation through gut microbiota metabolism.

Background and Objectives: Vitamin K (VK) plays a major role in modifying the binding of calcium in bones and blood vessels. Understanding the effect of VK on crystal formation in the kidney would contribute to advancing the treatment and prevention of kidney stones. Methods: Rats were treated with vitamin K1 (VK1) for 8 weeks. VK1 levels were detected and crystal formation were observed. HK2 cells were exposed to calcium oxalate monohydrate crystals. Apoptosis and cell viability were detected. Crystal deposition was analyzed using atomic absorption assay. The adenovirus vectors expressing matrix Gla protein (MGP) and siMGP were constructed to elucidate the effect and mechanism of VK1 on crystal formation. MGP expression in vivo and in vitro was analyzed by Western blot. The mRNA levels of monocyte chemoattractant protein-1 (MCP-1) and collagen I was measured by semiquantitative RT-PCR. Results: The concentrations of VK1 in whole blood and kidney tissues rose under treatment with VK1. Crystal formation was inhibited from the second to the 6th week, the frequency and quality of crystal formation decreased significantly, and the location of crystal formation was limited to a greater extent in the rats treated by VK1 compared to the control group. Warfarin treatment in the crystals-exposed HK2 cells significantly increased the number of crystals adhering to cells and the number of apoptotic cells and reduced cell viability. VK1 treatment reversed warfarin’s above influence. VK1 inhibited the upregulations of MCP-1 and collagen I in kidney tissues under crystal load. VK1 treatment increased MGP expression in vivo and in vitro, and MGP is necessary for VK1 to play a role in crystal deposition in cells. Conclusions: VK1 treatment can inhibit the formation of renal crystals in vivo. VK1 increases MGP expression and functions through MGP to reduce crystal deposition in cells and provide cell protection. Our findings suggest that VK1 treatment could be a potential strategy for the treatment and prevention of nephrolithiasis.

At present, the train-ground communication system based on the wireless communication protocol is a very important component of communication-based train control (CBTC) systems in intelligent transportation. Its information security is worthy of attention. In order to guarantee the security of the train-ground communication system, this paper proposes an improved AdaBoost multi-classification intrusion detection method based on the n-gram model. First, the n-gram model is used to model the state transitions of the IEEE 802.11 protocol. Then, a typical normal behavior set and typical abnormal behavior sets are obtained by learning and they can portray typical behaviors of their respective classes. Furthermore, a similarity measure algorithm is proposed to construct AdaBoost weak classifiers, which improves the classification effect of AdaBoost algorithm. At last, an AdaBoost multi-classification algorithm is presented to detect and identify the attacks. Experiments prove that the algorithm can effectively detect and distinguish attack types in the train-ground communication system.