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Background: Isoleucinyl‐tRNA synthetase (IARS) is encoded by the IARS1 gene and catalyzes the binding of isoleucine to specific tRNA. Objective: This study aims to investigate the pathogenicity of novel IARS1 variants and the genotype–phenotype association, in order to expand the spectrum of pathogenic variants and phenotypes of IARS1‐related disease and provide new evidence for the phenotypic spectrum of IARS1 variants. Methods: Clinical data of the proband were collected, and trio whole‐exome sequencing (WES) was performed on the proband and the parents. Candidate variants were validated using Sanger sequencing. Bioinformatics software was utilized to analyze the functional consequences of identified variants and predict their potential deleteriousness. Results: A 17‐month‐old female patient presented with microcephaly, left external ear malformation, decreased muscle strength and tone in all limbs, epileptic seizures, global developmental delay, and developmental regression. Trio WES identified compound heterozygous variants in the IARS1 gene, c.120‐1G>A and c.2164C>A, which were novel pathogenic and likely pathogenic variants, respectively. The phenotype of developmental regression has not been reported before. Only one patient with IARS1 compound heterozygous variants has been reported in the world to have an epileptic phenotype, and this is the second patient with an epileptic phenotype. Bioinformatics analysis revealed that the splicing variant disrupted the canonical splice donor site, while the missense variant altered the local electrostatics of the IARS1 protein surface, potentially leading to functional abnormalities. Conclusion: This study identified novel IARS1 variants and the phenotype of developmental regression, expanding the spectrum of pathogenic variants and phenotypes of IARS1‐related diseases and providing new evidence for the rare phenotype of epileptic seizures caused by IARS1 variants. [ABSTRACT FROM AUTHOR]

Background The association between different phenotypes and genotypes of circulating tumor cells (CTCs) and efficacy of neoadjuvant chemotherapy (NAC) remains uncertain. This study was conducted to evaluate the relationship of FTH1 gene-associated CTCs (F-CTC) with/without epithelial-mesenchymal transition (EMT) markers, or their dynamic changes with the efficacy of NAC in patients with non-metastatic breast cancer. Patients and Methods This study enrolled 120 patients with non-metastatic breast cancer who planned to undergo NAC. The FTH1 gene and EMT markers in CTCs were detected before NAC (T0), after 2 cycles of chemotherapy (T1), and before surgery (T2). The associations of these different types of CTCs with rates of pathological complete response (pCR) and breast-conserving surgery (BCS) were evaluated using the binary logistic regression analysis. Results F-CTC in peripheral blood ≥1 at T0 was an independent factor for pCR rate in patients with HER2-positive (odds ratio [OR]=0.08, 95% confidence interval [CI], 0.01-0.98, P =.048). The reduction in the number of F-CTC at T2 was an independent factor for BCS rate (OR = 4.54, 95% CI, 1.14-18.08, P =.03). Conclusions The number of F-CTC prior to NAC was related to poor response to NAC. Monitoring of F-CTC may help clinicians formulate personalized NAC regimens and implement BCS for patients with non-metastatic breast cancer. [ABSTRACT FROM AUTHOR]

Magnesium (Mg) plays a crucial role in crop growth, but how Mg supply level affects root growth and nutrient absorption in vegetable crops with different genotypes has not been sufficiently investigated. In this study, the responses of tomato (Solanum lycopersicum L.) and cucumber (Cucumis sativus L.) crops to different levels of Mg supply were explored. Four levels of Mg treatment (i.e., 0.2, 1.0, 2.0, 3.0 mmol/L) were applied under hydroponic conditions, denoted as Mg0.2, Mg1, Mg2, and Mg3, respectively. The results showed that with increasing Mg levels, the plant biomass, root growth, and nutrient accumulation in both vegetable crops all increased until reaching their maximum values under the Mg2 treatment and then decreased. The total biomass per tomato plant of Mg2 treatment was 30.9%, 14.0%, and 14.0% higher than that of Mg0.2, Mg1, and Mg3 treatments, respectively, and greater increases were observed in cucumber plant biomass (by 54.3%, 17.4%, and 19.9%, respectively). Compared with the Mg0.2 treatment, the potassium (K) and calcium (Ca) contents in various plant parts of both crops remarkably decreased under the Mg3 treatment. This change was accompanied by prominently increased Mg contents in various plant parts and para-hydroxybenzoic acid and oxalic acid contents in root exudates. Irrespective of Mg level, plant biomass, root growth, nutrient accumulation, and root exudation of organic acids were all higher in tomato plants than in cucumber plants. Our findings indicate that excessive Mg supply promotes the roots to exude phenolic acids and hinders the plants from absorbing K and Ca in different genotypes of vegetable crops despite no effect on Mg absorption. A nutritional deficiency of Mg stimulates root exudation of organic acids and increases the types of exuded organic acids, which could facilitate plant adaption to Mg stress. In terms of root growth and nutrient absorption, tomato plants outperform cucumber plants under low and medium Mg levels, but the latter crop is more tolerant to Mg excess. [ABSTRACT FROM AUTHOR]

Background: Oral squamous cell carcinoma (OSCC) has been recognized as a frequently occurring oral malignant tumor. Pyroptosis plays an extremely important role in the occurrence and development of cancer, but the role of pyroptosis in OSCC remains unclear. Methods: OSCC-related data were obtained from the TCGA and GEO databases. A PSscore risk model was constructed through LASSO regression analysis. The GEO database was utilized as the validation set of the model. The "ESTIMATE" and "CIBERSORT" algorithms were utilized to additionally evaluate the relationship between the immune cell score and PSscore. TIDE and IPS algorithms were used to assess patient response to immunotherapy. In addition, Western blot analysis and MTT assay was used to further validate key genes. Results: Comprehensive bioinformatics analysis showed that a low-PSscore had a significant survival advantage, richer immune cell infiltration, more active immune-related pathways, higher TME scores, and lower tumor purity. The results of TIDE and IPS analysis indicated that the high-PSscore group had higher immune escape potential and was less sensitive to immunotherapy. In contrast, the low-PSscore group patients might be more sensitive to PD1 and CTLA4 + PD1 immunotherapy. Univariate and multivariate COX results indicated that PSscore was an independent prognostic factor in OSCC patients. Another important finding is that BAK1 is a potential target of OSCC and is related to the Nod-like receptor signaling pathway. Knockdown of BAK1 can significantly reduce the proliferation of OSCC cells. Conclusion: The PSscore model could be utilized as a powerful prognostic indicator and can help in the development of new immunotherapies. [ABSTRACT FROM AUTHOR]

Most cancer‐related deaths are a result of metastasis. The development of small molecular inhibitors reversing cancer metastasis represents a promising therapeutic opportunity for cancer patients. This pan‐cancer analysis identifies oncogenic roles of membrane‐associated phosphatidylinositol transfer protein 3 (PITPNM3), which is crucial for cancer metastasis. Small molecules targeting PITPNM3 must be explored further. Here, PITPNM3‐selective small molecular inhibitors are reported. These compounds exhibit target‐specific inhibition of PITPNM3 signaling, thereby reducing metastasis of breast cancer cells. Besides, by using nanoparticle‐based delivery systems, these PITPNM3‐selective compounds loaded nanoparticles significantly repress metastasis of breast cancer in mouse xenograft models and organoid models. Notably, the results establish an important metastatic‐promoting role for PITPNM3 and offer PITPNM3 inhibition as a therapeutic strategy in metastatic breast cancer. [ABSTRACT FROM AUTHOR]

Anthracycline is a mainstay of treatment for breast cancer patients because of its antitumor activity. However, anthracycline resistance is a critical barrier in treating breast cancer. Thus, it is of great importance to uncover the molecular mechanisms underlying anthracycline resistance in breast cancer. Herein, we integrated transcriptome data, genetic alterations data, and clinical data of The Cancer Genome Atlas (TCGA) to identify the molecular mechanisms involved in anthracycline resistance in breast cancer. Two hundred and four upregulated genes and 1376 downregulated genes were characterized between the anthracycline-sensitive and anthracycline-resistant groups. It was found that drug resistance-associated genes such as ABCB5, CYP1A1, and CYP4Z1 were significantly upregulated in the anthracycline-resistant group. The gene set enrichment analysis (GSEA) suggested that the P53 signaling pathway, DNA replication, cysteine, and methionine metabolism pathways were associated with anthracycline sensitivity. Somatic TP53 mutation was a common genetic abnormality observed in the anthracycline-sensitive group, while CDH1 mutation was presented in the anthracycline-resistant group. Immune infiltration patterns were extremely different between the anthracycline-sensitive and anthracycline-resistant groups. Immune-associated chemokines and cytokines, immune regulators, and human leukocyte antigen genes were significantly upregulated in the anthracycline-sensitive group. These results reveal potential molecular mechanisms associated with anthracycline resistance. [ABSTRACT FROM AUTHOR]

This study aimed to explore the relationship between recurrent reproductive failure (RRF) and blocking antibody (BA) and lymphocytes, to explore the difference of immune status between recurrent spontaneous abortion (RSA) and recurrent implantation failure (RIF) patients. We undertook a retrospective analysis of BA and lymphocyte subsets detected by flow cytometry in 720 RRF patients (411 RSA and 309 RIF patients) who were treated at Shanxi Maternal and Child Health Hospital from April 2015 to October 2019. The BA negative rate of RRF patients was 81.80%, which was significantly higher than that of normal women (23.46%) (p < 0.05). There was no significant difference in BA negative rates between RSA and RIF patients. Compared with the normal value, the percentage of CD3+ T lymphocytes and CD3+CD4+ T lymphocytes in RRF patients were 71.1% (65.9–76.0) and 36.8% (32.5–41.9) respectively, which were significantly lower than the normal value (p < 0.05). The percentage of B cells in RSA patients [11.0 (8.8–13.9)] was significantly lower than that in RIF patients [11.9 (9.4–14.8)]. The occurrence of RRF is related to the lack of BA and the change of lymphoid subsets. There are some differences in immune status between RSA and RIF patients. [ABSTRACT FROM AUTHOR]

The free vibration of rotating bending-torsional composite Timoshenko beams (CTBs) with arbitrary boundary conditions is analyzed. The composite material coupled rigidity, Coriolis effects and the separation of the cross-section's mass and shear centers are considered and they will cause the bending-torsion coupled vibration of the beam. Based on the Hamilton's principle, the governing partial differential matrix equation of motion of the beam are formulated with variable coefficients. Those equations containing variable coefficients are expressed in a special matrix form in terms of the flexural translation, rotation of cross section and torsional rotation of the beam. The differential transform matrix method (DTMM), which is an improved approach from the traditional differential transform method (DTM), is proposed to deal with the governing matrix equation with corresponding boundary conditions. The mode shapes and natural frequencies of the beam are obtained. Cantilevers are calculated as examples to verify the present theory and investigate the dynamic characteristics of the rotating CTB. The present results are consistent with those reported in the literature and those calculated from COMSOL. The influence of the composite material rigidity, rotation speed, hub radius and axial load on the natural frequencies and mode shapes of the beam are studied, while the frequency veering and mode shift phenomena are observed. Furthermore, the beam's critical buckling loads corresponding to the axial load are found. [ABSTRACT FROM AUTHOR]

Purpose: Since the end of 2019, dialysis patients have been at risk of coronavirus disease 2019 (COVID-19) as well as other potential complications. Hence, we sought to describe the clinical characteristics of dialysis patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Methods: We reviewed clinical outcomes, which consisted of clinical data extracted from the medical records of 695 registered dialysis patients at the Dialysis Center of Central Hospital of Wuhan from January 13th, 2020, to February 29th, 2020, and performed statistical analysis. According to the results, there were 447, 227 and 21 hemodialysis (HD), peritoneal dialysis (PD) and combined HD and PD (HD&PD) cases, respectively. Results: During the outbreak of COVID-19, 36 dialysis patients were infected by SARS-CoV-2. Among those 36 patients, 32 (7.2%) were on HD, and 4 (1.8%) were on PD. When comparing SARS-CoV-2 infection between HD and PD, the relative risk was 4.07 (RR = 4.07, 95% CI 1.46–11.35). We noted a median age of 66 years during the observation period, and the number of male patients was 23 (63.9%). There were 15 fatal cases tested positive for SARS-CoV-2 (13 cases on HD and 2 cases on PD). By comparing mortality in the same period of 2018, 2019 and 2020, the all-cause mortality of hemodialysis patients was significantly higher in 2020 (4.89%) than in either 2018 (2.55%) or 2019 (1.97%). There was no significant difference in mortality from all causes excluding COVID-19, during the same period among the 3-year period. However, during the COVID-19 outbreak, the mortality from all causes excluding COVID-19 was 2.73%, which was slightly higher than that from COVID-19 (2.16%). Conclusions: Although COVID-19 seriously threatens the health of people with uremia, deaths from all causes excluding COVID-19 during the epidemic cannot be ignored. [ABSTRACT FROM AUTHOR]

A multi‐objective integrated optimization framework that considers the manufacturing process in the design of a tapered carbon‐fiber‐reinforced polymer (CFRP) rim structure was established. Firstly, the three‐zone symmetrically stacked CFRP rim structure was proposed and modeled. The bending and radial fatigue and 13° impact of the carbon/aluminum‐assembled wheel composed of CFRP rim and aluminum alloy spoke were analysed. Coupling lay‐up thickness, sequence and angle as design variables, multi‐objective integrated optimization design for the tapered CFRP rim structure was performed through radial basis function neural network surrogate model combined with an elitist non‐dominated sorting genetic algorithm approach. Pareto‐optimal solutions were obtained, and the trade‐off solution was selected through grey relational analysis coupled with entropy weighting method. Finally, the tapered CFRP rim was manufactured through molding and autoclave forming technology. The CFRP rim has a weight saving of 17.2% compared with the previously developed forged magnesium alloy rim of the same size. The bending and radial fatigue and 13° impact performance of the assembled wheel were then validated by corresponding physical test, results of which met GB 36581‐2018 standard. [ABSTRACT FROM AUTHOR]

Land‐use change from cereals to fruit orchards usually results in a high nutrient surplus in soil. The excessive accumulation of nitrogen (N) in soil, mainly as nitrate, leached from the root zone may serve as a long‐term source of surface or groundwater pollution. The N balances and nitrate accumulation in the soil profiles of cereal fields and kiwifruit orchards in the Yujiahe catchment, Shaanxi, China, were compared. Excessive N fertilisation resulted in an excessive N surplus (1,133 kg N ha−1 yr−1) in orchards (8‐times higher than that in cereal fields). More than 77.5% of nitrate in the soil profile (0–400 cm) of the orchards was below a soil depth of 100 cm. The average accumulated nitrate within a profile 0–400 cm of orchards was 3,288 kg N ha−1, which was 16‐fold higher than that of cereal fields. The accumulated nitrate in soil profiles on the downslope (5,959 kg N ha−1) was approximately 2 times higher than that of the upslope in the same sloping orchards. The accumulated nitrate in soil profiles at the lowland zone of the catchment was higher than that of the upland zone. Excessive nitrate moves not only vertically downwards to deeper soil depth but also laterally into lower elevations at both field and catchment scales. The total stored nitrate in the upper soil profile of 400 cm in the catchment was 464.8 Mg N, whereas 94.8% (440.8 Mg N) was in orchards. Thus, changing land use from cereal crops to orchards leads to a high nitrate accumulation in the catchment. [ABSTRACT FROM AUTHOR]

Background. Breast cancer (BC) is one of the most common malignant tumors in women around the world. Atorvastatin (ATO) was found to be associated with a decreased risk of recurrence and mortality in cancer. But the exact mechanism of its carcinostatic effects is unclear. The expression level of Ras homolog family member B (RhoB) in breast cancer cells was found to be upregulated after being treated with ATO. Thus, we conjecture that altered expression of RhoB induced by ATO may be decisive for the migration and progression of breast cancer. Methods. The effects of ATO on breast tumor cells in vivo and in vitro were detected by clone formation assay, CCK-8 assay, flow cytometry, wound healing, transwell assays, tumor xenograft model, and immunohistochemistry. Distribution of RhoB in different breast cancer tissues and its influence on prognosis were analyzed using the data from TCGA or GEO databases. The relationship between RhoB and PTEN/AKT pathway was detected by Western blotting and RT-qPCR. Results. ATO inhibits proliferation, invasion, EMT, and PTEN/AKT pathway and promotes apoptosis in breast tumor cells. In addition, ATO inhibits the volume and weight of breast tumor in tumor-bearing mice and upregulated RhoB in tumor tissues. The expression of RhoB in mRNA and protein level was upregulated in statin-treated breast cancer cells and downregulated in cancer tissues. Low expression of RhoB links with poor prognosis in patients with breast cancer (HR = 0.74[0.66–0.83], p =7e−8, log-rank test). Further research found that RhoB inhibits the proliferation, invasion, EMT, and PTEN/AKT signal pathway in breast tumor cells. Conclusions. The exact mechanism of ATO's carcinostatic effects in breast cancer is related to downregulating PTEN/AKT pathway via promoting RhoB. Our study also demonstrates the potential applicability of RhoB as a therapeutic target for breast cancer. [ABSTRACT FROM AUTHOR]

Summer fallow is very common in dryland agriculture to conserve rainwater and replenish soil fertility. However, bare land and intensive rainfall during summer fallow might result in a potential risk of N loss. We used a 15N-labelling method to study the loss of residual N fertilizer during summer fallow and its use by next wheat in the Loess Plateau. Our study included three treatments: without the addition of N (N0W0), with the addition of 50 kg ha−1 N (NW0) and with the addition of 50 kg ha−1 N plus 35% more water (NW). The N fertilizer (K15NO3) in solution was injected into the soil at a depth of 35 cm of the polyvinyl chloride (PVC) columns in field. The fates of 15N were followed after summer fallow and in the next season’s wheat (Triticum aestivum L.). The summer fallow of this study was a dry summer; however, fertilizer 15N was still leached down to 40-cm depth for the NW0 treatment; and for the NW treatment, the peak of 15N fertilizer was approximately 20 cm deeper. After summer fallow, the loss of the initially applied 15N was 26% in the soil profile for the NW0 treatment; and for the NW treatment, it increased to 37%. Soil 15N abundance in 0-20 cm of the NW0 and NW treatments was higher than the N0W0 treatment, indicating the upward movement of 15N in summer fallow. After the next wheat harvest, 15N uptake by wheat in the NW treatment decreased from 21.0 to 18.6% compared to the NW0 treatment. High rainfall during summer fallow increased residual N loss during summer fallow but decreased its use by the next crop. [ABSTRACT FROM AUTHOR]

This study is conducted to investigate stability and control problems within a finite-time interval for a 2D continuous-discrete system in Roesser model. The concepts of finite-time stability (FTS) and finite-time boundedness (FTB) are naturally extended to the 2D continuous-discrete system. Recursive relations between system states are first obtained, then sufficient conditions for FTS and FTB in the system are derived, and a finite-time controller is supplied to the system. Sufficient conditions for finite-time stabilization are also provided for the linear repetitive process. Examples of metal rolling operation are presented to illustrate the proposed method. [ABSTRACT FROM AUTHOR]

This paper investigates the passivity issues of discrete-time two-dimensional switched systems in Roesser model under a state-dependent switching law. Conditions for passivity of discrete-time two-dimensional switched systems are obtained without the requirement of passivity of subsystems. When the system states are completely available, state feedback controllers and switching laws are designed. In the case of partial state measurements, dynamic output feedback controllers and switching laws depending only on the state of the output feedback controllers are constructed to guarantee passivity of the closed-loop switched system. Finally, numerical examples are provided to illustrate the efficiency of the results. [ABSTRACT FROM PUBLISHER]

This paper investigates the problem of stability and robust stabilization of two-dimensional (2-D) continuous-discrete systems in Roesser model. Based on Kalman-Yakubovich-Popov (KYP) lemma, sufficient conditions of stability of the systems are proposed in terms of linear matrix inequalities (LMIs). Moreover, combining generalized KYP lemma with frequency-partitioning idea, the conservativeness of the stability conditions may be further reduced. Robust stabilization using state feedback is studied as well and stabilizing feedback gain matrices are constructed based on the solutions of certain LMIs. In addition, the stability analysis of a class of differential repetitive processes, a special case of 2-D continuous-discrete systems in Roesser model, can adopt the results in this manuscript. Numerical examples are presented to verify the effectiveness of the method. [ABSTRACT FROM AUTHOR]

An instantaneous frequency identification method of vibration signal based on linear chirplet transform and Wigner-Ville distribution is presented. This method has an obvious advantage in identifying closely spaced and time-varying frequencies. The matching pursuit algorithm is employed to select optimal chirplets, and a modified version of chirplet transform is presented to estimate nonlinear varying frequencies. Because of the high time resolution, the modified chirplet transform is superior to the original method. The proposed method is applied to time-varying systems with both linear and nonlinear varying stiffness and systems with closely spaced modes. A wavelet-based identification method is simulated to compare with the proposed method, with the comparison results showing that the chirplet-based method is effective and accurate in identifying both time-varying and closely spaced frequencies. A bat echolocation signal is used to verify the effectiveness of the modified chirplet transform. The result shows that it will significantly increase the accuracy of nonlinear frequency trajectory identification. [ABSTRACT FROM AUTHOR]

The transplantation of Artemisia arborescens are mainly relying on artificial cuttings, the seedling separation device is a key component to achieve planting mechanization of Artemisia arborescens. In order to obtain orderly feed of Artemisia arborescens seedlings rod, a kind of seedling separation device of Artemisia arborescens transplanter based on vibration mechanism was designed in this paper. The main components of seedling separation device were: motor, frame, reset device of leaf spring, ledger plate, guide rail for seedling, seedling box, crank-rocker mechanism and transmission agent etc. At first, the device structure of seedlings was reasonably simplified to crank-slider mechanism, and the mathematical modeling was created on basis of characteristics of crank-slider mechanism. In order to achieve the best power transmission, the motion analysis of device was conducted, and the angular displacement, angular velocity, angular acceleration of coupler and rocker were obtained. The Matlab software was used to analyze the movement of the crank-slider mechanism, and then optimized the structure parameters of seedlings vibrating device. The optimization results showed that, when the coupler, rocker were 499mm and 273mm respectively, the power transmission could achieve the best results. Then, spring steel which was the key component of seedlings device was imported from Pro/E into Ansys Workbench to carry on model analysis of vibration characteristics. Model analysis results showed that, as frequency increasing, bending deflection of spring steel occurred firstly, then converted to distortion, and the superimposed vibrations which could lead to severe deformation appeared at last. Therefore, the vibration frequency should be less than 98.66 Hz, and the rigidity of upper end of spring steel should be appropriately strengthened. The crank length, vibration frequency and orbital inclination were taken as experimental factors, and then experimental studies of Artemisia arborescens seedling separation device were conducted. The results of the range analysis showed that the orbital inclination had the greatest impact on the quality of seedlings, the vibration frequency had less impact, and the crank length had a minimal impact. Therefore, the optimized combination was as follows: the vibration frequency was 36 Hz, the orbital inclination was 6°, and the length of crank was 14 mm. With this optimized combination, the qualified rate of seedling separation device based on vibration mechanism can reach 86.30%. This research work realized the mechanical seedling separation of Artemisia arborescens seedlings rod, which provided a reference for the further study of Artemisia arborescens transplanter. [ABSTRACT FROM AUTHOR]

A new stick text segmentation method based on the sub connected area analysis is introduced in this paper. The foundation of this method is the sub connected area representation of text image that can represent all connected areas in an image efficiently. This method consists mainly of four steps: sub connected area classification, finding initial boundary following point, finding optimal segmentation point by boundary tracing, and text segmentation. This method is similar to boundary analysis method but is more efficient than boundary analysis. [ABSTRACT FROM AUTHOR]