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Objective: In this study, we investigated the correlation between insulin resistance (IR) and cardiopulmonary function during physical exams for male patients. Methods: We selected 124 healthy male participants in the physical examination center of our hospital. They were divided into 3 groups according to the homeostasis model assessment of insulin resistance values. The oxygen uptake, peak oxygen uptake (VO2/kg), heart rate, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured by a cardiopulmonary exercise function tester. We analyzed the correlation between the index of IR and cardiopulmonary function. Results: There were statistically significant differences in body mass index, waist circumference, fasting insulin level, anaerobic threshold SBP, maximum VO2/kg and maximum SBP among the 3 groups (p.05). The anaerobic threshold SBP, maximum VO2/kg and maximum SBP were all negatively correlated with the IR index. Conclusion: Our results indicate that IR is associated with cardiopulmonary function and that there are different correlations between the various cardiopulmonary function indexes and IR.

BackgroundNon-suicidal self-injury (NSSI) severely challenges mental health in adolescents. Childhood maltreatment experience acts as high-risk factor for adolescents to engage in NSSI behaviors. On the other hand, impulsivity or loss of control sets the threshold for NSSI execution. Here we examined the effects of childhood maltreatment on adolescent NSSI-related clinical outcomes and the potential role of impulsivity.MethodsWe assessed the clinical data of 160 hospitalized NSSI adolescents and recruited 64 age-matched healthy subjects as a control group. The clinical symptoms of NSSI are expressed by the NSSI frequency, depression, and anxiety measured by the Ottawa Self-Injury Inventory, the Beck Depression Inventory, and the Beck Anxiety Inventory. Childhood maltreatment and impulsivity were assessed with Childhood Trauma Questionnaire and Barratt Impulsiveness Scale.ResultsThe results showed that when compared to HC group, NSSI group is more likely to experience childhood maltreatment. Notably, NSSI group with Childhood maltreatment accompanies higher trait impulsivity and exacerbated clinical outcomes, such as NSSI frequency, depression and anxiety symptoms. Mediation analyses indicated that the association between childhood maltreatment and NSSI-related clinical outcomes was partially explained by impulsivity.ConclusionWe found that NSSI adolescents have a higher proportion of childhood maltreatment. Impulsivity plays a mediating role between childhood maltreatment and NSSI behaviors.

Background. Oxidative stress plays a role in carcinogenesis. This study explores the roles of oxidative stress-related genes (OSRGs) in lung adenocarcinoma (LAC). Besides, we construct a risk score model of OSRGs that evaluates the prognosis of LAC patients. Methods. OSRGs were downloaded from the Gene Set Enrichment Analysis (GSEA) website. The expression levels of OSRGs were confirmed in LAC tissues of the TCGA database. GO and KEGG analyses were used to evaluate the roles and mechanisms of oxidative stress-related differentially expressed genes (DEGs). Survival, ROC, Cox analysis, and AIC method were used to screen the prognostic DEGs in LAC patients. Subsequently, we constructed a risk score model of OSRGs and a nomogram. Further, this work investigated the values of the risk score model in LAC progression and the relationship between the risk score model and immune infiltration. Results. We discovered 163 oxidative stress-related DEGs in LAC, involving cellular response to oxidative stress and reactive oxygen species. Besides, the areas under the curve of CCNA2, CDC25C, ERO1A, CDK1, PLK1, ITGB4, and GJB2 were 0.970, 0.984, 0.984, 0.945, 0.984, 0.771, and 0.959, respectively. This indicates that these OSRGs have diagnosis values of LAC and are significantly related to the overall survival of LAC patients. ERO1A, CDC25C, and ITGB4 overexpressions were independent risk factors for the poor prognosis of LAC patients and were associated with risk scores in the risk model. High-risk score levels affected the poor prognosis of LAC patients. Notably, a high-risk score may be implicated in LAC progression via cell cycle, DNA replication, mismatch repair, and other mechanisms. Further, ERO1A, CDC25C, and ITGB4 expression levels were related to the immune infiltrating cells of LAC, including mast cells, NK cells, and CD8 T cells. Conclusion. In summary, ERO1A, CDC25C, and ITGB4 of OSRGs are associated with poor prognosis of LAC patients. We confirmed that the risk model based on the ERO1A, CDC25C, and ITGB4 is expected to assess the prognosis of LAC patients.

Quiescent cancer stem cells (CSC) play important roles in tumorigenesis, relapse, and resistance to chemoradiotherapy. However, the determinants of CSC quiescence and how they sustain themselves to generate tumors and relapse beyond resistance to chemoradiotherapy remains unclear. Here, we found that SET domain–containing protein 4 (SETD4) epigenetically controls breast CSC (BCSC) quiescence by facilitating heterochromatin formation via H4K20me3 catalysis. H4K20me3 localized to the promoter regions and regulated the expression of a set of genes in quiescent BCSCs (qBCSC). SETD4-defined qBCSCs were resistant to chemoradiotherapy and promoted tumor relapse in a mouse model. Upon activation, a SETD4-defined qBCSC sustained itself in a quiescent state by asymmetric division and concurrently produced an active daughter cell that proliferated to produce a cancer cell population. Single-cell sequence analysis indicated that SETD4+ qBCSCs clustered together as a distinct cell type within the heterogeneous BCSC population. SETD4-defined quiescent CSCs were present in multiple cancer types including gastric, cervical, ovarian, liver, and lung cancers and were resistant to chemotherapy. SETD4-defined qBCSCs had a high tumorigenesis potential and correlated with malignancy and chemotherapy resistance in clinical breast cancer patients. Taken together, the results from our previous study and current study on six cancer types reveal an evolutionarily conserved mechanism of cellular quiescence epigenetically controlled by SETD4. Our findings provide insights into the mechanism of tumorigenesis and relapse promoted by SETD4-defined quiescent CSCs and have broad implications for clinical therapies.Significance:These findings advance our knowledge on the epigenetic determinants of quiescence in cancer stem cell populations and pave the way for future pharmacologic developments aimed at targeting drug-resistant quiescent stem cells.

Supplementary Table S1 and Supplementary Figure S1 to S11

IntroductionPerennial Chinese licorice, Glycyrrhiza uralensis, is an important medicinal plant. Diorhabda tarsalis, a leaf beetle, is a serious insect pest on the plant and cause serious yield losses every year and is attracted to healthy and pest-damaged licorice by plant volatiles.AimThe biologically active components of the volatiles released from G. uralensis have not been reported; the components of the volatiles that attract D. tarsalis need to be identified. Such compounds could potentially be used for monitoring and mass-trapping pests.MethodsGC-EAD, GC-MS, EAG, Y-shaped olfactometer behavioral bioassays, and field trials were performed to identify the components and composition of active volatiles.ResultsMale and virgin female adults were generally attracted to volatiles from licorice, and volatiles from pest-infested plants were more attractive. Four compounds from licorice elicited a significant electrophysiological response (EAD) and were confirmed by EAG, including hexanal, (Z)-3-hexenal, (Z)-3-hexen-1-ol, and (E)-2-hexenal. With the exception of the (E)-2-hexenal, these molecules significantly attracted adults in individual behavioral bioassays, and a proportional mixture corresponding to beetle-damaged licorice of hexanal, (Z)-3-hexenal, (Z)-3-hexen-1-ol, and (E)-2-hexenal (8.78:15.26:57.24:18.72) was most effective for attracting D. tarsalis in the field, attracted a mean of 26 ± 7.19 beetles per trap.DiscussionD. tarsalis was attracted to volatiles from healthy and herbivore-induced G. uralensis under both laboratory and field conditions. The aforementioned compounds show considerable potential for commercial application to monitor and control D. tarsalis populations.

Introduction:Diorhabda tarsalis Weise is an important insect pest of the Chinese licorice Glycyrrhiza uralensis Fisch. Behavior of the beetle, including host location, oviposition site selection, self-defense, and aggregation, were regulated by plant volatiles or insect pheromones.Aim: In this study, Identification of ORs and function research on orco were carried out, these could lead to the development of understand for olfaction mechanism in D. tarsalis.Methods: ORs were identified by PacBio RS II platform to sequence the antennas of adult D. tarsalis, the function of orco was explored by dsRNA interference.Results: 29 odorant receptor candidate genes of D. tarsalis were obtained, which code for 130–479 amino acids. Phylogenetic trees of olfactory receptors were constructed with 243 ORs from eight Coleoptera species. DtarORco, DtarOR7 and DtarOR26 are specifically expressed in the antenna, and the expression levels were significantly higher than other DtarORs in antenna, there were no differential expression between male and female beetles. An odorant coreceptor gene (DtarORco) has characteristics of an odorant receptor family member, the encoded mature protein has a predicted molecular weight of 53.898 kDa, dsRNA L4440 expression vectors were constructed and successfully transformed into ribonuclease III-deficient Escherichia coli strain HT115 DE3. After interference treatment, the relative expression level of DtarORco in D. tarsalis antennae significantly decreased and electrophysiological responses to host localization odor signals significantly decreased. At the same time, beetles lost the ability to locate hosts.Discussion: The research on its mechanism of olfaction may lead to the development of new control measures that are environmentally friendly.

The present study explored the relationship between hypomagnesemia and outcome in community-acquired pneumonia (CAP) patients with type 2 diabetes mellitus (T2DM).The study was a retrospective cohort study, conducted on adult CAP patients with T2DM at The First Hospital of Qinhuangdao between January 2015 and December 2018. The primary outcome was all-cause deaths.In total, 480 CAP inpatients with T2DM were enrolled, and 71 patients (14.8%) had hypomagnesemia on admission. After one month and three months of follow-up, the hypomagnesemia group had a higher mortality rate than the normal magnesium group (plt;0.05). After six months of follow-up, the mortality rate remained higher in the hypomagnesemia group, however, this was not statistically significant (χ²=2.799, p=0.094). After 12 months and 24 months of follow-up, the mortality rates were similar between the hypomagnesemia and normal magnesium groups (plt;0.05). Based on multiple logistic regression analysis, hypomagnesemia was an independent risk factor for one-monthmortality(OR=3.858,95% CI: 1.637~9.088, p=0.002), three-month mortality (OR=3.083, 95% CI: 1.434~6.627, p=0.004) and six-month mortality (OR=2.551, 95% CI: 1.209~5.383, p=0.014).Hypomagnesemia is common in CAP inpatients with T2DM. Moreover, in these patients, hypomagnesemia at admission is associated with increased mortality in the short-term but not the long-term.

To investigate the expression level and prognostic value of miR-21, miR-18a, miR-146a, and Let-7b derived from serum exosomes in patients with multiple myeloma (MM).Serum exosomes were extracted from 57 MM patients and 20 healthy persons using ExoQuick exosome precipitation solution kit, and the relative expression level of miR-21, miR-18a, miR-146a, and Let-7b derived from serum exosomes was measured by RT-qPCR. Correlations of the expression levels of all miRNAs mentioned above with routine laboratory parameters were analyzed by Spearman correlation analysis. The relationship between the expression level of miR-21, miR-18a, miR-146a, and Let-7b derived from serum exosomes and overall survival of patients with MM was analyzed using the Kaplan-Meier survival curve.The expression levels of miR-21, miR-18a, and Let-7b derived from serum exosomes in patients with MM were significantly lower than those in the normal control group (P0.001), while the expression level of miR-146a between the two groups was not significantly different (P0.05). The expression level of miR-21 was strongly negatively correlated with serum βAberrant low expression levels of miR-21, miR-18a, and Let-7b derived from serum exosomes exist in patients with MM, which are associated with a worse overall survival rate.血清外泌体来源的miRNAs在多发性骨髓瘤中的临床研究.研究血清外泌体来源的miR-21、miR-18a、miR-146a、Let-7b在多发性骨髓瘤（MM）患者中的表达水平及其在预后评估中的价值。.采用ExoQuick试剂盒提取57例MM患者和20例健康体检者血清外泌体，用RT-qPCR检测血清外泌体中miR-21、miR-18a、miR-146a、Let-7b的相对表达水平，采用Spearman相关性分析研究miR-21、miR-18a、miR-146a、Let-7b表达水平与常规实验室指标之间的相关性，Kaplan-Meier生存曲线分析miR-21、miR-18a、miR-146a、Let-7b的表达水平与MM患者总体生存的关系。.MM患者血清外泌体来源的miR-21、miR-18a、Let-7b的表达水平均显著低于正常对照组（P0.001），而miR-146a在两组之间的表达水平无显著性差异（P0.05）。miR-21的表达水平与血清β血清外泌体来源的miR-21、miR-18a、Let-7b在MM患者中存在异常低表达，且与MM患者的总体生存率下降存在关联。.

BackgroundImmune system dysfunction has been proven to be an important pathological event in Alzheimer’s disease (AD). Mild cognitive impairment (MCI), as a transitional stage between normal cognitive function and AD, was an important research object for the screening of early diagnostic markers and therapeutic targets for AD. However, systematic assessment of peripheral immune system changes in MCI patients and consistent analysis with that in the CNS were still lacking.MethodsPeripheral blood transcriptome data from the AddNeuroMed Cohort (n = 711) was used as a training dataset to assess the abundance of 24 immune cells through ImmuCellAI and to identify MCI-related immune signaling pathways and hub genes. The expression level of the immune hub gene was validated in peripheral blood (n = 587) and brain tissue (78 entorhinal cortex, 140 hippocampi, 91 temporal cortex, and 232 frontal cortex) validation datasets. Finally, reliable immune hub genes were applied for Gene Set Enrichment Analysis and correlation analysis of AD pathological characteristics.ResultsMCI patients have early changes in the abundance of various types of immune cells in peripheral blood, accompanied by significant changes in NF-kB, TNF, JAK-STAT, and MAPK signaling pathways. Five hub immune-related differentially expressed genes (NFKBIA, CD4, RELA, CASP3, and HSP90AA1) were screened by the cytoHubba plugin in Cytoscape and the least absolute shrinkage and selection operator (LASSO) regression. Their expression levels were significantly correlated with infiltration score and the abundance of monocytes, natural killer cells, Th2 T cells, T follicular helper cells, and cytotoxic T cells. After validation with independent datasets derived from peripheral blood and brain, RELA and HSP90AA1 were identified as two reliable immune hub genes in MCI patients and had consistent changes in AD. The Gene Set Enrichment Analysis (GSEA) showed that their expression levels were closely associated with Alzheimer’s disease, JAK-STAT, calcium signaling pathway, etc. In addition, the expression level of RELA was positively correlated with β- and γ-secretase activity and Braak stage. The expression level of HSP90AA1 was negatively correlated with α- and β-secretase activity.ConclusionImmune system dysfunction was an early event in AD. It provides a new target for the early diagnosis and treatment of AD.

This research aimed to recover anthocyanin-rich extracts from blackberry (Rubus spp. Hull cultivar) by optimizing the processing conditions, and to characterize anthocyanin individuals and determine influences of optimization on enhancement of antioxidant and anti-hyperglycemic activities of anthocyanins as natural supplements. The ethanol concentration of 69.87%, HCl dosage of 0.53%, solid-to-liquid ratio of 1:19.06 at 47.68°C for 17.04 h were optimal to obtain the highest extraction yield of anthocyanins at 0.72 mg/g. By using AB-8 macroporous resins, the anthocyanin concentration of 3.0 mg/mL, ethanol concentration of 90%, and elution rate of 2.0 mL/min were selected to boost the anthocyanin purity up to be 60.11%. Moreover, the purified anthocyanin extracts from blackberry contained nine main pigments which could be divided into three aglycone-based forms, and cyanidin-3-O-glucoside was the most abundant among them. Due to the successive processes of extraction and purification, the blackberry purified anthocyanin extracts (BA-PAE) showed much higher bioactive capacities than the blackberry crude anthocyanin extracts (BA-CAE) and blackberry fruit slurry extracts (BA-FSE), e.g., DPPH and ABTS radical scavenging activities (EC50 = 0.08 and 0.04, 0.32 and 0.24, and 1.31 and 0.41 mg/mL), oxygen radical absorbance capacity (1.60, 0.59, and 0.15 mmol TEAC/g), cytoprotective effects against oxidative stress in PC12 cells (1.69-, 1.58-, and 1.50-fold cell viability compared to oxidative group), α-amylase and α-glucosidase inhibitory activities (IC50 = 0.10 and 0.06, 0.56 and 0.32, and 3.98 and 2.16 mg/mL), and antibacterial activity (93.23, 40.85, and 80.42% reduced biofilm).

LncRNA carbonyl reductase antisense RNA 1 (CBR3-AS1) is increased in cervical cancer and predicts poor prognosis. This study aims to investigate the underlying mechanism of lncRNA CBR3-AS1 in cervical cancer. LncRNA CBR3-AS1 and LASP1 expressions were significantly elevated in cervical cancer tissue and cells, whereas miR-3163 expression was significantly decreased in cervical cancer tissue and cells. High lncRNA CBR3-AS1 expression and LASP1 expression showed a lower overall survival rate, whereas high miR-3163 expression showed a higher overall survival rate. Correlation between clinicopathological parameters of cervical cancer patients and lncRNA CBR3-AS1, miR-3163, LASP1 expressions indicated that the expressions of lncRNA CBR3-AS1, miR-3163, and LASP1 were closely related with distant metastasis and lymphatic metastasis of cervical cancer. LncRNA CBR3-AS1 knockdown suppressed cervical cancer cell viability and inhibited cancer stem cell-like properties. Besides, we identified that lncRNA CBR3-AS1 interacted with miR-3163, and miR-3163 targeted to LASP1. Moreover, the correlation between lncRNA CBR3-AS1 and miR-3163, as well as the correlation between miR-3163 and LASP1 was confirmed. Finally, lncRNA CBR3-AS1 knockdown inhibited tumor growth and suppressed cancer stem cell-like properties of cervical cancer in vivo. Taken together, high expression of lncRNA CBR3-AS1 predicts poor prognosis in cervical cancer, and the lncRNA CBR3-AS1/miR-3163/LASP1 pathway plays a vital function in the modulation of cervical cancer cell proliferation and cancer stem cell-like properties.

Several studies have demonstrated the involvement of apolipoprotein C1 (APOC1) in multiple cancers. However, the role of APOC1 in esophageal cancer (ESCA) has not been elucidated. Hence, we examined the expression of APOC1 in ESCA tissues acquired from The Cancer Genome Atlas (TCGA) database and clinical samples from our hospital. An investigation of the association of APOC1 with the clinicopathological characteristics, prognosis, and diagnosis of ESCA was carried out on the basis of survival, receiver operating characteristics, and correlation analyses. Gene ontology, KEGG analysis, and protein-protein interaction network showed that co-expressed APOC1 genes were involved in the functions, mechanisms, and action network. The effects of APOC1 expression on ESCA cells were explored using CCK-8, migration and invasion assays. The relationship between APOC1 expression and ESCA immune-infiltrating cells and cell markers were examined using correlation analysis. We found that APOC1 was overexpressed in TCGA ESCA tissues and the same was validated in clinical ESCA tissues, with the area under the curve for APOC1 being 0.887. Overexpression of APOC1 was associated with short overall survival, disease-specific survival, progression-free interval, T stage, pathological stage, body mass index, and histological grade. Inhibition of APOC1 expression significantly reduced the proliferation, migration, and invasion of ESCA cells. Furthermore, APOC1 expression positively correlated with the ESTIMATE, immune, and stromal scores in ESCA. Overexpression of APOC1 correlated with the tumor purity, B cells, T helper cells, natural killer cells, cytotoxic cells, and other immune cells. Moreover, APOC1 was involved in ESCA progression via T cell receptor, B cell receptor, and other immune signaling pathways. Thus, APOC1 overexpression is expected to be a biomarker for dismal prognosis and diagnosis of ESCA. Inhibition of APOC1 expression significantly reduced the proliferation, migration, and invasion of ESCA cells. Overexpression of APOC1 was associated with the immune microenvironment in ESCA. Thus, APOC1 may be an efficient biomarker for proper prognosis and diagnosis of ESCA.

Triglyceride (TG) and its related metabolic indices, all recognized as surrogates of insulin resistance, have been demonstrated to be relevant to clinical prognosis. However, the relative value of these TG-related indices for predicting cardiovascular events among patients with acute coronary syndrome (ACS) has not been examined.The TG, the triglyceride-glucose (TyG) index, the atherogenic index of plasma, TG to high-density lipoprotein cholesterol ratio, and the lipoprotein combine index were assessed in 1694 ACS patients undergoing percutaneous coronary intervention. The primary endpoint was major adverse cardiovascular event (MACE), which was the composite of all-cause mortality, stroke, myocardial infarction, or unplanned repeat revascularization.During a median follow-up of 31 months, 345 patients (20.4%) had MACE. The risk of the MACE was increased with higher TG and the four TG-derived metabolic indices [TG-adjusted hazard ratio (HR) = 1.002, 95% CI: 1.001-1.003; TyG index-adjusted HR = 1.736, 95% CI: 1.398-2.156; atherogenic index of plasma-adjusted HR = 2.513, 95% CI: 1.562-4.043; TG to high-density lipoprotein cholesterol ratio-adjusted HR = 1.148, 95% CI: 1.048-1.258; and lipoprotein combine index-adjusted HR = 1.009, 95% CI: 1.004-1.014;TG and TG-derived metabolic indices were all strongly associated with MACE among ACS patients undergoing percutaneous coronary intervention. Among all the indices, TyG index showed the best ability to predict the risk of MACE.

PurposeCardiac syndrome X (CSX) is a condition with normal coronary angiography but angina pectoris. Chronic inflammation caused by Helicobacter pylori (H. pylori) infection may play a pathogenic role in CSX. Therefore, we conducted a meta-analysis to explore the relationship between H. pylori infection and risk of CSX.MethodsA systematic search in the Web of Science, Medline, Embase and Chinese databases (CNKI and Wanfang) was conducted up to October 2021. Articles on the association between H. pylori infection and the risk of CSX were included and were analyzed by R software (version 4.1.0).ResultsTen case-control studies involving 703 CSX patients and 731 healthy controls were included. H. pylori infection was associated with an increased risk of CSX (OR: 8.29, 95% CI: 4.64–14.82). We also found a significant association in those 25–40 years of age (OR: 1.34, 95% CI: 1.04–1.72), those 40–50 years of age (OR: 11.27, 95% CI: 4.29–29.61), those over 50 years of age (OR: 7.18, 95% CI: 3.59–14.36), those in developing countries [Iran (OR: 12.99, 95% CI: 8.61–19.60) and China (OR: 5.14, 95% CI: 3.09–8.56)]. However, this association was not apparent in a developed country [Italy (OR: 0.93, 95% CI: 0.37–2.33)].ConclusionsOur study suggested a possible association between H. pylori infection and the risk of CSX. Its pathogenicity is stronger in middle-aged individuals and some developing countries. However, more studies are needed to further investigate whether early eradication of H. pylori can reduce the incidence rate of CSX, especially in middle-aged individuals and some developing countries.

Cell cryopreservation is widely used for porcine genetic conservation; however, isolating and freezing primary cells in farms without adequate experimental equipment and environment poses a significant challenge. Therefore, it is necessary to establish a quick and simple method to freeze tissues on-site, which can be used for deriving primary fibroblasts when needed to achieve porcine genetic conservation. In this study, we explored a suitable approach for porcine ear tissue cryopreservation. The porcine ear tissues were cut into strips and frozen by direct cover vitrification (DCV) in the cryoprotectant solution with 15% EG, 15% DMSO and 0.1 M trehalose. Histological analysis and ultrastructural evaluation revealed that thawed tissues had normal tissue structure. More importantly, viable fibroblasts could be derived from these tissues frozen in liquid nitrogen for up to 6 months. Cells derived from thawed tissues did not show any cell apoptosis, had normal karyotypes and could be used for nuclear transfer. These results suggest that this quick and simple ear tissue cryopreservation method can be applied for porcine genetic conservation, especially in the face of a deadly emerging disease in pigs.

To explore the effect of hnRNPK/Beclin1 signaling on the drug resistance of imatinib in PhExpression level of hnRNPK was verified in the imatinib resistant and sensitive PhhnRNPK showed overexpressed in imatinib resistant leukemia cell line. After the expression level of hnRNPK was down-regulated by RNAi, the sensitivity of drug resistance lines to imatinib restored, while the expression level of LC3I/II and Beclin1 were consistant with the modulation of hnRNPK expression.hnRNP K/Beclin1 signaling may be involved in the development of imatinib resistance in PhhnRNPK/Beclin1信号异常对Ph探索hnRNPK/Beclin1信号异常与Ph用WB法检测hnRNPK在伊马替尼敏感和耐药细胞株中的表达水平差异。RNAi法沉默hnRNPK在耐药株中的表达水平。在hnRNPK表达调变前后，分别使用CCK-8法检测耐药细胞株对伊马替尼药物敏感性的变化，以及使用WB法检测自噬蛋白LC3I/II及Beclin1的表达水平变化.hnRNPK在伊马替尼耐药细胞株中的表达水平较敏感株明显增高，使用RNAi法降低hnRNPK的表达水平后，耐药株对伊马替尼的敏感性可以部分恢复，且自噬相关蛋白LC3I/II及Beclin1的表达与hnRNPK的表达变化一致.hnRNPK/Beclin1信号异常调控细胞自噬，进而参与Ph

BackgroundAlzheimer’s disease (AD) is the most common type of neurodegenerative disease. Tau pathology is one of the pathological features of AD, and its progression is closely related to the progress of AD. Immune system dysfunction is an important mediator of Tau pathological progression, but the specific molecular mechanism is still unclear. The purpose of this study is to determine the immune hub genes and peripheral immune cell infiltration associated with the Braak stages, and the molecular mechanisms between them.MethodsIn this study, 60 samples with different Braak stages in the GSE106241 dataset were used to screen Braak stages-related immune hub genes by using the WGCNA package in R and cytoHubba plugin. The temporal lobe expression data in the Alzdata database were used to verify the results. The correlation between the expression level of immune core genes and the pathological features of AD was analyzed to evaluate the abundance of peripheral immune cell infiltration and screened Braak stages-related cells. Finally, we used correlation analysis of immune hub genes and immune cells and Gene Set Enrichment Analysis (GSEA) of them.ResultsSeven genes (GRB2, HSP90AA1, HSPA4, IGF1, KRAS, PIK3R1, and PTPN11) were identified as immune core genes after the screening of the test datasets and validation of independent data. Among them, Kirsten rat sarcoma viral oncogene homolog (KRAS) and Phosphoinositide-3-Kinase Regulatory Subunit 1 (PIK3R1) were the most closely related to Tau and Aβ pathology in AD. In addition, the ImmuneScore increased gradually with the increase of Braak stages. Five types of immune cells (plasma cells, T follicular helper cells, M2 macrophage, activated NK cells, and eosinophils) were correlated with Braak stages. KRAS and PIK3R1 were the immune core genes most related to the abnormal infiltration of peripheral immune cells. They participated in the regulation of the pathological process of AD through axon guidance, long-term potentiation, cytokine–cytokine receptor interaction, RNA polymerase, etc.ConclusionThe KRAS and PIK3R1 genes were identified as the immune hub genes most associated with Tau pathological progress in AD. The abnormal infiltration of peripheral immune cells mediated by these cells was involved in the Tau pathological process. This provides new insights for AD.

Annual gross primary productivity (AGPP) is the basis for grain production and terrestrial carbon sequestration. Mapping regional AGPP from site measurements provides methodological support for analysing AGPP spatiotemporal variations thereby ensures regional food security and mitigates climate change. Based on 641 site-year eddy covariance measuring AGPP from China, we built an AGPP mapping scheme based on its formation and selected the optimal mapping way, which was conducted through analysing the predicting performances of divergent mapping tools, variable combinations, and mapping approaches in predicting observed AGPP variations. The reasonability of the selected optimal scheme was confirmed by assessing the consistency between its generating AGPP and previous products in spatiotemporal variations and total amount. Random forest regression tree explained 85 % of observed AGPP variations, outperforming other machine learning algorithms and classical statistical methods. Variable combinations containing climate, soil, and biological factors showed superior performance to other variable combinations. Mapping AGPP through predicting AGPP per leaf area (PAGPP) explained 86 % of AGPP variations, which was superior to other approaches. The optimal scheme was thus using a random forest regression tree, combining climate, soil, and biological variables, and predicting PAGPP. The optimal scheme generating AGPP of Chinese terrestrial ecosystems decreased from southeast to northwest, which was highly consistent with previous products. The interannual trend and interannual variation of our generating AGPP showed a decreasing trend from east to west and from southeast to northwest, respectively, which was consistent with data-oriented products. The mean total amount of generated AGPP was 7.03 ± 0.45 PgC yr

The aim of this work was to analyze the recrystallization behavior of cold rolled Aluminum/graphene composites during annealing. The Aluminum/graphene composite was cold rolled firstly, and then annealed at different temperature (250°C, 300°C, 350°C, 400°C) and for various time (1 h, 2 h, 8 h, 32 h). Full recrystallization did not occur until the annealing temperature was above 300 °C. With annealing temperature increasing from 250 to 300°C, the hardness of the composites decreased from 49.6 to 27.6 HV. Grain growth were not observed at high annealing temperature and longer annealing time, which suggested that Graphene has strong pinning effect on the grain boundary of Aluminum.

The purpose of this study was to evaluate the feasibility of the height-corrected definition of metabolic syndrome(MetS) in adolescents. A retrospective study was conducted on US adolescents aged 12 to 17 years. Waist-to-height ratio and blood pressure-to-height ratio were substituted for waist circumference and blood pressure when defining MetS in adolescents. The proportions of insulin resistance of adolescents with 1 (30.1%), 2 (50.7%), and ≥3 components (77.8%) of MetS were 2.578 ( P < .001), 6.882 ( P < .001), and 23.992 ( P < .001) times than the proportion of adolescents without the component of MetS (14.2%). The proportions of low-grade inflammation of adolescents with 1 (3.4%), 2 (5.3%), and ≥3 components (14.4%) of MetS were 2.050 ( P = .106), 3.699 ( P = .005), and 10.664 ( P < .001) times than the proportion of adolescents without the component of MetS (1.7%). This study demonstrates that height-corrected definition of MetS is a simple and accurate method for identifying insulin resistance and low-grade inflammation in adolescents.

A new seed-mediated growth technique for synthesizing gold nanorods (NRs) by using H2O2 as the weak reducer in the presence of a binary surfactant mixture is reported. Gold NRs prepared at different amounts of H2O2 and the gold seeds solution were characterized by transmission electron microscopy (TEM) and visible–near infrared spectroscopy. Gold NRs with tunable aspect ratio from 4.5 to 7 can be obtained and the corresponding longitudinal plasmonic wavelength of the produced gold NRs are tunable from 810 to 1140 nm. This method provides a new pathway for synthesis of gold NRs with a wide range of longitudinal plasmonic peaks, which have potential applications in optoelectronics and biomedicine.

Ultra-high-strength steels (UHSS), for instance, dual phase (DP) and martensitic steels, get growing challenges in strip metal forming processes of car industry manufacturing to achieve lightweight and improve passenger security. Predict and compensate for springback is still a major problems to be solved in cold roll forming (CRF) for complex section materials. In this study, the springback performance UHSS in cold roll forming is discussed by simulation and experimental methods. At the same time, one 3D FEA model was established to analyze the CRF process by COPPA RF and MSC MARC, in which planar swift’s model, anisotropic Hill’s 48 model, and Yid2000-2d model in the company with Yoshida-Uemori kinematic hardening pattern were investigated. Automobile threshold section CRF experiment and springback evaluation carried out through the comparison of numerical results. Considering Yoshida-Uemori kinematic hardening, the anisotropic Yid2000-2d model improves the springback prediction accuracy in CRF car threshold section in comparison with other models. The improved model is used to compensate the springback of product. A new method is proposed, which takes into account angle overbending compensation (AOC), small radius compensation (SRC), and revere-bending compensation (RBC) based on roll shape design. The method, which we call “USTB-Durable Integration of Springback Control (UDI),” is general for it considers the fact radius and angle would occur during springback. Compared with the AOC, SRC, and RBC method, the new method has higher precision especially for the springback compensation of ultra-high-strength complex section in CRF. The researchers are expected to conduct design engineer to calculate and compensate the springback trend before applying roller design to actual production.

Background Alzheimer's disease (AD) is the most common neurodegenerative disease and its pathogenesis is still unclear. There is dysbiosis of gut microbiota in AD patients. More importantly, dysbiosis of the gut microbiota has been observed not only in AD patients, but also in patients with mild cognitive impairment (MCI). However, the mechanism of gut microbiota dysbiosis in AD is poorly understood. Cholinergic anti-inflammatory pathway is an important pathway for the central nervous system (CNS) regulation of peripheral immune homeostasis, especially in the gut. Therefore, we speculated that dysfunction of cholinergic anti-inflammatory pathway is a potential pathway for dysbiosis of the gut microbiota in AD. Methods In this study, we constructed AD model mice by injecting Aβ1–42 into the lateral ventricle, and detected the cognitive level of mice by the Morris water maze test. In addition, 16S rDNA high-throughput analysis was used to detect the gut microbiota abundance of each group at baseline, 2 weeks and 4 weeks after surgery. Furthermore, immunofluorescence and western blot were used to detect alteration of intestinal structure of mice, cholinergic anti-inflammatory pathway, and APP process of brain and colon in each group. Results Aβ1–42 i.c.v induced cognitive impairment and neuron damage in the brain of mice. At the same time, Aβ1–42 i.c.v induced alteration of gut microbiota at 4 weeks after surgery, while there was no difference at the baseline and 2 weeks after surgery. In addition, changes in colon structure and increased levels of pro-inflammatory factors were detected in Aβ1–42 treatment group, accompanied by inhibition of cholinergic anti-inflammatory pathways. Amyloidogenic pathways in both the brain and colon were accelerated in Aβ1–42 treatment group. Conclusions The present findings suggested that Aβ in the CNS can induce gut microbiota dysbiosis, alter intestinal structure and accelerate the amyloidogenic pathways, which were related to inhibiting cholinergic anti-inflammatory pathways.

ObjectiveThe predictive performances of CURB-65 and pneumonia severity index (PSI) were poor in patients with diabetes. This study aimed to develop a tool for predicting the short-term and long-term outcomes of CAP in patients with diabetes.MethodsA retrospective study was conducted on 531 CAP patients with type 2 diabetes. The short-term outcome was in-hospital mortality. The long-term outcome was 24-month all-cause death. The APUA score was calculated according to the levels of Age (0-2 points), Pulse (0-2 points), Urea (0-2 points), and Albumin (0-4 points). The area under curves (AUCs) were used to evaluate the abilities of the APUA score for predicting short-term outcomes. Cox regression models were used for modeling relationships between the APUA score and 24-month mortality.ResultsThe AUC of the APUA score for predicting in-hospital mortality was 0.807 in patients with type 2 diabetes (PPPP=0.038).ConclusionThe APUA score is a simple and accurate tool for predicting short-term and long-term outcomes of CAP patients with diabetes.

This study was designed to predict the Q-markers of Citri Reticulatae Pericarpium volatile oil and conduct quantitative analysis by GC-MS. The common components of Citri Reticulatae Pericarpium volatile oil were detected by GC-MS. The network pharmacology approaches were utilized for constructing the component-target network and protein-protein interaction(PPI) network, followed by the GO and KEGG pathway enrichment analysis to clarify the pharmacological effects of common components. Molecular docking was conducted to observe the biological activities of common components, thus identifying the Q-markers of Citri Reticulatae Pericarpium volatile oil. The obtained Q-markers were subjected to quantitative analysis by GC-MS. The GC-MS analysis of 19 batches of Citri Reticulatae Pericarpium volatile oil revealed three common components, namely, D-limonene, γ-terpinene, and myrcene. The common components were analyzed based on network pharmacology, and the results showed that Citri Reticulatae Pericarpium volatile oil mainly acted on the core targets GABRA1, GABRA6, GABRA5, GABRA3, and GABRA2 through D-limonene and γ-terpinene, with five important pathways such as nicotine addiction and GABAergic synapse involved. The core targets were mainly distributed in olfactory region, cerebral cortex, cerebellum, basal ganglia, hippocampus, and amygdala to exert the pharmacological effects. As revealed by molecular docking, D-limonene and γ-terpinene exhibited good biological activities, so they were identified as the Q-markers of Citri Reticulatae Pericarpium volatile oil. The results of quantitative analysis showed that the volume fraction of D-limonene was within the range of 0.77-1.03 μL·mL~(-1), and that of γ-terpinene within the range of 0.04-0.13 μL·mL~(-1). The prediction of D-limonene and γ-terpinene as the Q-markers of Citri Reticulatae Pericarpium volatile oil has laid an experimental foundation for the establishment of the quality evaluation standard for Citri Reticulatae Pericarpium volatile oil.

Three diisobutylaminomethylated calix[4]resorcinarenes 4–6 were synthesized by the condensation reaction of resorcinarenes 1–3 with diisobutylamine and an excess of formaldehyde. The crystals and supramolecular structures of compounds 4–6 were determined by single crystal X-ray diffraction along with proton nuclear magnetic resonance spectroscopy. The resorcinarene molecules occur in the crystal in the bowl-like form, are stabilized by a collar of exquisite intramolecular hydrogen bonding networks which all proceed in the same direction around the upper rim of the macrocycle. Four amino groups involved in intramolecular hydrogen bonding enlarge the intramolecular cavity of the resorcinarene, which form an encapsulating with “lid” over an included CH2Cl2 guest molecule. Adjacent molecules of compounds 4–6 connect through intermolecular hydrogen bonds, which rotated and localized to a staggered orientation in order to minimize the steric repulsion between them. Dichloromethane acts as the guest molecule for the self-assembly of diisobutyaminomethylated calix[4]resorcinarenes supramolecular structures.

The aim of this study was to investigate the influence of rice wine (Jinbiao, Yinbiao, Wunianchen, Nv’erhong) on the endogenous protease activity, myofibrillar degradation, and quality characterist...

Two-step reactions of resorcin[4]arene (1) or methylresorcin[4]arene (2) with PPhCl2 and subsequent in situ oxidation with sulfur powder afforded a series of new thiophosphorylatocavitands 1a–1d or...

Co-crystallization of C-propyl-pyrogallol[4]arene (PgC3) with 4,4′-bipyridine (bpy) in ethanol afforded a multi-component complex (PgC3) · 3(bpy) ·(EtOH) (1) that consists of a one-dimensional brick-wall framework, which was formed by four pyrogallol[4]arene molecules and two juxtaposed bpy molecules, entrapping two other bpy molecules as guests within each cavity. Heating a mixture of PgC3 and trans-1,2-bis-(4-pyridyl)ethylene (bpe) in an ethanol-water mixed solvent allowed the isolation of a multi-component complex (PgC3) ·(bpe) · 2(EtOH) ·(H2O) (2), which has a two-dimensional wave-like polymer structure with the bpe molecules embedded in the wave trough between two PgC3 molecules. Single-crystal X-ray crystallography was utilized to investigate the hydrogen bonding networks of the multi-component complexes 1 and 2.

Self-assembly of the bowl-shaped C-alkylcalix[4]resorcinarene (alkyl = –iBu, CBCR; –CH2CH2Ph, CPCR) with the bifunctional spacer 4,4′-bipyridine (bipy) in alcohol solvent was investigated. Co-crystallization of CBCR with bipy in ethanol afforded a one-dimensional compound of CBCR·bipy·3EtOH (1). Heating a mixture of CPCR and bipy in ethanol led to the isolation of the compound CPCR·2bipy·EtOH (2), which has a one-dimensional wave-like polymer structure. Compounds 1 and 2 both crystallize in the triclinic space group P $$\bar{1}$$ , with a = 13.1615(2), b = 14.5201(3), c = 16.9082(4) A, α = 111.102(1)°, β = 96.976(1)°, γ = 103.979(1)°, and Z = 2 for 1, and a = 11.5175(4), b = 12.5727(5), c = 24.6775(10) A, α = 83.744(2)°, β = 89.306(2)°, γ = 71.110(2)°, and Z = 2 for 2. Two supramolecular structures based on C-alkylcalix[4]resorcinarene and 4,4′-bipyridine molecules have been synthesized and studied.

In this study, a magnetothermodynamic (MTD) therapy is introduced as an efficient systemic cancer treatment, by combining the magnetothermal effect and the reactive oxygen species (ROS)-related immunologic effect, in order to overcome the obstacle of limited therapeutic efficacy in current magnetothermal therapy (MTT). This approach was achieved by the development of an elaborate ferrimagnetic vortex-domain iron oxide nanoring and graphene oxide (FVIOs-GO) hybrid nanoparticle as the efficient MTD agent. Such a FVIOs-GO nanoplatform was shown to have high thermal conversion efficiency, and it was further proved to generate a significantly amplified ROS level under an alternating magnetic field (AMF). Both in vitro and in vivo results revealed that amplified ROS generation was the dominant factor in provoking a strong immune response at a physiological tolerable temperature below 40 °C in a hypoxic tumor microenvironment. This was supported by the exposure of calreticulin (CRT) on 83% of the 4T1 breast cancer cell surface, direct promotion of macrophage polarization to pro-inflammatory M1 phenotypes, and further elevation of tumor-infiltrating T lymphocytes. As a result of the dual action of magnetothermal effect and ROS-related immunologic effect, impressive in vivo systemic therapeutic efficacy was attained at a low dosage of 3 mg Fe/kg with two AMF treatments, as compared to that of MTT (high dosage of 6-18 mg/kg under four to eight AMF treatments). The MTD therapy reported here has highlighted the inadequacy of conventional MTT that solely relies on the heating effect of the MNPs. Thus, by employing a ROS-mediated immunologic effect, future cancer magnetotherapies can be designed with greatly improved antitumor capabilities.

The understanding of crack propagation characteristics and law of rocks during the loading process is of great significance for the exploitation and support of rock engineering. In this study, the crack propagation behavior of rocks in triaxial compression tests was investigated in detail. The main conclusions were as follows: 1) According to the evolution characteristics of crack axial strain, the differential stress-strain curve of rocks under triaxial compressive condition can be divided into three phases which are linear elastic phase, crack propagation phase, post peak phase, respectively; 2) The proposed models are applied to comparison with the test data of rocks under triaxial compressive condition and different temperatures. The theoretical data calculated by the models are in good agreement with the laboratory data, indicating that the proposed model can be applied to describing the crack propagation behavior and the nonlinear properties of rocks under triaxial compressive condition; 3) The inelastic compliance and crack initiation strain in the proposed model have a decrease trend with the increase of confining pressure and temperature. Peak crack axial strain increases nonlinearly with the inelastic compliance and the increase rate increases gradually. Crack initiation strain has a linear relation with peak crack axial strain.

To observe the curative efficacy of tyrosine kinase inhibitors (TKIs) in the treatment of e19a2 transcript (P230) CML chronic phase (CML-CP) patients.The clinical data of 11 P230 CML-CP patients were collected from July 2008 to December 2019. Blood routine examination, bone marrow cytology, chromosome, and BCR-ABL qualitative and quantitative tests were performed at initial diagnosis. After TKIs treatment, BCR-ABL (P230)/ABL in peripheral blood was regularly detected to evaluate molecular response by real-time quantitative PCR.There were 11 patients (7 males and 4 females) in chronic phase from 6 domestic hospitals enrolled, their median age was 46 years old (range from 19 to 56 years old). Among 4 patients treated with imatinib (400 mg, qd) firstly, 3 cases switched to nilotinib (400 mg, bid) and 1 case switched to dasatinib (100 mg, qd) due to failure to achieve best molecular response at the landmark time or mutation of ABL kinase. Then major molecular response (MMR) was obtained within 1 year. In addition, 5 patients were treated with nilotinib (300 mg, bid) and 2 patients with dasatinib (100 mg, qd) as first-line treatment, all of them got MMR within 6 months.For intolerance or resistance to imatinib, second-generation TKIs can enable P230 CML patients to achieve deeper molecular response, and MMR in a short time.酪氨酸激酶抑制剂治疗P230慢性髓系白血病临床疗效观察.观察酪氨酸激酶抑制剂（TKI）治疗e19a2转录本（P230）慢性髓系白血病（CML）慢性期患者的疗效。.收集2008年7月至2019年12月11例P230 CML慢性期患者临床资料，初诊时进行血常规、骨髓细胞学、染色体和BCR-ABL定性和定量检测，接受TKI治疗后，定期通过实时定量PCR方法检测外周血BCR-ABL（P230）/ABL评估分子学反应。.来自国内6家医院11例患者中男性7例，女性4例，中位年龄为46（19-56）岁。11例患者均处于慢性期，4例先接受伊马替尼（400 mg，qd）治疗的患者，由于在规定的时间界点未达到最佳分子学反应或出现ABL激酶区突变，其中3例改为尼洛替尼（400 mg，bid）治疗，1例改为达沙替尼（100 mg，qd）治疗，之后均在1年内获得主要分子学反应。另外5例使用尼洛替尼（300 mg，bid）、2例使用达沙替尼（100 mg，qd）作为一线治疗的患者在6个月内获得了主要分子学反应。.对伊马替尼不耐受或疗效不佳的P230 CML患者，二代TKI可使其达到更深层次分子学反应，且能在更短时间达到主要分子学反应。.

Aquaculture is one of the most efficient modes of animal protein production and plays an important role in global food security. Aquaculture animals exhibit extraordinarily diverse sexual phenotypes and underlying mechanisms, providing an ideal system to perform sex determination research, one of the important areas in life science. Moreover, sex is also one of the most valuable traits because sexual dimorphism in growth, size, and other economic characteristics commonly exist in aquaculture animals. Here, we synthesize current knowledge of sex determination mechanisms, sex chromosome evolution, reproduction strategies, and sexual dimorphism, and also review several approaches for sex control in aquaculture animals, including artificial gynogenesis, application of sex-specific or sex chromosome-linked markers, artificial sex reversal, as well as gene editing. We anticipate that better understanding of sex determination mechanisms and innovation of sex control approaches will facilitate sustainable development of aquaculture.

Background Sleep disorders persist in renal transplant patients and are an important determinant of low quality of life. This study aims to investigate the mediating role of rumination in the relationship between fatigue and sleep quality in kidney transplant recipients. Method A descriptive cross-sectional research design was implemented from April to September 2021.A general information questionnaire, Pittsburgh Sleep Quality Index (PSQI), Multidimensional Fatigue Inventory (MFI-20), and Rumination Response Scale (RRS) were used to investigate 192 kidney transplant patients who were re-examined at the outpatient departments of three first-class hospitals in Jinan, Shandong Province, China. The Pearson’s correlation coefficient and mediation analyses were used for the statistical and descriptive statistics analyses. Results The prevalence of sleep disorders among kidney transplant recipients was 19.3%. With rumination as a mediator, fatigue indirectly affected the patients’ sleep quality. This indirect effect was 0.10 (95% confidence interval: 0.154, 0.419). Medical staff should focus on fatigue symptoms and rumination of patients to enhance sleep quality of kidney transplant recipients. Conclusions The incidence of sleep disorders after renal transplantation was high.Rumination exerts a mediating role between fatigue and sleep quality.