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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.

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

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。.

BACKGROUND Paraneoplastic cerebellar degeneration (PCD), which is rare in clinical practice, is closely related to autoimmunity. Cases positive for anti-Yo antibodies (anti-Purkinje cytoplasmic antibody 1) are the main subtype of PCD. PCD is subacute cerebellar degeneration, and while it progresses over weeks to months, its resultant deficits last much longer. Cancer patients with anti-Yo antibody-positive PCD are very rare. Most of them are breast cancer or ovarian cancer patients but also occasionally lung cancer patients. CASE SUMMARY A 61-year-old woman presented with sudden vertigo, nausea, and vomiting for approximately 10 d. The patient's neurological examination showed torsion with downbeat nystagmus and ataxia of the right limb and trunk. Laboratory examination found that the patient's cerebrospinal fluid and serum were anti-Yo antibody-positive, positron emission tomography computed tomography showed an increased metabolic rate in the retroperitoneal lymph nodes, and the pathology of lymph node punctures in the retroperitoneum and neck suggested adenocarcinoma of the pancreaticobiliary duct, which strengthens the hypothesis of paraneoplastic origin. Intravenous immunoglobulin (IVIg) 0.4 g/kg/d for 5 d and methylprednisolone 160 mg for 3 d were initiated, which was reduced to 80 mg for 3 d and then to 40 mg for 7 d. After treatment with IVIg and a steroid, the patient's vertigo and ataxia alleviated. CONCLUSION The patient's vertigo and ataxia alleviated after treatment, suggesting that early immunotherapeutic intervention may have certain value in stopping neurological loss.

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.

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

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.

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.

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.

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

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.

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.

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.

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.

The extracellular electron transfer (EET) efficiency between electroactive microbes (EAMs) and electrode is a key factor determining the development of microbial electrochemical technology (MET). Currently, the low EET efficiency of EAMs limits the application of MET in the fields of organic matter degradation, electric energy production, seawater desalination, bioremediation and biosensing. Enhancement of the interaction between EAMs and electrode by interfacial engineering methods brings bright prospects for the improvement of the EET efficiency of EAMs. In view of the research in recent years, this mini-review systematically summarizes various interfacial engineering strategies ranging from electrode surface modification to hybrid biofilm formation, then to single cell interfacial engineering and intracellular reformation for promoting the electron transfer between EAMs and electrode, focusing on the applicability and limitations of these methodologies. Finally, the possible key directions, challenges and opportunities for future interfacial engineering to strengthen the microbial EET are proposed in this mini-review.

SPOCK1 is an extracellular proteoglycan and involved in tumor growth and metastasis in various cancers. 5-fluorouracil (5-FU) is commonly used for the treatment of colorectal cancer (CRC) in patients who receive concurrent chemoradiotherapy. However, the relationship between development of resistance to 5-FU and SPOCK1 remain unclear. In this study, we established two 5-fluorouracil (5-FU)-resistant CRC cell lines, HCT116/FU and LOVO/FU, and found that SPOCK1 is upregulated in 5-FU-resistance CRC cells compared with its parental cell line. knockdown of SPOCK1 in 5-FU-resistant CRC cells increases their sensitivity to 5-FU. In contrast, transient transfection of SPOCK1 enhanced HCT116 and LOVO cell resistance to 5-FU and reduced cell apoptosis. Mechanistically, SPOCK1 promoted 5-FU resistance by regulating PRRX1 expression and the downstream apoptosis signaling pathway. Taken together, our results revealed for the first time that SPOCK1 plays a crucial role in the resistance of CRC cells to 5-FU and indicated that targeting SPOCK1 may be a promising therapeutic strategy to overcome 5-FU resistance in CRC.

Lactic acid bacteria can provide benefits to human beings and transform phenolic substances to improve their potential functionality. It was of interest to develop black barley as a carrier of probiotics and nutraceutical supplement rich in more antioxidants. Due to fermentation, bacterial counting and free phenolic content in black barley increased to 9.54 ± 0.22 log cfu/mL and 5.61 ± 0.02 mg GAE/mL, respectively. Eleven phenolic compounds, including nine isoflavones and two nitrogenous compounds were characterized using UPLC-QTOF-MS, among which epicatechin, hordatine, and pelargonidin aglycone were largely enriched. Moreover, free phenolic extracts from fermented barley (F-BPE) played a greater role in scavenging DPPH radicals, reducing Fe

Knowledge of the sex determination system and sex-associated genes has important implications in physiology, ecology and evolution, but the mechanisms underlying sexual determination systems in turtles has not been fully elucidated, due to their remarkable variability and a lack of reference genomes in some species. In this report, we describe the first genome assembled at the chromosome scale for Mauremys mutica using Illumina and high-throughput chromatin conformation capture (Hi-C) technology. A total of 280.42 Gb of clean data were generated using the Pacific Biosciences platforms, which represented approximately 119× coverage of the Mauremys mutica genome. The assembly comprised 2.23 Gb with a contig N50 of 8.53 Mb and scaffold N50 of 141.98 Mb. Genome Hi-C scaffolding resulted in 26 pseudochromosomes containing 99.98% of the total assembly. Genome annotation predicted 24,751 protein-coding genes, and 97.23% of them were annotated. Comparative genomics analysis indicated that the lizard-snake-tuatara clade diverged from the bird-crocodilian-turtle clade at approximately 283.1-320.5 Mya. Additionally, positive selection of genes and gene families related to calcium signaling, neuroactive ligand-receptor interaction, and expansion of the hormone signaling pathway were identified, implicating their roles of sex regulation inMauremys mutica. High-quality genome assembly may provide a valuable genomic resource for further research investigating gene-environment interactions in Mauremys mutica.

Hereditary spastic paraplegia (HSP) is a group of genetic neurodegenerative disorders, which is characterized by the presence of progressive spasticity and weakness in bilateral lower limbs. Spastic paraplegia 62 (SPG62) caused by the endoplasmic reticulum lipid raft associated 1 (ERLIN1) gene mutation is a rare subtype of HSP. Herein, we report the case of the first Chinese SPG62 patient, explore the potential pathogenic mechanism and review ERLIN1-related HSP patients. A 23-year-old man had progressive difficulty in walking and gait abnormalities for more than 11 years. Physical examination showed slightly reduced muscle strength (5