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Jing-Jing Wu1,2, Yang Yang,3 Wen-Ting Peng,1 Jia-Chang Sun,1 Wu-Yi Sun,1 Wei Wei11Institute of Clinical Pharmacology of Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-Inflammatory and Immune Medicine, Hefei, Anhui 230032, People’s Republic of China; 2Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230601, People’s Republic of China; 3Department of Neurosurgery, The First Affiliated Hospital of University of Science and Technology of China, Hefei, Anhui 230036, People’s Republic of ChinaBackground: β2-adrenoceptors (β2-ARs) are expressed on the surface of immune cells, including tumor-associated macrophages (TAMs). Previous studies have demonstrated that the expression of β2-ARs in hepatocellular carcinoma (HCC) is significantly increased in vitro. However, the role of β2-AR in M2-polarized macrophages remains unclear. G protein-coupled receptor kinase 2 (GRK2) can regulate G protein-coupled receptor (GPCR). Previous studies showed that down-regulation of GRK2 in HCC contributes the HCC progression, but it still remains unclear whether the regulation of β2-AR in M2-polarized macrophages by GRK2 can promote HCC.Purpose: The present study was designed to investigate the role of activated β2-AR in M2-polarized macrophages in the HCC progression and GRK2 regulatory effect, as well as the underlying mechanisms involved.Results: The results demonstrated that the M2-polarized macrophages were increased with HCC progression. In vitro, the activation of β2-AR by terbutaline in M2-polarized macrophages elevated the proliferative, migratory and invasive attributes of HCC cells. Furthermore, GRK2 down-regulation in β2-AR activated M2-polarized macrophages activated the downstream cyclic adenosine monophosphate (cAMP)/protein kinase A/cAMP-response element binding protein and cAMP/interleukin-6/signal transducer and the activator of transcription 3 signaling pathways, contributing to the secretion of tumor-associated cytokines, and thus resulting in the promotion of malignant biological behavior in HCC cells.Conclusion: These findings suggest that the regulation of β2-AR occurs through the silencing of GRK2 in M2-polarized macrophages, which is conducive to HCC development, through its engagement in the activation of downstream signaling.Keywords: hepatocellular carcinoma, tumor microenvironment, macrophage, beta2-adrenoceptor, G protein-coupled receptor kinase 2, therapeutic target

Wei-Xian Chen,1,2 Ling-Yun Xu,1 Lin Cheng,1 Qi Qian,1 Xiao He,1 Wen-Ting Peng,1 Yu-Lan Zhu11Department of Breast Surgery, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou 213000, People’s Republic of China; 2Department of Post-doctoral Working Station, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou 213000, People’s Republic of ChinaBackground: Resistance to docetaxel is a major obstacle to effective treatment of breast cancer. Exosomal microRNAs (miRNAs) have recently been introduced in cell-to-cell transmission of chemoresistance between heterogeneous populations of tumor cells with diverse drug sensitivity. However, a systematic evaluation of the exosomal miRNA signature remains largely unclear.Method: miRNA expression profiles in exosomes from docetaxel-resistant (D/exo) and parental sensitive breast cancer cells (S/exo) were assessed using microarray. Bioinformatics analysis was performed to predict target genes of the dysregulated miRNAs and to uncover their potential roles in chemoresistance formation. Signaling pathways, gene ontology terms, transcription factors, protein–protein interactions, and hub genes were also constructed.Results: The selected exosomal miRNAs could modulate target genes responsible for MAPK, TGF-beta, Wnt, mTOR, and PI3K/Akt signaling pathways. Function enrichment analysis revealed the involvement of target genes in transcription regulation, protein phosphorylation, kinase activity, and protein binding. Enriched transcription factors including SP1, SP4, and EGR1 were obtained and a protein–protein interaction network was established. The hub genes for up-expressed and down-expressed exosomal miRNAs such as CCND1 and PTEN were identified.Conclusion: This bioinformatics study provides a comprehensive view of the function of dysregulated exosomal miRNAs, and may help us to understand exosome-mediated resistance transmission and overcome docetaxel resistance in future breast cancer therapy.Keywords: breast cancer, exosomes, microRNA, chemoresistance, docetaxel

Background: Liver transplantation (LT) is the only curative treatment for end-stage liver disease. However, LT recipients are susceptible to infection, which is the leading cause of early mortality after LT. Klebsiella pneumoniae infections (KPIs) in the bloodstream are common in LT recipients. We hypothesized that KPIs and carbapenem-resistant Klebsiella pneumoniae (CRKP) infections may affect the outcomes of LT recipients., Aim: To assess KPI incidence, timing, distribution, drug resistance, and risk factors following LT and its association with outcomes., Methods: This retrospective study included 406 patients undergoing LT at The Third Xiangya Hospital of Central South University, a tertiary hospital, from January 2015 to January 2023. We investigated the risk factors for KPIs and assessed the impact of KPIs and CRKP infections on the prognosis of LT recipients using logistic regression analysis., Results: KPI incidence was 7.9% ( n = 32), with lung/thoracic cavity the most frequent site of infection; the median time from LT to KPI onset was 7.5 d. Of 44 Klebsiella pneumoniae isolates, 43 (97.7%) and 34 (77.3%) were susceptible to polymyxin B or ceftazidime/avibactam and tigecycline, respectively; > 70% were resistant to piperacillin/ tazobactam, ceftazidime, cefepime, aztreonam, meropenem, and levofloxacin. Female sex [odds ratio (OR) = 2.827, 95% confidence interval (CI): 1.256-6.364; P = 0.012], pre-LT diabetes (OR = 2.794, 95%CI: 1.070-7.294; P = 0.036), day 1 post-LT alanine aminotransferase (ALT) levels ≥ 1500 U/L (OR = 3.645, 95%CI: 1.671-7.950; P = 0.001), and post-LT urethral catheter duration over 4 d (OR = 2.266, 95%CI: 1.016-5.054; P = 0.046) were risk factors for KPI. CRKP infections, but not KPIs, were risk factors for 6-month all-cause mortality post-LT., Conclusion: KPIs occur frequently and rapidly after LT. Risk factors include female sex, pre-LT diabetes, increased post-LT ALT levels, and urethral catheter duration. CRKP infections, and not KPIs, affect mortality., Competing Interests: Conflict-of-interest statement: All the Authors have no conflict of interest related to the manuscript., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: The efficacy and safety profile of tenofovir amibufenamide (TMF) in chronic hepatitis B (CHB) patients is not well-established., Aim: To compare the efficacy and safety of TMF and tenofovir alafenamide (TAF) over a 48-wk period in patients with CHB., Methods: A total of 215 subjects meeting the inclusion criteria were enrolled and divided into two groups: TMF group ( n = 106) and the TAF group ( n = 109). The study included a comparison of virological response (VR): Undetectable hepatitis B virus DNA levels, alanine transaminase (ALT) normalization rates, renal function parameters, and blood lipid profiles., Results: At 24 and 48 wk, VR rates for the TMF group were 53.57% and 78.57%, respectively, compared with 48.31% and 78.65% for the TAF group ( P > 0.05). The VR rates were also similar in both groups among patients with low-level viremia, both hepatitis B e antigen (HBeAg)-positive and HBeAg-negative subgroups. The TMF cohort showed ALT normalization and renal safety profiles similar to the TAF group. There was a notable increase in total cholesterol levels in the TAF group ( P = 0.045), which was not observed in the TMF group ( P > 0.05). In patients with liver cirrhosis, both groups exhibited comparable VR and ALT normalization rates and renal safety profiles. However, the fibrosis 4 score at 48 wk showed a significant reduction in the TAF group as compared to the TMF group within the liver cirrhosis subgroup., Conclusion: Our study found TMF is as effective as TAF in treating CHB and has a comparable safety profile. However, TAF may be associated with worsening lipid profiles., Competing Interests: Conflict-of-interest statement: We have no financial relationships to disclose., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with unfavorable outcomes. Developing therapeutic targets for TNBC remains a challenge. Here, we identified that acetyl-CoA acyltransferase 1 (ACAA1) is highly expressed in the luminal androgen receptor (LAR) subtype of TNBC compared with adjacent normal tissues in our TNBC proteomics dataset. Inhibition of ACAA1 restrained TNBC proliferation and potentiated the response to the cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor abemaciclib. Mechanistically, ACAA1 interacted with CDK4, and the inhibition of ACAA1 blocked RB transcriptional corepressor 1 (RB1) phosphorylation, resulting in G1-S cell-cycle arrest. Importantly, trimetazidine, a traditional drug for ischemic heart disease, caused a decrease in ACAA1 protein levels and enhanced the efficacy of abemaciclib in preclinical TNBC models. In conclusion, this study identifies that ACAA1 is a therapeutic target in TNBC and suggests the combination of trimetazidine and abemaciclib could be beneficial for ACAA1-high TNBCs., Significance: ACAA1 is highly expressed in TNBC, serving as a potential therapeutic target in ACAA1-high tumors and a predictive biomarker of resistance to CDK4/6 inhibitors for RB1-proficient patients., (©2023 American Association for Cancer Research.)

Objective: To analyze the incidence, the onset time, and the risk factors of delirium after liver transplantation (LT)., Methods: The clinical data of 211 patients who underwent LT at Third Xiangya Hospital, Central South University between January 2019 and December 2021 were collected to investigate the incidence and the onset time of postoperative delirium. Univariate analysis and multivariate logistic regression analysis were conducted to analyze the risk factors of delirium and to analyze the effect of delirium on clinical outcomes., Results: The incidence of delirium was 20.4% (43/211) and the median interval between LT and the onset of delirium was 19 hours. Univariate analysis showed that the preoperative Model for End-Stage Liver Disease (MELD) score≥22, preoperative length-of-stay≥7, liver cancer, preoperative hepatic encephalopathy, infections within 2 months before LT, preoperative lymphocyte value<0.5×10 9 L －1 , massive amount of intraoperative red blood cell infusion, and carbapenem antibiotics use for 3 days or longer were associated with postoperative delirium. Multivariate logistic regression analysis showed that preoperative infections within 2 months before LT (odds ratio [ OR ]=2.597, 95% confidence interval [ CI ]: 1.135-5.944, P =0.024), preoperative MELD score≥22 ( OR =2.967, 95% CI : 1.104-7.975, P =0.031), and preoperative hepatic encephalopathy ( OR =4.700, 95% CI : 2.043-10.602, P <0.001) were independent risk factors for delirium after LT, while carbapenems antibiotics use for 3 days or longer ( OR =0.192, 95% CI : 0.083-0.441, P <0.001) was a protective factor for postoperative delirium among LT recipients. Regarding clinical outcomes, patients with delirium had longer postoperative ICU length-of-stays than those without delirium did ( P =0.025)., Conclusion: There is a high incidence of postoperative delirium among patients who undergo LT and the onset time of delirium after LT is early. Risk factors include preoperative infections, high MELD score, and hepatic encephalopathy. On the other hand, the use of carbapenems can help prevent delirium., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Objective: To investigate the dietary nutrient intake and the nutritional status of children with Duchenne muscular dystrophy (DMD), and to explore the correlation between them, so as to provide theoretical basis for the formulation of proper nutritional treatment for children with DMD., Methods: A total of 223 children aged 2 to 14 years who came to West China Second University Hospital, Sichuan University from July 2017 to April 2021, and who were diagnosed with DMD by genetic testing were enrolled as the subjects of the study. Dietary assessment was conducted with a 3-day 24-hour dietary recall, and serum vitamin D level was measured by chemiluminescence method., Results: Only 33.2% of the children with DMD were found to be of normal nutritional status. The incidences of stunted growth, underweight, overweight and obesity were 13.5%, 14.4%, 14.3% and 8.1%, respectively. Among the children with DMD, those with serum vitamin D deficiency and insufficiency accounted for 9.0% and 89.7%, respectively. According to the dietary recall of the children with MDM, the daily energy ratio of carbohydrate, protein and fat were (47.40±6.64)%, (14.46±2.22)%, and (38.17±5.30)%, respectively. The daily intake of dietary calcium and vitamin D were (433.32±164.39) mg per day and (155.73±89.30) IU per day, respectively. The ratio of daily protein intake to the estimated average requirement for protein ( P =0.003) and ratio of daily energy intake to the estimated energy requirement ( P =0.007) were lower in children with stunted growth than those of DMD children of normal nutritional status., Conclusion: The dietary structure of children with DMD is obviously not suited to their condition and nutritional deficiency coexists with overnutrition among them. Further research needs to be done for developing appropriate nutritional guidance programs and standardized nutritional management measures for children with DMD., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Symbiotic nitrogen fixation provides large amounts of nitrogen for global agricultural systems with little environmental or economic costs. The basis of symbiosis is the nutrient exchange occurring between legumes and rhizobia, but key regulators controlling nutrient exchange are largely unknown. Here, we reveal that magnesium (Mg), an important nutrient factor that preferentially accumulates in inner cortical cells of soybean nodules, shows the most positive correlation with nodule carbon (C) import and nitrogen (N) export. We further identified a pair of Mg transporter genes, GmMGT4 and GmMGT5, that are specifically expressed in the nodule cortex, modulating both nodule Mg import and C-N transport processes. The GmMGT4&5-dependent Mg import activates the activity of a plasmodesmata-located β-1,3-glucanase GmBG2 and consequently keeps plasmodesmata permeable for C-N transport in nodule inner cortical cells. Our studies discovered an important regulating pathway for host plants fine-tuning nodule C-N trading to achieve optimal growth, which may be helpful for optimizing nutrient management for soybean production., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Quantum dynamical simulations are essential for a molecular-level understanding of light-induced processes in optoelectronic materials, but they tend to be computationally demanding. We introduce an efficient mixed quantum-classical nonadiabatic molecular dynamics method termed eXcitonic state-based Surface Hopping (X-SH), which propagates the electronic Schrödinger equation in the space of local excitonic and charge-transfer electronic states, coupled to the thermal motion of the nuclear degrees of freedom. The method is applied to exciton decay in a 1D model of a fullerene-oligothiophene junction, and the results are compared to the ones from a fully quantum dynamical treatment at the level of the Multilayer Multiconfigurational Time-Dependent Hartree (ML-MCTDH) approach. Both methods predict that charge-separated states are formed on the 10-100 fs time scale via multiple "hot-exciton dissociation" pathways. The results demonstrate that X-SH is a promising tool advancing the simulation of photoexcited processes from the molecular to the true nanomaterials scale.

Acute respiratory distress syndrome (ARDS) is a critical disease with a high mortality rate, characterized by obstinate hypoxemia caused by accumulation of alveolar fluid and excessive uncontrolled inflammation. Na,K-ATPase α1 (ATP1A1) subunit is an important component of Na,K-ATPase that transports Na + and K + and scavenges alveolar fluid. The function of Na,K-ATPase is always impaired during ARDS and results in more severe symptoms of ARDS. However, the regulatory mechanism of Na,K-ATPase after ARDS remains unclear. Here, we revealed ATP1A1 was downregulated post-transcriptionally by an E3 ligase component CUL4B mediated proteasomal degradation. Moreover, we found insulin could inhibit the upregulation of CUL4B in an insulin receptor cofactor HCF-1-dependent manner. Our study resolved the molecular mechanism underlying the clearance impairment of alveolar fluid and provided a clue for the usage of insulin as a potential therapeutic medicine for ARDS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Upon injury, the liver is capable of substantial regeneration from the original tissue until an appropriate functional size. The underlying mechanisms controlling the liver regeneration processes are not well elucidated. Previous studies have proposed that the transcription factor FoxO3 is involved in various liver diseases, but its exact role in the regulation of liver regeneration remains largely unclear. To directly test the detailed role of FoxO3 in liver regeneration, both a constitutive Albumin-Cre driver line and adeno-associated virus serotype 8 (AAV8)-Tbg-Cre (AAV-Cre)-injected adult FoxO3 fl/fl mice were subjected to 70% partial hepatectomy (PH). Our data demonstrate that FoxO3 deletion accelerates liver regeneration primarily by limiting polyploidization and promoting the proliferation of hepatocytes during liver regeneration. RNA-seq analysis indicates that FoxO3 deficiency greatly alters the expression of gene sets associated with cell proliferation and apoptosis during liver regeneration. Chromatin immunoprecipitation-PCR (ChIP-PCR) and luciferase reporter assays reveal that FoxO3 promotes the expression of Nox4 but suppresses the expression of Nr4a1 in hepatocytes. AAV8 virus-mediated overexpression of Nox4 and knockdown of Nr4a1 significantly suppressed hepatocyte proliferation and liver regeneration in FoxO3-deficient mice. We demonstrate that FoxO3 negatively controls hepatocyte proliferation through Nox4 upregulation and Nr4a1 downregulation, thereby ensuring appropriate functional regeneration of the liver. Our findings provide novel mechanistic insight into the therapeutic mechanisms of FoxO3 in liver damage and repair., (© 2022. The Author(s).)

Background: Head and neck squamous carcinoma (HNSC) is one of the most common malignant tumors with high incidence and poor prognosis. Transmembrane emp24 structural domain (TMED) proteins are involved in protein transport and vesicle budding processes, which have implicated various malignancies' progression. However, the roles of TMEDs in HNSC, especially in terms of development and prognosis, have not been fully elucidated. Methods: We applied TIMER 2.0, UALCAN, GEPIA 2, Kaplan-Meier plotter, GEO, The Human Protein Atlas (HPA), cBioPortal, Linkedomics, Metascape, GRNdb, STRING, and Cytoscape to investigate the roles of TMED family members in HNSC. Results: Compared with normal tissues, the mRNA expression levels of TMED1/2/4/5/7/8/9/10 were significantly increased in the TCGA HNSC dataset. And we combined GEPIA 2 and Kaplan-Meier Plotter to select TMED2/9/10 with prognostic value. Then we detected the levels of mRNA in the GEO HNSC database and the protein expression in HPA. It was found that the mRNA and protein expression levels of TMED2/9/10 were increased in HNSC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that TMED2/9/10 and their co-expressed genes promoted the malignant behavior of tumors by participating in biological processes such as intracellular transferase complex, protein transport, focal adhesion, intracellular protein processing. Single-cell analysis and immune infiltration analysis suggested that immune responses of cancer-associated fibroblasts and endothelial cells might be associated with prognosis. Finally, the transcription factors-genes network and protein-protein functional interaction network pointed to genes such as X-box binding protein 1 (XBP1) and TMED7, which might cooperate with TMED2/9/10 to change the progression of HNSC. Conclusions: Our study implied that TMED2/9/10 and related genes mightjointly affect the prognosis of HNSC, providing specific clues for further experimental research, personalized diagnosis strategies, and targeted clinical therapy for HNSC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer HZ declared a shared parent affiliation with the author(s) to the handling editor at the time of review., (Copyright © 2022 Gao, Zhang, Wang, Li, Peng, Guan, Liao and Liu.)

Designing molecular materials with very large exciton diffusion lengths would remove some of the intrinsic limitations of present-day organic optoelectronic devices. Yet, the nature of excitons in these materials is still not sufficiently well understood. Here we present Frenkel exciton surface hopping, an efficient method to propagate excitons through truly nano-scale materials by solving the time-dependent Schrödinger equation coupled to nuclear motion. We find a clear correlation between diffusion constant and quantum delocalization of the exciton. In materials featuring some of the highest diffusion lengths to date, e.g. the non-fullerene acceptor Y6, the exciton propagates via a transient delocalization mechanism, reminiscent to what was recently proposed for charge transport. Yet, the extent of delocalization is rather modest, even in Y6, and found to be limited by the relatively large exciton reorganization energy. On this basis we chart out a path for rationally improving exciton transport in organic optoelectronic materials., (© 2022. The Author(s).)

We report a comprehensive proteomic study of a 90-case cohort of paired samples of triple-negative breast cancer (TNBC) in quantification, phosphorylation, and DNA-binding capacity. Four integrative subtypes (iP-1-4) are stratified on the basis of global proteome and phosphoproteome, each of which exhibits distinct molecular and pathway features. Scaffold and co-expression network analyses of three proteomic datasets, integrated with those from genome and transcriptome of the same cohort, reveal key pathways and master regulators that, characteristic of TNBC subtypes, play important regulatory roles within and between scaffold sub-structures and co-expression communities. We find that NAE1 is a potential drug target for subtype iP-1, and a series of key molecules in fatty acid metabolism, such as AKT1/FASN, are plausible targets for subtype iP-2. Libraries of proteins, pathways and networks of TNBC provide a valuable molecular infrastructure for further clinical exploration and in-depth studies of the molecular mechanisms of the disease., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

In this study, black geotextile inter-row mulch, a weed control practice, was applied under a semi-arid climate to attenuate solar reflection in 2015-2017, and it concurrently increased soil temperature and fruit-zone high temperature duration and decreased low temperature duration. Inter-row mulch decreased anthocyanins concentrations in grapes in 2015-2016, and consistently inhibited flavonols accumulation in 2015-2017. Correlation analysis between microclimate parameters and flavonoids concentrations reflected the importance of solar reflection, fruit-zone high and low temperature duration, heat accumulation and soil temperature to flavonoids accumulation. Basal leaf removal, a widely applied practice to increase fruit-zone light exposure, was applied to mulch-treated grapevines to investigate if increasing incident light could mitigate the impact of inter-row mulch on flavonoids, and it had limited influence on anthocyanins whereas compensated the loss of flavonols in grapes caused by inter-row mulch. Notably, inter-row mulch wines showed less red and more yellow color than controls because of lower anthocyanins concentrations., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: β-arrestin2 and β2-adrenergic receptor (β2-AR) have important roles in malignant tumors, the present study aims to investigate the role of activated β2-AR in hepatic stellate cells (HSCs) during hepatocellular carcinoma (HCC) progression and the regulatory effect of β-arrestin2. Methods: Immunofluorescence and Western blot were used to detect the expression of β-arrestin2 and β2-AR in HSCs of liver tissues from human HCC samples and diethylnitrosamine (DEN)-induced HCC model mice. We next used β-arrestin2 -/- mice to demonstrate the regulatory role of β-arrestin2 in DEN mice. The subsets of T cells were quantified by flow cytometry. MTT and wound healing assay were applied to detect the proliferation and migration of cells. Co-immunoprecipitation assay was used to detect the link of β-arrestin2 and β2-AR in HSCs. Effect of β-arrestin2 overexpression on β2-AR downstream signaling pathway was verified by Western blot. The secretion of CCL2 was detected by ELISA. Results: The expression of β2-AR was significantly increased, while β-arrestin2 was decreased in HSCs of HCC tissues. And β-arrestin2 deficiency exacerbates DEN-induced HCC accompanied with increased β2-AR expression. The results of flow cytometry showed that the percentage of activated T cells decreased gradually after DEN injection. β-arrestin2 knockout down-regulated the ratio of activated T cells. In vitro , selective activation of β2-AR in HSCs promoted the proliferation and migration of HCC cells. β-arrestin2 overexpression enhanced co-immunoprecipitation of β-arrestin2 and β2-AR in activated HSCs, and decreased its downstream Akt phosphorylation. Akt inhibitor decreased secretion of CCL2 in activated HSCs. Conclusion: Our study demonstrated that β2-AR activation in HSCs induces the proliferation and migration of HCC cells may be through Akt signaling, and this effect appears to be regulated by β-arrestin2., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Copper nano-interconnects are ubiquitous in semiconductor devices. The electrical and thermal properties of copper nanowires (CuNWs) profoundly affect the performance of electronics. In contrast to the intensively studied electrical properties of CuNWs, the thermal conductivities of CuNWs have seldom been examined. In this study, the electrical resistivity and thermal conductivity of single CuNWs were investigated. The Bloch-Grüneisen formula was introduced to determine the mechanisms responsible for the obtained electrical resistivity of the CuNWs. High residual resistivity was found, which indicated strong structural scattering on the electron transport resulting from defect scattering and boundary scatterings at the copper-copper oxide interface and grain boundaries. The mean structural scattering distance was employed to appreciate the degree of structural scattering in the CuNWs. The residual resistivity and electron-phonon coupling parameter were found to increase with the degree of structural scattering. Moreover, the unified thermal resistivity was introduced to illustrate the mechanisms responsible for the CuNWs' thermal conductivities. Similarly, large values of residual unified thermal resistivity and electron-phonon-induced unified thermal resistivity were found. The obtained unified thermal resistivities of the CuNWs could also be qualitatively explained by the degree of structural scattering in the CuNWs. The results suggested that structural scattering was predominant in the electrical current transport and heat transfer in the nanowires. This study revealed the mechanisms of electrical resistivity and thermal conductivity of CuNWs, and the insights could assist in improving the design of semiconductor architectures.

In this study, fruit-zone microclimate was modified by three treatments, including inter-row mulch (M), the combination of leaf removal applied at the onset of veraison and inter-row mulch (MLR-BV), and the combination of leaf removal applied at complete veraison and inter-row mulch (MLR-EV), in a semi-arid climate in three consecutive years (2015-2017). M decreased fruit-zone reflected solar radiation from vineyard floor and low temperature (10-20 °C) duration, whereas it increased soil temperature and high temperature (> 30 °C) duration. MLR-BV and MLR-EV increased fruit-zone incident photosynthetically active radiation while decreased the duration of 20-25 °C compared to M. Notably, M significantly decreased grape total norisoprenoid concentrations in 2015-2017, and total terpenoid concentrations in 2015-2016. Applying leaf removal applied at the onset of veraison could compensate the decreases of total norisoprenoids and terpenoids caused by M when two treatments were applied together. Besides, M significantly increased grape total C 6 /C 9 compound concentrations, besides, (Z)-3-hexen-1-ol concentrations were significantly higher in grapes of M than those of MLR-BV in 2015-2017. Light exposure and high temperature duration after veraison had strong positive correlations with total norisoprenoids and terpenoids, besides, low temperature duration was positively correlated with total norisoprenoids. In addition, light exposure after veraison had strong negative correlations with total C 6 /C 9 compounds. With respect to the volatile compounds in wines, M significantly decreased the concentrations of isopentanol and ethyl acetate, and the concentrations of ethyl cinnamate, phenylacetaldehyde, phenylethyl alcohol and 3-methylthio-1-propanol were significantly lower in MLR-BV and MLR-EV than in M. The outcome of this study can assist winegrowers to properly adjust vineyard managements to optimize the concentrations of desired volatile compounds in grapes and wines., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: To determine the level and influencing factors of informal caregiver burden in gynaecological oncology inpatients receiving chemotherapy., Methods: This cross-sectional study enrolled gynaecological oncology patients and their informal caregivers between May 2018 and November 2018 and measured the caregivers' burden using the Caregiver Burden Inventory. The influencing factors were evaluated with univariate regression analysis and multivariate linear stepwise regression analysis., Results: A total of 138 patients and their informal caregivers completed the questionnaire. The mean ± SD total informal caregiver burden score was 53.18 ± 10.97. The highest mean ± SD score was recorded in the dimension of time-dependent burden (14.28 ± 2.74), followed by developmental burden (13.65 ± 2.15), physical burden (10.52 ± 2.07), social burden (7.61 ± 2.58) and emotional burden (7.12 ± 1.43). Multivariate analysis showed that the informal caregiver's sex, relationship to the patient, daily duration of care, presence of chronic health problems and the duration of the patient's disease were factors influencing the level of caregiver burden., Conclusions: The informal caregivers of gynaecological cancer patients hospitalized for chemotherapy experience a moderate level of burden. Nursing measures should be considered to reduce informal caregiver burden and improve the quality of lives of both patients and their caregivers.

Colorectal cancer (CRC) is a malignant cancer with high incidence and mortality in the world. Immunotherapy targeting neoantigens can induce durable tumor regression in cancer patients, but is almost limited to personalized precision therapy, due to the individual differences of unique neoantigens. With the discovery of many common oncogenic mutations, and such mutation-associated neoantigens could cover more patients, and hence are valuable in clinical field. However, whether the common neoantigens can be identified in CRC is unknown. Combining the somatic mutations data from 321 CRC patients with a filter standard and 7 predicted algorithms, we screened and obtained 25 HLA-A*1101-restricted common neoantigens with a high binding affinity (IC 50 <50 nmol/L) and presentation score (>0.90). Besides the positive epitope KRAS&#95;G12V 8-16 , 11 out of 25 common neoantigens specifically induced in vitro pre- stimulated cytotoxic lymphocyte (CTL) to secrete interferon gamma (IFN-γ). Moreover, combining cell-sorting technology and single-cell RNA sequencing, the immune repertoire profiles of C1orf170&#95;S418G 413-421 and KRAS&#95;G12V 8-16 -specific CTL were analyzed and validated. Their related T-cell receptor engineered T cell (TCR-T) cells could also recognize the neoantigens and secrete IFN-γ. Hence, we have established a method to screen for common neoantigens with immunogenicity in CRC based on the public somatic mutation library. It can provide essential peptide and TCR information for immunotherapies, such as peptides, dendritic cells (DC) vaccines, TCR-like antibodies, TCR-T, etc., for the CRC and other cancers, which has practical application value in the clinics.

Effective legume-rhizobia symbiosis depends on efficient nutrient exchange. Rhizobia need to synthesize iron-containing proteins for symbiotic nitrogen fixation (SNF) in nodules, which depends on host plant-mediated iron uptake into the symbiosome. We functionally investigated a pair of vacuolar iron transporter like (VTL) genes, GmVTL1a/b, in soybean (Glycine max) and evaluated their contributions to SNF, including investigations of gene expression patterns, subcellular localization, and mutant phenotypes. Though both GmVTL1a/b genes were specifically expressed in the fixation zone of the nodule, GmVTL1a was the lone member to be localized at the tonoplast of tobacco protoplasts, and shown to facilitate ferrous iron transport in yeast. GmVTL1a targets the symbiosome in infected cells, as verified by in situ immunostaining. Two vtl1 knockout mutants had lower iron concentrations in nodule cell sap and peribacteroid units than in wild-type plants, suggesting that GmVTL1 knockout inhibited iron import into symbiosomes. Furthermore, GmVTL1 knockout minimally affected soybean growth under nonsymbiotic conditions, but dramatically impaired nodule development and SNF activity under nitrogen-limited and rhizobia-inoculation conditions, which eventually led to growth retardation. Taken together, these results demonstrate that GmVTL1a is indispensable for SNF in nodules as a transporter of ferrous iron from the infected root cell cytosol to the symbiosome., (© 2020 The Authors. New Phytologist © 2020 New Phytologist Trust.)

Background: The lack of mass transfer in microgravity might be the underlying cause of disuse osteoporosis in astronauts after long-term space flights. The osteons are cylindrical structures and are the main structural units of the diaphysis in long bones., Methods: A multi-scale 3D fluid-solid coupled finite element model of osteon with a two-stage pore structure was developed using COMSOL software in order to investigate solute transport behaviors in the lacunar-canalicular system (LCS) induced by physiological strain loading. Certain small molecules that are necessary as solutes in tissue fluid for osteocyte metabolism were simplified to micro-particles. A comparative analysis of solute transport behaviors in the LCS induced by physiological strain loading was conducted with a frequency of 0.2-2.5 Hz in microgravity and the Earth's gravitational fields., Results: The average velocity of solute transport in lacunae in microgravity was 2-3 orders of magnitude lower than in Earth's gravitational field. The number of particles that represented solute transport quantity in the middle and deep lacunae increased steadily with a load frequency within the Earth's gravitational field. However, it differed based on the load frequency in microgravity, with the number of particles increasing with frequencies in the range of 0.2-0.5 Hz and 0.8-2 Hz, and decreasing with frequencies in the range of 0.5-0.8 Hz., Conclusions: A moving load with appropriate frequency could promote solute transport to the middle and deep lacunae, effectively preventing apoptosis of deep osteocytes due to a lack of nutrients. The results of this study provided theoretical guidance for preventing bone loss in astronauts during long-term space flights., Competing Interests: Declaration of competing interest None Declared., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Polymers are generally regarded as thermal insulators. The efficient heat transfer observed in the low-dimensional polymers in the literature mainly result from the larger crystallinity or improved polymer chain orientation in the low-dimensional polymers. However, the role of the amorphous domain on heat transfer in polymers remains unexplored. In this work, we report that the semicrystalline nylon polymer nanofibers can exhibit a very large thermal conductivity of 59.1 ± 3.1 W m -1 K -1 and the heat transfer in the semicrystalline polymer nanofibers was time-dependent. The thermal conductivity of the nanofibers could be modulated to span 3 orders of magnitude from being nearly insulated (∼0.27 ± 0.02 W m -1 K -1 ) to being highly thermal conductive after annealing (∼59.1 ± 3.1 W m -1 K -1 ). The time-dependent thermal conductivity was observed at a temperature lower than the gamma transition temperature of the polymer and was a result of the physical aging of the semicrystalline polymer. A phenomenological model was adopted to explain the time-dependent heat transfer of the semicrystalline nanofibers. The physical aging reduced the configuration disorder in the polymer and caused the heat transfer of the semicrystalline polymer to increase during the annealing process.

Paraquat (PQ) promotes cell senescence in brain tissue, which contributes to Parkinson's disease. Furthermore, PQ induces heart failure and oxidative damage, but it remains unknown whether and how PQ induces cardiac aging. Here, we demonstrate that PQ induces phenotypes associated with senescence of cardiomyocyte cell lines and results in cardiac aging-associated phenotypes including cardiac remodeling and dysfunction in vivo. Moreover, PQ inhibits the activation of Forkhead box O3 (FoxO3), an important longevity factor, both in vitro and in vivo. We found that PQ-induced senescence phenotypes, including proliferation inhibition, apoptosis, senescence-associated β-galactosidase activity, and p16 INK4a expression, were significantly enhanced by FoxO3 deficiency in cardiomyocytes. Notably, PQ-induced cardiac remolding, apoptosis, oxidative damage, and p16 INK4a expression in hearts were exacerbated by FoxO3 deficiency. In addition, both in vitro deficiency and in vivo deficiency of FoxO3 greatly suppressed the activation of antioxidant enzymes including catalase (CAT) and superoxide dismutase 2 (SOD2) in the presence of PQ, which was accompanied by attenuation in cardiac function. The direct in vivo binding of FoxO3 to the promoters of the Cat and Sod2 genes in the heart was verified by chromatin immunoprecipitation (ChIP). Functionally, overexpression of Cat or Sod2 alleviated the PQ-induced senescence phenotypes in FoxO3-deficient cardiomyocyte cell lines. Overexpression of FoxO3 and CAT in hearts greatly suppressed the PQ-induced heart injury and phenotypes associated with aging. Collectively, these results suggest that FoxO3 protects the heart against an aging-associated decline in cardiac function in mice exposed to PQ, at least in part by upregulating the expression of antioxidant enzymes and suppressing oxidative stress., (© 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

The ripeness of a grape is critical to berry composition and to the resultant wine. For wineries with a single cultivar occupying an extensive area, the total soluble solid of grapes can range from 22°Brix to 28°Brix. Accordingly, the influence of different harvest dates (ripeness) on berry compositions and on the resultant wine profile was investigated for Vitis vinifera L. cv. 'Cabernet Sauvignon.' Berry dehydration was observed as berry weight and juice yields decreased. Berry anthocyanins were concentrated and methylated anthocyanin levels fluctuated with increasing delays in harvesting. Hexanal and 2-hexenal levels in must decreased significantly as berries ripened. In the resultant wines, 2,3-butanediol levels increased. Wines harvested earlier were lighter, presented lower color intensity (CI) values and higher yellow% levels, and exhibited richer aroma profiles (compounds). Through a principal component analysis and discriminant analysis, the compounds characterizing each harvest date were identified., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The ability to predict and describe nonradiative processes in molecules via the identification and characterization of conical intersections is one of the greatest recent successes of theoretical chemistry. Only recently, however, has this concept been extended to materials science, where nonradiative recombination limits the efficiencies of materials for various optoelectronic applications. In this review, we present recent advances in the theoretical study of conical intersections in semiconductor nanomaterials. After briefly introducing conical intersections, we argue that specific defects in materials can induce conical intersections between the ground and first excited electronic states, thus introducing pathways for nonradiative recombination. We present recent developments in theoretical methods, computational tools, and chemical intuition for the prediction of such defect-induced conical intersections. Through examples in various nanomaterials, we illustrate the significance of conical intersections for nanoscience. We also discuss challenges facing research in this area and opportunities for progress.

A predictive theory connecting atomic structure to the rate of recombination would enable the rational design of semiconductor nanomaterials for optoelectronic applications. Recently our group has demonstrated that the theoretical study of conical intersections can serve this purpose. Here we review recent work in this area, focusing on the thesis that low-energy conical intersections in nanomaterials share a common feature: locality. We define a conical intersection as local if (a) the intersecting states differ by the excitation of an electron between spatially local orbitals, and (b) the intersection is accessed when the energies of these orbitals are tuned by local distortions of the geometry. After illustrating the locality of the conical intersection responsible for recombination at dangling bond defects in silicon, we demonstrate the locality of low-energy conical intersections in cases where locality may be a surprise. First, we demonstrate the locality of low-energy self-trapped conical intersections in a pristine silicon nanocrystal, which has no defects that one would expect to serve as the center of a local intersection. Second, we demonstrate that the lowest energy intersection in a silicon system with two neighboring dangling bond defects localizes to a single defect site. We discuss the profound implications of locality for predicting the rate of recombination and suggest that the locality of intersections could be exploited in the experimental study of recombination, where spectroscopic studies of molecular models of defects could provide new insights.

Quantitative evaluation of ecosystem service value and its spatial mapping is an effective way to determine priority conservation areas of cultural ecosystem services (CES). We used a combination of questionnaires and structured interviews with public participatory GIS (PPGIS) in Gongqing Forest Park in Shanghai to connect non-monetary CES values with spatially explicit information. This method applied spatial indicators of abundance, diversity and rarity to quantitatively assess the value of CES and their spatial distribution, and identified priority CES areas. The results showed the value of CES varied among landscape types. Relatively open grassland, riverside, and shrub areas were associated with high aesthetic value. Riverside areas were associated with the CES category concerned with inspiration and supporting social relationships. High diversity values mainly distributed in riverside areas, while forest and grassland areas were associated with high rarity values. The areas with the highest values for the abundance, diversity, and rarity indices were overlaid with eight gradient thresholds, which indicated that defining the 25% of ecological areas with the highest overall rating as CES priority areas was an effective threshold for CES identification and management. The methodology in this study leveraged PPGIS to spatially refe-rence, quantify, and user perception to establish relationships between landscape attributes, space, and experience. These results could provide an important basis for identifying, planning for, and managing priority conservation areas in urban protected areas.

A major cause of failure in chemotherapy is drug resistance of cancer cells. Exosomes have been introduced to spread chemoresistance through delivering miRNAs. However, a systematic evaluation of the exosomal miRNA expression profiles responsible for chemoresistance is still lacking. In the present study, miRNA signature differentially expressed in exosomes derived from adriamycin-resistant (A/exo) and parental breast cancer cells (S/exo) were analyzed by microarray and the results were confirmed by PCR. A total of 309 miRNAs were increased and 66 miRNAs were decreased significantly in A/exo compared with S/exo. Specifically, 52 novel miRNAs with increased expression levels >16.0-fold in A/exo were identified. After prediction of target genes for 13 of 52 selected novel miRNAs, pathway analysis, gene ontology (GO) terms, and protein-protein interactions (PPIs) were constructed. The results implied that these selected exosomal miRNAs inhibited target genes involved in transcriptional misregulation in cancer, MAPK, and Wnt signaling pathways. Functional enrichment analysis demonstrated that the target genes were mainly responsible for protein phosphorylation, transcription regulation, molecular binding, and kinase activity. In summary, the current bioinformatics study of exosomal miRNAs may offer a new understanding into mechanisms of chemoresistance, which is helpful to find potential exosomal miRNAs to overcome drug insensitivity in future breast cancer treatment., (© 2018 The Author(s).)

Visibly transparent luminescent solar concentrators (TLSC) have the potential to turn existing infrastructures into net-zero-energy buildings. However, the reabsorption loss currently limits the device performance and scalability. This loss is typically defined by the Stokes shift between the absorption and emission spectra of luminophores. In this work, the Stokes shifts (SS) of near-infrared selective-harvesting cyanines are altered by substitution of the central methine carbon with dialkylamines. We demonstrate varying SS with values over 80 nm and ideal infrared-visible absorption cutoffs. The corresponding TLSC with such modification shows a power conversion efficiency (PCE) of 0.4% for a >25 cm 2 device area with excellent visible transparency >80% and up to 0.6% PCE over smaller areas. However, experiments and simulations show that it is not the Stokes shift that is critical, but the total degree of overlap that depends on the shape of the absorption tails. We show with a series of SS-modulated cyanine dyes that the SS is not necessarily correlated to improvements in performance or scalability. Accordingly, we define a new parameter, the overlap integral, to sensitively correlate reabsorption losses in any LSC. In deriving this parameter, new approaches to improve the scalability and performance are discussed to fully optimize TLSC designs to enhance commercialization efforts.

G protein-coupled receptor kinases (GRKs) constitute seven subtypes of serine/threonine protein kinases that specifically recognize and phosphorylate agonist-activated G protein-coupled receptors (GPCRs), thereby terminating the GPCRs-mediated signal transduction pathway. Recent research shows that GRKs also interact with non-GPCRs and participate in signal transduction in non-phosphorylated manner. Besides, GRKs activity can be regulated by multiple factors. Changes in GRKs expression have featured prominently in various tumor pathologies, and they are associated with angiogenesis, proliferation, migration, and invasion of malignant tumors. As a result, GRKs have been intensively studied as potential therapeutic targets. Herein, we review evolving understanding of the function of GRKs, the regulation of GRKs activity and the role of GRKs in human malignant tumor pathophysiology.

d Rhamnose β-hederin (DRβ-H), an active component extracted from the traditional Chinese medicinal plant Clematis ganpiniana , has been reported to be effective against breast cancer. Recent studies have also indicated that the isolated exosomes (D/exo) from docetaxel-resistant breast cancer cells MCF-7 (MCF-7/Doc) were associated with resistance transmission by delivering genetic cargo. However, the relevance of D/exo during DRβ-H exposure remains largely unclear. In the present work, exosomes were characterized by morphology and size distribution. We reinforced the significant role of D/exo in spreading chemoresistance from MCF-7/Doc to recipient sensitive cells after absorption and internalization. DRβ-H could reduce the formation and release of D/exo. Next, we demonstrated that DRβ-H was able to reverse docetaxel resistance and that D/exo was responsible for DRβ-H-mediated resistance reversal. We also found that DRβ-H could decrease the expressions of several most abundant miRNAs ( miR-16, miR-23a, miR-24, miR-26a , and miR-27a ) transported by D/exo. Target gene prediction and pathway analysis showed the involvement of these selected miRNAs in pathways related to treatment failure. Our results suggested that DRβ-H could reduce D/exo secretion from MCF-7/Doc cells and induce the reduction in resistance transmission via D/exo., (© 2018 The Author(s).)

Time-dependent electronic structure methods are growing in popularity as tools for modeling ultrafast and/or nonlinear processes, for computing spectra, and as the electronic structure component of mean-field molecular dynamics simulations. Time-dependent configuration interaction (TD-CI) offers several advantages over the widely used real-time time-dependent density functional theory: namely, that it correctly models Rabi oscillations; it offers a spin-pure description of open-shell systems; and a hierarchy of TD-CI methods can be defined that systematically approach the exact solution of the time-dependent Schrodinger equation (TDSE). In this work, we present a novel TD-CI approach that extends TD-CI to large complete active-space configuration expansions. Such extension is enabled by use of a direct configuration interaction approach that eliminates the need to explicitly build, store, or diagonalize the Hamiltonian matrix. Graphics processing unit (GPU) acceleration enables fast solution of the TDSE even for large active spaces-up to 12 electrons in 12 orbitals (853776 determinants) in this work. A symplectic split operator propagator yields long-time norm conservation. We demonstrate the applicability of our approach by computing the response of a large molecule with a strongly correlated ground state, decacene (C 42 H 24 ), to various pulses (δ-function, transform limited, chirped). Our simulations predict that chirped pulses can be used to induce dipole-forbidden transitions. Simulations of decacene using the 6-31G(d) basis set and a 12 electrons/12 orbitals active space took 20.1 h to propagate for 100 fs with a 1 attosecond time step on a single NVIDIA K40 GPU. Convergence with respect to time step is found to depend on the property being computed and the chosen active space.

Objective: To study the effect of golden-hour body temperature bundle management strategy on admission temperature and clinical outcome in preterm infants with a gestational age of <34 weeks after birth., Methods: The preterm infants who were born in the delivery room of the West China Second University Hospital of Sichuan University and admitted to the department of neonatology of this hospital within 1 hour after birth from December 2015 to June 2016 and from January to May, 2017 were enrolled. The 173 preterm infants who were admitted from January to May, 2017 were enrolled as the intervention group and were given golden-hour body temperature bundle management. The 164 preterm infants who were admitted from December 2015 to June 2016 were enrolled as the control group and were given conventional body temperature management., Results: The intervention group had a significantly higher mean admission temperature than the control group (36.4±0.4°C vs 35.3±0.6°C; P<0.001). The incidence rate of hypothermia on admission in the intervention group was significantly lower than that in the control group (56.6% vs 97.6%; P<0.001). The intervention group had a significantly lower incidence rate of intracranial hemorrhage within one week after admission than the control group (15.0% vs 31.7%; P<0.05)., Conclusions: Golden-hour body temperature bundle management for preterm infants within one hour after birth can reduce the incidence of hypothermia on admission and improve clinical outcome.

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) 9 system has emerged as a powerful tool for knock-in of DNA fragments via donor plasmid and homology-independent DNA repair mechanism; however, conventional integration includes unnecessary plasmid backbone and may result in the unfaithful expression of the modified endogenous genes. Here, we report an efficient and precise CRISPR/Cas9-mediated integration strategy using a donor plasmid that harbors 2 of the same cleavage sites that flank the cassette at both sides. After the delivery of donor plasmid, together with Cas9 mRNA and guide RNA, into cells or fertilized eggs, concurrent cleavages at both sides of the exogenous cassette and the desired chromosomal site result in precise targeted integration without plasmid backbone. We successfully used this approach to precisely integrate the EGFP reporter gene into the myh6 locus or the GAPDH locus in Xenopus tropicalis or human cells, respectively. Furthermore, we demonstrate that replacing conventional terminators with the endogenous 3UTR of target genes in the cassette greatly improves the expression of reporter gene after integration. Our efficient and precise method will be useful for a variety of targeted genome modifications, not only in X. tropicalis, but also in mammalian cells, and can be readily adapted to many other organisms.-Mao, C.-Z., Zheng, L., Zhou, Y.-M., Wu, H.-Y., Xia, J.-B., Liang, C.-Q., Guo, X.-F., Peng, W.-T., Zhao, H., Cai, W.-B., Kim, S.-K., Park, K.-S., Cai, D.-Q., Qi, X.-F. CRISPR/Cas9-mediated efficient and precise targeted integration of donor DNA harboring double cleavage sites in Xenopus tropicalis.

Among a great variety of cell surface receptors, the largest superfamily is G protein-coupled receptors (GPCRs), also known as seven-transmembrane domain receptors. GPCRs can modulate diverse signal-transduction pathways through G protein-dependent or independent pathways which involve &beta;-arrestins, G protein receptor kinases (GRKs), ion channels, or Src kinases under physiological and pathological conditions. Recent studies have revealed the crucial role of GPCRs in the tumorigenesis and the development of cancer metastasis. We will sum up the functions of GPCRs&mdash;particularly those coupled to chemokines, prostaglandin, lysophosphatidic acid, endothelin, catecholamine, and angiotensin&mdash;in the proliferation, invasion, metastasis, and angiogenesis of hepatoma cells and the development of hepatocellular carcinoma (HCC) in this review. We also highlight the potential avenues of GPCR-based therapeutics for HCC.

Unmethylated CpG oligodeoxynucleotide (CpG-ODN), a Toll-like receptor 9 (TLR9) ligand, has been shown to protect against myocardial ischemia/reperfusion injury. However, the potential effects of CpG-ODN on myocardial infarction (MI) induced by persistent ischemia remains unclear. Here, we investigated whether and how CpG-ODN preconditioning protects against MI in mice. C57BL/6 mice were treated with CpG-ODN by i.p. injection 2 hr prior to MI induction, and cardiac function, and histology were analyzed 2 weeks after MI. Both 1826-CpG and KSK-CpG preconditioning significantly improved the left ventricular (LV) ejection fraction (LVEF) and LV fractional shortening (LVFS) when compared with non-CpG controls. Histological analysis further confirmed the cardioprotection of CpG-ODN preconditioning. In vitro studies further demonstrated that CpG-ODN preconditioning increases cardiomyocyte survival under hypoxic/ischemic conditions by enhancing stress tolerance through TLR9-mediated inhibition of the SERCA2/ATP and activation of AMPK pathways. Moreover, CpG-ODN preconditioning significantly increased angiogenesis in the infarcted myocardium compared with non-CpG. However, persistent TLR9 activation mediated by lentiviral infection failed to improve cardiac function after MI. Although CpG-ODN preconditioning increased angiogenesis in vitro, both the persistent stimulation of CpG-ODN and stable overexpression of TLR9 suppressed the tube formation of cardiac microvascular endothelial cells. CpG-ODN preconditioning significantly protects cardiac function against MI by suppressing the energy metabolism of cardiomyocytes and promoting angiogenesis. Our data also indicate that CpG-ODN preconditioning may be useful in MI therapy., (© 2017 Wiley Periodicals, Inc.)

Magnesium (Mg) is an essential element for the growth of both plants and bacteria. Low availability of Mg in agriculture can limit crop productivity and quality. In addition to direct effects on plant growth, limited Mg supply may also impact biological dinitrogen (N 2 ) fixation in nodules formed from symbiotic interactions between legumes and rhizobial bacteria. To date, the physiological mechanisms involved in Mg-dependent nodulation remains largely unknown. The objectives of this work were to assess how Mg supply affects nodule growth and development in symbiotic systems, and to test if any observed changes in nodule and soybean are correlated with Mg supply. Here, we found that external Mg supply enhanced nodule growth under nitrogen (N) limited conditions, and subsequently improved N 2 fixation and soybean growth. Mg supply altered neither nodule structure nor Mg homeostasis, but remarkably promoted nodule enlargement, resulting in an increase in the number of big nodules. In addition, high Mg supply decreased starch and sucrose accumulation in leaves, and increased their concentrations in roots, which consequently enhanced carbohydrate import into the rhizobia infection zone of nodules. In this study, Mg was shown to promote nodule growth in soybean. This Mg-promoted nodule growth is derived from Mg-facilitated alteration of carbohydrate partitioning and transport into nodules., (This article is protected by copyright. All rights reserved.)

Magnesium (Mg) is the second most abundant cation in plants, and, as such, is involved in numerous physiological and biochemical processes, including photosynthesis, enzyme activation, and synthesis of nucleic acids and proteins. Due to its relatively small ionic radius and large hydrated radius, Mg binds weakly to soil and root surfaces, and thereby is easily leached from soil. Mg deficiency not only affects crop productivity and quality, but also contributes to numerous chronic human diseases. Therefore, Mg nutrition in plants is an important issue in nutrition and food security. To acquire and maintain high concentrations of Mg, plants have evolved highly-efficient systems for Mg uptake, storage and translocation. Advances in the understanding of fundamental principles of Mg nutrition and physiology are required in order to improve Mg nutrient management, Mg stress diagnosis, and genetic marker assisted breeding efforts. The aims of this review are to highlight physiological and molecular mechanisms underlying Mg biological functions and to summarize recent developments in the elucidation of Mg transport systems in plants., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Xanthomonas campestris pv. campestris (Xcc) is the phytopathogen that causes black rot disease in cruciferous plants. The XCC2366 gene product is annotated as a protein belonging to the TetR family of transcriptional regulators. In this study, we evaluated the function and expression of the XCC2366 gene. Mutational analysis demonstrated that XCC2366 is involved in the resistance to acriflavin and is necessary for virulence in Xcc. In addition, the XCC2366 transcription initiation site was mapped at nucleotide A, 63 nucleotide upstream of the XCC2366 translation start codon. Furthermore, transcriptional analysis revealed that the expression of XCC2366 is induced in the presence of acriflavin. Reporter assay also showed that XCC2366 regulates its own expression under acriflavin-supplemented condition. To the best of our knowledge, acriflavin resistance-related gene in the crucifer pathogen Xcc was characterized for the first time.

Conical intersections are well known to introduce nonradiative decay pathways in molecules, but have only recently been implicated in nonradiative recombination processes in materials. Here we apply excited state ab initio molecular dynamics simulations based on a multireference description of the electronic structure to defective silicon nanocrystals up to 1.7 nm in diameter to search for accessible nonradiative recombination pathways. Dangling bond defects are found to induce conical intersections between the ground and first excited electronic states of five systems of various sizes. These defect-induced conical intersections are accessible at energies that are in the visible range (2.4-2.7 eV) and very weakly dependent on particle size. The dynamic simulations suggest that these intersections are accessed 40-60 fs after creation of a defect-localized excitation. This ultrafast recombination is attributed to the fact that Jahn-Teller distortion on the first excited state drives the defect directly towards a conical intersection with the ground electronic state.

Defects are known to introduce pathways for the nonradiative recombination of electronic excitations in semiconductors, but implicating a specific defect as a nonradiative center remains challenging for both experiment and theory. In this Perspective, we present recent progress toward this goal involving the identification and characterization of defect-induced conical intersections (DICIs), points of degeneracy between the ground and first excited electronic states of semiconductor materials that arise from the deformation of specific defects. Analysis of DICIs does not require the assumption of weak correlation between the electron and hole nor of stationary nuclei. It is demonstrated that in some cases an energetically accessible DICI is present even when no midgap state is predicted by single-particle theories (e.g., density functional theory). We review recent theoretical and computational developments that enable the location of DICIs in semiconductor nanomaterials and present insights into the photoluminescence of silicon nanocrystals gleaned from DICIs.

Objectives: To identify risk factors associated with feeding intolerance (FI) in preterm infants., Methods: Preterm infants treated in the neonatal unit of a hospital from August 2014 to January 2015 were recruited in this study. A clinical observation table was developed based on the reactive scope model. Data in relation to predictive homeostasis, reactive homeostasis, homeostatic overload, homeostatic failure and other aspects were collected and compared between those with and without FI.Alogistic regression model was established to determine predictors of FI., Results: 1.A total of 207 preterm infants were included in the study: 125 male and 82 female. They had an average gestational age of (33.48±1.66) weeks (ranging from 27 +2 to 37 weeks) and an average birth body mass of (2 019.55±334.38) g(ranging from 830 g to 3 120 g).2.The incidence of FI was 33.8%. FI in preterm infants often occurred during the period of being fed within 72 h.The main clinical manifestation of FI was gastric retentionin early-preterm infants and emesis in late-preterm infants.3.Gestational age, birth body mass, fetal distress, aminophylline application, intrauterine infection, breast milk feeding and interval between stools were associated with FI. Gestational age and birth body mass were found to be significant protectors of FI in the logistic regression model. FI declined with increased gestational age and birth body mass. Fetal distress, aminophylline application, and >3 d interval between stools were found to be significant risks of FI in the logistic regression model.4.The prediction model had a 92.73% forecast generation rate of return, with 97.14% sensitivity,88.32%specificity, and 91.30% accuracy., Conclusions: Low gestational age, low birth body mass, fetal distress,aminophylline application, and >3 d interval between stools are independent risk factors associate with FI. The prediction model can identify high risk cases of FI.

Background: Prior research has highlighted the significant relationship between gestational weight gain and pregnancy outcomes. Exercise is one of the main factors that affects body weight. Therefore, exercising appropriately during pregnancy is an important activity for promoting healthy pregnancy outcomes., Purpose: To explore the status and features of maternal exercise during pregnancy and to analyze the related influence factors using the "theory of reasoned action" in order to provide evidence-based guidance on exercise during pregnancy., Methods: Convenience sampling was used to recruit pregnant women from four hospitals of different administrative levels in Chengdu, China. A self-developed questionnaire was used to collect data. Data were input using Epidata and analyzed using SPSS 21.0., Results: Data provided by 587 pregnant women in their first trimester, 522 in their second trimester, and 522 in their third trimester were used in analysis. Significant differences were found between the three groups in terms of housework loading and lifting. Further, participants in the third trimester were significantly more likely to exercise less than 3 times per week and less than 30 minutes per session than their first and second trimester peers (p < .001). Structural equation modeling identified that: behavior intention had a significant effect on level of physical activity; attitudes and norms affected behavior by affecting intention; monthly income and educational background affected behavior by influencing attitude; and educational background affected behavior by influencing perceived norms., Conclusions: The findings of the present study support that personal situation, the family, and social norms impact the behavior of women significantly more during pregnancy than before pregnancy.

Background: Girdin was identified as a novel Akt substrate that contributes to a positive feedback loop between Girdin and Akt. Although several recent studies have demonstrated that Girdin is involved in tumor metastasis, the clinical implications of Girdin in breast cancer remain unclear., Methods: To retrospectively evaluate the prognostic value of Girdin in breast cancer, we performed an immunohistochemistry screening for Girdin using tissue microarrays constructed from 250 patients who were histologically confirmed as having invasive ductal breast carcinoma at the Fudan University Shanghai Cancer Center., Results: Our results demonstrated that the levels of Girdin in different subcellular distributions, including Girdin in the nucleus (GN) and the cytoplasm (GC) were each associated with the clinical parameters of breast cancer, including phospho-Akt (S473) [p = 0.014 for GN], phospho-Akt (T308) [p = 0.045 for GC], estrogen receptor (ER) [p = 0.012 for GN and p = 0.004 for GC], progesterone receptor (p = 0.028 for GC) and human epidermal growth factor receptor 2 status (p = 0.004 for GC). Moreover, we showed that elevated expression of GN indicated a worse disease-free survival (p = 0.032) and overall survival (p = 0.011) exclusively in the ER-positive breast cancer population., Conclusions: Cumulatively, our findings suggest that GN might serve as an important prognostic factor for ER-positive breast carcinoma.

We examine the performance of the asymptotically corrected model potential scheme on the two lowest singlet excitation energies of acenes with different numbers of linearly fused benzene rings (up to 5), employing both the real-time time-dependent density functional theory and the frequency-domain formulation of linear-response time-dependent density functional theory. The results are compared with the experimental data and those calculated using long-range corrected hybrid functionals and others. The long-range corrected hybrid scheme is shown to outperform the asymptotically corrected model potential scheme for charge-transfer-like excitations.

We investigated the loss of somatic mutations in TP53 and PIK3CA in breast cancer tissue after neoadjuvant chemotherapy (NCT) and the clinical relevance of the observed mutation profiles. Samples were derived from three cohorts: Cohort 1 consisting of 206 patients undergoing NCT with matched pre- and postchemotherapy tumor tissues; Cohort 2 consisting of 158 additional patients undergoing NCT; and Cohort 3, consisting of 81 patients undergoing chemotherapy with prechemotherapy tumor tissues. In the first cohort, somatic mutations in TP53 or PIK3CA were identified in 24.8% of the pre-NCT tumor samples but in only 12.1% of the post-NCT tumor samples (P < 0.001). Patients with initial TP53 and PIK3CA mutations who became negative for the mutations after NCT had a higher Miller-Payne score (P = 0.008), improved disease-free survival, and improved overall survival than those with no change or the opposite change. The association of loss of mutations in TP53 and PIK3CA and improved survival was successfully validated in the second cohort. In addition, 28.4% of the tumors showed intratumoral heterogeneity of somatic mutations in TP53 or PIK3CA, whereas 71.6% were homogeneous, either with or without the mutations. Our data reveal the novel concept that chemotherapy may reduce mutation frequency in patients with breast cancer. Furthermore, the loss of somatic mutations in TP53 and PIK3CA may be translated to biomarkers for prognosis via further verification, which may optimize the choice of sequential therapy and improve patient survival., (©2014 American Association for Cancer Research.)

Among chemotherapeutic agents, paclitaxel has shown great efficacy against breast cancer. Prediction of paclitaxel response may improve patient outcomes. Here we show, using exome sequencing, that in comparison with pre-treatment biopsies, two TEKT4 germline variations are enriched in post-treatment tumours. We find TEKT4 variations in ~ 10% of an independent cohort of 84 pairs of samples. Tektin4 (encoded by TEKT4) associates closely with tubulin in doublet microtubules and helps stabilize these structures. These two TEKT4 germline variations in a high cis linkage are biologically relevant, as the ectopic expression of variant TEKT4 deregulates the microtubule stability, antagonizes the paclitaxel-induced stabilizing effect of microtubules and increases paclitaxel resistance. Furthermore, TEKT4 germline variations are associated with reduced disease-free survival and overall survival compared with wild-type TEKT4 in patients undergoing paclitaxel-based chemotherapy. Taken together, we reveal a potential mechanism of resistance to paclitaxel through the acquisition of germline variations in breast cancer.