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For patients with colon or stomach adenocarcinoma, 5-fluorouracil (5-FU) is an essential component of systemic chemotherapy in the palliative and adjuvant settings. The post-transcriptional regulatory factor cytoplasmic polyadenylation element-binding protein 1 (CPEB1) has been reported to be linked to tumor metastasis. This study aimed to investigate the relationship between CPEB1 expression and 5-FU treatment response in patients with colon and stomach adenocarcinomas.The expression ofThe expression levels ofOur results indicate that the level of CPEB1 expression may be valuable for predicting the benefit of 5-FU treatment for patients with colon and stomach adenocarcinomas. We therefore propose that low CPEB1 expression may represent a novel biomarker for personalized 5-FU therapy.

Practical, metal-free heteroarylations of inert C–H and C–C bonds of unprotected aliphatic alcohols are achieved in a ‘stop-flow’ micro-tubing reactor, and can be readily scaled up by a continuous-flow method.

A quantum neural network (QNN) is a method to find patterns in quantum data and has a wide range of applications including quantum chemistry, quantum computation, quantum metrology, and quantum simulation. Efficiency and universality are two desirable properties of a QNN but are unfortunately contradictory. In this work, we examine a deep Ising Born machine (DIBoM), and show it has a good balance between efficiency and universality. More precisely, the DIBoM has a flexible number of parameters to be efficient, and achieves provable universality with sufficient parameters. The architecture of the DIBoM is based on generalized controlled-Z gates, conditional gates, and some other ingredients. To compare the universality of the DIBoM with other QNNs, we propose a fidelity-based expressivity measure, which may be of independent interest. Extensive empirical evaluations corroborate that the DIBoM is both efficient and expressive., Comment: 21 pages, 35 figures, accepted by Advanced Quantum Technologies

Jushan Sun,1 Yibiao He,1 Lei Bai,1 Zhipeng Wang,1 Zhu Cao,1 Yingmei Shao,2 Jinming Zhao1 1Department of Liver and Laparoscopic Surgery, Digestive and Vascular Surgery Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830054, People’s Republic of China; 2Xinjiang Uyghur Autonomous Region Clinical Research Center for Echinococcosis and Hepatobiliary Diseases, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830054, People’s Republic of ChinaCorrespondence: Jinming ZhaoDepartment of Liver and Laparoscopic Surgery, Digestive and Vascular Surgery Center, The First Affiliated Hospital of Xinjiang Medical University, No. 137 of Liyushan Street, Xinshi District, Urumqi, Xinjiang, 830054, People’s Republic of ChinaTel/Fax +86-991-4364529Email zhaojm_m@outlook.comObjective: To investigate the risk factors related to new-onset diabetes mellitus (NODM) and the significance of IL-6.Methods: A retrospective analysis was conducted on clinical data from 64 patients who received either a living donor liver transplantation or a donation after circulatory death from September 2013 to October 2020 and attended regular follow-up visits for six or more months. During follow-up, patients were randomized into groups and followed up until the completion of the study or the death of the patient.Results: The incidence of NODM was 31.25% (n = 20). The median age in the NODM group was 52.15 years (p < 0.01). Age (OR = 1.089; 95% CI: 0.0211– 0.1495, p = 0.003) and elevated preoperative IL-6 (OR = 1.122; 95% CI: 0.0619– 0.1677, p = 0.029) were found to be independent risk factors for NODM. HBV-induced liver cirrhosis, warm ischemia time (WIT), body mass index (BMI), and high preoperative fasting blood glucose (FBG) were also found to be risk factors for NODM. The recipient had a higher risk of NODM if the donor had a high BMI and poor hepatic function. The concentrations of IL-6, procalcitonin (PCT), FBG, and tacrolimus (TAC) in the first month postoperatively were significantly higher in the NODM group than in the NO-NODM group. The survival rate of the patients was not affected by NODM.Conclusion: HBV-induced liver cirrhosis, WIT, BMI, and high preoperative FBG levels are risk factors for NODM, and age and preoperative IL-6 levels are independent risk factors. To a certain extent, higher BMI and poor hepatic function had reference significance for the incidence of NODM. Patients with a high concentration of FBG, IL-6, and TAC in the first month postoperatively had an increased risk of suffering from NODM.Keywords: liver transplantation, HBV, IL-6, immunosuppressants, NODM

BACKGROUND: Pancreatic cancer (PC) is among the most prevalent and deadliest endocrine tumors, yet the mechanisms governing its pathogenesis remain to be fully clarified. While ubiquitin-conjugating enzyme E2C (UBE2C) has been identified as an important oncogene in several cancers, its importance in PC has yet to be established. METHODS: UBE2C expression in PC tumor samples and cell lines was examined via quantitative real-time polymerase chain reaction (qRT-PCR), while appropriate commercial kits were used to assess lactate production, ATP generation, and the uptake of glucose. RESULTS: UBE2C was found to be upregulated in PC patient tumors and correlated with poorer survival outcomes. In PC cell lines, the silencing of this gene suppressed the malignant activity of cells, thus supporting its identification as an oncogene in this cancer type. Mechanistically, UBE2C was found to promote enhanced matrix metalloproteinase (MMP) protein expression via activating the PI3K-Akt pathway. Moreover, it was found to bind to the epidermal growth factor receptor (EGFR), stabilizing it and driving additional PI3K-Akt pathway activation. UBE2C knockdown in PC cells impaired their uptake of glucose and their ability to produce lactate and ATP. CONCLUSIONS: In conclusion, the results of this study support a role for UBE2C as a driver of metastatic PC progression owing to its ability to bind to EGFR and to induce signaling via the PI3K-Akt pathway.

A dinucleating bis(β-diketiminate) ligand with a flexible bridge has been employed to synthesize zinc complexes. The ligand, abbreviated H2L (H2L = N-(4-((2-((4-((2,6-diisopropylphenyl)imino)pent-2...

The radical-mediated heteroarylation of unactivated remote C(sp3)–H bonds via intramolecular heteroaryl migration is achieved, leading to a variety of heteroaryl-substituted aliphatic ketones. A library of O-/S-/N-containing heteroaryls such as benzofuryl, benzothiazolyl, benzothienyl, benzoxazolyl, oxazolyl, and thiazolyl are amenable to the migration approach. The heteroaryl migration is triggered by an azido radical-mediated hydrogen atom abstraction from unactivated aliphatic C(sp3)–H bonds. The transformation features mild C–C bond cleavage, good selectivity for tertiary C(sp3)–H bonds, and broad functional group compatibility.

BACKGROUND: It remains unclear whether diabetic medications, such as metformin and insulin, affect the post-liver resection prognosis of hepatocellular carcinoma (HCC) patients complicated with diabetes mellitus (DM). This study try to find out the prognostic factors in HCC patients with DM and provide a better antidiabetic therapy after liver resection. METHODS: Patients presenting with HCC complicated with DM undergoing liver resection were enrolled in this study. They were examined and followed up every 3-6 months after surgery. Patients were divided into the antidiabetic treatment group and no antidiabetic treatment group according to whether they received medications for diabetes or not. Then patients in the antidiabetic treatment group were further divided into insulin group, metformin group, insulin plus metformin group and others group, according to the medications they received. Overall survival (OS) and recurrence-free survival (RFS) were compared among two groups and four subgoups. Comparative and multivariate analyses were performed to investigate the effects of DM medication on the prognosis of these HCC patients, using Cox proportional hazards model. RESULTS: The 1-, 3-, 5-, and 7-year OS rates for the antidiabetic treatment group were 87.5%, 75.5%, 48.7%, and 29.1%, respectively, and for the no antidiabetic treatment group, the OS rates were 85.4%, 57.7%, 33.6%, and 19.1%, respectively (P=0.007). The 1-, 3-, 5-, 7-year RFS rates for the antidiabetic treatment group were 76.4%, 53.5%, 28.5%, and 17.5%, respectively, and for the no antidiabetic treatment group, the RFS rates were 69.5%, 32.5%, 16.5%, and 10.7%, respectively (P=0.001). In subgroup analysis, There was no significant difference in either RFS (P=0.934) nor OS (P=0.412) among the different types of antidiabetic treatment regimens. Cox proportional hazard regression analysis revealed that tumor size (HR: 1.048), tumor number (HR: 1.626), vascular invasion (HR: 2.074, P=0.003), satellite tumor (HR: 1.592), Edmondson classification (HR: 1.468) and antidiabetic treatment (HR: 0.722) were independent prognostic factors of DFS, while tumor size (HR: 1.048), tumor number (HR: 1.779), vascular invasion (HR: 2.545), Edmondson classification (HR: 1.596) and antidiabetic treatment (HR: 0.713) were independent prognostic factors of OS. CONCLUSIONS: For HCC patients with DM, antidiabetic treatment should be recommended aggressively in order to improve the surgical outcome, regardless of which antidiabetic drugs are used.

Objectives: Increasing evidence confirmed that miRNA plays a critical role in the occurrence and development of ischemic stroke. Here, the aim of this study was to examine the function and mechanisms of miR-195 in vascular endothelial cell apoptosis induced by oxygen-glucose deprivation (OGD).Methods: This study intended to use OGD to simulate ischemia in vitro. The mRNA expression of miR-195, IKKα and NF-κB in human umbilical vein endothelial cells (HUVECs) were detected by RT-qPCR. The proliferation and apoptosis ability of HUVECs were evaluated using MTT assay, colony formation assay and flow cytometry, respectively. Western blot was applied to examine related protein expression. The interaction between miR-195 and IKKα was verified by dual-luciferase reporter gene assay.Results: OGD significantly inhibited cell viability and induced cell apoptosis in HUVECs. Meanwhile, OGD treatment notably decreased the expression of miR-195, as well as enhanced NF-κB expression. Moreover, miR-195 directly interacted with IKKα and suppressed its expression. Mechanically, overexpression of miR-195 exhibited pro-proliferation and anti-apoptotic effect on HUVECs treated with OGD through targeting IKKα-mediated NF-κB pathway. At the molecular level, through suppressing IKKα/NF-κB pathway, miR-195 inhibited the expression of pro-apoptotic protein Bax and active caspase-3, but increased the expression of anti-apoptotic Bcl-2 in HUVECs.Conclusions: Our finding uncovers the protective effect of miR-195 on the biological behavior of HUVECs via suppression of the NF-κB pathway induced by IKKα, which may provide a new potential strategy for ischemic stroke clinical treatment.

A copper-catalyzed C–H [3 + 2] annulation of N-substituted anilines with α-carbonyl alkyl bromides for the synthesis of 3,3′-disubstituted oxindoles is developed. Tandem C–H cycloamidation reactions of various α-carbonyl alkyl bromide derivatives including tertiary-α-bromoalkyl ketone esters, malonic esters and cycloalkanes, with N-aryl or alkyl substituted anilines, can be performed using this system, affording a vast array of valuable 3,3′-disubstituted oxindoles in moderate to good yields.

Purpose To determine whether early proteins from high-risk human papillomavirus (HPV) have the capacity to maintain cellular stemness. Patients and methods First, we isolated cancer stem cell like cells from two cervical cancer cell lines, SiHa and CaSki, using non-adhesive culture with serum-free medium. Second, we knocked down HPV16 E7 in SiHa sphere cells and overexpressed HPV16 E7 in U2OS sphere cells. Third, we used RNA-seq analysis and Western blotting to screen and identify the expression of differentially expressed genes in SiHa cells with HPV16 E7 knockdown. Results We found that both SiHa and CaSki cells grew as cell spheres (oncospheres) and shared the properties of cancer stem cells, including high expression of stem cell marker OCT4 and SOX2, self-renew, and resistance to chemotherapeutic drugs. The stem-like properties were deprived when HPV16 E7 was knocked down in SiHa sphere cells and maintained when HPV16 E7 was over-expressed in U2OS sphere cells. APH1B was up-regulated, among differential expression genes, in SiHa cells with HPV16 E7 knockdown and modulated cellular stemness and SiHa sphere cells with APH1B knockdown regained the stem-like properties deprived by E7 inhibition. Conclusion HPV16 E7 possesses the capacity to maintain cellular stemness and APH1B may participate in this process in cervical cancer sphere cells.

With an increasing population and changing diet structure, summer maize is increasingly becoming an important energy crop in China. However, traditional farmer practices for maize production are inefficient and unsustainable. To ensure food security and sustainable development of summer maize production in China, an improved, more sustainable farmer management system is needed. Establishing this system requires a comprehensive understanding of the limitations of current farming practice and the ways it could be improved. In our study, 235 plots from three villages in the North China Plain (NCP) were monitored. Maize production on farms was evaluated; our results showed that the maize yield and nitrogen partial factor productivity (PFPN) were variable on smallholder farms at 6.6–13.7 t ha−1 and 15.4–88.7 kg kg−1, respectively. Traditional farming practices also have a large environmental impact (nitrogen surplus: −64.2–323.78 kg ha−1). Key yield components were identified by agronomic diagnosis. Grain yield depend heavily on grain numbers per hectare rather than on the 1000-grain weight. A set of improved management practices (IP) for maize production was designed by employing a boundary line (BL) approach and tested on farms. Results showed that the IP could increase yield by 18.4% and PFPN by 31.1%, compared with traditional farmer practices (FP), and reduce the nitrogen (N) surplus by 57.9 kg ha−1. However, in terms of IP effect, there was a large heterogeneity among different smallholder farmers' fields, meaning that, precise technologies were needed in different sites especially for N fertilizer management. Our results are valuable for policymakers and smallholder farmers for meeting the objectives of green development in agricultural production.

North China Plain (NCP) is the primary winter wheat production region in China, characterized by smallholder farming systems. Whereas the winter wheat average yield of smallholder farmers is currently low, the yield potential and limiting factors driving the current yield gap remain unclear. Therefore, increasing the wheat yield in NCP is essential for the national food security. This study monitored wheat yield, management practices and soil nutrient data in 132 farmers' fields of Xushui County, Baoding City, Hebei Province during 2014–2016. These data were analyzed using variance and path analysis to determine the yield gap and the contribution of yield components (i.e., spikes per hectare, grain number per spike and 1000-grain weight) to wheat yield. Then, the limiting factors of yield components and the optimizing strategies were identified by a boundary line approach. The results showed that the attainable potential yield for winter wheat was 10 514 kg ha−1. The yield gaps varied strongly between three yield groups (i.e., high, middle and low), which were divided by yield level and contained 44 farmers in each group, and amounted to 2493, 1636 and 814 kg ha−1, respectively. For the three yield components, only spikes per hectare was significantly different (P6.598 × 06 ha−1), the seeding rate should range from 210–300 kg ha−1, seeding date should range from 3th to 8th October, and basal N input should range from 90–180 kg ha−1. Compared to these reasonable ranges of management measures, most of the farmers' practices were not suitable, and both lower and higher levels of management existed. It is concluded that the strategies for optimizing yield components could be achieved by improving wheat seeding quality and optimizing farmers' nutrient management practices in the NCP.

Quantum causality violates classical intuitions of cause and effect and is a unique quantum feature different from other quantum phenomena such as entanglement and quantum nonlocality. In order to avoid the detection loophole in quantum causality, we initiate the study of the detection efficiency requirement for observing quantum causality. We first show that previous classical causal inequalities require detection efficiency at least 95.97% (89.44%) to show violation with quantum (nonsignaling) correlations. Next we derive a classical causal inequality I_{222} and show that it requires lower detection efficiency to be violated, 92.39% for quantum correlations and 81.65% for nonsignaling correlations, hence substantially reducing the requirement on detection. Then we extend this causal inequality to the case of multiple measurement settings and analyze the corresponding detection efficiency. After that, we show that previous quantum causal inequalities require detection efficiency at least 94.29% to violate with nonsignaling correlations. We subsequently derive a quantum causal bound J_{222} that has a lower detection efficiency requirement of 91.02% for violation with nonsignaling correlations. Our work paves the way towards an experimental demonstration of quantum causality and shows that causal inequalities significantly differ from Bell inequalities in terms of the detection efficiency requirement., Comment: 18 pages, 7 figures

Background: Targeting inflammatory microenvironment is a promising anti-tumor strategy. Paeonol is a phenolic compound with effective anti-inflammatory and anti-tumor properties. However, the effects of paeonol on non-small cell carcinoma (NSCLC) have not been fully investigated. Here, we evaluated the effects of paeonol on proliferation and metastasis of NSCLC and elucidated the underlying mechanisms.Methods: The effects of paeonol on inflammatory cytokines were determined by cell proliferation and ELISA assays. Assays of wound healing, single cell migration and perforation invasion were used to evaluate migration and invasion of NSCLC cells. Expression of marker proteins in epithelial-mesenchymal transition (EMT) and matrix metalloproteinase (MMP) family enzymes were detected by Western blot assays. Nude mouse A549 cells transplantation tumor model was used to study the anti-lung cancer effects of paeonol in vivo. TUNEL stanining were used to detect the apoptosis of tumor cells in A549 lung cancer mice, and Ki67 analysis was used to detect the proliferation of tumor cells in A549 lung cancer mice. Immunohistochemistry was used to detect the effects of paeonol on signaling molecules in tumor tissues.Results: Paeonol inhibited A549 cancer cell migration and invasion in vitro. Paeonol inhibited secreaion of inflammatory cytokines in A549 cells, including tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and transforming growth factor (TGF)-β. Paeonol altered the expression of marker proteins involved in EMT and MMP family enzymes. In addition, paeonol inhibited the transcriptional activity of nuclear factor-κB (NF-κB) and phosphorylation of signal transducers and activators of transcription 3 (STAT3). Paeonol inhibited the growth of A549 cells transplanted tumors in nude mice.Conclusion: Paeonol potently inhibited NSCLC cell growth, migration and invasion associated with disruption of STAT3 and NF-κB pathways, suggesting that it could be a promising anti-metastatic candidate for tumor chemotherapy.

Go has long been considered as a testbed for artificial intelligence. By introducing certain quantum features, such as superposition and collapse of wavefunction, we experimentally demonstrate a quantum version of Go by using correlated photon pairs entangled in polarization degree of freedom. The total dimension of Hilbert space of the generated states grows exponentially as two players take turns to place the stones in time series. As nondeterministic and imperfect information games are more difficult to solve using nowadays technology, we excitedly find that the inherent randomness in quantum physics can bring the game nondeterministic trait, which does not exist in the classical counterpart. Some quantum resources, like coherence or entanglement, can also be encoded to represent the state of quantum stones. Adjusting the quantum resource may vary the average imperfect information (as comparison classical Go is a perfect information game) of a single game. We further verify its non-deterministic feature by showing the unpredictability of the time series data obtained from different classes of quantum state. Finally, by comparing quantum Go with a few typical games that are widely studied in artificial intelligence, we find that quantum Go can cover a wide range of game difficulties rather than a single point. Our results establish a paradigm of inventing new games with quantum-enabled difficulties by harnessing inherent quantum features and resources, and provide a versatile platform for the test of new algorithms to both classical and quantum machine learning., 16 pages, 5 figures, 3 extended data figures, 3 supplementary figures

Measurement-device-independent quantum key distribution removes all detector-side attacks in quantum cryptography, and in the meantime doubles the secure distance. The source side, however, is still vulnerable to various attacks. In particular, the continuous phase randomization assumption on the source side is normally not fulfilled in experimental implementation and may potentially open a loophole. In this work, we first show that indeed there are loopholes for imperfect phase randomization in measurement-device-independent quantum key distribution by providing a concrete attack. Then we propose a discrete-phase-randomized measurement-device-independent quantum key distribution protocol as a solution to close this source-side loophole., 8 pages, 3 figures