Bis{(E)-2-[(2-chloro-3-pyrid­yl)imino­meth­yl]-6-meth­oxy­phenolato-κ2 N,O 1}copper(II)

In the title mononuclear copper(II) complex, [Cu(C13H10ClN2O2)2], the CuII ion, lying on an inversion center, is four-coordinated in a trans-CuN2O2 square-planar geometry by two phenolate O and two imino N atoms from two symmetry-related N,O-bidentate Schiff base ligands. The shortest Cu⋯Cu distance is 7.5743 (9) Å. However, there are weak intra­molecular electrostatic inter­actions between the Cu atom and the Cl atom of the ligand, with a Cu⋯Cl distance of 3.3845 (9) Å

Comparison of variations detection between whole-genome amplification methods used in single-cell resequencing

Background: Single-cell resequencing (SCRS) provides many biomedical advances in variations detection at the single-cell level, but it currently relies on whole genome amplification (WGA). Three methods are commonly used for WGA: multiple displacement amplification (MDA), degenerate-oligonucleotide-primed PCR (DOP-PCR) and multiple annealing and looping-based amplification cycles (MALBAC). However, a comprehensive comparison of variations detection performance between these WGA methods has not yet been performed. Results: We systematically compared the advantages and disadvantages of different WGA methods, focusing particularly on variations detection. Low-coverage whole-genome sequencing revealed that DOP-PCR had the highest duplication ratio, but an even read distribution and the best reproducibility and accuracy for detection of copy-number variations (CNVs). However, MDA had significantly higher genome recovery sensitivity (~84 %) than DOP-PCR (~6 %) and MALBAC (~52 %) at high sequencing depth. MALBAC and MDA had comparable single-nucleotide variations detection efficiency, false-positive ratio, and allele drop-out ratio. We further demonstrated that SCRS data amplified by either MDA or MALBAC from a gastric cancer cell line could accurately detect gastric cancer CNVs with comparable sensitivity and specificity, including amplifications of 12p11.22 (KRAS) and 9p24.1 (JAK2, CD274, and PDCD1LG2). Conclusions: Our findings provide a comprehensive comparison of variations detection performance using SCRS amplified by different WGA methods. It will guide researchers to determine which WGA method is best suited to individual experimental needs at single-cell level

Full-length single-cell RNA-seq applied to a viral human cancer:applications to HPV expression and splicing analysis in HeLa S3 cells

Background: Viral infection causes multiple forms of human cancer, and HPV infection is the primary factor in cervical carcinomas Recent single-cell RNA-seq studies highlight the tumor heterogeneity present in most cancers, but virally induced tumors have not been studied HeLa is a well characterized HPV+ cervical cancer cell line Result: We developed a new high throughput platform to prepare single-cell RNA on a nanoliter scale based on a customized microwell chip Using this method, we successfully amplified full-length transcripts of 669 single HeLa S3 cells and 40 of them were randomly selected to perform single-cell RNA sequencing Based on these data, we obtained a comprehensive understanding of the heterogeneity of HeLa S3 cells in gene expression, alternative splicing and fusions Furthermore, we identified a high diversity of HPV-18 expression and splicing at the single-cell level By co-expression analysis we identified 283 E6, E7 co-regulated genes, including CDC25, PCNA, PLK4, BUB1B and IRF1 known to interact with HPV viral proteins Conclusion: Our results reveal the heterogeneity of a virus-infected cell line It not only provides a transcriptome characterization of HeLa S3 cells at the single cell level, but is a demonstration of the power of single cell RNA-seq analysis of virally infected cells and cancers

Authoritarianism in the Living Room: Everyday Disciplines, Senses, and Morality in Taiwan’s Military Villages

With the nationalist government – Kuomintang (KMT) – retreating from mainland China in 1949, some 600,000 military personnel relocated to Taiwan. The military seized former Japanese colonial properties and built its own settlements, establishing temporary military dependents’ villages called juancun (眷村). When the prospect of counter-attacking the mainland vanished, the KMT had to face the reality of settling permanently in Taiwan. How, then, did the KMT’s authoritarian power enter the everyday lives of its own support group? In this article I will focus on the coercive elements of KMT authoritarianism, which permeated these military villages in Taiwan. I will look at the coercive mechanisms through the analytical lens of Foucauldian discipline. I argue that disciplinary techniques such as surveillance, disciplining of the body and the senses, as well as the creation of morality regimes played an important role in the cooptation of village residents into KMT authoritarianism by normalising and naturalising it

From hyper- to hypoinsulinemia and diabetes: effect of KCNH6 on insulin secretion

Glucose-stimulated insulin secretion from islet β cells is mediated by K channels. However, the role of non-K K channels in insulin secretion is largely unknown. Here, we show that a non-K K channel, KCNH6, plays a key role in insulin secretion and glucose hemostasis in humans and mice. KCNH6 p.P235L heterozygous mutation co-separated with diabetes in a four-generation pedigree. Kcnh6 knockout (KO) or Kcnh6 p.P235L knockin (KI) mice had a phenotype characterized by changing from hypoglycemia with hyperinsulinemia to hyperglycemia with insulin deficiency. Islets from the young KO mice had increased intracellular calcium concentration and increased insulin secretion. However, islets from the adult KO mice not only had increased intracellular calcium levels but also had remarkable ER stress and apoptosis, associated with loss of β cell mass and decreased insulin secretion. Therefore, dysfunction of KCNH6 causes overstimulation of insulin secretion in the short term and β cell failure in the long term.Yang et al. show that KCNH6 plays a key role in insulin secretion and glucose hemostasis in humans and mice. Dysfunction of KCNH6 results in a hyperinsulinemia phenotype in the short term and hypoinsulinemia and diabetes in the long term

Visible-Light-Mediated Construction of Pyrroloindolines via an Amidyl Radical Cyclization/Carbon Radical Addition Cascade: Rapid Synthesis of (±)-Flustramide B

The development of visible-light-mediated synthesis of pyrroloindolines via an amidyl radical cyclization–carbon radical functionalization cascade is reported. The transformation shows a broad substrate scope, tolerating a variety of substitutions on indole aromatic rings and N-centers. Different functionalized alkene systems could be used as radical acceptors. Relying on this strategy, a rapid synthesis of flustramide B was achieved

Inosine enhances tumor mitochondrial respiration by inducing Rag GTPases and nascent protein synthesis under nutrient starvation

Abstract Metabolic heterogeneity of tumor microenvironment (TME) is a hallmark of cancer and a big barrier to cancer treatment. Cancer cells display diverse capacities to utilize alternative carbon sources, including nucleotides, under poor nutrient circumstances. However, whether and how purine, especially inosine, regulates mitochondrial metabolism to buffer nutrient starvation has not been well-defined yet. Here, we identify the induction of 5′-nucleotidase, cytosolic II (NT5C2) gene expression promotes inosine accumulation and maintains cancer cell survival in the nutrient-poor region. Inosine elevation further induces Rag GTPases abundance and mTORC1 signaling pathway by enhancing transcription factor SP1 level in the starved tumor. Besides, inosine supplementary stimulates the synthesis of nascent TCA cycle enzymes, including citrate synthesis (CS) and aconitase 1 (ACO1), to further enhance oxidative phosphorylation of breast cancer cells under glucose starvation, leading to the accumulation of iso-citric acid. Inhibition of the CS activity or knockdown of ACO1 blocks the rescue effect of inosine on cancer survival under starvation. Collectively, our finding highlights the vital signal role of inosine linking mitochondrial respiration and buffering starvation, beyond serving as direct energy carriers or building blocks for genetic code in TME, shedding light on future cancer treatment by targeting inosine metabolism

Cervical Disc Arthroplasty for the Treatment of Noncontiguous Cervical Degenerative Disc Disease: Results of Mid‐ to Long‐Term Follow‐up

Objective The long‐term results of cervical disc arthroplasty (CDA) for noncontiguous cervical degenerative disc disease (CDDD) are still uncertain. Moreover, it is unclear whether CDA delays or avoids the degeneration of the intermediate segment (IS), leading to controversy in the field. Therefore, this study aimed to investigate the mid‐ to long‐term clinical and radiographic outcomes of CDA in treating noncontiguous CDDD and to explore whether the IS degenerated faster after CDA than other non‐surgically treated adjacent segments. Methods We retrospectively analyzed patients with noncontiguous CDDD who underwent CDA in our department between January 2008 and July 2018. The patients were divided into the CDA and hybrid surgery (HS) groups, and clinical and radiographic outcomes were evaluated at routine postoperative intervals. Clinical outcomes were assessed using the Japanese Orthopaedic Association (JOA), neck disability index (NDI), and visual analogue scale (VAS), while radiographic outcomes included cervical lordosis (CL), C2‐C7 range of motion (ROM), segmental ROM, and disc angle (DA) at the arthroplasty level. Complications were also evaluated.Pre‐ and postoperative values were compared using paired t‐tests or Wilcoxon rank‐sum tests. Independent Student t‐tests or Mann–Whitney U tests analyzed continuous data between CDA and HS groups, while chi‐square or Fisher exact tests assessed categorical data. Results Sixty‐four patients with noncontiguous CDDD, with 31 in the CDA group and 33 in the HS group, were evaluated. The mean follow‐up time was over 70 months. The most frequently involved levels were C4/5 and C5/6. Both groups showed significant improvements in JOA, NDI, and VAS values after surgery. Although CL was maintained, the CL in the CDA group was consistently lower than that in the HS group (p < 0.05). There was a significant decrease in C2‐C7 ROM (p < 0.05), but at the last follow‐up, the C2‐C7 ROM in the CDA group was greater than that in the HS group (p < 0.05). At the last follow‐up, 44.3% of arthroplasty levels had developed heterotopic ossification (HO), and 48.45% had developed anterior bone loss (ABL). In addition, adjacent segment degeneration (ASDeg) was observed in the IS (22.7%), superior adjacent segment (20.6%)and inferior adjacent segment (21.9%). Conclusion CDA or CDA combined with fusion are viable treatments for noncontiguous CDDD, with satisfactory outcomes after mid‐to‐long‐term follow‐up. ASDeg is similar in non‐surgical segments after 70 months of follow‐up. ROM of the IS issimilar to preoperative levels, indicating CDA does not increase the risk of IS degeneration