bluuebunny/crossref_metadata_2025_split huggingface dataset:
One‐Pot Biocatalytic In Vivo Methylation‐Hydroamination of Bioderived Lignin Monomers to Generate a Key Precursor to L‐DOPA
Authors: Galman James L. , Parmeggiani Fabio , Seibt Lisa , Birmingham William R. , Turner Nicholas J. 
Published: December 2021

AbstractElectron‐rich phenolic substrates can be derived from the depolymerisation of lignin feedstocks. Direct biotransformations of the hydroxycinnamic acid monomers obtained can be exploited to produce high‐value chemicals, such as α‐amino acids, however the reaction is often hampered by the chemical autooxidation in alkaline or harsh reaction media. Regioselective O‐methyltransferases (OMTs) are ubiquitous enzymes in natural secondary metabolic pathways utilising an expensive co‐substrate S‐adenosyl‐l‐methionine (SAM) as the methylating reagent altering the physicochemical properties of the hydroxycinnamic acids. In this study, we engineered an OMT to accept a variety of electron‐rich phenolic substrates, modified a commercial E. coli strain BL21 (DE3) to regenerate SAM in vivo, and combined it with an engineered ammonia lyase to partake in a one‐pot, two whole cell enzyme cascade to produce the l‐DOPA precursor l‐veratrylglycine from lignin‐derived ferulic acid.
A Mechanistically Inspired Halenium Ion Initiated Spiroketalization: Entry to Mono‐ and Dibromospiroketals
Authors: Ashtekar Kumar Dilip , Gholami Hadi , Moemeni Mehdi , Chakraborty Ankush , Kiiskila Lindsey , Ding Xinliang , Toma Edmond , Rahn Christopher , Borhan Babak 
Published: December 2021

AbstractEmploying halenium affinity (HalA) as a guiding tool, the weak nucleophilic character of alkyl ketones was modulated by the templating effect of a tethered 2‐tetrahydropyranyl(THP)‐protected alcohol towards realizing a bromenium ion initiated spiroketalization cascade. Addition of ethanol aided an early termination of the cascade by scavenging the THP group after the halofunctionalization stage, furnishing monobromospiroketals. Alternatively, exclusion of ethanol from the reaction mixture biased the transient oxocarbenium towards α‐deprotonation that precedes a second bromofunctionalization event thus, furnishing dibrominated spiroketals. The regio‐ and stereoselectivity exploited in the current methodology provides a novel and rapid access to the dibrominated spiroketal motifs exhibited by several natural products.
Modulating the Excited State Chirality of Dynamic Chemical Reactions in Chiral Micelles
Authors: Yang Xuefeng , Jin Xue , Zhou Lili , Duan Pengfei , Fan Yaxun , Wang Yilin 
Published: December 2021

AbstractChirality generation and transfer is not only of critical importance in resolving the origin of biological homochirality, but also is of great significance for exploring the chirality‐related functionalities in nanomaterials and supramolecular systems. Although modulating the ground state chirality in chiral nanomaterials has been widely demonstrated, it remains a big challenge to steer the excited state chirality (circularly polarized luminescence, CPL). Herein, we present a kind of chiral spherical micelles constructed by chiral cationic gemini surfactants, whose surfaces and cavities could co‐assemble with hydrophilic and hydrophobic emitters concurrently. Subsequently, the hydrophilic and hydrophobic emitters could be endowed with CPL activity in the aqueous phase. Additionally, the cavities of such micelles can be regarded as the powerful chiral confined space, which could effectively modulate the excited state chirality of dynamic chemical reactions, enabling color‐adjustable CPL emission.
Sensitive Quantification of MicroRNA in Blood through Multi‐amplification Toehold‐Mediated DNA‐Strand‐Displacement Paper‐Spray Mass Spectrometry (TSD‐PS MS)
Authors: Yang Yanmei , Wang Weiqing , Liu Huimin , Tong Lili , Mu Xiaoyan , Chen Zhenzhen , Tang Bo 
Published: December 2021

AbstractAccurate quantification of disease‐signature microRNAs (miRNAs) in biomedical samples is in high demand for clinical diagnosis but still challenging because of the low abundance of miRNAs and complicating interferences in the milieus. Here, we report a multi‐amplification strategy based on paper‐spray mass spectrometry (PS MS) for the analysis of miRNAs in blood. A toehold‐mediated DNA‐strand‐displacement reaction (TSD) is employed to amplify the signal chain and to ensure the specificity. The signal chain is then cleaved by UV light to release signal molecules for detection. Moreover, the paper spray method can efficiently filter out interfering substances in the blood and further enhance the sensitivity of detection. This concept is successfully demonstrated in the prototypical detection of the cancer biomarker miRNA‐141 in blood and serum. The proposed TSD‐PS MS approach provides an efficient method for the sensitive detection of oligonucleotides at low concentration in complicated milieus.
A newly developed layered model to analytically predict the piezoelectric property of polymeric foams: Cellular geometry consideration
Authors: Daryadel Mahsa , Azdast Taher 
Published: December 2021

AbstractPiezoelectric property refers to the ability of materials to convert mechanical energy into electrical energy and vice versa. The development of science and technology and their orientation towards digital life will increase the need to use this property more and more. Polymeric foams are one of the materials that show high piezoelectric property. So far, only layered model has been proposed to predict the piezoelectric property of these materials. But to the best knowledge of the authors, there is no comprehensive research to investigate the accuracy of this model. Therefore, in this study, the obtained theoretical results from the layered model are compared to the experimental results and the accuracy of this model is investigated. Also, the presented solution by other authors to improve the accuracy of this model is studied. Finally, a new approach is developed to predict piezoelectric property of polymeric foams. The results show that the presented approach in this study increases the accuracy of the layered model compared to previous approaches. Considering the cellular structure of the polymeric foam as hexagonal geometry, the error is obtained 0.2%. Furthermore, the effect of different structural parameters on the maximum remnant charge density is investigated.
Decreased carboxylesterase expression associated with increased susceptibility to insecticide in Mythimna separata
Authors: Liu Yan , Li Shuangyu , Yang Hongjia , Chen Yaru , Fan Dong 
Published: December 2021

AbstractCarboxylesterases are one of the three major types of detoxification enzyme in insects. In this study, we screened 12 full‐length carboxylesterase cDNA sequences from the oriental armyworm Mythimna separata; they were named MsCarE1–MsCarE12 and registered in GenBank with accession numbers MK440541–MK440552. Treatment of fourth instar larvae of M. separata with the LD50 of the insecticide chlorantraniliprole increased the expression levels of MsCarE3 and MsCarE4, while treatment with the LD50 of lambda‐cyhalothrin significantly increased the expression levels of MsCarE5 and MsCarE10. Spatiotemporal expression detection showed that MsCarE3, MsCarE4, MsCarE5, and MsCarE10 were expressed at different developmental stages and in different tissues of M. separata and their expression levels were different. Induction using a high dose of chlorantraniliprole resulted in lower expression of MsCarE3 and MsCarE4. LD50 of lambda‐cyhalothrin induced higher expression of MsCarE5 and MsCarE10, while LD70 induced higher MsCarE10 expression at 3, 6, and 12 h after treatment. RNA interference successfully inhibited the expression of MsCarE3, MsCarE4, MsCarE5, and MsCarE10, to different degrees at different time points. Silencing of MsCarE5, or MsCarE5 and MsCarE10 simultaneously changed carboxylesterase activity and increased the susceptibility of M. separata larvae to lambda‐cyhalothrin. This study provides a new method to increase the insect susceptibility to insecticide.
Therapeutic Effect of Cyclin‐Dependent Kinase 4/6 Inhibitor on Dermal Fibrosis in Murine Models of Systemic Sclerosis
Authors: Yamamoto Akio , Saito Tetsuya , Hosoya Tadashi , Kawahata Kimito , Asano Yoshihide , Sato Shinichi , Mizoguchi Fumitaka , Yasuda Shinsuke , Kohsaka Hitoshi 
Published: December 2021

ObjectiveOne of the histologic characteristics of systemic sclerosis (SSc) is an increased number of dermal myofibroblasts, and transforming growth factor β (TGFβ) plays a crucial role in the promotion of myofibroblast differentiation from fibroblasts, leading to dermal fibrosis. This study was undertaken to 1) examine whether inhibition of the cell cycle with a cyclin‐dependent kinase 4/6 (CDK4/6) inhibitor suppresses the proliferation of fibroblasts and their differentiation into myofibroblasts, and 2) assess the therapeutic effects of a CDK4/6 inhibitor, administered as monotherapy or in combination with a TGFβ receptor (TGFβR) inhibitor, on dermal fibrosis in murine models of SSc.MethodsFibroblasts obtained from the skin of patients with SSc were cultured in the presence or absence of TGFβ. The effects of palbociclib, a CDK4/6 inhibitor, on fibroblast proliferation and TGFβ‐induced differentiation into myofibroblasts were examined using bromodeoxyuridine uptake assays as well as immunofluorescence and immunoblotting analyses. Murine models of HOCl‐ and bleomycin‐induced dermal fibrosis were used to study the effect of a CDK4/6 inhibitor on dermal fibrosis, with the CDK4/6 inhibitor treatment administered as monotherapy or in combination with galunisertib, a TGFβR inhibitor.ResultsAddition of a CDK4/6 inhibitor to the cell cultures suppressed the proliferation of human dermal SSc fibroblasts and their TGFβ‐induced differentiation into myofibroblasts, without inhibiting canonical and noncanonical TGFβ signals. In murine models of dermal fibrosis, treatment of mice with a CDK4/6 inhibitor decreased dermal thickness and collagen content, as well as dermal fibroblast proliferation and the numbers of myofibroblasts. Combination therapy with the CDK4/6 inhibitor and TGFβR inhibitor resulted in additive antifibrotic effects. Mechanistically, the CDK4/6 inhibitor suppressed the expression of cellular communication network 2 and cadherin‐11, which are proteins that have important roles in the development and progression of fibrosis.ConclusionResults of this study demonstrate the therapeutic effect of a CDK4/6 inhibitor on dermal fibrosis when administered as monotherapy or in combination with a TGFβR inhibitor. CDK4/6 inhibitors, including palbociclib used in the present study, may represent novel agents for the treatment of SSc, which, if used in combination with a TGFβR inhibitor, might result in increased efficacy.
Reimagining systematic anatomy: The conclusion of the quartet
Authors: Neumann Paul E. 
Published: December 2021

AbstractThe central dogma of systematic anatomy is the well‐known hierarchy of anatomical structures: body‐systems‐organs‐tissues‐cells. This schema omits extracellular matrix and extracellular fluids, which account for a significant proportion of body mass, and distorts the meanings of the terms system, organ and tissue in anatomy. These faults are partially due to oversimplification, presumably intended for educational purposes, and confusion of anatomy's organ systems with physiological systems. A revised schema of the hierarchy of systematic anatomy is presented that is more complete and more consistent with the long history of anatomy.
Enhanced Immunostimulatory Activity of Covalent DNA Dendrons
Authors: Kawamoto Yusuke , Liu Wen , Yum Ji Hye , Park Soyoung , Sugiyama Hiroshi , Takahashi Yuki , Takakura Yoshinobu 
Published: December 2021

AbstractThe present study focused on the design and synthesis of covalent DNA dendrons bearing multivalent cytosine‐phosphate‐guanine oligodeoxynucleotides (CpG ODNs) that can stimulate the immune system through the activation of TLR9. These dendrons were synthesized using branching trebler phosphoramidite containing three identical protecting groups that enabled the simultaneous synthesis of multiple strands on a single molecule. Compared with linear ODNs, covalent DNA dendrons were found to be more resistant to nuclease degradation and were more efficiently taken up by macrophage‐like RAW264.7 cells. Cellular uptake was suggested to be mediated by macrophage scavenger receptors. The covalent DNA dendrons composed of multivalent immunostimulatory branches enhanced the secretion of proinflammatory cytokines TNF‐α and IL‐6 from RAW264.7 cells, and 9‐branched DNA dendrons showed the highest enhancement. Given their enhanced efficacy, we expect covalent DNA dendrons to be useful structures of oligonucleotide medicines.
Tbx18 promoted the conversion of human‐induced pluripotent stem cell‐derived cardiomyocytes into sinoatrial node‐like pacemaker cells
Authors: Zhang Wei , Zhao Hongyi , Quan Dajun , Tang Yanhong , Wang Xi , Huang Congxin 
Published: December 2021

AbstractSinoatrial node (SAN) pacemaker cells originate from T‐box transcription factor 18 (Tbx18)‐expressing progenitor cells. The present study aimed to investigate whether overexpression of human transcription factor Tbx18 could reprogram human‐induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CMs) into SAN‐like pacemaker cells (SANLPCs) in vitro. In the study, hiPSCs were first differentiated into hiPSC‐CMs through regulating the Wnt/β‐catenin pathway, then purified hiPSC‐CMs were transfected by Tbx18 adenovirus (Tbx18‐CMs group) or green fluorescent protein (GFP) adenovirus (GFP‐CMs group). The beating frequency of the Tbx18‐CMs group was significantly higher than that of the hiPSC‐CMs group and GFP‐CMs group. Compared with the other two groups, the expression levels of hyperpolarization‐activated cyclic nucleotide‐gated potassium channel isoform 4, connexin‐45 in the Tbx18‐CMs group were markedly upregulated, while the expressions of transcription factor NKX2.5, CX43 were significantly downregulated. Whole‐cell patch‐clamp results illustrated that action potential and “funny” current (If) similar to SAN pacemaker cells could be recorded in the Tbx18‐CMs group. In conclusion, this present study demonstrated that overexpression of Tbx18 promoted the conversion of hiPSC‐CMs into SANLPCs.
Research progress of Bub3 gene in malignant tumors
Authors: Wang Chenyang , Cheng Dating , Pan Chenglong , Wang Chunyan , Nie Zhi 
Published: December 2021

AbstractThe spindle assembly checkpoint (SAC) is a highly conserved monitoring system that ensures a fidelity of chromosome segregation during mitosis. Bub3, a mitotic Checkpoint Protein, is a member of the Bub protein family, and an important factor in the SAC. Abnormal expression of Bub3 results in mitotic defects, defective spindle gate function, chromosomal instability and the development of aneuploidy cells. Aneuploidy is a state of abnormal karyotype that has long been considered as a marker of tumorigenesis. Karyotypic heterogeneity in tumor cells, known as “chromosomal instability” (CIN), can be used to distinguish cancerous cells from their normal tissue counterpart. In this review, we summarize the expression and clinical significance of Bub3 in a variety of tumors and suggest that it has potential in the treatment of cancer.
HPV16 E6/E7 stabilize PGK1 protein by reducing its poly‐ubiquitination in cervical cancer
Authors: Liu Shikai , Song Lili , Yao Hairong , Zhang Liang 
Published: December 2021

AbstractThis study aimed to explore the expression profile, prognostic value, regulatory effect, and the underlying mechanism of dysregulation of phosphoglycerate kinase 1 (PGK1) in high‐risk human papillomavirus (HPV)‐positive cervical epithelial squamous cell carcinoma (CESC). Bioinformatic analysis was performed using the CESC subset of The Cancer Genome Atlas (TCGA)‐Cervical Cancer (CESC) and normal cervix in The Genotype‐Tissue Expression (GTEx) project. HPV‐16 positive CaSki and SiHa cells were used as in vitro cell models. Results showed that compared to the normal cervix, CESC tissues had significantly higher expression of PGK1. CESC patients with the higher 50% expression of PGK1 had substantially shorter disease‐specific survival (DSS), and progression‐free survival (PFS) compared to the cases with the lower 50% expression of PGK1. PGK1 knockdown impaired, but PGK1 overexpression enhanced the proliferation, colony formation, aerobic glycolytic activities (lactate production, intracellular ATP levels, glucose uptake, and extracellular acidification rate), migration, and invasion of CaSki and SiHa cells. HPV‐16 E6/E7 knockdown in CaSki and SiHa cells had limited influence on PGK1 transcription but significantly decreased the half‐life of PGK1 protein. E6/E7 knockdown mediated PGK1 downregulation could be blocked by adding MG‐132. PGK1 poly‐ubiquitination was significantly enhanced after E6/E7 knockdown. In conclusion, this study showed that PGK1 expression might serve as a prognostic biomarker in cervical cancer. Its upregulation contributes to enhanced aerobic glycolysis, migration, and invasion of CESC cells. HPV16 E6/E7 stabilizes PGK1 protein by reducing its poly‐ubiquitination.
The identification of a novel splicing mutation in the DMD gene of a Chinese family
Authors: Liu Wanlu , Shi Xinwei , Li Yuqi , Qiao Fuyuan , Wu Yuanyuan 
Published: December 2021

AbstractThe proband is a five‐year‐old boy diagnosed with Duchenne muscular dystrophy (DMD) by clinical manifestations and laboratory examination, but clinical phenotype of his parents is normal. In the study, his mother had a second pregnancy, and they went to obstetrics for genetic counseling to make informed reproductive choices.
Stimuli‐Responsive Polymers with Room‐Temperature Phosphorescence
Authors: Gu Fan , Ma Xiang 
Published: December 2021

AbstractTaking advantages of the impressing behaviors of room‐temperature phosphorescence (RTP), the explorations in RTP materials are not only limited to efficient emission and ultralong lifetime of phosphorescence. The discovery and creation of stimuli‐responsive properties have become the major pursuit, which will lay a solid foundation for future applications in RTP materials. Based on this, a review centered on recent progress of stimuli‐responsive RTP materials is summarized to show frontier development in polymer systems. Different kinds of stimuli‐responsive factors including light, oxygen, temperature, mechanical force and pH regulations are investigated in this review. Many potential applications and promising strategies are deeply discussed with the hope to assist future studies in this area.
Glycoenzyme Tool Development: Principles, Screening Methods, and Recent Advances†
Authors: Cui Tongxiao , Man Yi , Wang Feifei , Bi Shuyang , Lin Liang , Xie Ran 
Published: December 2021

Comprehensive SummaryTo elucidate the relationship between carbohydrate structure and its biological function, glycoenzyme tools are widely applied in a variety of physiological and pathological scenarios. Intricate adjustment via glycoenzyme engineering improved the catalytic efficiency, extended the repertoire of accessible catalytic reactions, and tailored novel substrate specificities. In this review, we introduce the principles of glycoenzyme engineering and summarize the recent advances in the rational design and directed evolution of these enzymes, with an emphasis on screening methods in directed evolution. We also excerpt novel detection methods in glycobiology that can be adapted for the development of next‐generation glycoenzyme tools.
Psychosocial factors associated with genetic testing status among African American women with ovarian cancer: Results from the African American Cancer Epidemiology Study
Authors: McBride Colleen M. , Pathak Sarita , Johnson Courtney E. , Alberg Anthony J. , Bandera Elisa V. , Barnholtz‐Sloan Jill S. , Bondy Melissa L. , Cote Michele L. , Moorman Patricia G. , Peres Lauren C. , Peters Edward S. , Schwartz Ann G. , Terry Paul D. , Schildkraut Joellen M. 
Published: December 2021

BackgroundRacial disparities in the uptake of cancer genetic services are well documented among African American (AA) women. Understanding the multiple social and psychological factors that can influence the uptake of genetic testing among AA women is needed.MethodsData came from 270 AA women diagnosed with ovarian cancer and participating in a population‐based, case‐control study of ovarian cancer who were asked about genetic testing. Logistic regression analyses tested the associations of predisposing, enabling, and need factors with reported genetic testing uptake.ResultsOne‐third of the sample (35%) reported having had genetic testing. In the multivariable model, AA women with higher incomes had more than double the odds of being tested than those with the lowest income (odds ratio [OR] for $25,000‐$74,999, 2.04; 95% confidence interval [CI], 1.06‐3.99; OR for ≥$75,000, 2.32; 95% CI, 0.92‐5.94). AA women who reported employment discrimination were significantly less likely to report genetic testing than those who did not report job discrimination (OR, 0.39; 95% CI, 0.14‐0.95). Marital status, Medicaid versus other insurance, prayer frequency, and perceived social support were significantly associated with genetic testing uptake in bivariate analyses but were not significant contributors in multivariable analyses.ConclusionsConsistent with other studies of AA women, a minority of African American Cancer Epidemiology Study participants had undergone genetic testing. Having a lower income and experiencing job discrimination decreased the likelihood of testing. These results provide foundational evidence supporting the need for interventions to improve the uptake of genetic testing among AA women by reducing cost barriers and providing credible assurances that genetic results will be kept private and not affect social factors such as employability.