bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Proton‐Activatable DNA‐Based Nanosystem Enables Co‐Delivery of CRISPR/Cas9 and DNAzyme for Combined Gene Therapy
Authors: Li Feng , Song Nachuan , Dong Yuhang , Li Shuai , Li Linghui , Liu Yujie , Li Zhemian , Yang Dayong 
Published: January 2022

AbstractCRISPR/Cas9 is emerging as a platform for gene therapeutics, and the treatment efficiency is expected to be enhanced by combination with other therapeutic agents. Herein, we report a proton‐activatable DNA‐based nanosystem that enables co‐delivery of Cas9/sgRNA and DNAzyme for the combined gene therapy of cancer. Ultra‐long ssDNA chains, which contained the recognition sequences of sgRNA in Cas9/sgRNA, DNAzyme sequence and HhaI enzyme cleavage site, were synthesized as the scaffold of the nanosystem. The DNAzyme cofactor Mn2+ was used to compress DNA chains to form nanoparticles and acid‐degradable polymer‐coated HhaI enzymes were assembled on the surface of nanoparticles. In response to protons in lysosome, the polymer coating was decomposed and HhaI enzyme was consequently exposed to recognize and cut off the cleavage sites, thus triggering the release of Cas9/sgRNA and DNAzyme to regulate gene expressions to achieve a high therapeutic efficacy of breast cancer.
Genetic influences on dentognathic morphology in the Jirel population of Nepal
Authors: Hardin Anna M. , Knigge Ryan P. , Duren Dana L. , Williams‐Blangero Sarah , Subedi Janardan , Mahaney Michael C. , Sherwood Richard J. 
Published: January 2022

AbstractPatterns of genetic variation and covariation impact the evolution of the craniofacial complex and contribute to clinically significant malocclusions in modern human populations. Previous quantitative genetic studies have estimated the heritabilities and genetic correlations of skeletal and dental traits in humans and nonhuman primates, but none have estimated these quantitative genetic parameters across the dentognathic complex. A large and powerful pedigree from the Jirel population of Nepal was leveraged to estimate heritabilities and genetic correlations in 62 maxillary and mandibular arch dimensions, incisor and canine lengths, and post‐canine tooth crown areas (N ≥ 739). Quantitative genetic parameter estimation was performed using maximum likelihood‐based variance decomposition. Residual heritability estimates were significant for all traits, ranging from 0.269 to 0.898. Genetic correlations were positive for all trait pairs. Principal components analyses of the phenotypic and genetic correlation matrices indicate an overall size effect across all measurements on the first principal component. Additional principal components demonstrate positive relationships between post‐canine tooth crown areas and arch lengths and negative relationships between post‐canine tooth crown areas and arch widths, and between arch lengths and arch widths. Based on these findings, morphological variation in the human dentognathic complex may be constrained by genetic relationships between dental dimensions and arch lengths, with weaker genetic correlations between these traits and arch widths allowing for variation in arch shape. The patterns identified are expected to have impacted the evolution of the dentognathic complex and its genetic architecture as well as the prevalence of dental crowding in modern human populations.
Mode of uterine milk secretion in the white shark
Authors: Tomita Taketeru , Nakamura Masaru , Nozu Ryo , Ogawa Nobuhiro , Toda Minoru , Sato Keiichi 
Published: January 2022

AbstractExamination of the uterus of a dead female white shark (Carcharodon carcharias), which contained the earliest known white shark embryos, revealed that the uterine wall produces lipid‐rich secretion (histotroph or “uterine milk”) for embryonic nutrition. Uterine tissue was processed for light and electron microscopy, and immunohistochemical techniques to identify its secretory mechanism. Our results indicate that the white shark uterus secretes lipids via holocrine secretion. This type of secretion is characterized by the release of large lipid droplets accumulated in the epithelial cells into the uterine lumen through cell disintegration. The secretory epithelium of the uterus is stratified, and new surface epithelial cells are continuously supplied from deeper epithelial layers to replace the dead secretory cells at the surface. This vertical replacement possibly facilitates the active renewal of the surface epithelium, which is necessary for maintaining holocrine secretory mechanisms. These secretory mechanisms are different from those of myliobatiform stingrays, another elasmobranch taxon that exhibits lipid histotrophy. This may reflect the different origins of lipid histotrophy between these taxa.
Fabrication of Isomorphously Substituted W‐MFI Membrane with High Performance for Ethanol Separation from Water
Authors: Saulat Hammad , Yang Jianhua , Wensen Song , Raza Waseem , He Gaohong 
Published: January 2022

AbstractIsomorphous substitution of heteroatoms is an effective platform for finely tuning the pore chemistry, pore structure, and surface properties of the zeolite framework as catalysts or separation membranes. A continuous and compact isomorphously substituted tungsten (W)‐MFI membrane was firstly developed on coarse α‐Al2O3 tube dip‐coated with W‐MFI seeds using hydrothermal secondary growth and pretreated synthesis solution. The synthesized W‐MFI membrane is found to be ethanol permselective having a pervaporation based separation factor and flux of 69 and 2.50 kg/m2 h, respectively while exhibiting the highest separation index of 170 kg/m2 h for the separation of 5 wt% ethanol‐water mixture among the reported heteroatoms substituted and α‐Al2O3 supported tubular MFI membranes. The isomorphous substitution of W improves the hydrophobicity and also plays a significant role for the enhanced separation performance.
Enhancing effect of borneol on pharmacokinetics of ginsenoside Rb1, ginsenoside Rg1, and notoginsenoside R1 in healthy volunteers after oral administration of compound Danshen dropping pills
Authors: Zheng Dayong , Chu Yang , Li Shuming , Zhou Shuiping , Li Wei , Xie Yuesheng , Sun He 
Published: January 2022

AbstractBorneol (Bingpian), a monoterpenoid pharmaceutical ingredient, is commonly used as a main composition in traditional Chinese medicine preparations such as compound Danshen dropping pills (CDDP) and has also been approved by the U.S. Food and Drug Administration as a flavoring substance or adjuvant in food. Borneol plays a regulating and guiding role as a messenger drug in CDDP. However, the effect of borneol on the pharmacokinetics of the components of CDDP in human plasma is unclear. In this study, we investigate the effects of borneol on the pharmacokinetics of ginsenoside Rb1 (Rb1), ginsenoside Rg1 (Rg1), and notoginsenoside R1 (NR1) in CDDP. We used a double‐cycle crossover‐administration model in 12 healthy male volunteers, administered CDDP with borneol (drug T) and without borneol (drug R). The selective response monitoring mode was used for MS quantification in the positive mode. As a result, we found that borneol could significantly affect the pharmacokinetic parameters of notoginsenosides and increase the absorption and systemic exposure of Rb1, Rg1, and NR1 in human plasma by ~1.85–3.71 times.
Quantitation of plasma angiotensin II in healthy Chinese subjects by a validated liquid chromatography tandem mass spectrometry method
Authors: Lo Clara Wai‐Shan , Tsui Teresa Kam‐Chi , Ma Ronald Ching‐Wan , Chan Michael Ho‐Ming , Ho Chung‐Shun 
Published: January 2022

AbstractQuantitation of plasma angiotensin (Ang) II, the active mediator of the renin–angiotensin system, is challenging owing to its low physiological concentration. We report a validated liquid chromatography–mass spectrometry (LCMS) method to overcome this challenge. Ang II was extracted from EDTA plasma by an offline solid‐phase extraction procedure with a Waters MAX μElution plate. LCMS quantitation was performed on the Waters TQS system, monitoring the 3+ ions of the peptide. The analytical performance of the LCMS method was validated. The stability of Ang II was studied with or without the presence of a protease inhibitor. Local reference intervals were established from 143 healthy normotensive subjects (57% female, 21–60 years old). The Ang II LCMS method had a measurable range of 3.3–700 pmol/L. The between‐batch precision coefficient of variation was <7% over Ang II concentrations of 8.6–110 pmol/L. No significant matrix interference and carryover were observed. There was no significant difference in Ang II concentration in EDTA blood and plasma for at least 2h and 1 h at room temperature, respectively. Ang II was stable for at least 1 year when stored at −80°C, with or without the protease inhibitor. Age‐dependent Ang II reference intervals were established: 4.4–17.7 pmol/L (21–30 years) and 3.9–12.8 pmol/L (31–60 years). The present LCMS method is suitable for quantitation of plasma Ang II to study the renin‐angiotensin system.
Increased mitochondrial fission drives the reprogramming of fatty acid metabolism in hepatocellular carcinoma cells through suppression of Sirtuin 1
Authors: Wu Dan , Yang Yi , Hou Yiran , Zhao Zifeng , Liang Ning , Yuan Peng , Yang Tao , Xing Jinliang , Li Jibin 
Published: January 2022

AbstractBackgroundMitochondria are dynamic organelles that constantly change their morphology through fission and fusion processes. Recently, abnormally increased mitochondrial fission has been observed in several types of cancer. However, the functional roles of increased mitochondrial fission in lipid metabolism reprogramming in cancer cells remain unclear. This study aimed to explore the role of increased mitochondrial fission in lipid metabolism in hepatocellular carcinoma (HCC) cells.MethodsLipid metabolism was determined by evaluating the changes in the expressions of core lipid metabolic enzymes and intracellular lipid content. The rate of fatty acid oxidation was evaluated by [3H]‐labelled oleic acid. The mitochondrial morphology in HCC cells was evaluated by fluorescent staining. The expression of protein was determined by real‐time PCR, iimmunohistochemistry and Western blotting.ResultsActivation of mitochondrial fission significantly promoted de novo fatty acid synthesis in HCC cells through upregulating the expression of lipogenic genes fatty acid synthase (FASN), acetyl‐CoA carboxylase1 (ACC1), and elongation of very long chain fatty acid protein 6 (ELOVL6), while suppressed fatty acid oxidation by downregulating carnitine palmitoyl transferase 1A (CPT1A) and acyl‐CoA oxidase 1 (ACOX1). Consistently, suppressed mitochondrial fission exhibited the opposite effects. Moreover, in vitro and in vivo studies revealed that mitochondrial fission‐induced lipid metabolism reprogramming significantly promoted the proliferation and metastasis of HCC cells. Mechanistically, mitochondrial fission increased the acetylation level of sterol regulatory element‐binding protein 1 (SREBP1) and peroxisome proliferator‐activated receptor coactivator 1 alpha (PGC‐1α) by suppressing nicotinamide adenine dinucleotide (NAD+)/Sirtuin 1 (SIRT1) signaling. The elevated SREBP1 then upregulated the expression of FASN, ACC1 and ELOVL6 in HCC cells, while PGC‐1α/PPARα suppressed the expression of CPT1A and ACOX1.ConclusionsIncreased mitochondrial fission plays a crucial role in the reprogramming of lipid metabolism in HCC cells, which provides strong evidence for the use of this process as a drug target in the treatment of this malignancy.
Femvertising or femwashing? Women's perceptions of authenticity
Authors: Hainneville Valentine , Guèvremont Amélie , Robinot Élisabeth 
Published: January 2022

AbstractStereotypes in advertising are recognized as contributing to the perpetuation of inequalities. In response to this, femvertising—“advertising that employs pro‐female talents, messages, and imagery to empower women and girls” (SheKnows, 2014)—is increasingly observed in the marketplace. Despite femvertising's prevalence, current research has failed to identify women's core understanding of it. The objectives of this research are to conceptualize femvertising from a consumer perspective, explore the nature of authentic femvertising, and differentiate it from femwashing. In‐depth interviews were conducted with 17 women. The findings help uncover femvertising's complex meaning as perceived by consumers and distinguish it from femwashing. The results suggest that the concepts of femvertising and femwashing coexist in consumers' minds. Six dimensions of authentic femvertising are identified: transparency, consistency, identification, diversity, respect, and challenging stereotypes. This research contributes to the consumer research, advertising, and branding literature; encourages a broader societal reflection about gender stereotypes; and offers several managerial implications.
Caged Iridium Catalyst for Hydrosilylation of Alkynes with High Site Selectivity
Authors: Li Qiaosheng , Gu Defa , Yu Dongdong , Liu Yuzhou 
Published: January 2022

AbstractThe proximity and orientation of the reacting groups can be different in organic cages from in free solution, thus affecting the selectivity of the reaction. Herein, we reported a synthetic strategy to encapsulate iridium nanoparticles (Ir‐NP@COP1‐T) within organic cages in the homogeneous solution. Ir‐NP@COP1‐T showed good selectivity in the hydrosilylation reaction of alkynes. Our work provides a new perspective to the catalysis field by using soluble microporous cages as support for inorganic nano particles.
Curcumin alters distinct molecular pathways in breast cancer subtypes revealed by integrated miRNA/mRNA expression analysis
Authors: Nirgude Snehal , Desai Sagar , Choudhary Bibha 
Published: January 2022

AbstractBackgroundCurcumin is well known for its anticancer properties. Its cytotoxic activity has been documented in several cancer cell lines, including breast cancer. The pleiotropic activity of curcumin as an antioxidant, an antiangiogenic, antiproliferative, and pro‐apoptotic, is due to its diverse targets, such as signaling pathways, protein/enzyme, or noncoding gene.AimThis study aimed to identify key miRNAs and mRNAs induced by curcumin in breast cancer cells MCF7, T47D (hormone positive), versus MDA‐MB231 (hormone negative) using comparative analysis of global gene expression profiles.MethodsRNA was isolated and subjected to mRNA and miRNA library sequencing to study the global gene expression profile of curcumin‐treated breast cancer cells. The differential expression of gene and miRNA was performed using the DESeq R package. The enriched pathways were studied using cluster profileR, and integrated miRNA–mRNA analysis was carried out using miRtarvis and miRmapper tools.ResultsCurcumin treatment led to upregulation of 59% TSGs in MCF7, 21% in MDA‐MB‐231 cells, and 36% TSGs in T47D, and downregulation of 57% oncogenes in MCF7, 76% in MDA‐MB‐231, and 91% in T47D. Similarly, curcumin treatment led to upregulation of 32% TSmiRs in MCF7, 37.5% in MDA‐MB231, and 62.5% in T47D, and downregulation of 77% oncomiRs in MCF7, 50% in MDA‐MB231 and 28.6% in T47D. Integrated analysis of miRNA–mRNA led to the identification of a common NFKB pathway altered by curcumin in all three cell lines. Analysis of uniquely enriched pathway revealed non‐integrin membrane–ECM interactions and laminin interactions in MCF7; extracellular matrix organization and degradation in MDA‐MB‐231 and cell cycle arrest and G2/M transition in T47D.ConclusionCurcumin regulates miRNA and mRNA in a cell type‐specific manner. The integrative analysis led to the detection of miRNAs and mRNAs pairs, which can be used as biomarkers associated with carcinogenesis, diagnostic, and treatment response in breast cancer.
Pharmacokinetics, Bioequivalence, and Safety Studies of Amlodipine Besylate in Healthy Subjects
Authors: Chen Bin , Chen ZhiMin , Lv DongQing , Sun Yuan , Chen HuaFang 
Published: January 2022

AbstractThis study aimed to evaluate the bioequivalence of 2 amlodipine besylate tablet formulations, a generic formulation and an original formulation, and to investigate their pharmacokinetic and safety profiles. This study was designed as a randomized, open‐label, single‐dose, crossover, dual‐period study and was divided into fasting and postprandial human bioequivalence trials. In the first trial after overnight fasting, 28 subjects were given 5‐mg amlodipine besylate tablets via oral administration, and blood specimens were obtained up to 144 hours after dosing; another 28 subjects had a high‐fat meal 1 hour before drug administration and proceeded the same as the fasting trial. Bioequivalence was evaluated using 90%CIs for the ratio test/reference of log area under the concentration–time curve (AUC) from time 0 to the last quantifiable concentration, log AUC from time 0 to infinity, and log peak concentration. The plasma concentrations were measured by high‐performance liquid chromatography–tandem mass spectrometry. The safety was assessed throughout the study. The results show that no significant differences were observed between the pharmacokinetic profiles of the test and reference amlodipine besylate tablets in the fasting and postprandial trials. The 90%CIs of the peak concentration, AUC from time 0 to the last quantifiable concentration and AUC from time 0 to infinity of amlodipine in the 2 trials were within the commonly accepted bioequivalence criteria of 80% to 125%. Compared with the pharmacokinetic parameters of the fasting and postprandial trials, food had no significant effect on exposure of amlodipine besylate. There was no significant difference in safety statistical results between the 2 groups. The results suggest that generic and original amlodipine besylate tablets are bioequivalent with similar safety profiles.
Design and Synthesis of Crosslinked Helix Dimers as Protein Tertiary Structure Mimics
Authors: Hong Seong Ho , Nguyen Thu , Arora Paramjit 
Published: January 2022

AbstractCrosslinked helix dimers (CHDs) are synthetic tertiary helical structure motifs designed to modulate interactions of proteins with binding partners. Helix dimers serve as mimics of coiled coils, which are known to be implicated in a multitude of protein complexes. Coiled coils are typically stable in long peptides (>21‐28 residues), because sufficient intra‐ and interstrand contacts are not available in short peptides to coax strand assembly. To engineer conformationally stable CHDs in short sequences, we introduced a covalent linkage in place of an interhelical salt bridge and sculpted the helical interface with optimal hydrophobic packing. CHDs have shown efficacy for the disruption of targeted protein‐protein interactions in biochemical, cellular, and animal models. This article describes our optimized approach to design and synthesize parallel and antiparallel helical tertiary structure mimics. Synthesis of CHDs involves conjugation of individual peptide segments, purification of the mono‐conjugated strand, and alkylation of the two independent strands to yield crosslinked dimers. © 2022 Wiley Periodicals LLC.Basic Protocol 1: Protocol for bis‐triazole CHDsBasic Protocol 2: Protocol for dibenzyl ether CHDs
A novel generic modulo‐2 graph with full set taxonomical conversion to parallel prefix adders
Authors: Rahimi M. , Ghaznavi‐Ghoushchi M. B. 
Published: January 2022

AbstractThis paper proposes a novel generic modulo‐2 graph that can be converted to parallel prefix adders (PPA). Also, a conversion algorithm for converting the proposed graph to PPAs is proposed in this paper. The conversation algorithm can be applied onN‐bitGeneric modulo‐2 graph, and this graph is converted toN‐bitPPAs. When the proposed conversion algorithm is applied to generic modulo‐2 graph, this graph is converted to Brent‐Kung, Sklansky, Kogge‐Stone, Harris, Ladner‐Fischer, Han‐Carlson, and Knowles adders. Moreover, PPAs are shown in trilinear coordinates to represent the final PPAs, which generic graph converted to them. Furthermore, the add operation is done by generic graph and also the correctness of add function of this graph is investigated by “Boolean decision diagram.”
Bile cytology diagnosis in challenging cases: Validation of diagnostic bile cytology criteria and extensive study for immunocytochemical markers
Authors: Sano Naoki , Tabata Kenichi , Oda Tomohiro , Yanagita Miki , Suzuki Tomoko , Komatsubara Toshihide , Kawata Hirotoshi , Fukushima Noriyoshi 
Published: January 2022

AbstractBackgroundBile cytology is useful in diagnosing biliary tract lesions, albeit often challenging due to equivocal findings. To achieve better diagnoses for clinical decisions, we conducted cytomorphological and immunocytochemical studies of bile cytology cases.Materials and methodsWe re‐evaluated 40 bile cytology cases with initial equivocal diagnoses, taken from the cytology records of Jichi Medical University Hospital, including 1778 bile cytology specimens. First, we assessed the cases by the diagnostic bile cytology criteria of the Japanese Society of Clinical Cytology. Second, we searched for useful immunocytochemical markers by extensive immunohistochemical analyses using tissue microarray for 10 antibodies: S100P, IMP3, GLUT1, p53, S100A4, Mapsin, MUC17, CD10, MDM2, and SMAD4. Microarrays were from 257 extrahepatic bile duct carcinoma cases. To elucidate the utility of immunocytochemistry, we applied selected markers to immunocytochemical evaluation of the equivocal cases after cell transfer.ResultsThe criteria indicated a sensitivity 60%, specificity 87%, and accuracy 70%. Irregularly overlapping (88%), arranged (96%), and shaped (76%) nuclei were more common in malignant cases, while enlarged nuclei were more frequent in benign cases (67% vs. 28%). We applied S100P and IMP3, which showed higher accuracy (88% and 77%) in tissue microarray, to immunocytochemistry. The sensitivity of S100P and IMP3 were 69% and 70%, respectively. The specificity of S100P and IMP3 were 50% and 100%, respectively.ConclusionThe criteria showed a certain effectiveness even in challenging cases, and some pitfalls associated with reactive changes of benign cells. Although comprehensive diagnosis including cytomorphology seems preferable, S100P and IMP3 are promising immunocytochemical markers.
Vertical integration in healthcare: What does literature say about improvements on quality, access, efficiency, and costs containment?
Authors: Amado Guilherme C. , Ferreira Diogo C. , Nunes Alexandre M. 
Published: January 2022

AbstractIntroductionVertical integration models involve integrating services from different levels of care (e.g., primary care, acute care, post‐acute care). Therefore, one of their main objectives is to increase continuity of care, potentially improving outcomes like efficiency, quality, and access or even enabling cost containment.ObjectivesThis study conducts a literature review and aims at contributing to the contentious discussion regarding the effects of vertical integration reforms in terms of efficiency, costs containment, quality, and access.MethodsWe performed a systematic search of the literature published until February 2020. The articles respecting the conceptual framework were included in an exhaustive analysis to study the impact of vertical integration on costs, prices of care, efficiency, quality, and access.ResultsA sample of 64 papers resulted from the screening process. The impact of vertical integration on costs and prices of care appears to be negative. Decreases in technical efficiency upon vertical integration are practically out of the question. Nevertheless, there is no substantial inclination to visualise a positive influence. The same happens with the quality of care. Regarding access, the lack of available articles on this outcome limits conjectures.ConclusionsIn summary, it is not clear yet whether vertically integrated healthcare providers positively impact the overall delivery care system. Nevertheless, the recent growing trend in the number of studies suggests a promising future on the analysis of this topic.