bluuebunny/crossref_metadata_2025_split huggingface dataset:
The association of 20 short tandem repeat loci of autosomal chromosome with male schizophrenia
Authors: Yang Chun , Ba Huajie , Zou Huihui , Zhou Xianju 
Published: June 2022

AbstractIntroductionSchizophrenia's heritability and familial transmission have been known for several decades. The male‐specific Y chromosome plays an important role in schizophrenia. Short tandem repeats (STRs)have been recognized as risk genes in the development of schizophrenia. Here, we investigated the association between male schizophrenia and Y‐chromosomal STRs loci.MethodsWe recruited 355 patients with schizophrenia and 473 healthy males for physical examination and amplified them with a PowerPlex 21 System fluorescence‐labeled composite amplification System. Then, the resultant products were separated by electrophoresis and further detected. Finally, differences in allele and genotype frequency distributions of STR loci were observed.ResultsOur results showed that all 20 STR loci were in accordance with Hardy–Weinberg's law (p > .05). There were statistically significant differences in alleles of D13S317 and D5S818 loci and genotype frequency distribution between the two groups (alleles: p = .039, p = .022, respectively; genotype: p = .0004, p = .011, respectively). However, there was no difference in the other autosomal 18 STR loci between the two groups (p > .05). Univariate analysis showed that the frequency distribution differences of allele 11 and genotype 10‐11 at the D13S317 locus between the two groups were significant (compared to the controls, p = 0.005, odds ratio (OR) = 1.37, 95%b confidence interval (CI) = 1.10–1.71, compared to the controls, p = .0000002, OR = 3.92, 95% CI = 2.27–6.77, respectively). The frequency distribution differences of allele 7 and genotype 7‐10 at D5S818 between the two groups were significant (compared to the controls, p = .0006, OR = 3.42, 95% CI = 1.63–7.16, compared to the controls, p = .0011, OR = 8.24, 95% CI = 1.83–37.05, respectively).ConclusionPolymorphisms of the D13S317 and D5S818 loci may be predisposing factors for schizophrenia.
Chemical Constituents of the Stem Bark of the Hybrid Plant Citrus × paradisi Macfad. (Rutaceae)
Authors: Essombe Malolo Fanny‐Aimée , Bellier Tabekoueng George , Dongmo Tekapi Tsopgni Willifred , Nguemdjo Chimeze Valery Wilfried , Kenmogne Kouam Ariane , Mas‐Claret Eduard , Langat Moses K. , Ndom Jean Claude , Frese Marcel , Sewald Norbert , Duplex Wansi Jean 
Published: June 2022

AbstractThe stem bark of Citrus × paradisi Macfad. (Rutaceae) gave (23S)‐isolimonexic acid (1), limonin (2), citracridone II (3), citpressine II (4), citpressine I (5), grandisine (6), 2‐hydroxynoracronycine (7), citracridone I (8), 5‐methoxyseselin (9), umbelliferone (10), scopoletin (11), naringenin (12), apigenin (13), friedelin (14), agrostophyllinone (15) and stigmasterol‐3‐O‐β‐D‐glucopyranoside (16). The structures of the compounds were determined using NMR and MS spectroscopic data, and by comparison with published data. The relative configuration of 1 was proposed as (23S)‐isolimonexic acid using NOE studies. Hydrogenation reaction of compound 3 led to the new derivative 3’,4’‐dihydrocitracridone II (3a). Cytotoxicity activities against the human adenocarcinoma alveolar basal epithelial cell lines A549 and the Caucasian prostate adenocarcinoma cell lines PC3, using the MTT assays showed that the methanol crude extract was significant with IC50 values of 30.1 and 31.7 μg/mL, respectively, with the positive control, doxorubicin giving an IC50 of 0.9 μM. In addition, compounds 3, 7 and 8 gave moderate cytotoxic activities with IC50 values of 33.1, 31.2 and 32.5 μM for A549 cells and 35.7, 33.8 and 34.9 μM for PC3 cells, respectively. The hydrogenated 3a was less active than 3, suggesting that the presence of the double bond in pyrans is important for structure‐activity relationship.
The binding between NPM and H2B proteins signals for the diabetes‐associated centrosome amplification
Authors: Xu Si X. , Han Ya W. , Guo Jia Li , Bian Xue K. , Hu Hong M. , Lee Shao C. 
Published: June 2022

AbstractDiabetes not only increases the risk for cancer but also promotes cancer metastasis. Centrosome amplification (CA) is sufficient to initiate tumorigenesis and can enhance the invasion potential of cancer cells. We have reported that diabetes can induce CA, with diabetic pathophysiological factors as the triggers, which involves the signaling of nucleophosmin (NPM). Thus, CA can serve as a candidate biological link between diabetes and cancer. In the present study, we attempted to identify the NPM binding partners and investigated whether the binding between NPM and its partner mediated the CA. We confirmed that high glucose, insulin, and palmitic acid cancer could elicit CA in the HCT16 colon cancer cells and found that the experimental treatment increased the binding between NPM and H2B, but not between p‐NPM and H2B. The molecular docking analysis supported the fact that NPM and H2B could bind to each other through various amino acid residues. The treatment also increased the colocalization of NPM and H2B in the cytosol. Importantly, disruption of the NPM1–H2B complex by individual knockdown of the protein level of NPM or H2B led to the inhibition of the treatment‐evoked CA. In conclusion, our results suggest that the binding between NPM and H2B proteins signals for the CA by high glucose, insulin, and palmitic acid.
Percutaneous mechanical thrombectomy and extracorporeal membranous oxygenation: A case series
Authors: Mously Haytham , Hajjari Jamal , Chami Tarek , Hammad Tarek , Schilz Robert , Carman Teresa , Elgudin Yakov , Abu‐Omar Yasir , Pelletier Marc P. , Shishehbor Mehdi H. , Li Jun 
Published: June 2022

AbstractBackgroundMassive or high‐risk pulmonary embolism (PE) is a potentially life‐threatening diagnosis with significant morbidity and mortality if treatment is delayed. Extracorporeal membrane oxygenation (ECMO) and large bore thrombectomy (LBT) in isolation have been used to stabilize and treat patients with massive PE, however, literature describing the combination of both modalities is lacking. We present a case series involving 9 patients who underwent combined ECMO and LBT and their outcomes.MethodsThis was a retrospective chart review of patients with confirmed PE, who underwent LBT and ECMO. We retrospectively captured clinical, therapeutic, and outcome data at the time of pulmonary embolism response team (PERT) activation and during the follow‐up period for up to 90 days.ResultsNine patients who had PERT activation with confirmed PE diagnosis have undergone combined LBT and ECMO initiation since the advent of our PERT program. The median age was 57 (range 28–68) years. Six patients out of 9 (55%) had cardiac arrest before therapy. All patients exhibited right heart strain on computed tomography and echocardiogram. The median ECMO duration was 5 days (range 2.3–11.6 days), with mean hospitalization of 16.1 days (range 1.5–30.9). Mortality was 22% at 90‐day follow‐up period.ConclusionPatients with massive pulmonary embolism who suffer cardiac arrest have significant morbidity and mortality. ECMO in combination with LBT is a viable treatment option for patients with significant hemodynamic compromise.
Stability Enhancement of Iron‐based Perovskite Catalysts by A‐site Substitution for Oxidative Transposition of α‐Bromostyrene to Phenacyl Bromide
Authors: Shibata Satomi , Kamata Keigo , Hara Michikazu 
Published: June 2022

AbstractLaFeO3 nanoparticles, which were synthesized by the sol‐gel method using aspartic acid, acted as efficient and stable heterogeneous catalysts for the oxidative transformation of α‐bromostyrene to phenacyl bromide using only air under mild conditions without the need for additives and light irradiation. The stability of Fe‐containing perovskite oxides was significantly improved by changing the A‐site metal cation from alkaline metals to lanthanum. LaFeO3 showed much higher catalytic activities than other Fe3+/Fe2+‐containing simple oxides. Mechanistic studies showed the involvement of a radical‐type mechanism involving surface adsorbed O2 species over p‐type LaFeO3. Such an active oxygen species was applicable to the aerobic oxidative cleavage of 1,1‐diphenylethylene and oxidative coupling of p‐toluenethiol.
Electron‐Rich Silicon Containing Phosphinanes for Rapid Pd‐Catalyzed C−X Coupling Reactions**
Authors: Kräh Sabrina , Kachel Iris , Trapp Oliver 
Published: June 2022

AbstractPalladium‐catalyzed cross‐coupling reactions are among the most useful and efficient methods for direct access to complex structures in organic synthesis. However, heteroatom‐containing compounds can complicate such coupling reactions due to their competitive coordination with the palladium catalyst and electronic effects. As a result, good yields are often only obtained under harsher reaction conditions, such as high temperatures and long reaction times. Here the design of a highly active phosphine ligand is reported that provides excellent yields for C−N coupling reactions at ambient temperature. Incorporation of the phosphorus atom into a cyclohexane ring maintains the pyramidal structure of the phosphorus while reducing steric hindrance. This, and a silicon atom in the cyclohexane moiety, results in an electron‐rich phosphinane ligand. This novel silicon containing SabPhos ligand can be obtained in excellent yields in a straightforward synthesis. In palladium catalyzed reactions, this ligand facilitates the coupling of a broad range of heteroaryl chlorides via C−C bonds with boronic acids and C−N bonds with secondary amines in excellent yields under mild conditions.
Different Enzyme Conformations Induce Different Mechanistic Traits in HIV‐1 Protease
Authors: Coimbra João T. S. , Neves Rui P. P. , Cunha Ana V. , Ramos Maria J. , Fernandes Pedro A. 
Published: June 2022

AbstractThe influence of the dynamical flexibility of enzymes on reaction mechanisms is a cornerstone in biological sciences. In this study, we aim to 1) study the convergence of the activation free energy by using the first step of the reaction catalysed by HIV‐1 protease as a case study, and 2) provide further evidence for a mechanistic divergence in this enzyme, as two different reaction pathways were seen to contribute to this step. We used quantum mechanics/molecular mechanics molecular dynamics simulations, on four different initial conformations that led to different barriers in a previous study. Despite the sampling, the four activation free energies still spanned a range of 5.0 kcal ⋅ mol−1. Furthermore, the new simulations did confirm the occurrence of an unusual mechanistic divergence, with two different mechanistic pathways displaying equivalent barriers. An active‐site water molecule is proposed to influence the mechanistic pathway.
Natural Products from Annonaceae as Potential Antichagasic Agents
Authors: Barros de Menezes Renata Priscila , Fechine Tavares Josean , Kato Massuo Jorge , da Rocha Coelho Francisco Alex , Sousa dos Santos Airton Lucas , da Franca Rodrigues Klinger Antonio , Sessions Zoe L. , Muratov Eugene N. , Scotti Luciana , Tullius Scotti Marcus 
Published: June 2022

AbstractChagas disease, a neglected tropical disease, is endemic in 21 Latin American countries and particularly prevalent in Brazil. Chagas disease has drawn more attention in recent years due to its expansion into non‐endemic areas. The aim of this work was to computationally identify and experimentally validate the natural products from an Annonaceae family as antichagasic agents. Through the ligand‐based virtual screening, we identified 57 molecules with potential activity against the epimastigote form of T. cruzi. Then, 16 molecules were analyzed in the in vitro study, of which, six molecules displayed previously unknown antiepimastigote activity. We also evaluated these six molecules for trypanocidal activity. We observed that all six molecules have potential activity against the amastigote form, but no molecules were active against the trypomastigote form. 13‐Epicupressic acid seems to be the most promising, as it was predicted as an active compound in the in silico study against the amastigote form of T. cruzi, in addition to having in vitro activity against the epimastigote form.
Amyloid‐β Inspired Short Peptide Amphiphile Facilitates Synthesis of Silver Nanoparticles as Potential Antibacterial Agents
Authors: Tripathi Satyendra K. , Kesharwani Khushboo , Kaul Grace , Akhir Abdul , Saxena Deepanshi , Singh Ramesh , Mishra Narendra K. , Pandey Archna , Chopra Sidharth , Joshi Khashti B. 
Published: June 2022

AbstractAn amyloid‐β inspired biocompatible short peptide amphiphile (sPA) molecule was used for controlled and targeted delivery of bioactive silver nanoparticles via transforming sPA nanostructures. Such sPA‐AgNPs hybrid structures can be further used to develop antibacterial materials to combat emerging bacterial resistance. Due to the excellent antibacterial activity of silver, the growth of clinically relevant bacteria was inhibited in the presence of AgNPs‐sPA hybrids. Bacterial tests demonstrated that the high biocompatibility and low cytotoxicity of the designed sPA allow it to work as a model drug delivery agent. It therefore shows great potential in locally addressing bacterial infections. The results of our study suggest that these nanodevices have the potential to trap and then engage in the facile delivery of their chemical payload at the target site, thereby working as potential delivery materials. This system has potential therapeutic value for the treatment of microbiota triggered progression of neurodegenerative diseases.
Confinement Effects in Dynamics of Ionic Liquids with Polymer‐Grafted Nanoparticles
Authors: Liu Siqi , Li Ruhao , Tyagi Madhusudan , Akcora Pinar 
Published: June 2022

AbstractIonic liquid mixed with poly(methyl methacrylate)‐grafted Fe3O4 nanoparticle aggregates at low particle concentrations was found to exhibit different dynamics and ionic conductivity than that of pure ionic liquid in our previous studies. In this work, we report on the quasi‐elastic neutron scattering results of ionic liquid containing polymer‐grafted Fe3O4 nanoparticles at higher particle concentrations. The diffusivity of imidazolium (HMIM+) cations of 1‐hexyl‐3‐methylimidazolium bis(trifluoromethylsulfonyl)imide (HMIM‐TFSI) in the presence of poly(methyl methacrylate)‐grafted Fe3O4 nanoparticles is discussed through the confinement. Analysis of the elastic incoherent structure factor revealed that the confinement radius decreased with the addition of grafted particles in HMIM‐TFSI/solvent mixture. We propose the confinement that is induced by the high concentration of grafted particles shrinks the HMIM‐TFSI restricted volume. We further conjecture that this enhanced diffusivity occurs as a result of the local ordering of cations within aggregates of poly(methyl methacrylate)‐grafted Fe3O4 nanoparticles.
Base‐Free Aerobic Oxidation of Furfuralcohols and Furfurals to Furancarboxylic Acids over Nitrogen‐Doped Carbon‐Supported AuPd Bowl‐Like Catalyst
Authors: Guan Wen , Zhang Yunlei , Yan Changhao , Chen Yao , Wei Yanan , Cao Yu , Wang Fang , Huo Pengwei 
Published: June 2022

AbstractUpgrading furfuralcohols and furfurals to furancarboxylic acids is of great significance for high value‐added downstream chemicals synthesis and biomass conversion. Developing an efficient catalyst is the key to acquiring a completely sustainable process. Herein, nitrogen‐doped carbon‐supported bimetallic AuPd bowl‐like catalysts were synthesized. The surface wettability of nitrogen‐doped carbon was well adjusted by the nitrification process. Benefiting from the alloying effect of bimetallic AuPd catalyst and the formation of hydroxyl radical initiated by H2O dissociation on the hydrophilic surface of nitrated nitrogen‐doped carbon, base‐free aerobic oxidation of 5‐hydroxymethylfurfural (HMF) could produce the highest 2,5‐furandicarboxylic acid (FDCA) yield of 93.9 %. In‐situ infrared spectroscopy uncovered adsorption configuration of HMF, and the nitrated carbon surface was favorable for HMF and intermediates to enter the active sites, greatly promoting the catalytic oxidation process. Employing other furfuralcohols (furfuryl alcohol, furan‐2,5‐diyldimethanol, 2,5‐bishydroxymethylfuran) as well as furfural and 5‐methylfurfural as starting materials, 35.6–95.4 % yield of furancarboxylic acids (FDCA, 2‐furoic acid, 5‐methyl‐2‐furoic acid) were also obtained. Moreover, the developed catalysts could maintain excellent stability and activity after four successive runs. This deep insight into the role of bimetallic synergy and surface wettability provides a basis for the rational design of the highly efficient catalysts for the oxidation of furfuralcohols and furfurals and related reactions.
Nicotinamide‐N‐methyltransferase is a promising metabolic drug target for primary and metastatic clear cell renal cell carcinoma
Authors: Reustle Anna , Menig Lena‐Sophie , Leuthold Patrick , Hofmann Ute , Stühler Viktoria , Schmees Christian , Becker Michael , Haag Mathias , Klumpp Verena , Winter Stefan , Büttner Florian A. , Rausch Steffen , Hennenlotter Jörg , Fend Falko , Scharpf Marcus , Stenzl Arnulf , Bedke Jens , Schwab Matthias , Schaeffeler Elke 
Published: June 2022

AbstractBackgroundThe metabolic enzyme nicotinamide‐N‐methyltransferase (NNMT) is highly expressed in various cancer entities, suggesting tumour‐promoting functions. We systematically investigated NNMT expression and its metabolic interactions in clear cell renal cell carcinoma (ccRCC), a prominent RCC subtype with metabolic alterations, to elucidate its role as a drug target.MethodsNNMT expression was assessed in primary ccRCC (n = 134), non‐tumour tissue and ccRCC‐derived metastases (n = 145) by microarray analysis and/or immunohistochemistry. Findings were validated in The Cancer Genome Atlas (kidney renal clear cell carcinoma [KIRC], n = 452) and by single‐cell analysis. Expression was correlated with clinicopathological data and survival. Metabolic alterations in NNMT‐depleted cells were assessed by nontargeted/targeted metabolomics and extracellular flux analysis. The NNMT inhibitor (NNMTi) alone and in combination with the inhibitor 2‐deoxy‐D‐glucose for glycolysis and BPTES (bis‐2‐(5‐phenylacetamido‐1,3,4‐thiadiazol‐2‐yl)ethyl‐sulfide) for glutamine metabolism was investigated in RCC cell lines (786‐O, A498) and in two 2D ccRCC‐derived primary cultures and three 3D ccRCC air–liquid interface models.ResultsNNMT protein was overexpressed in primary ccRCC (p = 1.32 × 10–16) and ccRCC‐derived metastases (p = 3.92 × 10–20), irrespective of metastatic location, versus non‐tumour tissue. Single‐cell data showed predominant NNMT expression in ccRCC and not in the tumour microenvironment. High NNMT expression in primary ccRCC correlated with worse survival in independent cohorts (primary RCC—hazard ratio [HR] = 4.3, 95% confidence interval [CI]: 1.5–12.4; KIRC—HR = 3.3, 95% CI: 2.0–5.4). NNMT depletion leads to intracellular glutamine accumulation, with negative effects on mitochondrial function and cell survival, while not affecting glycolysis or glutathione metabolism. At the gene level, NNMT‐depleted cells upregulate glycolysis, oxidative phosphorylation and apoptosis pathways. NNMTi alone or in combination with 2‐deoxy‐D‐glucose and BPTES resulted in inhibition of cell viability in ccRCC cell lines and primary tumour and metastasis‐derived models. In two out of three patient‐derived ccRCC air–liquid interface models, NNMTi treatment induced cytotoxicity.ConclusionsSince efficient glutamine utilisation, which is essential for ccRCC tumours, depends on NNMT, small‐molecule NNMT inhibitors provide a novel therapeutic strategy for ccRCC and act as sensitizers for combination therapies.
Single‐cell RNA sequencing reveals the characteristics of cerebrospinal fluid tumour environment in breast cancer and lung cancer leptomeningeal metastases
Authors: Ruan Haoyu , Wang Zhe , Sun Ziwei , Wei Jia , Zhang Lei , Ju Huanyu , Wang Ting , Zhang Chao , Guan Ming , Pan Shiyang 
Published: June 2022

AbstractLeptomeningeal metastases (LM) occur in patients with breast cancer (BC) and lung cancer (LC) showing exceptionally poor prognosis. The cerebrospinal fluid (CSF) tumour microenvironment (TME) of LM patients is not well defined at a single‐cell level. Based on the 10× genomics single‐cell RNA sequencing (scRNA‐seq) data from GEO database including five patient‐derived CSF samples of BC‐LM and LC‐LM, and four patient‐derived CSF samples of idiopathic intracranial hypertension (IIH) as controls, we analysed single‐cell transcriptome characteristics of CSF TME in LM patients compared to controls simultaneously and comprehensively. In addition, we performed 10× genomics scRNA‐seq on CSF cells derived from a BC‐LM patient to help generate a solid conclusion. The CSF macrophages in LM patients showing M2‐subtype signature and the emergence of regulatory T cells in LM confirmed the direction of tumour immunity toward immunosuppression. Then, the characteristics of CSF circulating tumour cells (CTCs) of breast cancer LM (BC‐LM) patients were classified into five molecular subtypes by PAM50 model. The communication between macrophages and five subtype‐specific CSF‐CTCs showed largest number of ligand‐receptor interactions. The five subtypes‐specific CSF‐CTCs showed great heterogeneities which were manifested in cell proliferation and cancer‐testis antigens expression. Gene regulatory networks (GRNs) analysis revealed that transcription factor SREBF2 was universally activated in the five subtypes‐specific CSF‐CTCs. Our results will provide inspiration on new directions of the mechanism research, diagnosis and therapy of LM.
Undifferentiated carcinoma with osteoclast‐like giant cells of pancreas on cytology: A case report with review of literature
Authors: Gupta Kanishk , Goyal Surbhi , Chaudhary Dimple , Sakhuja Puja , Narang Poonam , Nag Hirdaya Hulas 
Published: June 2022

AbstractUndifferentiated carcinoma with osteoclast‐like giant cells (UC‐OGC) is a rare malignant neoplasm accounting for <1% of pancreatic masses. Very few case reports and small series have described the cytomorphological features of this entity. We report a case of UC‐OGC arising in the pancreas presenting with liver metastasis in a 56‐year‐old man diagnosed by guided fine‐needle aspiration cytology (FNAC). A characteristic biphasic pattern comprising of malignant mononuclear cells with scattered bland giant cells were the hallmark features for cytological diagnosis. Our case along with review of cytology literature emphasize the utility of FNAC and the cell block in the diagnosis and management of this rare entity.
Transition Metal Scaffolds Used To Bring New‐to‐Nature Reactions into Biological Systems
Authors: Liu Yifei , Lai Ka Lun , Vong Kenward 
Published: June 2022

AbstractAs a means to develop new tools to manipulate biological systems, transition metals have been looked upon as an area of high potential due to the bioorthogonality of new‐to‐nature reactions. To facilitate their incorporation into complex biological systems, researchers have mainly focused on the development of metal catalyst complexes, protein scaffolds, and nanocarriers to protect and preserve the biocatalytic activity of transition metals. The intent of this review is to summarize these structural scaffolds, which has steadily allowed researchers to push transition metal usage not previously thought possible within bacteria, mammalian cells, and higher‐level organisms.