bluuebunny/crossref_metadata_2025 huggingface dataset:
Photoactivatable metabolic warheads enable precise and safe ablation of target cells in vivo
Authors: Benson Sam , de Moliner Fabio , Fernandez Antonio , Kuru Erkin , Asiimwe Nicholas L. , Lee Jun-Seok , Hamilton Lloyd , Sieger Dirk , Bravo Isabel R. , Elliot Abigail M. , Feng Yi , Vendrell Marc
Published: April 2021

Photoactivatable molecules enable ablation of malignant cells under the control of light, yet current agents can be ineffective at early stages of disease when target cells are similar to healthy surrounding tissues. In this work, we describe a chemical platform based on amino-substituted benzoselenadiazoles to build photoactivatable probes that mimic native metabolites as indicators of disease onset and progression. Through a series of synthetic derivatives, we have identified the key chemical groups in the benzoselenadiazole scaffold responsible for its photodynamic activity, and subsequently designed photosensitive metabolic warheads to target cells associated with various diseases, including bacterial infections and cancer. We demonstrate that versatile benzoselenadiazole metabolites can selectively kill pathogenic cells - but not healthy cells - with high precision after exposure to non-toxic visible light, reducing any potential side effects in vivo. This chemical platform provides powerful tools to exploit cellular metabolic signatures for safer therapeutic and surgical approaches.
Mitochondrion-specific dendritic lipopeptide liposomes for targeted sub-cellular delivery
Authors: Jiang Lei , Zhou Sensen , Zhang Xiaoke , Li Cheng , Ji Shilu , Mao Hui , Jiang Xiqun
Published: April 2021

The mitochondrion is an important sub-cellular organelle responsible for the cellular energetic source and processes. Owing to its unique sensitivity to heat and reactive oxygen species, the mitochondrion is an appropriate target for photothermal and photodynamic treatment for cancer. However, targeted delivery of therapeutics to mitochondria remains a great challenge due to their location in the sub-cellular compartment and complexity of the intracellular environment. Herein, we report a class of the mitochondrion-targeted liposomal delivery platform consisting of a guanidinium-based dendritic peptide moiety mimicking mitochondrion protein transmembrane signaling to exert mitochondrion-targeted delivery with pH sensitive and charge-reversible functions to enhance tumor accumulation and cell penetration. Compared to the current triphenylphosphonium (TPP)-based mitochondrion targeting system, this dendritic lipopeptide (DLP) liposomal delivery platform exhibits about 3.7-fold higher mitochondrion-targeted delivery efficacy. Complete tumor eradication is demonstrated in mice bearing 4T1 mammary tumors after combined photothermal and photodynamic therapies delivered by the reported DLP platform.
Proteomics of protein trafficking by in vivo tissue-specific labeling
Authors: Droujinine Ilia A. , Meyer Amanda S. , Wang Dan , Udeshi Namrata D. , Hu Yanhui , Rocco David , McMahon Jill A. , Yang Rui , Guo JinJin , Mu Luye , Carey Dominique K. , Svinkina Tanya , Zeng Rebecca , Branon Tess , Tabatabai Areya , Bosch Justin A. , Asara John M. , Ting Alice Y. , Carr Steven A. , McMahon Andrew P. , Perrimon Norbert
Published: April 2021

Conventional approaches to identify secreted factors that regulate homeostasis are limited in their abilities to identify the tissues/cells of origin and destination. We established a platform to identify secreted protein trafficking between organs using an engineered biotin ligase (BirA*G3) that biotinylates, promiscuously, proteins in a subcellular compartment of one tissue. Subsequently, biotinylated proteins are affinity-enriched and identified from distal organs using quantitative mass spectrometry. Applying this approach in Drosophila, we identify 51 muscle-secreted proteins from heads and 269 fat body-secreted proteins from legs/muscles, including CG2145 (human ortholog ENDOU) that binds directly to muscles and promotes activity. In addition, in mice, we identify 291 serum proteins secreted from conditional BirA*G3 embryo stem cell-derived teratomas, including low-abundance proteins with hormonal properties. Our findings indicate that the communication network of secreted proteins is vast. This approach has broad potential across different model systems to identify cell-specific secretomes and mediators of interorgan communication in health or disease.
Poly(fluorenyl aryl piperidinium) membranes and ionomers for anion exchange membrane fuel cells
Authors: Chen Nanjun , Wang Ho Hyun , Kim Sun Pyo , Kim Hae Min , Lee Won Hee , Hu Chuan , Bae Joon Yong , Sim Eun Seob , Chung Yong-Chae , Jang Jue-Hyuk , Yoo Sung Jong , Zhuang Yongbing , Lee Young Moo
Published: April 2021

Low-cost anion exchange membrane fuel cells have been investigated as a promising alternative to proton exchange membrane fuel cells for the last decade. The major barriers to the viability of anion exchange membrane fuel cells are their unsatisfactory key components—anion exchange ionomers and membranes. Here, we present a series of durable poly(fluorenyl aryl piperidinium) ionomers and membranes where the membranes possess high OH− conductivity of 208 mS cm−1 at 80 °C, low H2 permeability, excellent mechanical properties (84.5 MPa TS), and 2000 h ex-situ durability in 1 M NaOH at 80 °C, while the ionomers have high water vapor permeability and low phenyl adsorption. Based on our rational design of poly(fluorenyl aryl piperidinium) membranes and ionomers, we demonstrate alkaline fuel cell performances of 2.34 W cm−2 in H2-O2 and 1.25 W cm−2 in H2-air (CO2-free) at 80 °C. The present cells can be operated stably under a 0.2 A cm−2 current density for ~200 h.
Metal-free oxidative cross-coupling enabled practical synthesis of atropisomeric QUINOL and its derivatives
Authors: Jiang Peng-Ying , Fan Kai-Fang , Li Shaoyu , Xiang Shao-Hua , Tan Bin
Published: April 2021

As an important platform molecule, atropisomeric QUINOL plays a crucial role in the development of chiral ligands and catalysts in asymmetric catalysis. However, efficient approaches towards QUINOL remain scarce, and the resulting high production costs greatly impede the related academic research as well as downstream industrial applications. Here we report a direct oxidative cross-coupling reaction between isoquinolines and 2-naphthols, providing a straightforward and scalable route to acquire the privileged QUINOL scaffolds in a metal-free manner. Moreover, a NHC-catalyzed kinetic resolution of QUINOL N-oxides with high selectivity factor is established to access two types of promising axially chiral Lewis base catalysts in optically pure forms. The utility of this methodology is further illustrated by facile transformations of the products into QUINAP, an iconic ligand in asymmetric catalysis.
Tetradiketone macrocycle for divalent aluminium ion batteries
Authors: Yoo Dong-Joo , Heeney Martin , Glöcklhofer Florian , Choi Jang Wook
Published: April 2021

Contrary to early motivation, the majority of aluminium ion batteries developed to date do not utilise multivalent ion storage; rather, these batteries rely on monovalent complex ions for their main redox reaction. This limitation is somewhat frustrating because the innate advantages of metallic aluminium such as its low cost and high air stability cannot be fully taken advantage of. Here, we report a tetradiketone macrocycle as an aluminium ion battery cathode material that reversibly reacts with divalent (AlCl2+) ions and consequently achieves a high specific capacity of 350 mAh g−1 along with a lifetime of 8000 cycles. The preferred storage of divalent ions over their competing monovalent counterparts can be explained by the relatively unstable discharge state when using monovalent AlCl2+ ions, which exert a moderate resonance effect to stabilise the structure. This study opens an avenue to realise truly multivalent aluminium ion batteries based on organic active materials, by tuning the relative stability of discharged states with carrier ions of different valence states.
Characterization of a strong covalent Th3+–Th3+ bond inside an Ih(7)-C80 fullerene cage
Authors: Zhuang Jiaxin , Morales-Martínez Roser , Zhang Jiangwei , Wang Yaofeng , Yao Yang-Rong , Pei Cuiying , Rodríguez-Fortea Antonio , Wang Shuao , Echegoyen Luis , de Graaf Coen , Poblet Josep M. , Chen Ning
Published: April 2021

The nature of the actinide-actinide bonds is of fundamental importance to understand the electronic structure of the 5felements. It has attracted considerable theoretical attention, but little is known experimentally as the synthesis of these chemical bonds remains extremely challenging. Herein, we report a strong covalent Th-Th bond formed between two rarely accessible Th3+ions, stabilized inside a fullerene cage nanocontainer as Th2@Ih(7)-C80. This compound is synthesized using the arc-discharge method and fully characterized using several techniques. The single-crystal X-Ray diffraction analysis determines that the two Th atoms are separated by 3.816 Å. Both experimental and quantum-chemical results show that the two Th atoms have formal charges of +3 and confirm the presence of a strong covalent Th-Th bond insideIh(7)-C80. Moreover, density functional theory and ab initio multireference calculations suggest that the overlap between the 7s/6dhybrid thorium orbitals is so large that the bond still exists at Th-Th separations larger than 6 Å. This work demonstrates the authenticity of covalent actinide metal-metal bonds in a stable compound and deepens our fundamental understanding offelement metal bonds.
Cooperation-based concept formation in male bottlenose dolphins
Authors: King Stephanie L. , Connor Richard C. , Krützen Michael , Allen Simon J.
Published: April 2021

In Shark Bay, Western Australia, male bottlenose dolphins form a complex nested alliance hierarchy. At the first level, pairs or trios of unrelated males cooperate to herd individual females. Multiple first-order alliances cooperate in teams (second-order alliances) in the pursuit and defence of females, and multiple teams also work together (third-order alliances). Yet it remains unknown how dolphins classify these nested alliance relationships. We use 30 years of behavioural data combined with 40 contemporary sound playback experiments to 14 allied males, recording responses with drone-mounted video and a hydrophone array. We show that males form a first-person social concept of cooperative team membership at the second-order alliance level, independently of first-order alliance history and current relationship strength across all three alliance levels. Such associative concepts develop through experience and likely played an important role in the cooperative behaviour of early humans. These results provide evidence that cooperation-based concepts are not unique to humans, occurring in other animal societies with extensive cooperation between non-kin.
Bioactive hierarchical silk fibers created by bioinspired self-assembly
Authors: Fan Linpeng , Li Jing-Liang , Cai Zengxiao , Wang Xungai
Published: April 2021

Artificial recapitulation of the hierarchy of natural protein fibers is crucial to providing strategies for developing advanced fibrous materials. However, it is challenging due to the complexity of the natural environment. Inspired by the liquid crystalline spinning of spiders, we report the development of natural silk-like hierarchical fibers, with bundles of nanofibrils aligned in their long-axis direction, by self-assembly of crystallized silk fibroin (SF) droplets. The formation of self-assembled SF fibers is a process of coalesced droplets sprouting to form a branched fibrous network, which is similar to the development of capillaries in our body. The as-assembled hierarchical SF fibers are highly bioactive and can significantly enhance the spreading and growth of human umbilical vein endothelial cells compared to the natural SF fibers. This work could help to understand the natural silk spinning process of spiders and provides a strategy for design and development of advanced fibrous biomaterials for various applications.
One-hour coherent optical storage in an atomic frequency comb memory
Authors: Ma Yu , Ma You-Zhi , Zhou Zong-Quan , Li Chuan-Feng , Guo Guang-Can
Published: April 2021

Photon loss in optical fibers prevents long-distance distribution of quantum information on the ground. Quantum repeater is proposed to overcome this problem, but the communication distance is still limited so far because of the system complexity of the quantum repeater scheme. Alternative solutions include transportable quantum memory and quantum-memory-equipped satellites, where long-lived optical quantum memories are the key components to realize global quantum communication. However, the longest storage time of the optical memories demonstrated so far is approximately 1 minute. Here, by employing a zero-first-order-Zeeman magnetic field and dynamical decoupling to protect the spin coherence in a solid, we demonstrate coherent storage of light in an atomic frequency comb memory over 1 hour, leading to a promising future for large-scale quantum communication based on long-lived solid-state quantum memories.
Structural studies of phosphorylation-dependent interactions between the V2R receptor and arrestin-2
Authors: He Qing-Tao , Xiao Peng , Huang Shen-Ming , Jia Ying-Li , Zhu Zhong-Liang , Lin Jing-Yu , Yang Fan , Tao Xiao-Na , Zhao Ru-Jia , Gao Feng-Yuan , Niu Xiao-Gang , Xiao Kun-Hong , Wang Jiangyun , Jin Changwen , Sun Jin-Peng , Yu Xiao
Published: April 2021

Arrestins recognize different receptor phosphorylation patterns and convert this information to selective arrestin functions to expand the functional diversity of the G protein-coupled receptor (GPCR) superfamilies. However, the principles governing arrestin-phospho-receptor interactions, as well as the contribution of each single phospho-interaction to selective arrestin structural and functional states, are undefined. Here, we determined the crystal structures of arrestin2 in complex with four different phosphopeptides derived from the vasopressin receptor-2 (V2R) C-tail. A comparison of these four crystal structures with previously solved Arrestin2 structures demonstrated that a single phospho-interaction change results in measurable conformational changes at remote sites in the complex. This conformational bias introduced by specific phosphorylation patterns was further inspected by FRET and 1H NMR spectrum analysis facilitated via genetic code expansion. Moreover, an interdependent phospho-binding mechanism of phospho-receptor-arrestin interactions between different phospho-interaction sites was unexpectedly revealed. Taken together, our results provide evidence showing that phospho-interaction changes at different arrestin sites can elicit changes in affinity and structural states at remote sites, which correlate with selective arrestin functions.
Neurexins regulate presynaptic GABAB-receptors at central synapses
Authors: Luo Fujun , Sclip Alessandra , Merrill Sean , Südhof Thomas C.
Published: April 2021

Diverse signaling complexes are precisely assembled at the presynaptic active zone for dynamic modulation of synaptic transmission and synaptic plasticity. Presynaptic GABAB-receptors nucleate critical signaling complexes regulating neurotransmitter release at most synapses. However, the molecular mechanisms underlying assembly of GABAB-receptor signaling complexes remain unclear. Here we show that neurexins are required for the localization and function of presynaptic GABAB-receptor signaling complexes. At four model synapses, excitatory calyx of Held synapses in the brainstem, excitatory and inhibitory synapses on hippocampal CA1-region pyramidal neurons, and inhibitory basket cell synapses in the cerebellum, deletion of neurexins rendered neurotransmitter release significantly less sensitive to GABAB-receptor activation. Moreover, deletion of neurexins caused a loss of GABAB-receptors from the presynaptic active zone of the calyx synapse. These findings extend the role of neurexins at the presynaptic active zone to enabling GABAB-receptor signaling, supporting the notion that neurexins function as central organizers of active zone signaling complexes.
Recommendations for acceleration of vaccine development and emergency use filings for COVID-19 leveraging lessons from the novel oral polio vaccine
Authors: Thiel Natalie , Selwyn Casey , Murphy Georgina , Simpson Shmona , Chakrabarti Ajoy C.
Published: April 2021

A new oral polio vaccine, nOPV2, has become the first vaccine to pursue a WHO Emergency Use Listing. Many lessons were learned as part of the accelerated development plan and submission, which have been categorized under the following sections: regulatory, clinical development, chemistry manufacturing and controls, and post-deployment monitoring. Efforts were made to adapt findings from these studies to COVID-19 vaccine candidates. Specific concepts for accelerating COVID-19 vaccine development across multiple functional domains were also included. The goals of this effort were twofold: (1) to help familiarize vaccine developers with the EUL process; and (2) to provide general guidance for faster development and preparations for launch during the COVID-19 pandemic.
A multidimensional measure of polypharmacy for older adults using the Health and Retirement Study
Authors: Carr Ewan , Federman Alex , Dzahini Olubanke , Dobson Richard J. , Bendayan Rebecca
Published: April 2021

Polypharmacy is commonly defined based on the number of medications taken concurrently using standard cut-offs, but several studies have highlighted the need for a multidimensional assessment. We developed a multidimensional measure of polypharmacy and compared with standard cut-offs. Data were extracted for 2141 respondents of the 2007 Prescription Drug Survey, a sub-study of the Health Retirement Study. Latent classes were identified based on multiple indicators of polypharmacy, including quantity, temporality and risk profile. A four-class model was selected based on fit statistics and clinical interpretability: ‘High risk, long-term’ (Class 1), ‘Low risk, long-term’ (Class 2), ‘High risk, short-term’ (Class 3), and ‘High risk for drug interactions, medium-term, regular’ (Class 4). Classes differed regarding sex, cohabitation, disability and multimorbidity. Participants in the ‘low risk’ class tended to be male, cohabitating, and reported fewer health conditions, compared to ‘high risk’ classes. Polypharmacy classes were compared to standard cut-offs (5+ or 9+ medications) in terms of overlap and mortality risk. The three ‘high risk’ classes overlapped with the groups concurrently taking 5+ and 9+ medications per month. However, the multidimensional measure further differentiated individuals in terms of risk profile and temporality of medication taking, thus offering a richer assessment of polypharmacy.
Nanoparticle composite TPNT1 is effective against SARS-CoV-2 and influenza viruses
Authors: Chang Sui-Yuan , Huang Kuo-Yen , Chao Tai-Ling , Kao Han-Chieh , Pang Yu-Hao , Lu Lin , Chiu Chun-Lun , Huang Hsin-Chang , Cheng Ting-Jen Rachel , Fang Jim-Min , Yang Pan-Chyr
Published: April 2021

A metal nanoparticle composite, namely TPNT1, which contains Au-NP (1 ppm), Ag-NP (5 ppm), ZnO-NP (60 ppm) and ClO2 (42.5 ppm) in aqueous solution was prepared and characterized by spectroscopy, transmission electron microscopy, dynamic light scattering analysis and potentiometric titration. Based on the in vitro cell-based assay, TPNT1 inhibited six major clades of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with effective concentration within the range to be used as food additives. TPNT1 was shown to block viral entry by inhibiting the binding of SARS-CoV-2 spike proteins to the angiotensin-converting enzyme 2 (ACE2) receptor and to interfere with the syncytium formation. In addition, TPNT1 also effectively reduced the cytopathic effects induced by human (H1N1) and avian (H5N1) influenza viruses, including the wild-type and oseltamivir-resistant virus isolates. Together with previously demonstrated efficacy as antimicrobials, TPNT1 can block viral entry and inhibit or prevent viral infection to provide prophylactic effects against both SARS-CoV-2 and opportunistic infections.
Hyperoxia-activated circulating extracellular vesicles induce lung and brain injury in neonatal rats
Authors: Ali Anum , Zambrano Ronald , Duncan Matthew R. , Chen Shaoyi , Luo Shihua , Yuan Huijun , Chen Pingping , Benny Merline , Schmidt Augusto , Young Karen , Kerr Nadine , de Rivero Vaccari Juan Pablo , Keane Robert W. , Dietrich W. Dalton , Wu Shu
Published: April 2021

Hyperoxia-induced lung injury plays a key role in the development of bronchopulmonary dysplasia (BPD), characterized by inflammatory injury and impaired lung development in preterm infants. Although BPD is a predictor of poor neurodevelopmental outcomes, currently it is uncertain how lung injury contributes to brain injury in preterm infants. Extracellular vesicles (EVs) are a heterogeneous group of cell-derived membranous structures that regulate intercellular and inter-organ communications. Gasdermin D (GSDMD) has emerged as a key executor of inflammasome-mediated cell death and inflammation. In this study, we utilized a neonatal rat model of BPD to assess if hyperoxia stimulates lung release of circulating EVs and if these EVs induce lung and brain injury. We found that hyperoxia-exposed rats had elevated numbers of plasma-derived EVs compared to rats maintained in room air. These EVs also had increased cargos of surfactant protein C, a marker of type II alveolar epithelial cells (AEC), and the active (p30) form of GSDMD. When these EVs were adoptively transferred into normal newborn rats via intravenous injection, they were taken up both by lung and brain tissues. Moreover, EVs from hyperoxic animals induced not only the pathological hallmarks of BPD, but also brain inflammatory injury in recipient rats, as well as inducing cell death in cultured pulmonary vascular endothelial cells and neural stem cells (NSC). Similarly, hyperoxia-exposed cultured AEC-like cells released EVs that also contained increased GSDMD-p30 and these EVs induced pyroptotic cell death in NSC. Overall, these data indicate that hyperoxia-activated circulating EVs mediate a lung to brain crosstalk resulting in brain injury and suggest a mechanism that links lung injury and neurodevelopmental impairment in BPD infants.
The antiviral effect of metformin on zika and dengue virus infection
Authors: Farfan-Morales Carlos Noe , Cordero-Rivera Carlos Daniel , Osuna-Ramos Juan Fidel , Monroy-Muñoz Irma Eloisa , De Jesús-González Luis Adrián , Muñoz-Medina José Esteban , Hurtado-Monzón Arianna M. , Reyes-Ruiz José Manuel , del Ángel Rosa María
Published: April 2021

The Dengue (DENV) and zika (ZIKV) virus infections are currently a public health concern. At present, there is no treatment or a safe and effective vaccine for these viruses. Hence, the development of new strategies as host-directed therapy is required. In this sense, Metformin (MET), an FDA-approved drug used for the treatment of type 2 diabetes, has shown an anti-DENV effect in vitro by activating AMPK and reducing HMGCR activity. In this study, MET treatment was evaluated during in vitro and in vivo ZIKV infection and compared to MET treatment during DENV infection. Our results demonstrated that MET has a broad in vitro antiviral spectrum. MET inhibited ZIKV infection in different cell lines, but it was most effective in inhibiting DENV and yellow fever virus (YFV) infection in Huh-7 cells. However, the drug failed to protect against ZIKV infection when AG129 immunodeficient mice were used as in vivo model. Interestingly, MET increased DENV-infected male mice's survival time, reducing the severe signs of the disease. Together, these findings indicate that, although MET was an effective antiviral agent to inhibit in vitro and in vivo DENV infection, it could only inhibit in vitro ZIKV infection.
Detection of pro angiogenic and inflammatory biomarkers in patients with CKD
Authors: Jalal Diana , Sanford Bridget , Renner Brandon , Ten Eyck Patrick , Laskowski Jennifer , Cooper James , Sun Mingyao , Zakharia Yousef , Spitz Douglas , Dokun Ayotunde , Attanasio Massimo , Jones Kenneth , Thurman Joshua M.
Published: April 2021

Cardiovascular disease (CVD) is the most common cause of death in patients with native and post-transplant chronic kidney disease (CKD). To identify new biomarkers of vascular injury and inflammation, we analyzed the proteome of plasma and circulating extracellular vesicles (EVs) in native and post-transplant CKD patients utilizing an aptamer-based assay. Proteins of angiogenesis were significantly higher in native and post-transplant CKD patients versus healthy controls. Ingenuity pathway analysis (IPA) indicated Ephrin receptor signaling, serine biosynthesis, and transforming growth factor-β as the top pathways activated in both CKD groups. Pro-inflammatory proteins were significantly higher only in the EVs of native CKD patients. IPA indicated acute phase response signaling, insulin-like growth factor-1, tumor necrosis factor-α, and interleukin-6 pathway activation. These data indicate that pathways of angiogenesis and inflammation are activated in CKD patients’ plasma and EVs, respectively. The pathways common in both native and post-transplant CKD may signal similar mechanisms of CVD.
Master Blaster: an approach to sensitive identification of remotely related proteins
Authors: Janaki Chintalapati , Gowri Venkatraman S. , Srinivasan Narayanaswamy
Published: April 2021

Genome sequencing projects unearth sequences of all the protein sequences encoded in a genome. As the first step, homology detection is employed to obtain clues to structure and function of these proteins. However, high evolutionary divergence between homologous proteins challenges our ability to detect distant relationships. In the past, an approach involving multiple Position Specific Scoring Matrices (PSSMs) was found to be more effective than traditional single PSSMs. Cascaded search is another successful approach where hits of a search are queried to detect more homologues. We propose a protocol, ‘Master Blaster’, which combines the principles adopted in these two approaches to enhance our ability to detect remote homologues even further. Assessment of the approach was performed using known relationships available in the SCOP70 database, and the results were compared against that of PSI-BLAST and HHblits, a hidden Markov model-based method. Compared to PSI-BLAST, Master Blaster resulted in 10% improvement with respect to detection of cross superfamily connections, nearly 35% improvement in cross family and more than 80% improvement in intra family connections. From the results it was observed that HHblits is more sensitive in detecting remote homologues compared to Master Blaster. However, there are true hits from 46-folds for which Master Blaster reported homologs that are not reported by HHblits even using the optimal parameters indicating that for detecting remote homologues, use of multiple methods employing a combination of different approaches can be more effective in detecting remote homologs. Master Blaster stand-alone code is available for download in the supplementary archive.
SARS pandemic exposure impaired early childhood development in China
Authors: Fan Yunfei , Wang Huiyu , Wu Qiong , Zhou Xiang , Zhou Yubo , Wang Bin , Han Yiqun , Xue Tao , Zhu Tong
Published: April 2021

Social and mental stressors associated with the pandemic of a novel infectious disease, e.g., COVID-19 or SARS may promote long-term effects on child development. However, reports aimed at identifying the relationship between pandemics and child health are limited. A retrospective study was conducted to associate the SARS pandemic in 2003 with development milestones or physical examinations among longitudinal measurements of 14,647 children. Experiencing SARS during childhood was associated with delayed milestones, with hazard ratios of 3.17 (95% confidence intervals CI: 2.71, 3.70), 3.98 (3.50, 4.53), 4.96 (4.48, 5.49), or 5.57 (5.00, 6.20) for walking independently, saying a complete sentence, counting 0–10, and undressing him/herself for urination, respectively. These results suggest relevant impacts from COVID-19 on child development should be investigated.
Diagnostic potential of hypoxia-induced genes in liquid biopsies of breast cancer patients
Authors: Peiró Carlos Henrique F. , Perez Matheus M. , de Aquino Glauco S. A. , Encinas Jéssica F. A. , Sousa Luiz Vinícius de A. , da Veiga Glaucia Luciano , del Giglio Auro , Fonseca Fernando L. A. , da Costa Aguiar Alves Beatriz
Published: April 2021

In tumor cells, higher expression of glucose transporter proteins (GLUT) and carbonic anhydrases (CAIX) genes is influenced by hypoxia-induced factors (HIF).Thus, we aimed to study the expression profile of these markers in sequential peripheral blood collections performed in breast cancer patients in order to verify their predictive potential in liquid biopsies. Gene expressions were analyzed by qPCR in tumor and blood samples from 125 patients and 25 healthy women. Differential expression was determined by the 2(−ΔCq) method. Expression of HIF-1α and GLUT1 in the blood of breast cancer patients is significantly higher (90–91 and 160–161 fold increased expression, respectively; p < 0.0001) than that found in healthy women. Their diagnostic power was confirmed by ROC curve. CAIX is also more expressed in breast cancer women blood, but its expression was detected only in a few samples. But none of these genes could be considered predictive markers. Therefore, evaluation of the expression of HIF-1α and GLUT1 in blood may be a useful laboratory tool to complement the diagnosis of breast cancer, in addition to being useful for follow-up of patients and of women with a family history of breast cancer.
Chronic intermittent ethanol promotes ventral subiculum hyperexcitability via increases in extrinsic basolateral amygdala input and local network activity
Authors: Bach Eva C. , Ewin Sarah E. , Baldassaro Alexandra D. , Carlson Hannah N. , Weiner Jeffrey L.
Published: April 2021

The hippocampus, particularly its ventral domain, can promote negative affective states (i.e. stress and anxiety) that play an integral role in the development and persistence of alcohol use disorder (AUD). The ventral hippocampus (vHC) receives strong excitatory input from the basolateral amygdala (BLA) and the BLA-vHC projection bidirectionally modulates anxiety-like behaviors. However, no studies have examined the effects of chronic alcohol on the BLA-vHC circuit. In the present study, we used ex vivo electrophysiology in conjunction with optogenetic approaches to examine the effects of chronic intermittent ethanol exposure (CIE), a well-established rodent model of AUD, on the BLA-vHC projection and putative intrinsic vHC synaptic plasticity. We discovered prominent BLA innervation in the subicular region of the vHC (vSub). CIE led to an overall increase in the excitatory/inhibitory balance, an increase in AMPA/NMDA ratios but no change in paired-pulse ratios, consistent with a postsynaptic increase in excitability in the BLA-vSub circuit. CIE treatment also led to an increase in intrinsic network excitability in the vSub. Overall, our findings suggest a hyperexcitable state in BLA-vSub specific inputs as well as intrinsic inputs to vSub pyramidal neurons which may contribute to the negative affective behaviors associated with CIE.
Computational and experimental mechanical performance of a new everolimus-eluting stent purpose-built for left main interventions
Authors: Samant Saurabhi , Wu Wei , Zhao Shijia , Khan Behram , Sharzehee Mohammadali , Panagopoulos Anastasios , Makadia Janaki , Mickley Timothy , Bicek Andrew , Boismier Dennis , Murasato Yoshinobu , Chatzizisis Yiannis S.
Published: April 2021

Left main (LM) coronary artery bifurcation stenting is a challenging topic due to the distinct anatomy and wall structure of LM. In this work, we investigated computationally and experimentally the mechanical performance of a novel everolimus-eluting stent (SYNERGY MEGATRON) purpose-built for interventions to large proximal coronary segments, including LM. MEGATRON stent has been purposefully designed to sustain its structural integrity at higher expansion diameters and to provide optimal lumen coverage. Four patient-specific LM geometries were 3D reconstructed and stented computationally with finite element analysis in a well-validated computational stent simulation platform under different homogeneous and heterogeneous plaque conditions. Four different everolimus-eluting stent designs (9-peak prototype MEGATRON, 10-peak prototype MEGATRON, 12-peak MEGATRON, and SYNERGY) were deployed computationally in all bifurcation geometries at three different diameters (i.e., 3.5, 4.5, and 5.0 mm). The stent designs were also expanded experimentally from 3.5 to 5.0 mm (blind analysis). Stent morphometric and biomechanical indices were calculated in the computational and experimental studies. In the computational studies the 12-peak MEGATRON exhibited significantly greater expansion, better scaffolding, smaller vessel prolapse, and greater radial strength (expressed as normalized hoop force) than the 9-peak MEGATRON, 10-peak MEGATRON, or SYNERGY (p < 0.05). Larger stent expansion diameters had significantly better radial strength and worse scaffolding than smaller stent diameters (p < 0.001). Computational stenting showed comparable scaffolding and radial strength with experimental stenting. 12-peak MEGATRON exhibited better mechanical performance than the 9-peak MEGATRON, 10-peak MEGATRON, or SYNERGY. Patient-specific computational LM stenting simulations can accurately reproduce experimental stent testing, providing an attractive framework for cost- and time-effective stent research and development.
Clinical features and disease severity in an Iranian population of inpatients with COVID-19
Authors: Nabavi Shima , Javidarabshahi Zahra , Allahyari Abolghasem , Ramezani Mohammad , Seddigh-Shamsi Mohsen , Ravanshad Sahar , AkbariRad Mina , Ebrahimzadeh Farnoosh , Khatami Shohre , Emadzadeh Maryam , Saeedian Neda , Zarifian Ahmadreza , Miri Maryam , Rezaeetalab Fariba , Hejazi Sepide , Basiri Reza , Mozdourian Mahnaz
Published: April 2021

Coronavirus disease 2019 (COVID-19) can present with a variety of symptoms. Severity of the disease may be associated with several factors. Here, we review clinical features of COVID-19 inpatients with different severities. This cross-sectional study was performed in Imam Reza hospital, Mashhad, Iran, during February–April 2020. COVID-19 patients with typical computed tomography (CT) patterns and/or positive reverse-transcriptase polymerase chain reaction (RT-PCR) were included. The patients were classified into three groups of moderate, severe, and critical based on disease severity. Demographic, clinical, laboratory, and radiologic findings were collected and compared. P < 0.05 was considered statistically significant. Overall, 200 patients with mean age of 69.75 ± 6.39 years, of whom 82 (41%) were female were studied. Disease was severe/critical in the majority of patients (167, 83.5%). Disease severity was significantly associated with age, malignant comorbidities, dyspnea, nausea/vomiting, confusion, respiratory rate, pulse rate, O2 saturation, extent of CT involvement, serum C-reactive protein (CRP), pH, pO2, and aspartate transaminase (P < 0.05). Moreover, complications including shock, coagulopathy, acidosis, sepsis, acute respiratory distress syndrome (ARDS), intensive care unit (ICU) admission, and intubation were significantly higher in patients with higher severities (P < 0.05). O2 saturation, nausea/vomiting, and extent of lung CT involvement were independent predictors of severe/critical COVID-19 (OR 0.342, 45.93, and 25.48, respectively; P < 0.05). Our results indicate O2 saturation, nausea/vomiting, and extent of lung CT involvement as independent predictors of severe COVID-19 conditions. Serum CRP levels and pO2 were also considerably higher patients with higher severity and can be used along with other factors to predict severe disease in COVID-19 patients.
Vegfa promoter gene hypermethylation at HIF1α binding site is an early contributor to CKD progression after renal ischemia
Authors: Sánchez-Navarro Andrea , Pérez-Villalva Rosalba , Murillo-de-Ozores Adrián Rafael , Martínez-Rojas Miguel Ángel , Rodríguez‐Aguilera Jesús Rafael , González Norma , Castañeda-Bueno María , Gamba Gerardo , Recillas-Targa Félix , Bobadilla Norma A.
Published: April 2021

Chronic hypoxia is a major contributor to Chronic Kidney Disease (CKD) after Acute Kidney Injury (AKI). However, the temporal relation between the acute insult and maladaptive renal response to hypoxia remains unclear. In this study, we analyzed the time-course of renal hemodynamics, oxidative stress, inflammation, and fibrosis, as well as epigenetic modifications, with focus on HIF1α/VEGF signaling, in the AKI to CKD transition. Sham-operated, right nephrectomy (UNx), and UNx plus renal ischemia (IR + UNx) groups of rats were included and studied at 1, 2, 3, or 4 months. The IR + UNx group developed CKD characterized by progressive proteinuria, renal dysfunction, tubular proliferation, and fibrosis. At first month post-ischemia, there was a twofold significant increase in oxidative stress and reduction in global DNA methylation that was maintained throughout the study. Hif1α and Vegfa expression were depressed in the first and second-months post-ischemia, and then Hif1α but not Vegfa expression was recovered. Interestingly, hypermethylation of the Vegfa promoter gene at the HIF1α binding site was found, since early stages of the CKD progression. Our findings suggest that renal hypoperfusion, inefficient hypoxic response, increased oxidative stress, DNA hypomethylation, and, Vegfa promoter gene hypermethylation at HIF1α binding site, are early determinants of AKI-to-CKD transition.
Eye-tracking indices of impaired encoding of visual short-term memory in familial Alzheimer’s disease
Authors: Pavisic Ivanna M. , Pertzov Yoni , Nicholas Jennifer M. , O’Connor Antoinette , Lu Kirsty , Yong Keir X. X. , Husain Masud , Fox Nick C. , Crutch Sebastian J.
Published: April 2021

The basis of visual short-term memory (VSTM) impairments in preclinical Alzheimer’s disease (AD) remains unclear. Research suggests that eye movements may serve as indirect surrogates to investigate VSTM. Yet, investigations in preclinical populations are lacking. Fifty-two individuals from a familial Alzheimer’s disease (FAD) cohort (9 symptomatic carriers, 17 presymptomatic carriers and 26 controls) completed the “Object-localisation” VSTM task while an eye-tracker recorded eye movements during the stimulus presentation. VSTM function and oculomotor performance were compared between groups and their association during encoding investigated. Compared to controls, symptomatic FAD carriers showed eye movement patterns suggestive of an ineffective encoding and presymptomatic FAD carriers within 6 years of their expected age at symptom onset, were more reliant on the stimuli fixation time to achieve accuracy in the localisation of the target. Consequently, for shorter fixation times on the stimuli, presymptomatic carriers were less accurate at localising the target than controls. By contrast, the only deficits detected on behavioural VSTM function was in symptomatic individuals. Our findings provide novel evidence that encoding processes may be vulnerable and weakened in presymptomatic FAD carriers, most prominently for spatial memory, suggesting a possible explanation for the subtle VSTM impairments observed in the preclinical stages of AD.
Flatness and boundness of photonic drumhead surface state in a metallic lattice
Authors: Wang Yu , Zhou Xiaoxi , Li Shanshan , Zhang Wenya , Hu Chuandeng , Lu Weixin , Hou Bo
Published: April 2021

Nodal chain (NC) semi-metals have the degeneracy of interlacing rings in their band structure in momentum space. With the projection of degenerate rings towards crystal boundaries, there is a special type of surface dispersion appearing at surface Brillouin zone and termed drumhead surface state (DSS). Previously, experimental investigations on photonic NC and DSS have been done on metallic photonic crystals at microwave frequencies. However, far-field detection of DSS and its coupling to radiative modes in free space have not been studied. In the work, we analyze the photonic DSS in a metallic lattice by angle-resolved far-field reflection measurement and numerical simulation at terahertz (THz) frequencies, and reveal its flatness and boundness in band structure, even in the radiation continuum. Particularly, the DSS band can be tuned being from negatively dispersive via flat to positively dispersive by a single surface parameter, and the DSS at Γ point in surface Brillouin zone is in fact a symmetry-protected bound state in the continuum. Our results might have some potential applications towards THz photonics.
Revisiting traditional SSR based methodologies available for elephant genetic studies
Authors: Marasinghe M. S. L. R. P. , Nilanthi R. M. R. , Hathurusinghe H. A. B. M. , Sooriyabandara M. G. C. , Chandrasekara C. H. W. M. R. B. , Jayawardana K. A. N. C. , Kodagoda M. M. , Rajapakse R. C. , Bandaranayake P. C. G.
Published: April 2021

Asian elephant (Elephas maximus) plays a significant role in natural ecosystems and it is considered as an endangered animal. Molecular genetics studies on elephants’ dates back to 1990s. Microsatellite markers have been the preferred choice and have played a major role in ecological, evolutionary and conservation research on elephants over the past 20 years. However, technical constraints especially related to the specificity of traditionally developed microsatellite markers have brought to question their application, specifically when degraded samples are utilized for analysis. Therefore, we analyzed the specificity of 24 sets of microsatellite markers frequently used for elephant molecular work. Comparative wet lab analysis was done with blood and dung DNA in parallel with in silico work. Our data suggest cross-amplification of unspecific products when field-collected dung samples are utilized in assays. The necessity of Asian elephant specific set of microsatellites and or better molecular techniques are highlighted.
Ka-band planar slotted waveguide array based on groove gap waveguide technology with a glide-symmetric holey metasurface
Authors: Herrán Luis Fernando , Algaba Brazalez Astrid , Rajo-Iglesias Eva
Published: April 2021

The design of a planar slot array in groove gap waveguide technology implemented by glide-symmetric holes as Electromagnetic Band Gap structure is here presented. Despite the advantages of using holes instead of pins in terms of manufacturing simplicity and cost,the larger size of the holes compared to pins needs to be considered when designing slot arrays without grating lobes. A 1 to 4 corporate feed network is designed using this technology as well. Corrugations are included to further reduce the grating lobes. Experimental results support the viability of the proposed concept for designing glide-symmetric planar arrays of any size.
Transcriptome analysis identifies differentially expressed genes in the progenies of a cross between two low phytic acid soybean mutants
Authors: Jin Hangxia , Yu Xiaomin , Yang Qinghua , Fu Xujun , Yuan Fengjie
Published: April 2021

Phytic acid (PA) is a major antinutrient that cannot be digested by monogastric animals, but it can decrease the bioavailability of micronutrients (e.g., Zn and Fe). Lowering the PA content of crop seeds will lead to enhanced nutritional traits. Low-PA mutant crop lines carrying more than one mutated gene (lpa) have lower PA contents than mutants with a single lpa mutant gene. However, little is known about the link between PA pathway intermediates and downstream regulatory activities following the mutation of these genes in soybean. Consequently, we performed a comparative transcriptome analysis using an advanced generation recombinant inbred line with low PA levels [2mlpa (mips1/ipk1)] and a sibling line with homozygous non-mutant alleles and normal PA contents [2MWT (MIPS1/IPK1)]. An RNA sequencing analysis of five seed developmental stages revealed 7945 differentially expressed genes (DEGs) between the 2mlpa and 2MWT seeds. Moreover, 3316 DEGs were associated with 128 metabolic and signal transduction pathways and 4980 DEGs were annotated with 345 Gene Ontology terms related to biological processes. Genes associated with PA metabolism, photosynthesis, starch and sucrose metabolism, and defense mechanisms were among the DEGs in 2mlpa. Of these genes, 36 contributed to PA metabolism, including 22 genes possibly mediating the low-PA phenotype of 2mlpa. The expression of most of the genes associated with photosynthesis (81 of 117) was down-regulated in 2mlpa at the late seed developmental stage. In contrast, the expression of three genes involved in sucrose metabolism was up-regulated at the late seed developmental stage, which might explain the high sucrose content of 2mlpa soybeans. Furthermore, 604 genes related to defense mechanisms were differentially expressed between 2mlpa and 2MWT. In this study, we detected a low PA content as well as changes to multiple metabolites in the 2mlpa mutant. These results may help elucidate the regulation of metabolic events in 2mlpa. Many genes involved in PA metabolism may contribute to the substantial decrease in the PA content and the moderate accumulation of InsP3–InsP5 in the 2mlpa mutant. The other regulated genes related to photosynthesis, starch and sucrose metabolism, and defense mechanisms may provide additional insights into the nutritional and agronomic performance of 2mlpa seeds.
Postoperative cognitive functions in patients with benign intracranial lesions
Authors: Bette Stefanie , Ruhland Julia M. , Wiestler Benedikt , Barz Melanie , Meyer Bernhard , Zimmer Claus , Ryang Yu-Mi , Ringel Florian , Gempt Jens
Published: April 2021

The aim of this study was to assess pre- and postoperative cognitive functions in patients who underwent surgery for benign intracranial lesions. In total, 58 patients (21 men, 37 women, mean age 51.6 years [range 24–76 years]) with benign intracranial lesions (including benign tumors and vascular lesions) and neuralgia of the trigeminal nerve were included in this prospective study. Extensive cognitive testing was used to categorize attention, memory, and executive functions. Mood and pain were assessed preoperatively (t0, mean 3.7 days before surgery), immediately after surgery/during inpatient stay (t1, mean 7.6 days after surgery), and at first outpatient check-up (t2, mean 99.5 days after surgery). All 58 patients were tested at t0 and t1, but at t2 only 24 patients were available at t2. The data were categorized as improvement/stable condition or deterioration and shown as percentages. The pre- and postoperative values of BDI-II and mood were compared by the Wilcoxon test for paired samples. Binary logistic regression analyses were performed to identify parameters influencing cognition in the subgroup of meningioma patients. Immediately after surgery (t1), the percentage of patients with improvement/stable condition was > 50% in all categories in the majority of subtests (attention: 12/14 subtests, memory: 11/13 subtests, executive functions: 6/9 subtests). Similar results were shown at t2. Mood and pain did not change significantly after surgery. Factors like age, Karnofsky performance status, and tumor volume were not shown as significant influencing factors for cognitive functions in meningioma patients. The results of this study suggest that—in contrast to neuroepithelial tumors—cognitive functions do not deteriorate after surgery of benign intracranial lesions. Further studies are necessary to evaluate the results of this study.