bluuebunny/crossref_metadata_2025 huggingface dataset:
Ligand-induced activation and G protein coupling of prostaglandin F2α receptor
Authors: Wu Canrong , Xu Youwei , He Qian , Li Dianrong , Duan Jia , Li Changyao , You Chongzhao , Chen Han , Fan Weiliang , Jiang Yi , Eric Xu H.
Published: May 2023

Prostaglandin F2α (PGF2α), an endogenous arachidonic acid metabolite, regulates diverse physiological functions in many tissues and cell types through binding and activation of a G-protein-coupled receptor (GPCR), the PGF2α receptor (FP), which also is the primary therapeutic target for glaucoma and several other diseases. Here, we report cryo-electron microscopy (cryo-EM) structures of the human FP bound to endogenous ligand PGF2α and anti-glaucoma drugs LTPA and TFPA at global resolutions of 2.67 Å, 2.78 Å, and 3.14 Å. These structures reveal distinct features of FP within the lipid receptor family in terms of ligand binding selectivity, its receptor activation, and G protein coupling mechanisms, including activation in the absence of canonical PIF and ERY motifs and Gq coupling through direct interactions with receptor transmembrane helix 1 and intracellular loop 1. Together with mutagenesis and functional studies, our structures reveal mechanisms of ligand recognition, receptor activation, and G protein coupling by FP, which could facilitate rational design of FP-targeting drugs.
Surface manipulation for prevention of migratory viscous crude oil fouling in superhydrophilic membranes
Authors: Zhao Yuanyuan , Yang Xiaobin , Cheng Zhongjun , Lau Cher Hon , Ma Jun , Shao Lu
Published: May 2023

Here, we present a proactive fouling prevention mechanism that endows superhydrophilic membranes with antifouling capability against migratory viscous crude oil fouling. By simulating the hierarchical architecture/chemical composition of a dahlia leaf, a membrane surface is decorated with wrinkled-pattern microparticles, exhibiting a unique proactive fouling prevention mechanism based on a synergistic hydration layer/steric hindrance. The density functional theory and physicochemical characterizations demonstrate that the main chains of the microparticles are bent towards Fe3+ through coordination interactions to create nanoscale wrinkled patterns on smooth microparticle surfaces. Nanoscale wrinkled patterns reduce the surface roughness and increase the contact area between the membrane surface and water molecules, expanding the steric hindrance between the oil molecules and membrane surface. Molecular dynamic simulations reveal that the water-molecule densities and strengths of the hydrogen bonds are higher near the resultant membrane surface. With this concept, we can successfully inhibit the initial adhesion, migration, and deposition of oil, regardless of the viscosity, on the membrane surface and achieve migratory viscous crude oil antifouling. This research on the PFP mechanism opens pathways to realize superwettable materials for diverse applications in fields related to the environment, energy, health, and beyond.
Interim safety and immunogenicity results from an NDV-based COVID-19 vaccine phase I trial in Mexico
Authors: Ponce-de-León Samuel , Torres Martha , Soto-Ramírez Luis Enrique , Calva Juan José , Santillán-Doherty Patricio , Carranza-Salazar Dora Eugenia , Carreño Juan Manuel , Carranza Claudia , Juárez Esmeralda , Carreto-Binaghi Laura E. , Ramírez-Martínez Luis , Paz De la Rosa Georgina , Vigueras-Moreno Rosalía , Ortiz-Stern Alejandro , López-Vidal Yolanda , Macías Alejandro E. , Torres-Flores Jesús , Rojas-Martínez Oscar , Suárez-Martínez Alejandro , Peralta-Sánchez Gustavo , Kawabata Hisaaki , González-Domínguez Irene , Martínez-Guevara José Luis , Sun Weina , Sarfati-Mizrahi David , Soto-Priante Ernesto , Chagoya-Cortés Héctor Elías , López-Macías Constantino , Castro-Peralta Felipa , Palese Peter , García-Sastre Adolfo , Krammer Florian , Lozano-Dubernard Bernardo
Published: May 2023

There is still a need for safe, efficient, and low-cost coronavirus disease 2019 (COVID-19) vaccines that can stop transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we evaluated a vaccine candidate based on a live recombinant Newcastle disease virus (NDV) that expresses a stable version of the spike protein in infected cells as well as on the surface of the viral particle (AVX/COVID-12-HEXAPRO, also known as NDV-HXP-S). This vaccine candidate can be grown in embryonated eggs at a low cost, similar to influenza virus vaccines, and it can also be administered intranasally, potentially to induce mucosal immunity. We evaluated this vaccine candidate in prime-boost regimens via intramuscular, intranasal, or intranasal followed by intramuscular routes in an open-label non-randomized non-placebo-controlled phase I clinical trial in Mexico in 91 volunteers. The primary objective of the trial was to assess vaccine safety, and the secondary objective was to determine the immunogenicity of the different vaccine regimens. In the interim analysis reported here, the vaccine was found to be safe, and the higher doses tested were found to be immunogenic when given intramuscularly or intranasally followed by intramuscular administration, providing the basis for further clinical development of the vaccine candidate. The study is registered under ClinicalTrials.gov identifier NCT04871737.
Advanced hybrid nanosheet membranes with stable nanochannels for ultrafast molecular separation
Authors: Guo Qi , Xu Mao , Tang Qi , Liu Yuchen , Zhang Weiyu , Guo Chan , Zhao Xiaoli , Zhu Yujun , Ye Sheng , Liu Dan , Lei Weiwei , Chen Cheng
Published: May 2023

Lamellar graphene oxide (GO) membranes have gained substantial interest for molecular separation processes. However, GO membranes have shown inefficient separation performance levels due to their possession of sufficient functional groups that lead to swelling under applied hydraulic pressure. Herein, we demonstrate a highly stable and ultrafast filtrable graphene oxide-boron nitride (GOBN) hybrid membrane by incorporating boron nitride (BN) nanosheets into a GO membrane to restrict swelling and provide efficient hydraulic pressure separation characteristics. This new heterostructure retains the GOBN membrane microstructure and provides more nanochannels around the incorporation sites due to the small size of BN nanosheets; this phenomenon increases the permeance to 1310 Lm−2h−1bar−1, which is nearly six times higher than that of the pure GO membrane, with a high rejection reaching 99.2% for aqueous organic dyes. More importantly, the GOBN hybrid membrane shows an impressive permeance and dye molecule rejection performance characteristic across a range of organic solvents, such as methanol, ethanol, and isopropyl alcohol; the performance characteristics are better than those for the GO membrane. Our GOBN membrane with a stable microstructure opens opportunities for developing a high-performance multiple solvent nanofiltration membrane that surpasses the permeability-selectivity trade-off.
Widespread somatic L1 retrotransposition in normal colorectal epithelium
Authors: Nam Chang Hyun , Youk Jeonghwan , Kim Jeong Yeon , Lim Joonoh , Park Jung Woo , Oh Soo A , Lee Hyun Jung , Park Ji Won , Won Hyein , Lee Yunah , Jeong Seung-Yong , Lee Dong-Sung , Oh Ji Won , Han Jinju , Lee Junehawk , Kwon Hyun Woo , Kim Min Jung , Ju Young Seok
Published: May 2023

Throughout an individual’s lifetime, genomic alterations accumulate in somatic cells1–11. However, the mutational landscape induced by retrotransposition of long interspersed nuclear element-1 (L1), a widespread mobile element in the human genome12–14, is poorly understood in normal cells. Here we explored the whole-genome sequences of 899 single-cell clones established from three different cell types collected from 28 individuals. We identified 1,708 somatic L1 retrotransposition events that were enriched in colorectal epithelium and showed a positive relationship with age. Fingerprinting of source elements showed 34 retrotransposition-competent L1s. Multidimensional analysis demonstrated that (1) somatic L1 retrotranspositions occur from early embryogenesis at a substantial rate, (2) epigenetic on/off of a source element is preferentially determined in the early organogenesis stage, (3) retrotransposition-competent L1s with a lower population allele frequency have higher retrotransposition activity and (4) only a small fraction of L1 transcripts in the cytoplasm are finally retrotransposed in somatic cells. Analysis of matched cancers further suggested that somatic L1 retrotransposition rate is substantially increased during colorectal tumourigenesis. In summary, this study illustrates L1 retrotransposition-induced somatic mosaicism in normal cells and provides insights into the genomic and epigenomic regulation of transposable elements over the human lifetime.
Structural basis of catalytic activation in human splicing
Authors: Schmitzová Jana , Cretu Constantin , Dienemann Christian , Urlaub Henning , Pena Vladimir
Published: May 2023

Pre-mRNA splicing follows a pathway driven by ATP-dependent RNA helicases. A crucial event of the splicing pathway is the catalytic activation, which takes place at the transition between the activated Bact and the branching-competent B* spliceosomes. Catalytic activation occurs through an ATP-dependent remodelling mediated by the helicase PRP2 (also known as DHX16)1–3. However, because PRP2 is observed only at the periphery of spliceosomes3–5, its function has remained elusive. Here we show that catalytic activation occurs in two ATP-dependent stages driven by two helicases: PRP2 and Aquarius. The role of Aquarius in splicing has been enigmatic6,7. Here the inactivation of Aquarius leads to the stalling of a spliceosome intermediate—the BAQR complex—found halfway through the catalytic activation process. The cryogenic electron microscopy structure of BAQR reveals how PRP2 and Aquarius remodel Bact and BAQR, respectively. Notably, PRP2 translocates along the intron while it strips away the RES complex, opens the SF3B1 clamp and unfastens the branch helix. Translocation terminates six nucleotides downstream of the branch site through an assembly of PPIL4, SKIP and the amino-terminal domain of PRP2. Finally, Aquarius enables the dissociation of PRP2, plus the SF3A and SF3B complexes, which promotes the relocation of the branch duplex for catalysis. This work elucidates catalytic activation in human splicing, reveals how a DEAH helicase operates and provides a paradigm for how helicases can coordinate their activities.
A spatio-temporal dataset on food flows for four West African cities
Authors: Karg Hanna , Akoto-Danso Edmund K. , Amprako Louis , Drechsel Pay , Nyarko George , Lompo Désiré Jean-Pascal , Ndzerem Stephen , Sidibé Seydou , Hoschek Mark , Buerkert Andreas
Published: May 2023

Gaining insight into the food sourcing practices of cities is important to understand their resilience to climate change, economic crisis, as well as pandemics affecting food supply and security. To fill existing knowledge gaps in this area food flow data were collected in four West African cities - Bamako (Mali), Bamenda (Cameroon), Ouagadougou (Burkina Faso), and Tamale (Ghana). The data cover, depending on the city, road, rail, boat, and air traffic. Surveys were conducted for one week on average during the peak harvest, lean, and rainy seasons, resulting in a dataset of over 100,000 entries for 46 unprocessed food commodities. The data collected includes information on the key types of transportation used, quantity, source, and destination of the food flows. The data were used to delineate urban foodsheds and to identify city-specific factors constraining rural-urban linkages. The data can also be employed to inform academic and policy discussions on urban food system sustainability, to validate other datasets, and to plan humanitarian aid and food security interventions.
Preoperative imaging for hyperparathyroidism often takes upper parathyroid adenomas for lower adenomas
Authors: Van den Bruel Annick , Bijnens Jacqueline , Van Haecke Helena , Vander Poorten Vincent , Dick Catherine , Vauterin Tom , De Geeter Frank
Published: May 2023

We retrospectively evaluated how accurately preoperative imaging localizes parathyroid adenoma in superior versus inferior parathyroids. Over 6 years, 104 patients with primary hyperparathyroidism underwent parathyroid surgery in a single centre. Of these, 103 underwent ultrasound, 97 [99mTc]pertechnetate/MIBI SPECT/CT and 30 [18F]fluorocholine (FCH) PET/CT. One patient with a unilateral double adenoma was excluded from the analysis. Surgical findings with histopathologic confirmation of adenoma were used as the standard. Ultrasound misjudged 5 of 48 detected lower adenomas as upper, but 14 of 29 upper adenomas as lower (error rate 10 vs 48%, p = 0.0002). The corresponding error rates for [99mTc]pertechnetate/MIBI SPECT/CT were 3 versus 55% (p = 0.000014), and for [18F]FCH PET/CT 17 versus 36% (p = 0.26). Our results suggest that about half of the superior parathyroid adenomas which are detected, are erroneously assigned to the inferior position by both ultrasound and SPECT/CT imaging whereas the opposite mistake is significantly less frequent with ultrasound and SPECT/CT.
Plasma asymmetric dimethylarginine is associated with vulnerable plaque and long-term outcomes in stable coronary artery disease
Authors: Huang Shao-Sung , Huang Wei-Chieh , Tsai Chuan-Tsai , Chen Ying-Ying , Lee Sheng-Hua , Lu Tse-Min
Published: May 2023

Asymmetric dimethylarginine (ADMA) is considered to be an atherogenic molecule. We aimed to investigate the relationship between ADMA and plaque vulnerability assessed by optical coherence tomography (OCT) in patients with stable coronary artery disease (CAD). Two hundred and forty-five patients with stable CAD undergoing OCT-guided percutaneous coronary intervention were included in this study and were divided into two groups according to their ADMA levels. Micro-vessel, macrophage accumulation, thin-cap fibroatheroma, intra-plaque calcium and lipid core content, and vulnerable score (VS) were evaluated by OCT analysis. The patients with higher ADMA levels had significantly higher calcium and lipid content (p < 0.001, respectively). There were significantly more micro-vessel and macrophage (32.8%, p = 0.004 and 52.5%, p < 0.001, respectively) and higher VS (87.7 ± 17.6, p < 0.001) in the higher ADMA group. Moreover, plasma ADMA level was significantly correlated with the intra-plaque lipid, calcium content and VS (p < 0.001, respectively). Plasma ADMA level was identified as an independent predictor of future adverse cardiovascular events, following OCT-guided PCI. In patients with stable CAD, higher plasma ADMA levels were significantly associated with the presence of intra-plaque lipid, calcification, vulnerable plaque, and poor long-term outcomes.
Design, construction, and validation of an in-situ groundwater trace element analyzer with applications in carbon storage
Authors: Hartzler Daniel A. , Bhatt Chet R. , McIntyre Dustin L.
Published: May 2023

It is estimated that carbon emissions should reach net-zero by 2050 to meet important climate targets. Carbon capture is likely necessary to reach these targets, requiring a long-term storage solution such as geological carbon sequestration. However, as with any subsurface activity, leakage can occur, potentially impacting groundwater quality near the storage site. Rapid detection is essential to mitigate damage to this resource. Since CO2 will acidify groundwater, the concentrations of acid soluble minerals and associated cations will increase. Thus, an in-situ, real-time element analysis system based on laser-induced breakdown spectroscopy (LIBS) is under development to monitor these elements. The system splits the traditional LIBS system into a miniature, all-optical sensor head built around a passively Q-switch laser fiber coupled to a control unit. Previous work has validated the LIBS technique for use at high pressure as well as the split system design. In this work, a fieldable prototype sensor is developed and tested in an onsite monitoring well where trace elements concentrations (approx. 0–3 ppm) were tracked over 20 days. These concentrations varied in response to local rainfall, diluting with increased rain, demonstrating the ability of a LIBS-based sensor to track trace elements under real-world conditions.
Network pharmacology to explore the mechanism of scutellarin in the treatment of brain ischaemia and experimental verification of JAK2/STAT3 signalling pathway
Authors: Jia Qiu-Ye , Chen Hao‑Lun , Qi Zhi , Zhang Xiao‑Li‑Na , Zheng Li-Yang , Liu Teng-Teng , Yuan Yun , Yang Li , Wu Chun‑Yun
Published: May 2023

Scutellarin is used to treat brain ischaemia. However, its underlying mechanism of action remains unclear. This study aimed to elucidate the potential mechanism of action of scutellarin in brain ischaemia through network pharmacology and experimental verification. The JAK2/STAT3 signalling pathway was identified and experimentally verified. Expression of JAK2/STAT3 signalling related proteins in TNC-1 astrocytes with BV-2 microglia-conditioned medium (CM), CM + lipopolysaccharide (LPS) (CM + L), and CM pretreated with scutellarin + LPS (CM + SL) was analysed by Western Blot and immunofluorescence staining. Expression levels of JAK2, p-JAK2, STAT3, and p-STAT3 were evaluated in astrocytes pre-treated with AG490. Middle cerebral artery occlusion (MCAO) in rats was performed in different experimental groups to detect expression of the above biomarkers. Network pharmacology suggested that the JAK2/STAT3 signalling pathway is one of the mechanisms by which scutellarin mitigates cerebral ischaemic damage. In TNC-1 astrocytes, p-JAK2 and p-STAT3 expression were significantly up-regulated in the CM + L group. Scutellarin promoted the up-regulation of various markers and AG490 neutralised the effect of scutellarin. In vivo, up-regulation of p-JAK2 and p-STAT3 after ischaemia is known. These results are consistent with previous reports. Scutellarin further enhanced this upregulation at 1, 3, and 7 d after MCAO. Scutellarin exerts its therapeutic effects on cerebral ischaemia by activating the astrocyte JAK2/STAT3 signalling, which provides a firm experimental basis for its clinical application.
Stochastic resonance analysis of a coupled high-speed maglev vehicle-bridge coupled system under bounded noise
Authors: Li Yan-xia , Yu Zhi-wu , Xu Lei
Published: May 2023

Coupled oscillations typically occur in maglev vehicle-bridge coupled systems excited by bounded noise caused by guideway irregularities. The paper employed Hamilton equations to derive the corresponding canonical transformation equations and determined the critical stable regions for two kinds of resonances using the largest Lyapunov exponents. The results show that the critical stable region between the excitation amplitude and the resonant frequency ratio is a valley shape when the system has external resonance only. When considering both internal and external resonances, the critical stable region between the excitation amplitude and resonant frequency ratio presents a small saddle shape. Energy transfers from the first to the second oscillator under with both internal and extrinsic resonance. As the guideway irregularities’ coefficients increase, the maximum Lyapunov exponents of the two conditions change from negative to positive, which means that the system varies from a stable state to instability.
Predictors of long-term neutralizing antibody titers following COVID-19 vaccination by three vaccine types: the BOOST study
Authors: Prather Aric A. , Dutcher Ethan G. , Robinson James , Lin Jue , Blackburn Elizabeth , Hecht Frederick M. , Mason Ashley E. , Fromer Elena , Merino Bresh , Frazier Remi , O’Bryan Julia , Drury Stacy , Epel Elissa S.
Published: May 2023

As concerns related to the COVID-19 pandemic continue, it is critical to understand the impact of vaccination type on neutralizing antibody response durability as well as to identify individual difference factors related to decline in neutralization. This was a head-to-head comparison study following 498 healthy, community volunteers who received the BNT162b2 (n = 287), mRNA-1273 (n = 149), and Ad26.COV2.S (n = 62). Participants completed questionnaires and underwent blood draws prior to vaccination, 1 month, and 6 months after the vaccination series, and neutralizing antibody (nAB) titers at 1- and 6-months post vaccination were quantified using a high-throughput pseudovirus assay. Over 6 months of follow-up, nABs declined in recipients of BNT162b2 and mRNA-1273, while nABs in recipients of Ad26.COV2.S showed a significant increase. At the 6-month time point, nABs to Ad26.COV2.S were significantly higher than nABs to BNT162b2 and equivalent to mRNA-1273. Irrespective of follow-up timing, being older was associated with lower nAB for participants who received BNT162b2 and Ad26.COV2.S but not for those who received mRNA-1273. A higher baseline BMI was associated with a lower nAB for Ad26.COV2.S recipients but not for recipients of other vaccines. Women and non-smokers showed higher nAB compared to men and current smokers, respectively. The durability of neutralizing antibody responses differed by vaccine type and several sociodemographic factors that predicted response. These findings may inform booster recommendations in the future.
Intriguing physicochemical properties and impact of co-dopants on N-doped graphene oxide based ZnS nanowires for photocatalytic application
Authors: Dake D. V. , Raskar N. D. , Mane V. A. , Sonpir R. B. , Stathatos E. , Vasundhara M. , Meena R. , Asokan K. , Dole B. N.
Published: May 2023

Superparamagnetic N-doped graphene oxide (GO)- with ZnS nanowires was synthesized by a one-step hydrothermal method by doping dilute amounts of Ga, Cr, In, and Al ions for water treatment and biomedical applications. In these experiments, to enhance their properties, 2% of Ga3+, In3+, and or Al3+ were codoped along with 2% Cr ions in these ZnS nanowires. The nanocomposite with the composition, In0.02Cr0.02Zn0.96S, has better photocatalytic efficiency than other co-doped nanocomposites. The In (metalloids) and Cr (transition metal ion) are the best combinations to increase the magnetic properties which are beneficial for photocatalytic activity. Synthesized nanocomposite materials were characterized by several techniques such as X-ray diffraction, Field emission-scanning electron microscope (FESEM) with EDAX, vibrating sample magnetometer (VSM), UV–Vis, X-ray photoelectron spectroscopy (XPS), and fluorescence spectroscopy. The correlation of intriguing magnetic properties with their photocatalytic properties is also discussed. XPS was employed for the detection of surface defects, phase transformation, and the nature of chemical components present in the nanocomposites. The Frankel and substitutional defects have a direct impact on photocatalytic activity that was determined from the fluorescence (FL) spectroscopy. FL and XPS reveal that the Cr and In codoped composite has a higher percentage of defects hence its photocatalytic efficiency reaches 94.21%.
Usefulness of the BACES score in nontuberculous mycobacterial pulmonary disease for various clinical outcomes
Authors: Kim Hyung-Jun , Song Myung Jin , Kwon Byoung Soo , Kim Yeon Wook , Lim Sung Yoon , Lee Yeon-Joo , Park Jong Sun , Cho Young-Jae , Lee Choon-Taek , Lee Jae Ho
Published: May 2023

A uniform prognostic marker is needed for nontuberculous mycobacterial pulmonary disease (NTM-PD) due to the diverse clinical course. We aimed to seek the utility of the BACES score, originally derived to predict all-cause mortality, for various outcomes. To calculate the BACES score, one point was given for each of the following factors: body mass index < 18.5 kg/m2, age ≥ 65 years, presence of cavities, elevated erythrocyte sedimentation rate, or male sex. The study included 681 patients, of whom 97 (14.2%), 189 (27.7%), 192 (28.2%), 143 (21.0%), 47 (6.9%), and 13 (1.9%) had BACES scores of 0 to 5. Those with greater BACES scores were more likely to experience dyspnea, body weight loss, and anorexia. With severe disease, the risk of disease progression increased while the rate of treatment culture conversion decreased. After adjustment of comorbidities, higher BACES score was independently associated with the risk of mortality from respiratory causes or infection. As a simple and efficient bedside tool for assessing the severity of NTM-PD, the BACES score has the potential to be utilized as a surrogate marker for uniform severity assessment.
Targeting Poly(ADP)ribose polymerase in BCR/ABL1-positive cells
Authors: Hiroki Haruka , Ishii Yuko , Piao Jinhua , Namikawa Yui , Masutani Mitsuko , Honda Hiroaki , Akahane Koshi , Inukai Takeshi , Morio Tomohiro , Takagi Masatoshi
Published: May 2023

BCR/ABL1 causes dysregulated cell proliferation and is responsible for chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph1-ALL). In addition to the deregulatory effects of its kinase activity on cell proliferation, BCR/ABL1 induces genomic instability by downregulating BRCA1. PARP inhibitors (PARPi) effectively induce cell death in BRCA-defective cells. Therefore, PARPi are expected to inhibit growth of CML and Ph1-ALL cells showing downregulated expression of BRCA1. Here, we show that PARPi effectively induced cell death in BCR/ABL1 positive cells and suppressed colony forming activity. Prevention of BCR/ABL1-mediated leukemogenesis by PARP inhibition was tested in two in vivo models: wild-type mice that had undergone hematopoietic cell transplantation with BCR/ABL1-transduced cells, and a genetic model constructed by crossing Parp1 knockout mice with BCR/ABL1 transgenic mice. The results showed that a PARPi, olaparib, attenuates BCR/ABL1-mediated leukemogenesis. One possible mechanism underlying PARPi-dependent inhibition of leukemogenesis is increased interferon signaling via activation of the cGAS/STING pathway. This is compatible with the use of interferon as a first-line therapy for CML. Because tyrosine kinase inhibitor (TKI) monotherapy does not completely eradicate leukemic cells in all patients, combined use of PARPi and a TKI is an attractive option that may eradicate CML stem cells.
LncTUG1 contributes to the progression of hepatocellular carcinoma via the miR-144-3p/RRAGD axis and mTOR/S6K pathway
Authors: Chen Weixi , Bai Zekun , Bai Wen , Wang Wei , Guo Jiapei , Guo Mengnan , Sai Yingying , Shi Jun , Wu Jinghua
Published: May 2023

Hepatocellular carcinoma (HCC) is a symptomatic disease involed multi-stage program. Here, we elucidated the molecular mechanism of LncTUG1 in the regulation of HCC evolvement. And that may in all likelyhood supply a innovative latent target for HCC’s diagnoses and prognosis. LncRNA TUG1, miR-144-3p, RRAGD and mTOR signaling pathway were screened as target genes in the database, and their expression levels at the cytological level were verified utilized qRT-PCR, Western Blot and immunohistochemistry. Then, we adopted CCK-8, Transwell and flow cytometry assays to estimate cell proliferation, invasion and apoptosis. By use of luciferase reporter assay, the relationships of LncRNA TUG1, miR-144-3p and RRAGD was confirmed. In addition, the LncRNA TUG1-miR-144-3p-RRAGD-mTOR signaling pathway in HCC cells was verified adopted rescue experiment and confirmed by xenotransplantation animal experiment. LncTUG1 in HCC tissues from three databases were identified and further verified through qRT-PCR in HCC cells (Huh7, Hep3B). Knockdown the LncTUG1 could increase apoptosis and inhibite invasion and proliferation in HCC cells. Using inhibitors and activators of the mTOR/S6K pathway, LncTUG1 was confirmed to regulate HCC progression by the mTOR/S6K pathway. Luciferase reporter assay demonstrated that TUG1 negatively regulates miR-144-3p. Furthermore, miR-144-3p negativly regulates RRAGD by way of interacting with the 3′UTR of the RRAGD mRNA in HCC utilized luciferase reporter assay. In vivo, we also discovered that neoplasm weight and tumor volume reduced significantly in subcutaneous xenograft nude mouse models derived from sh-LncTUG1-expressing Huh7 cells. And the expressions of p-mTOR, p-S6K and RRAGD were decreased obviously while the miR144-3p increased in subcutaneous xenograft nude mouse models. In a word, the research suggests that LncTUG1 targets miR-144-3p while miR-144-3p binds to RRAGD mRNA, which induces mTOR/S6K pathway activation and promotes the progression of HCC.
Landslide detection and inventory updating using the time-series InSAR approach along the Karakoram Highway, Northern Pakistan
Authors: Hussain Sajid , Pan Bin , Afzal Zeeshan , Ali Muhammad , Zhang Xianlong , Shi Xianjian , Ali Muhammad
Published: May 2023

Karakoram Highway (KKH) is frequently disrupted by geological hazards mainly landslides which pose a serious threat to its normal operation. Using documented inventory, optical imagery interpretation, and frequency-area statistics, the features of slope failure, the spatial distribution, and their link to numerous contributing factors have all been effectively explored along the KKH. An updated inventory for the area was recreated using the interferometric synthetic aperture radar (InSAR) persistent scatterer (PS) technology to further investigate millimetre-accurate measurements of slope deformation (Vslope). Utilizing the PS approach, Sentinel-1 data from Jan 2018 to Jan 2022 were processed by which we obtained a deformation rate (VSlope) that varies between 0 and 364 mm/year. A total number of 234 landslides were cited from the literature and classified while 29 new potential landslides were detected and several pre-existing landslides were redefined by the InSAR approach, which was incorporated to generate an updated landslide susceptibility model with 86.6% of prediction precision in the area under curve method. As previous studies done by applying the InSAR technique incorporated a short span temporally and they missed some highly deforming zones like Budalas and Khanabad landslides, contain mean velocities > 50 mm/yr, which we studied individually in this work. In this study, a comprehensive application of the InSAR technique to assessing its performance in detecting and analysing landslides has been applied. The deformation velocity (Vslope) model shows high displacement in some regions, which needed to be further investigated by geoscientists, and the updated developed landslide inventory and susceptibility map can be used for land use planning and landslide mitigation strategies.
RNA-sequencing transcriptome analysis of Avicennia marina (Forsk.) Vierh. leaf epidermis defines tissue-specific transcriptional response to salinity treatment
Authors: Li Huan , Lv Chao-Tian , Li Yun-Tao , Gao Guo-Yv , Meng Ya-Fei , You Yv-Le , Tian Qi , Liang Kun-Qi , Chen Yu , Chen Hao , Xia Chao , Rui Xiang-Yun , Zheng Hai-Lei , Wei Ming-Yue
Published: May 2023

Avicennia marina (Forsk.) Vierh. is a typical mangrove plant. Its epidermis contains salt glands, which can secrete excess salts onto the leaf surfaces, improving the salt tolerance of the plants. However, knowledge on the epidermis-specific transcriptional responses of A. marina to salinity treatment is lacking. Thus, physiological and transcriptomic techniques were applied to unravel the salt tolerance mechanism of A. marina. Our results showed that 400 mM NaCl significantly reduced the plant height, leaf area, leaf biomass and photosynthesis of A. marina. In addition, 1565 differentially expressed genes were identified, of which 634 and 931 were up- and down-regulated. Based on Kyoto Encyclopedia of Genes and Genomes metabolic pathway enrichment analysis, we demonstrated that decreased gene expression, especially that of OEE1, PQL2, FDX3, ATPC, GAPDH, PRK, FBP and RPE, could explain the inhibited photosynthesis caused by salt treatment. Furthermore, the ability of A. marina to cope with 400 mM NaCl treatment was dependent on appropriate hormone signalling and potential sulfur-containing metabolites, such as hydrogen sulfide and cysteine biosynthesis. Overall, the present study provides a theoretical basis for the adaption of A. marina to saline habitats and a reference for studying the salt tolerance mechanism of other mangrove plants.
A portable immunosensor provides sensitive and rapid detection of Borrelia burgdorferi antigen in spiked blood
Authors: Kim Sangsik , Samanta Kamalika , Nguyen Brandon T. , Mata-Robles Samantha , Richer Luciana , Yoon Jeong-Yeol , Gomes-Solecki Maria
Published: May 2023

There are no assays for detecting B. burgdorferi antigen in blood of infected Lyme disease individuals. Here, we provide proof-of-principle evidence that we can quantify B. burgdorferi antigen in spiked blood using a portable smartphone-based fluorescence microscope that measures immunoagglutination on a paper microfluidic chip. We targeted B. burgdorferi OspA to develop a working prototype and added examples of two antigens (OspC and VlsE) that have diagnostic value for discrimination of Lyme disease stage. Using an extensively validated monoclonal antibody to OspA (LA-2), detection of OspA antigen had a broad linear range up to 100 pg/mL in 1% blood and the limit of detection (LOD) was 100 fg/mL (= 10 pg/mL in undiluted blood), which was 1000 times lower than our target of 10 ng/mL. Analysis of the two other targets was done using polyclonal and monoclonal antibodies. OspC antigen was detected at LOD 100 pg/mL (= 10 ng/mL of undiluted blood) and VlsE antigen was detected at LOD 1–10 pg/mL (= 0.1–1 ng/mL of undiluted blood). The method is accurate and was performed in 20 min from sample to answer. When optimized for detecting several B. burgdorferi antigens, this assay may differentiate active from past infections and facilitate diagnosis of Lyme disease in the initial weeks of infection, when antibody presence is typically below the threshold to be detected by serologic methods.
Severe lymphopenia as a prognostic factor in rectal cancer patients receiving adjuvant chemoradiotherapy: a retrospective study
Authors: Li Shuang , Yao Weiping , Liu Ruiqi , Lu Yanwei , Zhang Haibo , Liang Xiaodong
Published: May 2023

The relationship between total lymphocyte counts (TLCs) and survival is not well documented in rectal cancer. This study aimed to investigate the association between TLCs and disease-free survival (DFS) and identify factors associated with lymphopenia in locally advanced rectal cancer patients receiving chemoradiotherapy. Thirty-six patients with locally advanced rectal cancer were retrospectively analyzed. TLCs were evaluated before surgery (pre-S), before radiotherapy (pre-RT), and during concurrent chemoradiotherapy (CCRT). The relationship between TLCs and DFS was analyzed by univariate and multivariate analysis. Potential clinical factors associated with lymphopenia were also evaluated. Median TLC declined significantly during radiotherapy. Severe lymphopenia during CCRT was significantly associated with poorer DFS on Kaplan–Meier analysis (p = 0.01), univariate regression analysis (p = 0.036), and multivariate regression analysis (p = 0.038). Pre-S TLCs (p = 0.009) and pre-RT TLCs (p = 0.042) were significantly associated with severe lymphopenia on univariate regression analysis; however, only pre-S TLCs (p = 0.026) were significantly associated with severe lymphopenia on multivariate regression analysis. Severe lymphopenia was a predictor of poorer DFS in patients with locally advanced rectal cancer receiving adjuvant chemoradiotherapy. Pre-S TLCs were predictors of severe lymphopenia. Further study is warranted to reduce the rate of severe lymphopenia.
Influence of in utero fetal death on perineal tears in vaginal deliveries
Authors: Boudry Thibaud , Lallemant Marine , Ramanah Rajeev , Mottet Nicolas
Published: May 2023

The aim of this work was to evaluate and compare the incidence of perineal tears and Obstetrical anal sphincter injuries (OASIS) after vaginal delivery following a in utero fetal death (IUFD) compared with those with a live-birth. We conducted a single-center, retrospective cohort study using a database of all women who underwent a spontaneous vaginal delivery in the level III maternity ward. Exclusion criteria were breech presentation, cesarean section birth, instrumental delivery, multiple pregnancy, delivery before 24 + 6 weeks of gestation (WG) and termination of pregnancy for medical reasons. Women from the database were divided into two groups: an "in utero fetal death" (IUFD) group and a control group. Women were included in the IUFD group if they had a spontaneous vaginal delivery following a fetal demise after 24 + 6 WG in cephalic presentation between January 2006 and June 2020. Women in the "control" group were selected from the same database and were included if they underwent a spontaneous vaginal delivery of a live fetus in cephalic presentation, after 24 + 6 WG, during the same period. Each woman in the "IUFD" group was matched to two women (ratio 1:2) in the control group for parity, maternal age, body mass index, gestation and birth weight. The primary outcome was the presence of a sutured or unsutured perineal tear. During the study period, 31,208 patients delivered at a level III maternity hospital. Among them, 215 and 430 women were included in the IUFD group and the control group respectively. The two groups were comparable for all demographic and clinical characteristics except for an epidural analgesia (92% versus 70% in the control group, p < 0.01) and labor induction (86% versus 17% in the control group, p < 0.01). The incidence of any perineal tears was 13% (28/15) in the IUFD group versus 16% (70/430) in the control group. Relative risk of any perineal tears was non significative (RR = 0.8 IC95% [0.5–1.2]). The incidence of first-degree perineal tears was 10% in the IUFD group and 11% in the control group. The incidence of second-degree perineal tears was 18% in the IUFD group and 28% in the control group. Relative risk of first-degree perineal tears (RR = 0.88 95% CI [0.5–1.4]) and second-degree tears (RR = 0.51 95% CI [0.2–1.4]) were non significative. No obstetrical anal sphincter injury was found in either group. Vaginal delivery following a fetal demise did not appear to be either a risk factor or a protective factor for perineal tears. But there as a trend toward a lower incidence of second degree perineal tears in this context.
Multimodal fusion models for pulmonary embolism mortality prediction
Authors: Cahan Noa , Klang Eyal , Marom Edith M. , Soffer Shelly , Barash Yiftach , Burshtein Evyatar , Konen Eli , Greenspan Hayit
Published: May 2023

Pulmonary embolism (PE) is a common, life threatening cardiovascular emergency. Risk stratification is one of the core principles of acute PE management and determines the choice of diagnostic and therapeutic strategies. In routine clinical practice, clinicians rely on the patient’s electronic health record (EHR) to provide a context for their medical imaging interpretation. Most deep learning models for radiology applications only consider pixel-value information without the clinical context. Only a few integrate both clinical and imaging data. In this work, we develop and compare multimodal fusion models that can utilize multimodal data by combining both volumetric pixel data and clinical patient data for automatic risk stratification of PE. Our best performing model is an intermediate fusion model that incorporates both bilinear attention and TabNet, and can be trained in an end-to-end manner. The results show that multimodality boosts performance by up to 14% with an area under the curve (AUC) of 0.96 for assessing PE severity, with a sensitivity of 90% and specificity of 94%, thus pointing to the value of using multimodal data to automatically assess PE severity.
Studying the mechanism and kinetics of fuel desulfurization using CexOy/NiOx piezo-catalysts as a new low-temperature method
Authors: Ahmed Sangar S. , Amiri Omid , Rahman Karwan M. , Ismael Savana J. , Rasul Noor S. , Mohammad Darya , Babakr Karukh A. , Abdulrahman Nabaz A.
Published: May 2023

In order to advance desulfurization technology, a new method for excellent oxidative desulfurization of fuel at room temperature will be of paramount importance. As a novel desulfurization method, we developed piezo-catalysts that do not require adding any oxidants and can be performed at room temperature. A microwave method was used to prepare CeO2/Ce2O3/NiOx nanocomposites. Model and real fuel desulfurization rates were examined as a function of synthesis parameters, such as microwave power and time, and operation conditions, such as pH and ultrasonic power. The results showed that CeO2/Ce2O3/NiOx nanocomposites demonstrated outstanding piezo-desulfurization at room temperature for both model and real fuels. Furthermore, CeO2/Ce2O3/NiOx nanocomposites exhibited remarkable reusability, maintaining 79% of their piezo-catalytic activity even after 17 repetitions for desulfurization of real fuel. An investigation of the mechanism of sulfur oxidation revealed that superoxide radicals and holes played a major role. Additionally, the kinetic study revealed that sulfur removal by piezo-catalyst follows a second-order reaction kinetic model.
A kinetic-based stopped-flow DPPH• method
Authors: Angeli Lucrezia , Morozova Ksenia , Scampicchio Matteo
Published: May 2023

The reaction kinetics of antioxidants with free radicals is crucial to screen their functionality. However, studying antioxidant-radical interactions is very challenging for fast electron-donor substances, such as ascorbic acid, because the reaction ends in a few seconds. Accordingly, this work proposes a rapid and sensitive method for the determination of the absolute rate constant of the reaction between fast antioxidants and DPPH•. The method consists of a stopped-flow spectrophotometric system, which monitors the decay of DPPH• during its interaction with antioxidants. A kinetic-based reaction mechanism fits the experimental data. Kinetic parameters include a second order kinetics (k1) and, depending on the type of antioxidant, a side reaction (k2). Ascorbic acid was the fastest antioxidant (k1 = 21,100 ± 570 M−1 s−1) in comparison with other eleven phenols, showing k1 values from 45 to 3070 M−1 s−1. Compounds like catechin, epicatechin, quercetin, rutin, and tannic, ellagic and syringic acids presented a side reaction (k2 from 15 to 60 M−1 s−1). Among seven fruit juices, strawberry was the fastest, while red plum the slowest. Overall, the proposed kinetic-based DPPH• method is simple, rapid, and suitable for studying the activity and capacity of different molecules, and food samples rich in fast antioxidants, like fruit juices.
Small RNA transcriptome analysis using parallel single-cell small RNA sequencing
Authors: Li Jia , Zhang Zhirong , Zhuang Yinghua , Wang Fengchao , Cai Tao
Published: May 2023

miRNA and other forms of small RNAs are known to regulate many biological processes. Single-cell small RNA sequencing can be used to profile small RNAs of individual cells; however, limitations of efficiency and scale prevent its widespread application. Here, we developed parallel single-cell small RNA sequencing (PSCSR-seq), which can overcome the limitations of existing methods and enable high-throughput small RNA expression profiling of individual cells. Analysis of PSCSR-seq data indicated that diverse cell types could be identified based on patterns of miRNA expression, and showed that miRNA content in nuclei is informative (for example, cell type marker miRNAs can be detected in isolated nuclei). PSCSR-seq is very sensitive: analysis of only 732 peripheral blood mononuclear cells (PBMCs) detected 774 miRNAs, whereas bulk small RNA analysis would require input RNA from approximately 106 cells to detect as many miRNAs. We identified 42 miRNAs as markers for PBMC subpopulations. Moreover, we analyzed the miRNA profiles of 9,533 cells from lung cancer biopsies, and by dissecting cell subpopulations, we identified potentially diagnostic and therapeutic miRNAs for lung cancers. Our study demonstrates that PSCSR-seq is highly sensitive and reproducible, thus making it an advanced tool for miRNA analysis in cancer and life science research.
Deep ocean water alters the cholesterol and mineral metabolism of squid Todarodes pacificus and suppresses its weight loss
Authors: Hatano Kaito , Yoshida Masa-Aki , Hirayama Jun , Kitani Yoichiro , Hattori Atsuhiko , Ogiso Shouzo , Watabe Yukina , Sekiguchi Toshio , Tabuchi Yoshiaki , Urata Makoto , Matsumoto Kyoko , Sakatoku Akihiro , Srivastav Ajai K. , Toyota Kenji , Matsubara Hajime , Suzuki Nobuo
Published: May 2023

This study is the first to demonstrate that deep ocean water (DOW) has physiological significant effects on squid. After 36 h of rearing squids, those reared with DOW had significantly higher total and free cholesterol levels and lower alanine transaminase activity in hemolymph as compared with those reared with surface sea water (SSW). SSW rearing also resulted in 6.95% weight loss, while DOW rearing caused only 2.5% weight loss, which might be due to liver metabolism suppression. Furthermore, both monovalent (sodium, chloride, and potassium ions) and divalent (calcium, inorganic phosphorus, and magnesium ions) ions in hemolymph were elevated when reared with DOW compared to those when reared with SSW. A study of genes expressed in the brain revealed that five genes were specifically remarked in DOW rearing. Most altered genes were neuropeptides, including those from vasopressin superfamily. These neuropeptides are involved in cholesterol and/or mineral metabolisms and physiological significant effects on squid. This study is the first report the effects of DOW on cholesterol and mineral metabolism of squid and will contribute to squid aquaculture using DOW.
Brain-wide dendrites in a near-optimal performance of dynamic range and information transmission
Authors: Lin Congping , Xu Fan , Zhang Yiwei
Published: May 2023

Dendrites receive and process signals from other neurons. The range of signal intensities that can be robustly distinguished by dendrites is quantified by the dynamic range. We investigate the dynamic range and information transmission efficiency of dendrites in relation to dendritic morphology. We model dendrites in a neuron as multiple excitable binary trees connected to the soma where each node in a tree can be excited by external stimulus or by receiving signals transmitted from adjacent excited nodes. It has been known that larger dendritic trees have a higher dynamic range. We show that for dendritic tress of the same number of nodes, the dynamic range increases with the number of somatic branches and decreases with the asymmetry of dendrites, and the information transmission is more efficient for dendrites with more somatic branches. Moreover, our simulated data suggest that there is an exponential association (decay resp.) of overall relative energy consumption (dynamic range resp.) in relation to the number of somatic branches. This indicates that further increasing the number of somatic branches (e.g. beyond 10 somatic branches) has limited ability to improve the transmission efficiency. With brain-wide neuron digital reconstructions of the pyramidal cells, 90% of neurons have no more than 10 dendrites. These suggest that actual brain-wide dendritic morphology is near optimal in terms of both dynamic range and information transmission.