bluuebunny/crossref_metadata_2025 huggingface dataset:
A roadmap to establish a comprehensive platform for sustainable manufacturing of natural products in yeast
Authors: Naseri Gita
Published: April 2023

Secondary natural products (NPs) are a rich source for drug discovery. However, the low abundance of NPs makes their extraction from nature inefficient, while chemical synthesis is challenging and unsustainable.Saccharomyces cerevisiaeandPichia pastorisare excellent manufacturing systems for the production of NPs. This Perspective discusses a comprehensive platform for sustainable production of NPs in the two yeasts through system-associated optimization at four levels: genetics, temporal controllers, productivity screening, and scalability. Additionally, it is pointed out critical metabolic building blocks in NP bioengineering can be identified through connecting multilevel data of the optimized system using deep learning.
Intracytoplasmic membranes develop in Geobacter sulfurreducens under thermodynamically limiting conditions
Authors: Howley Ethan , Mangus Anna , Williams Dewight , Torres César I.
Published: April 2023

Geobacter sulfurreducensis an electroactive bacterium capable of reducing metal oxides in the environment and electrodes in engineered systems1,2.Geobacter sp. are the keystone organisms in electrogenic biofilms, as their respiration consumes fermentation products produced by other organisms and reduces a terminal electron acceptor e.g. iron oxide or an electrode. To respire extracellular electron acceptors with a wide range of redox potentials,G. sulfurreducenshas a complex network of respiratory proteins, many of which are membrane-bound3–5. We have identified intracytoplasmic membrane (ICM) structures inG. sulfurreducens. This ICM is an invagination of the inner membrane that has folded and organized by an unknown mechanism, often but not always located near the tip of a cell. Using confocal microscopy, we can identify that at least half of the cells contain an ICM when grown on low potential anode surfaces, whereas cells grown at higher potential anode surfaces or using fumarate as electron acceptor had significantly lower ICM frequency. 3D models developed from cryo-electron tomograms show the ICM to be a continuous extension of the inner membrane in contact with the cytoplasmic and periplasmic space. The differential abundance of ICM in cells grown under different thermodynamic conditions supports the hypothesis that it is an adaptation to limited energy availability, as an increase in membrane-bound respiratory proteins could increase electron flux. Thus, the ICM provides extra inner-membrane surface to increase the abundance of these proteins.G. sulfurreducensis the first Thermodesulfobacterium or metal-oxide reducer found to produce ICMs.
Glycosylated nanoparticle-based PfCSP vaccine confers long-lasting antibody responses and sterile protection in mouse malaria model
Authors: Ludwig Julia , Scally Stephen W. , Costa Giulia , Hoffmann Sandro , Murugan Rajagopal , Lossin Jana , Prieto Katherine , Obraztsova Anna , Lobeto Nina , Franke-Fayard Blandine , Janse Chris J. , Lebas Celia , Collin Nicolas , Binter Spela , Kellam Paul , Levashina Elena A. , Wardemann Hedda , Julien Jean-Philippe
Published: April 2023

The development of an effective and durable vaccine remains a central goal in the fight against malaria. Circumsporozoite protein (CSP) is the major surface protein of sporozoites and the target of the only licensed Plasmodium falciparum (Pf) malaria vaccine, RTS,S/AS01. However, vaccine efficacy is low and short-lived, highlighting the need for a second-generation vaccine with superior efficacy and durability. Here, we report a Helicobacter pylori apoferritin-based nanoparticle immunogen that elicits strong B cell responses against PfCSP epitopes that are targeted by the most potent human monoclonal antibodies. Glycan engineering of the scaffold and fusion of an exogenous T cell epitope enhanced the anti-PfCSP B cell response eliciting strong, long-lived and protective humoral immunity in mice. Our study highlights the power of rational vaccine design to generate a highly efficacious second-generation anti-infective malaria vaccine candidate and provides the basis for its further development.
Rapid single-cell physical phenotyping of mechanically dissociated tissue biopsies
Authors: Soteriou Despina , Kubánková Markéta , Schweitzer Christine , López-Posadas Rocío , Pradhan Rashmita , Thoma Oana-Maria , Györfi Andrea-Hermina , Matei Alexandru-Emil , Waldner Maximilian , Distler Jörg H. W. , Scheuermann Stefan , Langejürgen Jens , Eckstein Markus , Schneider-Stock Regine , Atreya Raja , Neurath Markus F. , Hartmann Arndt , Guck Jochen
Published: April 2023

During surgery, rapid and accurate histopathological diagnosis is essential for clinical decision making. Yet the prevalent method of intra-operative consultation pathology is intensive in time, labour and costs, and requires the expertise of trained pathologists. Here we show that biopsy samples can be analysed within 30 min by sequentially assessing the physical phenotypes of singularized suspended cells dissociated from the tissues. The diagnostic method combines the enzyme-free mechanical dissociation of tissues, real-time deformability cytometry at rates of 100–1,000 cells s−1 and data analysis by unsupervised dimensionality reduction and logistic regression. Physical phenotype parameters extracted from brightfield images of single cells distinguished cell subpopulations in various tissues, enhancing or even substituting measurements of molecular markers. We used the method to quantify the degree of colon inflammation and to accurately discriminate healthy and tumorous tissue in biopsy samples of mouse and human colons. This fast and label-free approach may aid the intra-operative detection of pathological changes in solid biopsies.
Viruses interact with hosts that span distantly related microbial domains in dense hydrothermal mats
Authors: Hwang Yunha , Roux Simon , Coclet Clément , Krause Sebastian J. E. , Girguis Peter R.
Published: April 2023

Many microbes in nature reside in dense, metabolically interdependent communities. We investigated the nature and extent of microbe-virus interactions in relation to microbial density and syntrophy by examining microbe-virus interactions in a biomass dense, deep-sea hydrothermal mat. Using metagenomic sequencing, we find numerous instances where phylogenetically distant (up to domain level) microbes encode CRISPR-based immunity against the same viruses in the mat. Evidence of viral interactions with hosts cross-cutting microbial domains is particularly striking between known syntrophic partners, for example those engaged in anaerobic methanotrophy. These patterns are corroborated by proximity-ligation-based (Hi-C) inference. Surveys of public datasets reveal additional viruses interacting with hosts across domains in diverse ecosystems known to harbour syntrophic biofilms. We propose that the entry of viral particles and/or DNA to non-primary host cells may be a common phenomenon in densely populated ecosystems, with eco-evolutionary implications for syntrophic microbes and CRISPR-mediated inter-population augmentation of resilience against viruses.
Very-large-scale integrated quantum graph photonics
Authors: Bao Jueming , Fu Zhaorong , Pramanik Tanumoy , Mao Jun , Chi Yulin , Cao Yingkang , Zhai Chonghao , Mao Yifei , Dai Tianxiang , Chen Xiaojiong , Jia Xinyu , Zhao Leshi , Zheng Yun , Tang Bo , Li Zhihua , Luo Jun , Wang Wenwu , Yang Yan , Peng Yingying , Liu Dajian , Dai Daoxin , He Qiongyi , Muthali Alif Laila , Oxenløwe Leif K. , Vigliar Caterina , Paesani Stefano , Hou Huili , Santagati Raffaele , Silverstone Joshua W. , Laing Anthony , Thompson Mark G. , O’Brien Jeremy L. , Ding Yunhong , Gong Qihuang , Wang Jianwei
Published: April 2023

Graphs have provided an expressive mathematical tool to model quantum-mechanical devices and systems. In particular, it has been recently discovered that graph theory can be used to describe and design quantum components, devices, setups and systems, based on the two-dimensional lattice of parametric nonlinear optical crystals and linear optical circuits, different to the standard quantum photonic framework. Realizing such graph-theoretical quantum photonic hardware, however, remains extremely challenging experimentally using conventional technologies. Here we demonstrate a graph-theoretical programmable quantum photonic device in very-large-scale integrated nanophotonic circuits. The device monolithically integrates about 2,500 components, constructing a synthetic lattice of nonlinear photon-pair waveguide sources and linear optical waveguide circuits, and it is fabricated on an eight-inch silicon-on-insulator wafer by complementary metal–oxide–semiconductor processes. We reconfigure the quantum device to realize and process complex-weighted graphs with different topologies and to implement different tasks associated with the perfect matching property of graphs. As two non-trivial examples, we show the generation of genuine multipartite multidimensional quantum entanglement with different entanglement structures, and the measurement of probability distributions proportional to the modulus-squared hafnian (permanent) of the graph’s adjacency matrices. This work realizes a prototype of graph-theoretical quantum photonic devices manufactured by very-large-scale integration technologies, featuring arbitrary programmability, high architectural modularity and massive manufacturing scalability.
Precise modulation of transcription factor levels identifies features underlying dosage sensitivity
Authors: Naqvi Sahin , Kim Seungsoo , Hoskens Hanne , Matthews Harold S. , Spritz Richard A. , Klein Ophir D. , Hallgrímsson Benedikt , Swigut Tomek , Claes Peter , Pritchard Jonathan K. , Wysocka Joanna
Published: April 2023

Transcriptional regulation exhibits extensive robustness, but human genetics indicates sensitivity to transcription factor (TF) dosage. Reconciling such observations requires quantitative studies of TF dosage effects at trait-relevant ranges, largely lacking so far. TFs play central roles in both normal-range and disease-associated variation in craniofacial morphology; we therefore developed an approach to precisely modulate TF levels in human facial progenitor cells and applied it to SOX9, a TF associated with craniofacial variation and disease (Pierre Robin sequence (PRS)). Most SOX9-dependent regulatory elements (REs) are buffered against small decreases in SOX9 dosage, but REs directly and primarily regulated by SOX9 show heightened sensitivity to SOX9 dosage; these RE responses partially predict gene expression responses. Sensitive REs and genes preferentially affect functional chondrogenesis and PRS-like craniofacial shape variation. We propose that such REs and genes underlie the sensitivity of specific phenotypes to TF dosage, while buffering of other genes leads to robust, nonlinear dosage-to-phenotype relationships.
Risk factors and a novel cerebral infarction extent scoring system for postoperative cerebral ischemia in patients with ischemic Moyamoya disease
Authors: Chen Yuanbing , Gong Xuan , Yang Zeng , Chen Fenghua , Wang Junyu
Published: April 2023

Postoperative cerebral ischemic complication is the most common complication of revascularization surgery for patients with moyamoya disease (MMD). This retrospective study was conducted on 63 patients with ischemic MMD. Postoperative ischemia occurred in 15 of the 70 revascularization operations performed for patients after surgical revascularization, translating to an incidence of 21.4%. Univariate analysis revealed that onset infarction (p = 0.015), posterior cerebral artery involvement (p = 0.039), strict perioperative management (p = 0.001), interval time between transient ischemic attack (TIA) or infarction presentation and operation (p = 0.002) and preoperatively cerebral infarction extent score (CIES) (p = 0.002) were significantly associated with postoperative cerebral ischemia. Multivariate analysis revealed that strict perioperative management (OR = 0.163; p = 0.047), and preoperatively CIES (OR = 1.505; p = 0.006) were independently associated with postoperative cerebral ischemia-related complications. After comprehensive improvement of perioperative management protocol, the incidence of symptomatic infarction declined to 7.4% (4 out of 54). Analysis of the area under the receiver operating characteristic curve (AUROC) indicated CIES was a predictor for both postoperative ischemia and high follow-up modified Rankin Scale scores. In summary, strict perioperative management and CIES were identified as independent risk factors for postoperative ischemic complications in ischemic MMD, demonstrating that comprehensive and individualized perioperative management improve postoperative outcomes in patients with MMD. Furthermore, application of CIES to evaluate pre-existing cerebral infarction can improve the management of patients.
Application of asymmetrical configuration in electrochemical noise to investigate corrosion inhibition of aluminum alloy by Ranunculus Arvensis/silver nanoparticles
Authors: Sajadi Ghazal Sadat , Naghizade Razieh , Hosseini Seyed Mohammad Ali
Published: April 2023

Asymmetric Configuration (As-Co) in the electrochemical noise (EN) was used to evaluateRanunculus Arvensis/ silver nanoparticles (RA/Ag NPs) as corrosion inhibitor for aluminum alloy (AA 2030) when gets exposed to 3.5% NaCl media. The ECN results of Asymmetric Configuration (As-Co) and Symmetric Configuration (Sy-Co) were interpreted using wavelet and statistical methods. The standard deviation of partial signal (SDPS) plots derived using of wavelet. The SDPS plot of As-Co demonstrated that the quantity of electric charge (Q) decreased with the addition of the inhibitor up to the optimum amount (200 ppm) due to the decreased corrosion rate. Moreover, the use of As- Co leads to record signal of one electrode and prevent recording extra signals arising from two identical electrodes which confirmed by the statistical parameters. The As-Co made of Al alloys were more satisfactory for estimating inhibiting effect of RA/Ag NPs compared to Sy-Co. Besides, aqueous extract ofRanunculus Arvensis(RA) plant as reducing agent mediates the synthesis of silver nanoparticles (RA/Ag NPs). The prepared NPs have been elaborately characterized using Field-Emission Scanning Electron Microscopy (FESEM), X-Ray Diffraction (XRD) analysis, and Fourier-Transform Infrared Spectroscopy (FT-IR) that revealed suitable synthesize of the RA/Ag NPs.
Association of ovine gammaherpesvirus 2 with an outbreak of acute respiratory disease in dairy cattle
Authors: Headley Selwyn Arlington , Dall Agnol Alais Maria , Bessegato José Antonio , Frucchi Ana Paula Souza , Maturana Érika Fernandes Lopes , Rodrigues Rafael Vince , Xavier Ana Aparecida Correa , Alfieri Alice Fernandes , Alfieri Amauri Alcindo
Published: April 2023

This study investigated the cause of an outbreak of an acute respiratory disease syndrome followed by episodes of diarrhea in a dairy cattle herd from Southern Brazil. Deep nasal swabs (DNS) from asymptomatic calves, calves with pulmonary discomfort, and diarrheic calves after episodes of respiratory distress were used in molecular assays designed to detect the principal pathogens associated with bovine respiratory disease (BRD). Fecal samples were used for the molecular detection of bovine enteric disease agents. Pulmonary tissues from three calves and a cow that died were evaluated by molecular assays to identify 11 agents associated with the development of BRD. The intestinal and pulmonary fragments of one calf and the cow revealed atrophic enteritis and interstitial pneumonia by histopathology, respectively. Immunohistochemistry (IHC) identified intralesional antigens of a malignant catarrhal fever virus, genus Macavirus, within epithelial cells of the lungs and intestines. Molecular assays amplified ovine gammaherpesvirus 2 (OvGHV2) from most of the DNS, and the pulmonary and intestinal fragments from the animals that died, confirming that the Macavirus identified by IHC was OvGHV2. Concomitant pulmonary infections of OvGHV2 with bovine gammaherpesvirus 6 and bovine coronavirus were identified. Additionally, bovine viral diarrhea virus 1b and Aichivirus B were detected in the fecal samples. These findings demonstrated that OvGHV2, a Macavirus, was the disease agent most frequently (81.2%; 13/16) associated with singular pulmonary infections during this outbreak of BRD, suggesting that this virus may be another potential agent of respiratory disease of cattle.
Accurate real space iterative reconstruction (RESIRE) algorithm for tomography
Authors: Pham Minh , Yuan Yakun , Rana Arjun , Osher Stanley , Miao Jianwei
Published: April 2023

Tomography has made a revolutionary impact on the physical, biological and medical sciences. The mathematical foundation of tomography is to reconstruct a three-dimensional (3D) object from a set of two-dimensional (2D) projections. As the number of projections that can be measured from a sample is usually limited by the tolerable radiation dose and/or the geometric constraint on the tilt range, a main challenge in tomography is to achieve the best possible 3D reconstruction from a limited number of projections with noise. Over the years, a number of tomographic reconstruction methods have been developed including direct inversion, real-space, and Fourier-based iterative algorithms. Here, we report the development of a real-space iterative reconstruction (RESIRE) algorithm for accurate tomographic reconstruction. RESIRE iterates between the update of a reconstructed 3D object and the measured projections using a forward and back projection step. The forward projection step is implemented by the Fourier slice theorem or the Radon transform, and the back projection step by a linear transformation. Our numerical and experimental results demonstrate that RESIRE performs more accurate 3D reconstructions than other existing tomographic algorithms, when there are a limited number of projections with noise. Furthermore, RESIRE can be used to reconstruct the 3D structure of extended objects as demonstrated by the determination of the 3D atomic structure of an amorphous Ta thin film. We expect that RESIRE can be widely employed in the tomography applications in different fields. Finally, to make the method accessible to the general user community, the MATLAB source code of RESIRE and all the simulated and experimental data are available at https://zenodo.org/record/7273314.
Comparisons of efficacy and safety between preserved and preservative-free brimonidine tartrate in glaucoma and ocular hypertension: a parallel-grouped, randomized trial
Authors: Kim Ko Eun , Lee Chang Kyu , Shin Jonghoon , Kim Yuri , Rho Seungsoo
Published: April 2023

This multicenter (four institutions), randomized, investigator-masked, parallel-group clinical trial evaluated and compared the efficacy and safety of preservative-free and preserved brimonidine tartrate 0.15% in open-angle glaucoma and ocular hypertension. Sixty eyes of 60 patients with intraocular pressure (IOP) ≥ 15 mmHg diagnosed with open-angle glaucoma or ocular hypertension were randomized to preserved (n = 31) and preservative-free (n = 29) brimonidine groups. The enrolled eyes received brimonidine monotherapy three times daily. Main outcome measures were corneal/conjunctival staining score, ocular surface disease index, patient satisfaction score, drug tolerance, and drug adherence rate 12 weeks post first administration. Secondary outcome measurements included visual acuity, IOP, drug tolerance, tear-film break-up time, hemodynamic changes including blood pressure and heart rates, and ocular adverse events. After 12 weeks, both preserved and preservative-free groups showed similar IOP reduction, corneal and conjunctival staining scores, drug tolerance, and adherence rates. The preservative-free group showed significantly better tear-film break-up time and higher patient satisfaction regarding drug use and management. Systolic and diastolic blood pressure reductions during the 12 weeks were significantly lower in the preserved group than in the preservative-free group. Preservative-free brimonidine tartrate showed comparable efficacy and safety, better corneal tear film stability, and patient satisfaction than preserved brimonidine.
Characterizing quantum circuits with qubit functional configurations
Authors: Hu Zixuan , Kais Sabre
Published: April 2023

We develop a systematic framework for characterizing all quantum circuits with qubit functional configurations. The qubit functional configuration is a mathematical structure that can classify the properties and behaviors of quantum circuits collectively. Major benefits of classifying quantum circuits in this way include: 1. All quantum circuits can be classified into corresponding types; 2. Each type characterizes important properties (such as circuit complexity) of the quantum circuits belonging to it; 3. Each type contains a huge collection of possible quantum circuits allowing systematic investigation of their common properties. We demonstrate the theory’s application to analyzing the hardware-efficient ansatzes of variational quantum algorithms. For potential applications, the functional configuration theory may allow systematic understanding and development of quantum algorithms based on their functional configuration types.
Deformation characteristics test and mechanism of arbor taproot soil complex in rainforests
Authors: Du Peng , Zhou Dequan , Liu Xiaoling , Feng Yujie
Published: April 2023

This study performed large-scale single shear tests on Haikou red clay and arbor taproot to explore the anti-sliding effect and deformation characteristics of rainforest arbor roots under a shallow landslide. The law of root deformation and the root–soil interaction mechanism were revealed. The results indicated the significant reinforcing effect of arbor roots on the shear strength and ductility of soil, which increased with the decrease of normal stress. The soil reinforcement mechanism of arbor roots was attributed to their friction and retaining effects through an analysis of the movement of soil particles and the deformation pattern of roots during the shear process. The root morphology of arbors under shear failure could be described using an exponential function. Consequently, an advanced Wu model which better reflected the stress state and deformation of roots was proposed based on the concept of curve segment superposition. The results are believed to a reliable experimental and theoretical basis for the in-depth study of soil consolidation and sliding resistance effects of arbor roots, and further lay a foundation for the slope protection by arbor roots.
Exploring nurses' multitasking in clinical settings using a multimethod study
Authors: Kim Yoojin , Lee Mi Ja , Choi Mona , Cho Eunhee , Ryu Gi Wook
Published: April 2023

Nurses often multitask in the process of managing patient care and communicating with healthcare providers simultaneously within a limited time, which can negatively affect patient care and safety. In this multimethod research, we conducted a time and motion study to record nursing activities using eye trackers for 23 participants (9 nurses and 14 patients). The frequency and duration of single and multitasking activities were analyzed. Additionally, we conducted focus group interviews (FGIs) with 12 nurses (2–5 nurses per group) to further investigate their multitasking experience. The total duration of the eye tracker recordings was 3,399 min. Daily nursing activities comprised 23.7%, 21.1%, and 12.5% of scheduled medication, documentation, and monitoring and measurement, respectively. Among these activities, nurses mostly carry out scheduled medication, monitoring, and measurement together. Three themes emerged in the FGIs: "Being involved in every little task regarding patient care," "Getting swamped by the complexity of symptoms and problems of the patients at a given time," and "Getting interrupted at work too often." Nurses performed multiple activities while cooperating with other healthcare providers and providing care to patients. It is important to create an environment where nurses can focus on essential nursing activities to improve patient safety.
Epidemiological and clinical characterization of a population-based cohort of cutaneous malignant melanoma patients in the South Region of Portugal
Authors: Alves da Costa Filipa , Ramos Adriana , Bernardo Catarina , Cardoso Borges Fábio , Costa Miranda Ana ,   the ROR-Sul network
Published: April 2023

An historical population-based cohort study was conducted aiming to estimate the incidence of cutaneous malignant melanoma in the South Region of Portugal between Jan 2016 and June 2017; to clinically characterize the diagnosed individuals; to describe instituted treatment; and to estimate survival outcomes. Data were extracted from a cancer registry (ROR-Sul) covering 4,800,000 inhabitants (46% of the Portuguese population) and included a total of 789 individuals meeting eligibility criteria. The crude incidence rate (18 months) of melanoma was 13.36/100,000 inhabitants and the Age-Standardized Incidence Rate per 100,000 World population was 9.65/100,000 inhabitants. The most common histological subtypes identified were superficial extension, followed by malignant melanoma and nodular melanoma. Most cases were diagnosed in stage I (50.39%), equally distributed by sex and with a median age of 65 years. During the study period, 174 recurrence events were recorded (23.45%) and recurrence-free survival rate was significantly lower in more advanced stages. Patients had a two-fold risk of recurrence/death when in presence of ulcerated tumors [adjusted hazard ratio (adj HR) = 2.28; 95% confidence interval (CI) 1.40–3.70]. Overall survival rate at 3-years was 80.54% (95% CI 77.58–83.15), higher than previous national reports, and considerably higher for individuals diagnosed at earlier stages (p < 0.001). We have also identified differential survival outcomes in stages II–III explained by the uptake of sentinel lymph node biopsy. The epidemiologic and clinical characteristics of malignant melanoma patients studied are consistent with international literature. The incidence and rates observed suggests additional public health campaigns are needed to modify behaviours of the Portuguese population and thus reduce their risk.
Association between human papillomavirus particle production and the severity of recurrent respiratory papillomatosis
Authors: Yamada Satoshi , Itoh Toshiya , Ikegami Taro , Imai Atsushi , Mochizuki Daiki , Nakanishi Hiroshi , Ishikawa Ryuji , Kita Junya , Nakamura Yuki , Takizawa Yoshinori , Okamura Jun , Noda Yoshihiro , Iwashita Toshihide , Hariyama Takahiko , Suzuki Mikio , Misawa Kiyoshi , Kawasaki Hideya
Published: April 2023

Recurrent respiratory papillomatosis (RRP) has a wide range of severity. We investigate the relationship between human papillomavirus (HPV) particle production and severity of RRP. From September 2005 to June 2021, 68 RRP samples (from 29 patients) were included. HPV type was determined. HPV viral load, physical status, and demographic and clinical characteristics were assessed. Immunohistochemistry (IHC) was performed for p16, Ki-67, L1, and E4. We used NanoSuit-CLEM (correlative light and electron microscopy) and transmission electron microscopy (TEM) to examine the samples. The total number of surgeries in HPV-positive and HPV-negative cases were 3.78 (n = 55/68, range: 1–16) and 1.30 (n = 13/68, range: 1–3), respectively (p = 0.02). IHC showed that L1 and E4 were correlated and expressed on the tumour surface. NanoSuit-CLEM and TEM revealed HPV particles in L1-positive nuclei. L1 IHC-positive cases had a shorter surgical interval (p < 0.01) and more frequent surgeries (p = 0.04). P16 IHC, viral load, and physical status were not associated with disease severity. This study visualised HPV particle production in RRP for the first time. Persistent HPV particle infection was associated with severity. We suggest L1 IHC for evaluating RRP severity in addition to the Derkay score.
Thianthrene polymers as 4 V-class organic mediators for redox targeting reaction with LiMn2O4 in flow batteries
Authors: Hatakeyama-Sato Kan , Sadakuni Karin , Kitagawa Kan , Oyaizu Kenichi
Published: April 2023

Redox targeting reaction is an emerging idea for boosting the energy density of redox-flow batteries: mobile redox mediators transport electrical charges in the cells, whereas large-density electrode-active materials are fixed in tanks. This study reports 4 V-class organic polymer mediators using thianthrene derivatives as redox units. The higher potentials than conventional organic mediators (up to 3.8 V) enable charging LiMn2O4 as an inorganic cathode offering a large theoretical volumetric capacity of 500 Ah/L. Soluble or nanoparticle polymer design is beneficial for suppressing crossover reactions (ca. 3% after 300 h), simultaneously contributing to mediation reactions. The successful mediation cycles observed by repeated charging/discharging steps indicate the future capability of designing particle-based redox targeting systems with porous separators, benefiting from higher energy density and lower cost.
Diagnostic accuracy of using multiple cytokines to predict aldosterone-producing adenoma
Authors: Qin Fei , Wen Hong , Zhong Xiaoge , Pan Yajin , Lai Xiaomei , Yang Tingting , Huang Jing , Yu Jie , Li Jianling
Published: April 2023

Here, we aimed to study the important cytokines in plasma to identify the aldosterone-producing adenoma (APA). 19 unilateral primary aldosteronism (UPA) patients and 19 healthy people were divided into UPA group and Control group, and the serum of bilateral adrenal veins and inferior vena cava collected by adrenal blood sampling (AVS) in UPA patients and the serum from the healthy subjects were all used to detect multiple cytokines by Luminex immunoassays. Additionally, The UPA patients subjected to laparoscopic adrenalectomy were divided into different groups by pathological results for further study. According our results, IP-10, CXCL9 and RANTES were significantly higher in UPA group compared with control group, and the combination of the three cytokines have significant predictive power for predicting UPA, while the correlational analyses demonstrated that IP-10 and CXCL9 were positively correlated with BP and HR, while EGF was positively correlated with HDL. Additionally, IL-1b was suggested to be the most potential diagnostic biomarker to discriminate the APA and unilateral adrenal hyperplasia (UAH). The present findings might suggest a possibility of IP-10, CXCL9 and RANTES served as a sign to help UPA diagnosis and finally used to assist the diagnosis of APA, while IL-1b was suggested to be the most potential diagnostic biomarker to identify the APA from the UAH patients.
Intracellular bioaccumulation of the rare earth element Gadolinium in ciliate cells resulting in biogenic particle formation and excretion
Authors: Kohl Jana , Schweikert Michael , Klaas Norbert , Lemloh Marie-Louise
Published: April 2023

Ciliates are abundant unicellular organisms capable of resisting high concentrations of metal ions in the environment caused by various anthropogenic activities. Understanding the cellular pathways involved in resistance to and detoxification of elements is required to predict the impact of ciliates on environmental element cycles. Here, we investigated the so far unknown process of tolerance, cellular uptake and bioaccumulation of the emerging rare earth element gadolinium (Gd) in the common ciliate Tetrahymena pyriformis. Gd treatment results in the intracellular formation and excretion of biogenic Gd-containing particles. This cellular process effectively removes dissolved Gd from the organic growth medium by 53.37% within 72 h. Based on light and electron microscopic observations, we postulate a detoxification pathway: Cells take up toxic Gd3+ ions from the medium by endocytosis, process them into stable Gd-containing particles within food vacuoles, and exocytose them. Stable biogenic particles can be isolated, which are relatively homogeneous and have a diameter of about 3 µm. They consist of the elements Gd, C, O, P, Na, Mg, K, and Ca. These findings broaden the view of metal ion accumulation by protists and are of relevance to understand environmental elemental cycles and may inspire approaches for metal recovery or bioremediation.
A new hazard scenario at Vesuvius: deadly thermal impact of detached ash cloud surges in 79CE at Herculaneum
Authors: Pensa Alessandra , Giordano Guido , Corrado Sveva , Petrone Pier Paolo
Published: April 2023

Diluted pyroclastic density currents are capable to cause huge devastation and mortality around volcanoes, and temperature is a crucial parameter in assessing their lethal power. Reflectance analysis on carbonized wood from ancient Herculaneum allowed a new reconstruction of the thermal events that affected buildings and humans during the 79CE Vesuvius eruption. Here we show that the first PDC entered the town was a short-lived, ash cloud surge, with temperatures of 555–495 °C, capable of causing instant death of people, while leaving only a few decimeters of ash on ground, which we interpret as detached from high concentration currents. The subsequent pyroclastic currents that progressively buried the town were mostly higher concentration PDCs at lower temperatures, between 465 and 390 and 350–315 °C. Charcoal proved to be the only proxy capable of recording multiple, ephemeral extreme thermal events, thus revealing for the first time the real thermal impact of the 79CE eruption. The lethal impact documented for diluted PDC produced during ancient and recent volcanic eruptions suggests that such hazard deserves greater consideration at Vesuvius and elsewhere, especially the underestimated hazard associated with hot detached ash cloud surges, which, though short lived, may expose buildings to severe heat damages and people to death.
Mechanical thrombectomy of distal cerebral vessel occlusions of the anterior circulation
Authors: Sepp Dominik , Hernandez Petzsche Moritz Roman , Zarth Teresa , Wunderlich Silke , Ikenberg Benno , Maegerlein Christian , Zimmer Claus , Berndt Maria Teresa , Boeckh-Behrens Tobias , Kirschke Jan Stefan
Published: April 2023

Mechanical thrombectomy (MT) is frequently performed for distal medium vessel occlusions (DMVO) of the anterior circulation in acute stroke patients. However, evidence for its clinical benefit remains scarce. In this study, we aim to investigate clinical course and safety outcomes of MT in comparison to standard medical therapy (SMT) in DMVO. This single-center retrospective observational study included 138 consecutive patients treated for DMVO of the anterior circulation between 2015 and 2021. To reduce the risk of selection bias, propensity score matching (PSM) of patients with MT versus SMT was performed for the covariates NIHSS and mRS at admission. Out of all 138 patients, 48 (34.8%) received MT and 90 (65.2%) received SMT only. Overall, patients treated with MT showed significantly higher NIHSS and mRS scores at admission. Post 1:1 PSM, there was a trend toward a better NIHSS improvement in patients with MT (median 4 vs. 1, P = 0.1). No significant differences were observed in the occurrence of symptomatic intracranial hemorrhage or mortality between the groups before and after PSM. A subgroup analysis showed significantly higher NIHSS improvement (median 5 versus 1, P = 0.01) for patients with successful MT (≥ mTICI 2b). Mechanical thrombectomy for distal medium vessel occlusions (DMVO) in the anterior circulation appeared safe and feasible. Successful recanalization was associated with clinical improvement. Larger, multi-center, randomized-controlled trials are required to corroborate these findings.
The potential clinical utility of cell-free DNA for gastric cancer patients treated with nivolumab monotherapy
Authors: Inagaki Chiaki , Kawakami Hisato , Maeda Daichi , Sakai Daisuke , Urakawa Shinya , Nishida Kentaro , Kudo Toshihiro , Doki Yuichiro , Eguchi Hidetoshi , Wada Hisashi , Satoh Taroh
Published: April 2023

To assess the potential clinical utility of cell-free DNA (cfDNA)-based biomarkers for identifying gastric cancer (GC) patients who benefit from nivolumab. From 31 GC patients treated with nivolumab monotherapy (240 mg/body, Bi-weekly) in 3rd or later line setting, we prospectively collected blood samples at baseline and before the 3rd dose. We compared cfDNA-based molecular findings, including microsatellite instability (MSI) status, to tissue-based biomarkers. We assessed the clinical value of blood tumor mutation burden (bTMB) and copy number alterations (CNA) as well as the cfDNA dynamics. The concordance between deficient-MMR and cfDNA-based MSI-high was 100% (3/3). Patients with bTMB ≥ 6 mut/Mb had significantly better progression-free survival (PFS) and overall survival (OS); however, such significance disappeared when excluding MSI-High cases. The combination of bTMB and CNA positivity identified patients with survival benefit regardless of MSI status (both PFS and OS, P < 0.001), with the best survival in those with bTMB≥6mut/Mb and CNAnegative. Moreover, patients with decreased bTMB during treatment had a better disease control rate (P = 0.04) and longer PFS (P = 0.04). Our results suggest that a combination of bTMB and CNA may predict nivolumab efficacy for GC patients regardless of MSI status. bTMB dynamics have a potential utility as an on-treatment biomarker.
An improved plastination method for strengthening bamboo culms, without compromising biodegradability
Authors: Osmond Reeghan , H. Margoto Olivia , Basar Ibrahim Alper , Olfatbakhsh Tina , Eskicioglu Cigdem , Golovin Kevin , Milani Abbas S.
Published: April 2023

Biomaterials are increasingly being designed and adapted to a wide range of structural applications, owing to their superior mechanical property-to-weight ratios, low cost, biodegradability, and CO2 capture. Bamboo, specifically, has an interesting anatomy with long tube-like vessels present in its microstructure, which can be exploited to improve its mechanical properties for structural applications. By filling these vessels with a resin, e.g. an applied external loading would be better distributed in the structure. One recent method of impregnating the bamboo is plastination, which was originally developed for preserving human remains. However, the original plastination process was found to be slow for bamboo impregnation application, while being also rather complicated/methodical for industrial adaptation. Accordingly, in this study, an improved plastination method was developed that is 40% faster and simpler than the original method. It also resulted in a 400% increase in open-vessel impregnation, as revealed by Micro-X-ray Computed Tomography imaging. The improved method involves three steps: acetone dehydration at room temperature, forced polymer impregnation with a single pressure drop to − 23 inHg, and polymer curing at 130 °C for 20 min. Bamboo plastinated using the new method was 60% stronger flexurally, while maintaining the same modulus of elasticity, as compared to the virgin bamboo. Most critically, it also maintained its biodegradability from cellulolytic enzymes after plastination, as measured by a respirometric technique. Fourier transform infrared-attenuated total reflection, and thermogravimetric analyses were conducted and showed that the plastinated bamboo’s functional groups were not altered significantly during the process, possibly explaining the biodegradability. Finally, using cone calorimetry, plastinated bamboo showed a faster ignition time, due to the addition of silicone, but a lower carbon monoxide yield. These results are deemed as a promising step forward for further improvement and application of this highly abundant natural fiber in engineering structures.
Tunable multichannel Fibonacci one-dimensional terahertz photonic crystal filter
Authors: Sepahvandi V. , Rezaei B. , Aly A. H.
Published: April 2023

This paper proposes a multichannel terahertz optical filter based on a one-dimensional photonic crystal with a third-order Fibonacci structure, including a bulk Dirac semimetal. The tuning of the optical properties of the proposed structure has been theoretically studied as a function of the Dirac semimetals' Fermi energy. Furthermore, the effects of the Fibonacci structure's periodic number and light's incident angle on optical channels were investigated. The results reveal that changes in the Fermi energy and incident angle remarkably affect the frequency and transmission of the optical channels. Additionally, the number of optical channels increases by increasing the periodic number of the Fibonacci structure.
Metabolomics analysis of follicular fluid in ovarian endometriosis women receiving progestin-primed ovary stimulation protocol for in vitro fertilization
Authors: Guo Haiyan , Zhu Qianqian , Gao Hongyuan , Lyu Qifeng , Chai Weiran , Wu Ling , Li Bin
Published: April 2023

This study aimed to investigate the metabolite profile and inflammatory state of follicular fluid (FF) in women with stage III–IV ovarian endometriosis (OE) who underwent in vitro fertilization (IVF). A cohort of 20 consecutive patients with OE were recruited and received progestin-primed ovary stimulation (PPOS) protocol (study group), while another 20 OE patients received one-month ultra-long term protocol (control group) for IVF in this prospective, nonrandomized study. FF samples were obtained from dominant follicles during oocyte retrieval, and liquid chromatography-mass spectrometry (LC–MS) was used to investigate the metabolites profile of FF. Results showed that significant increases in the levels of proline, arginine, threonine, and glycine in patients who received PPOS protocol compared to the control group (P < 0.05). A panel of three metabolites (proline, arginine, and threonine) was identified as specific biomarkers of OE patients using PPOS protocol. Additionally, levels of interleukin-1β, regulated on activation, normal T cell expressed and secreted, and tumor necrosis factor-α markedly decreased in women who received PPOS protocol compared to the control group (P < 0.05). In conclusion, PPOS protocol regulates the metabolism of several amino acids in the FF, which may play critical roles in the oocyte development and blastocyst formation, and their specific mechanism should be further elucidated.
Uncovering the special microbiota associated with occurrence and progression of gastric cancer by using RNA-sequencing
Authors: Ai Bin , Mei Yue , Liang Dong , Wang Tengjiao , Cai Hui , Yu Dong
Published: April 2023

Gastric cancer (GC) has been identified as the third deadly cancer in the world. Accumulating researches suggest a potential role of microorganisms in tumorigenesis. However, the composition of microbiota in GC tissues is not clear and it changes throughout the different stages of GC remain mostly elusive. Our study integrated RNA-Seq data of 727 samples derived from gastric tissues across four datasets and revealed its microbial composition. In order to remove the false positive results, core taxa were defined and characterized. Based on it, we analyzed the influence of biological factors on its composition. The pan-microbiome of gastric tissues was estimated to be over than 1400 genera. Seventeen core genera were identified. Among them, Helicobacter, Lysobacter were significantly enriched in normal tissues, while Pseudomonas was enriched in tumor tissues. Interestingly, Acinetobacter, Pasteurella, Streptomyces, Chlamydia, and Lysobacter, showed a significant increase trend during tumor development and formed strong intra/inter-correlations among them or with other genera. Furthermore, we found that tumor stage played an important role in altering the microbial composition of GC tissues. This study provides support for the in-depth study of tumor microbiome, and the specific microbiome excavated provides a possibility for the subsequent identification of potential biomarkers for GC.
Tat-malate dehydrogenase fusion protein protects neurons from oxidative and ischemic damage by reduction of reactive oxygen species and modulation of glutathione redox system
Authors: Kwon Hyun Jung , Hahn Kyu Ri , Kang Min Soo , Choi Jung Hoon , Moon Seung Myung , Yoon Yeo Sung , Hwang In Koo , Kim Dae Won
Published: April 2023

Malate dehydrogenase (MDH) plays an important role in the conversion of malate to oxaloacetate during the tricarboxylic acid cycle. In this study, we examined the role of cytoplasmic MDH (MDH1) in hydrogen peroxide (H2O2)-induced oxidative stress in HT22 cells and ischemia-induced neuronal damage in the gerbil hippocampus. The Tat-MDH1 fusion protein was constructed to enable the delivery of MDH1 into the intracellular space and penetration of the blood–brain barrier. Tat-MDH1, but not MDH1 control protein, showed significant cellular delivery in HT22 cells in a concentration- and time-dependent manner and gradual intracellular degradation in HT22 cells. Treatment with 4 μM Tat-MDH1 significantly ameliorated 200 μM H2O2-induced cell death, DNA fragmentation, and reactive oxygen species formation in HT22 cells. Transient increases in MDH1 immunoreactivity were detected in the hippocampal CA1 region 6–12 h after ischemia, but MDH1 activity significantly decreased 2 days after ischemia. Supplementation of Tat-MDH1 immediately after ischemia alleviated ischemia-induced hyperlocomotion and neuronal damage 1 and 4 days after ischemia. In addition, treatment with Tat-MDH1 significantly ameliorated the increases in hydroperoxides, lipid peroxidation, and reactive oxygen species 2 days after ischemia. Tat-MDH1 treatment maintained the redox status of the glutathione system in the hippocampus 2 days after ischemia. These results suggest that Tat-MDH1 exerts neuroprotective effects by reducing oxidative stress and maintaining glutathione redox system in the hippocampus.
The locatability of Pearson algorithm for multi-source location in complex networks
Authors: Wang Hong-Jue , Hu Zhao-Long , Tao Li , Shao Shuyu , Wang Shi-Zhe
Published: April 2023

We study locating propagation sources in complex networks. We proposed an multi-source location algorithm for different propagation dynamics by using sparse observations. Without knowing the propagation dynamics and any dynamic parameters, we can calculate node centrality based on the character that positive correlation between inform time of nodes and geodesic distance between nodes and sources. The algorithm is robust and have high location accuracy for any number of sources. We study locatability of the proposed source location algorithm and present a corresponding strategy to select observer nodes based on greedy algorithm. All simulations on both model and real-world networks proved the feasibility and validity of this algorithm.