bluuebunny/crossref_metadata_2025 huggingface dataset:
Elevated expression of TLR2 and its correlation with disease activity and clinical manifestations in adult-onset Still’s disease
Authors: Han Jae Ho , Ahn Mi-Hyun , Jung Ju-Yang , Kim Ji-Won , Suh Chang-Hee , Kwon Ji Eun , Yim Hyunee , Kim Hyoun-Ah
Published: June 2022

This study investigated the role of Toll-like receptor 1 (TLR1), TLR2, TLR4, TLR7, and TLR9 in patients with adult-onset Still’s disease (AOSD). This study included 20 patients with AOSD and 15 healthy controls (HCs). TLR expression in the peripheral blood was quantified using flow cytometry; TLR expression pattern, in the skin lesions and lymph nodes (LNs) of patients with AOSD, was evaluated immunohistochemically. Significantly higher mean intensities of cells presenting TLR2 and TLR7 from whole blood were observed in patients with AOSD than in HCs. TLR2 expression in whole cells correlated with systemic scores, levels of lactate dehydrogenase and ferritin and serum levels of interleukin-1β (IL-1β), IL-6, and IL-18. The percentage of TLR2-positive inflammatory cells was higher in skin biopsy samples from patients with AOSD than those in HCs. TLR9-expressing positive inflammatory cell counts were higher in skin lesions from patients with AOSD than those in the HC, eczema, and psoriasis groups. The expression levels of TLR1, TLR4, TLR7, and TLR9 were higher in LNs of patients with AOSD than in those with T cell lymphoma and reactive lymphadenopathy. Circulating TLR2- and TLR7-positive cells may contribute to the pathogenesis of AOSD. Furthermore, immunohistochemical staining for TLRs in skin lesions and LNs may aid in differentiating AOSD from similar conditions.
Support for mechanical advantage hypothesis of grasping cannot be explained only by task mechanics
Authors: Rajakumar Banuvathy , Dutta Swarnab , Varadhan S. K. M.
Published: June 2022

Successful object interaction during daily living involves maintaining the grasped object in static equilibrium by properly arranging the fingertip contact forces. According to the mechanical advantage hypothesis of grasping, during torque production tasks, fingers with longer moment arms would produce greater normal force than those with shorter moment arms. Previous studies have probed this hypothesis by investigating the force contributions of individual fingers through systematic variations (or perturbations) of the properties of the grasped handle. In the current study, we examined the validity of this hypothesis in a paradigm wherein the thumb tangential force was constrained to a minimal constant magnitude. This was achieved by placing the thumb on a freely movable slider platform. The total mass of the handle was systematically varied by adding external loads directly below the center of mass of the handle. Our findings suggest that the mechanical advantage hypothesis manifests only during the heaviest loading condition when a threshold difficulty is reached. We infer that the support for the mechanical advantage hypothesis depends not only on the physical parameters but also on the individual ability to manage the task.
Study on a risk model for prediction and avoidance of unmanned environmental hazard
Authors: Qiu Chengqun , Zhang Shuai , Ji Jie , Zhong Yuan , Zhang Hui , Zhao Shiqiang , Meng Mingyu
Published: June 2022

Comprehensive research is conducted on the design and control of the unmanned systems for electric vehicles. The environmental risk prediction and avoidance system is divided into the prediction part and the avoidance part. The prediction part is divided into environmental perception, environmental risk assessment, and risk prediction. In the avoidance part, according to the risk prediction results, a conservative driving strategy based on speed limit is adopted. Additionally, the core function is achieved through the target detection technology based on deep learning algorithm and the data conclusion based on deep learning method. Moreover, the location of bounding box is further optimized to improve the accuracy of SSD target detection method based on solving the problem of imbalanced sample categories. Software such as MATLAB and CarSim are applied in the system. Bleu-1 was 67.1, bleu-2 was 45.1, bleu-3 was 29.9 and bleu-4 was 21.1. Experiments were carried out on the database flickr30k by designing the algorithm. Bleu-1 was 72.3, bleu-2 was 51.8, bleu-3 was 37.1 and bleu-4 was 25.1. From the comparison results of the simulations of unmanned vehicles with or without a system, it can provide effective safety guarantee for unmanned driving.
Effects of paternal high-fat diet and maternal rearing environment on the gut microbiota and behavior
Authors: Korgan Austin C. , Foxx Christine L. , Hashmi Heraa , Sago Saydie A. , Stamper Christopher E. , Heinze Jared D. , O’Leary Elizabeth , King Jillian L. , Perrot Tara S. , Lowry Christopher A. , Weaver Ian C. G.
Published: June 2022

Exposing a male rat to an obesogenic high-fat diet (HFD) influences attractiveness to potential female mates, the subsequent interaction of female mates with infant offspring, and the development of stress-related behavioral and neural responses in offspring. To examine the stomach and fecal microbiome’s potential roles, fecal samples from 44 offspring and stomach samples from offspring and their fathers were collected and bacterial community composition was studied by 16 small subunit ribosomal RNA (16S rRNA) gene sequencing. Paternal diet (control, high-fat), maternal housing conditions (standard or semi-naturalistic housing), and maternal care (quality of nursing and other maternal behaviors) affected the within-subjects alpha-diversity of the offspring stomach and fecal microbiomes. We provide evidence from beta-diversity analyses that paternal diet and maternal behavior induced community-wide shifts to the adult offspring gut microbiome. Additionally, we show that paternal HFD significantly altered the adult offspring Firmicutes to Bacteroidetes ratio, an indicator of obesogenic potential in the gut microbiome. Additional machine-learning analyses indicated that microbial species driving these differences converged on Bifidobacterium pseudolongum. These results suggest that differences in early-life care induced by paternal diet and maternal care significantly influence the microbiota composition of offspring through the microbiota-gut-brain axis, having implications for adult stress reactivity.
Respiratory dysfunction in two rodent models of chronic epilepsy and acute seizures and its link with the brainstem serotonin system
Authors: Kouchi Hayet , Ogier Michaël , Dieuset Gabriel , Morales Anne , Georges Béatrice , Rouanet Jean-Louis , Martin Benoît , Ryvlin Philippe , Rheims Sylvain , Bezin Laurent
Published: June 2022

Patients with drug-resistant epilepsy can experience respiratory alterations, notably during seizures. The mechanisms underlying long-term alterations in respiratory function remain unclear. As the brainstem 5-HT system is a prominent modulator of respiratory function, this study aimed at determining whether epilepsy is associated with alterations in both the respiratory function and brainstem serotonin (5-HT) system in rats. Epilepsy was triggered by pilocarpine-induced status epilepticus in rats. Our results showed that 30–50% of epileptic (EPI) rats exhibited a sharp decrease in oxygen consumption (SDOC), low metabolic rate of oxygen, and slow regular ventilation (EPI/SDOC + rats). These alterations were detected only in rats with chronic epilepsy, independent of behavioral seizures, were persistent over time, and not associated with death. In these rats, 5-HT fiber density in the nucleus tractus solitarius was lower than that in the control and EPI/SDOC− rats. Both EPI/SDOC + rats and DBA/2 mice that present with audiogenic-induced seizure followed by fatal respiratory arrest—a model of sudden and expected death in epilepsy—had increased transcript levels of tryptophan hydroxylase 2 and 5-HT presynaptic transporter. Thus, our data support that 5-HT alterations are associated with chronic and acute epilepsy-related respiratory dysfunction.
Nanomechanical variability in the early evolution of vertebrate dentition
Authors: Shohel Mohammad , Ray Kamal K. , Tivanski Alexei V. , McAdams Neo E. B. , Bancroft Alyssa M. , Cramer Bradley D. , Forbes Tori Z.
Published: June 2022

Conodonts are an extinct group of primitive jawless vertebrates whose elements represent the earliest examples of a mineralized feeding apparatus in vertebrates. Their relative relationship within vertebrates remains unresolved. As teeth, conodont elements are not homologous with the dentition of vertebrates, but they exhibit similarities in mineralization, growth patterns, and function. They clearly represent an early evolutionary experiment in mineralized dentition and offer insight into analogous dentition in other groups. Unfortunately, analysis of functional performance has been limited to a handful of derived morphologies and material properties that may inform ecology and functional analysis are virtually unknown. Here we applied a nanoscale approach to evaluate material properties of conodont bioapatite by utilizing Atomic Force Microscopy (AFM) nanoindentation to determine Young’s modulus (E) along multiple elements representing different ontogenetic stages of development in the coniform-bearing apparatus of Dapsilodus obliquicostatus. We observed extreme and systematic variation in E along the length (oral to aboral) of each element that largely mirrors the spatial and ontogenetic variability in the crystalline structure of these specimens. Extreme spatial variability of E likely contributed to breakage of elements that were regularly repaired/regrown in conodonts but later vertebrate dentition strategies that lacked the ability to repair/regrow likely required the development of different material properties to avoid structural failure.
Revisiting sea-level budget by considering all potential impact factors for global mean sea-level change estimation
Authors: Wang Fengwei , Shen Yunzhong , Chen Qiujie , Geng Jianhua
Published: June 2022

Accurate estimates of global sea-level change from the observations of Altimetry, Argo and Gravity Recovery and Climate Experiment (GRACE) and GRACE Follow-on (GRACE-FO) are of great value for investigating the global sea-level budget. In this study, we analyzed the global sea-level change over the period from January 2005 to December 2019 by considering all potential impact factors, i.e. three factors for Altimetry observations (two Altimetry products, ocean bottom deformation (OBD) and glacial isostatic adjustment (GIA)), three factors for Argo observations (four Argo products, salinity product error and deep-ocean steric sea-level change), and seven factors for GRACE/GRACE-FO observations including three official RL06 solutions, five spatial filtering methods, three GIA models, two C20 (degree 2 order 0) products, Geocenter motion, GAD field and global mass conservation. The seven impact factors of GRACE/GRACE-FO observations lead to ninety combinations for the post-procession of global mean barystatic sea-level change estimation, whose rates range from 2.00 to 2.45 mm/year. The total uncertainty of global barystatic sea-level change rate is ± 0.27 mm/year at the 95% confidence level, estimated as the standard deviation of the differences between the different datasets constituting the ensembles. The statistical results show that the preferred GIA model developed by Caron et al. in 2018 can improve the closure of the global sea-level budget by 0.20–0.30 mm/year, which is comparable with that of neglecting the halosteric component. About 30.8% of total combinations (GRACE/GRACE-FO plus Argo) can close the global sea-level budget within 1-sigma (0.23 mm/year) of Altimetry observations, 88.9% within 2-sigma. Once the adopted factors including GRACE/GRACE-FO solutions from Center for Space Research (CSR), Caron18 GIA model, SWENSON filtering and Argo product from China Second Institute of Oceanography, the linear trend of global sterodynamic sea-level change derived from GRACE/GRACE-FO plus Argo observations is 3.85 ± 0.14 mm/year, nearly closed to 3.90 ± 0.23 mm/year of Altimetry observations.
Cretaceous Antodicranomyia (Diptera: Limoniidae) and their paleohabitat
Authors: Kania-Kłosok Iwona , Perrichot Vincent , Krzemiński Wiesław
Published: June 2022

New representatives of the Cretaceous cranefly genus Antodicranomyia (Diptera: Limoniidae) are reported from Albian-Cenomanian Charentese (French) amber. The newly reported specimens allow for an emended diagnosis of the type species A. azari, as well as the description of a new species, Antodicranomyia rubra sp. nov., which is mostly distinguished from the type species by features of its wing venation, antennae, and genitalia. As a rare, extinct genus known only from French amber, Antodicranomyia is compared with its closest relative genera Antocha, Dicranomyia and Antohelia. The evolutionary implications and paleohabitat of Antodicranomyia are discussed. The new discovery adds to the knowledge of the crane flies’ diversity and evolution in the mid-Cretaceous.
Synergistic interactions of repurposed drugs that inhibit Nsp1, a major virulence factor for COVID-19
Authors: Kao Hung-Teh , Orry Andrew , Palfreyman Michael G. , Porton Barbara
Published: June 2022

Nsp1 is one of the first proteins expressed from the SARS-CoV-2 genome and is a major virulence factor for COVID-19. A rapid multiplexed assay for detecting the action of Nsp1 was developed in cultured lung cells. The assay is based on the acute cytopathic effects induced by Nsp1. Virtual screening was used to stratify compounds that interact with two functional Nsp1 sites: the RNA-binding groove and C-terminal helix-loop-helix region. Experimental screening focused on compounds that could be readily repurposed to treat COVID-19. Multiple synergistic combinations of compounds that significantly inhibited Nsp1 action were identified. Among the most promising combinations are Ponatinib, Rilpivirine, and Montelukast, which together, reversed the toxic effects of Nsp1 to the same extent as null mutations in the Nsp1 gene.
Computation of vertical fluid mobility of CO$$_{2}$$, methane, hydrogen and hydrocarbons through sandstones and carbonates
Authors: Lodhia Bhavik Harish , Clark Stuart Raymond
Published: June 2022

Over the last decade, there has been an irreversible shift from hydrocarbon exploration towards carbon storage, low-carbon energy generation and hydrogen exploration. Whilst basin modelling techniques may be used to predict the migration of hydrocarbons through sedimentary basins on geological timescales, there remains little understanding of how fluids behave at the basin scale on present-day timescales. We apply the Darcy flow equation to present an algorithm to determine the basin-scale mobilities and maximum vertical velocity, $$v_{max}$$

v

max

, of CO$$_{2}$$

2

, methane, hydrogen and hydrocarbons with depth for sandstone and carbonate. $$v_{max}$$

v

max

for CO$$_{2}$$

2

and methane are on scales of m/year, whilst values for hydrocarbon fluids are an order of magnitude smaller than for other fluids. Our results indicate that the fluid mobility of subsurface CO$$_{2}$$

2

may be sensitive to surface and near-surface temperature variations. $$v_{max}$$

v

max

for hydrogen is approximately 2–10 times greater than hydrocarbon fluids, yielding important consequences for the future use of basin modelling software for determining hydrogen migration for exploration and storage.
Non-invasive vagus nerve stimulation in epilepsy patients enhances cooperative behavior in the prisoner’s dilemma task
Authors: Oehrn Carina R. , Molitor Lena , Krause Kristina , Niehaus Hauke , Schmidt Laura , Hakel Lukas , Timmermann Lars , Menzler Katja , Knake Susanne , Weber Immo
Published: June 2022

The vagus nerve constitutes a key link between the autonomic and the central nervous system. Previous studies provide evidence for the impact of vagal activity on distinct cognitive processes including functions related to social cognition. Recent studies in animals and humans show that vagus nerve stimulation is associated with enhanced reward-seeking and dopamine-release in the brain. Social interaction recruits similar brain circuits to reward processing. We hypothesize that vagus nerve stimulation (VNS) boosts rewarding aspects of social behavior and compare the impact of transcutaneous VNS (tVNS) and sham stimulation on social interaction in 19 epilepsy patients in a double-blind pseudo-randomized study with cross-over design. Using a well-established paradigm, i.e., the prisoner’s dilemma, we investigate effects of stimulation on cooperative behavior, as well as interactions of stimulation effects with patient characteristics. A repeated-measures ANOVA and a linear mixed-effects model provide converging evidence that tVNS boosts cooperation. Post-hoc correlations reveal that this effect varies as a function of neuroticism, a personality trait linked to the dopaminergic system. Behavioral modeling indicates that tVNS induces a behavioral starting bias towards cooperation, which is independent of the decision process. This study provides evidence for the causal influence of vagus nerve activity on social interaction.
Patient-specific brain arteries molded as a flexible phantom model using 3D printed water-soluble resin
Authors: Nilsson Daniel P. G. , Holmgren Madelene , Holmlund Petter , Wåhlin Anders , Eklund Anders , Dahlberg Tobias , Wiklund Krister , Andersson Magnus
Published: June 2022

Visualizing medical images from patients as physical 3D models (phantom models) have many roles in the medical field, from education to preclinical preparation and clinical research. However, current phantom models are generally generic, expensive, and time-consuming to fabricate. Thus, there is a need for a cost- and time-efficient pipeline from medical imaging to patient-specific phantom models. In this work, we present a method for creating complex 3D sacrificial molds using an off-the-shelf water-soluble resin and a low-cost desktop 3D printer. This enables us to recreate parts of the cerebral arterial tree as a full-scale phantom model ($$10\times 6\times 4$$

10
×
6
×
4

 cm) in transparent silicone rubber (polydimethylsiloxane, PDMS) from computed tomography angiography images (CTA). We analyzed the model with magnetic resonance imaging (MRI) and compared it with the patient data. The results show good agreement and smooth surfaces for the arteries. We also evaluate our method by looking at its capability to reproduce 1 mm channels and sharp corners. We found that round shapes are well reproduced, whereas sharp features show some divergence. Our method can fabricate a patient-specific phantom model with less than 2 h of total labor time and at a low fabrication cost.
Analysis of hepatic fibrosis markers in the serum of chronic hepatitis B patients according to basal core promoter/precore mutants
Authors: Lefeuvre Caroline , Roux Marine , Blanchard Simon , Le Guillou-Guillemette Hélène , Boursier Jérôme , Lunel-Fabiani Françoise , Jeannin Pascale , Pivert Adeline , Ducancelle Alexandra
Published: June 2022

The A1762T/G1764A double mutant in the basal core promoter (BCP) region of the hepatitis B virus (HBV) is associated with severe hepatic lesions while the G1899A mutation with the double mutant is associated with a significant reduction in the risk of severe fibrosis. This study aims to measure a number of markers in the serum of patients with chronic HBV infection and to assess relationships between these markers and BCP/precore mutants with consideration of the stage of fibrosis. The serum levels of resistin, TGF-β1, MMP-1, TIMP-1, collagen IA1 and PDGF-BB, which are markers that are known to be involved in the process of hepatic fibrosis, were assayed. The serum levels of PDGF-BB and TIMP-1, and the mutation profile were independently associated with advanced fibrosis. A higher level of TIMP-1 was associated with advanced fibrosis regardless of the mutation status, and a higher level of PDGF-BB was associated with nonsevere fibrosis in patients infected with viruses harboring the A1762T/G1764A or A1762T/G1764A/G1899A mutations. Our results suggest an impact of the A1762T/G1764A mutant on the biological pathway related to TGF-β1 and PDGF-BB. In vitro studies are needed to understand the impact of these mutants on the serum secretion of markers involved in fibrosis severity.
Identifying long-range synaptic inputs using genetically encoded labels and volume electron microscopy
Authors: Ayuso-Jimeno Irene P. , Ronchi Paolo , Wang Tianzi , Gallori Catherine E. , Gross Cornelius T.
Published: June 2022

Enzymes that facilitate the local deposition of electron dense reaction products have been widely used as labels in electron microscopy (EM) for the identification of synaptic contacts in neural tissue. Peroxidases, in particular, can efficiently metabolize 3,3′-diaminobenzidine tetrahydrochloride hydrate (DAB) to produce precipitates with high contrast under EM following heavy metal staining, and can be genetically encoded to facilitate the labeling of specific cell-types or organelles. Nevertheless, the peroxidase/DAB method has so far not been reported to work in a multiplexed manner in combination with 3D volume EM techniques (e.g. Serial blockface electron microscopy, SBEM; Focused ion beam electron microscopy, FIBSEM) that are favored for the large-scale ultrastructural assessment of synaptic architecture However, a recently described peroxidase with enhanced enzymatic activity (dAPEX2) can efficienty deposit EM-visible DAB products in thick tissue without detergent treatment opening the possibility for the multiplex labeling of genetically defined cell-types in combination with volume EM methods. Here we demonstrate that multiplexed dAPEX2/DAB tagging is compatible with both FIBSEM and SBEM volume EM approaches and use them to map long-range genetically identified synaptic inputs from the anterior cingulate cortex to the periaqueductal gray in the mouse brain.
Genome-wide analysis of the C2H2 zinc finger protein gene family and its response to salt stress in ginseng, Panax ginseng Meyer
Authors: Jiang Yue , Liu Lingyu , Pan Zhaoxi , Zhao Mingzhu , Zhu Lei , Han Yilai , Li Li , Wang Yanfang , Wang Kangyu , Liu Sizhang , Wang Yi , Zhang Meiping
Published: June 2022

The C2H2 zinc finger protein (C2H2-ZFP) gene family plays important roles in response to environmental stresses and several other biological processes in plants. Ginseng is a precious medicinal herb cultivated in Asia and North America. However, little is known about the C2H2-ZFP gene family and its functions in ginseng. Here, we identified 115 C2H2-ZFP genes from ginseng, defined as the PgZFP gene family. It was clustered into five groups and featured with eight conserved motifs, with each gene containing one to six of them. The family genes are categorized into 17 gene ontology subcategories and have numerous regulatory elements responsive to a variety of biological process, suggesting their functional differentiation. The 115 PgZFP genes were spliced into 228 transcripts at seed setting stage and varied dramatically in expression across tissues, developmental stages, and genotypes, but they form a co-expression network, suggesting their functional correlation. Furthermore, four genes, PgZFP31, PgZFP78-01, PgZFP38, and PgZFP39-01, were identified from the gene family that were actively involved in plant response to salt stress. These results provide new knowledge on origin, differentiation, evolution, and function of the PgZFP gene family and new gene resources for C2H2-ZFP gene research and application in ginseng and other plant species.
Depolarization time and extracellular glutamate levels aggravate ultraearly brain injury after subarachnoid hemorrhage
Authors: Murai Satoshi , Hishikawa Tomohito , Takeda Yoshimasa , Okura Yasuko , Fushimi Miki , Kawase Hirokazu , Takahashi Yu , Kidani Naoya , Haruma Jun , Hiramatsu Masafumi , Sugiu Kenji , Morimatsu Hiroshi , Date Isao
Published: June 2022

Early brain injury after aneurysmal subarachnoid hemorrhage (SAH) worsens the neurological outcome. We hypothesize that a longer duration of depolarization and excessive release of glutamate aggravate neurological outcomes after SAH, and that brain hypothermia can accelerate repolarization and inhibit the excessive release of extracellular glutamate and subsequent neuronal damage. So, we investigated the influence of depolarization time and extracellular glutamate levels on the neurological outcome in the ultra-early phase of SAH using a rat injection model as Experiment 1 and then evaluated the efficacy of brain hypothermia targeting ultra-early brain injury as Experiment 2. Dynamic changes in membrane potentials, intracranial pressure, cerebral perfusion pressure, cerebral blood flow, and extracellular glutamate levels were observed within 30 min after SAH. A prolonged duration of depolarization correlated with peak extracellular glutamate levels, and these two factors worsened the neuronal injury. Under brain hypothermia using pharyngeal cooling after SAH, cerebral perfusion pressure in the hypothermia group recovered earlier than that in the normothermia group. Extracellular glutamate levels in the hypothermia group were significantly lower than those in the normothermia group. The early induction of brain hypothermia could facilitate faster recovery of cerebral perfusion pressure, repolarization, and the inhibition of excessive glutamate release, which would prevent ultra-early brain injury following SAH.
Predictive value of neutrophil-to-lymphocyte ratio for distant metastasis in gastric cancer patients
Authors: Zhang Xin , Wang Xuan , Li Wenxing , Sun Tuanhe , Diao Dongmei , Dang Chengxue
Published: June 2022

As a systemic inflammatory marker, the significance of NLR in predicting tumor prognosis and early lymph node metastasis is well known, including gastric cancer (GC). However, whether NLR can reflect GC metastasis status remains to be explored. We retrospectively enrolled 1667 GC patients treated in our hospital from December 2010 to December 2018. Patients were grouped according to the presence or absence of metastases. Receiver operating characteristics (ROC) curve analysis was used to evaluate the diagnostic efficacy of markers in assessing GC metastasis. Then we conducted a joint ROC curve analysis. The effects of clinicopathological parameters on GC metastasis were assessed using multiple logistic regression analysis. 743 (44.6%) patients were diagnosed with metastatic GC. Patients with GC metastases have younger age, higher CEA, CA19-9, CA72-4 and NLR. Based on the comparison of AUC, NLR has diagnostic efficacy comparable to that of GC markers. The AUC of NLR combined with GC markers had significantly higher predicting efficacy than that without combination for assessing peritoneal metastasis (P = 0.013), osseous metastasis (P = 0.017) and hepatic metastasis (P < 0.001). In multiple logistic regression analysis, age, NLR, CEA, CA19-9 and CA72-4 were found to be independently associated with GC metastasis (all P < 0.05). NLR was a risk factor of GC metastasis. Combining CEA, CA19-9, CA72-4 and NLR could better predict metastases in GC.
Thermally-induced drift of A-site cations at solid–solid interface in physically paired lead halide perovskites
Authors: Cuzzupè Daniele T. , Ünlü Feray , Lê Khan , Bernhardt Robin , Wilhelm Michael , Grosch Matthias , Weißing Rene , Fischer Thomas , van Loosdrecht Paul H. M. , Mathur Sanjay
Published: June 2022

The promise of hybrid organic–inorganic halide perovskite solar cells rests on their exceptional power conversion efficiency routinely exceeding 25% in laboratory scale devices. While the migration of halide ions in perovskite thin films has been extensively investigated, the understanding of cation diffusion remains elusive. In this study, a thermal migration of A‑site cations at the solid–solid interface, formed by two physically paired MAPbI3 and FAPbI3 perovskite thin films casted on FTO, is demonstrated through continuous annealing at comparably low temperature (100 °C). Diffusion of methylammonium (CH3NH3+, MA+) cations into the low‑symmetry yellow δ‑FAPbI3 phase triggers a transition from the yellow (δ) to black (α) phase evident in the distinctive color change and verified by shifts in absorption bands and X‑ray diffraction patterns. Intermixing of the A‑site cations MA+ and FA+ (CH(NH2)2+) occurred for both systems, α‑MAPbI3/δ‑FAPbI3 and α‑MAPbI3/α‑FAPbI3. The structural and compositional changes in both cases support a thermally activated ion drift unambiguously demonstrated through changes in the absorption and X-ray photoelectron spectra. Moreover, the physical contact annealing (PCA) leads to healing of defects and pinholes in α‑MAPbI3 thin films, which was correlated to longer recombination lifetimes in mixed MAxFA1−xPbI3 thin films obtained after PCA and probed by ultrafast transient absorption spectroscopy.
Chronic kidney disease is a key predictive factor for potential myocardial ischaemia and poor prognosis in asymptomatic patients with diabetes mellitus
Authors: Honda Yuki , Wakabayashi Kohei , Sato Chisato , Ikeda Naoko , Sato Ken , Suzuki Toshiaki , Shibata Keita , Shinke Toshiro
Published: June 2022

Some asymptomatic patients with diabetes mellitus (DM) have critical coronary artery disease (CAD), although the guidelines do not recommend aggressive screening for CAD in asymptomatic patients. Chronic kidney disease (CKD) is among the serious co-morbidities of severe systemic atherosclerosis. Thus, CKD may be associated with potential myocardial ischaemia. Therefore, the present study aimed to determine the impact of CKD on the incidence of silent myocardial ischaemia (SMI) and the long-term outcomes in asymptomatic patients with DM. This study investigated 461 consecutive patients with DM. All patients who were asymptomatic and self-sufficient in daily life underwent the ergometer exercise (ERG) test. Coronary angiography was performed if the stress test was positive, or if the patient did not achieve 90% of the target heart rate. The primary end point included major adverse cardiac and cerebrovascular events (MACCE) including death, non-fatal myocardial infarction and stroke. The median follow-up duration after study enrolment was 35 months for the entire cohort of 461 patients. Eighty-one patients were diagnosed with SMI. The estimated glomerular filtration rate was significantly lower in the SMI group (70.5 ± 23.8 vs. 81.8 ± 30.0 mL/min/1.73 m2, P < 0.001). SMI occurred more frequently in patients with advanced CKD [27/103, (26.2%) in stages 3–5], whereas only 5/68 (7.3%) patients without CKD, 13/81 (16.0%) patients with stage 1 CKD and 36/209, (17.2%) in stage 2, had SMI. The Kaplan–Meier curves revealed that, patients with SMI had poor clinical outcomes (log-rank: P = 0.016). The incidence of MACCE (log-rank: P = 0.009) was higher in patients with severe CKD > stage 3a in the SMI subgroup. Urinary albumin (mg/gCr) was associated with MACCE in the SMI subgroup [HR 3.37, 95%CI (1.170–9.521), P = 0.025] after adjusting for age, sex, and conventional risk factors. SMI was more prevalent in patients with CKD and the incidence was proportional to the CKD stage in asymptomatic patients with DM. Those Patients with CKD and SMI exhibited poor clinical outcomes. CKD may be a key factor for the identification and management of SMI in asymptomatic patients with DM in routine clinical practice.

Trial Registration: UMIN000038340.
Predicting mortality in critically ill patients requiring renal replacement therapy for acute kidney injury in a retrospective single-center study of two cohorts
Authors: Järvisalo Mikko J. , Kartiosuo Noora , Hellman Tapio , Uusalo Panu
Published: June 2022

Half of the critically ill patients with renal replacement therapy (RRT) dependent acute kidney injury (AKI) die within one year despite RRT. General intensive care prediction models perform inadequately in AKI. Predictive models for mortality would be an invaluable complementary tool to aid clinical decision making. We aimed to develop and validate new prediction models for intensive care unit (ICU) and hospital mortality customized for patients with RRT dependent AKI in a retrospective single-center study. The models were first developed in a cohort of 471 critically ill patients with continuous RRT (CRRT) and then validated in a cohort of 193 critically ill patients with intermittent hemodialysis (IHD) as the primary modality for RRT. Forty-two risk factors for mortality were examined at ICU admission and CRRT initiation, respectively, in the first univariate models followed by multivariable model development. Receiver operating characteristics curve analyses were conducted to estimate the area under the curve (AUC), to measure discriminative capacity of the models for mortality. AUCs of the respective models ranged between 0.76 and 0.83 in the CRRT model development cohort, thereby showing acceptable to excellent predictive power for the mortality events (ICU mortality and hospital mortality). The models showed acceptable external validity in a validation cohort of IHD patients. In the IHD validation cohort the AUCs of the MALEDICT RRT initiation model were 0.74 and 0.77 for ICU and hospital mortality, respectively. The MALEDICT model shows promise for mortality prediction in critically ill patients with RRT dependent AKI. After further validation, the model might serve as an additional clinical tool for estimating individual mortality risk at the time of RRT initiation.
Effect of adhesive coating on calcium, phosphate, and fluoride release from experimental and commercial remineralizing dental restorative materials
Authors: Par Matej , Gubler Andrea , Attin Thomas , Tarle Zrinka , Tarle Andro , Prskalo Katica , Tauböck Tobias T.
Published: June 2022

This study investigated the potential of adhesive coating for hindering the reactivity of ion-releasing dental restorative materials. Experimental composites were prepared by replacing 10 or 20 wt% of reinforcing fillers with two types of bioactive glass. A glass ionomer, a giomer, and an alkasite were used as representatives of commercial ion-releasing materials. Restorative material specimens were coated with an etch-and-rinse adhesive, 1-step self-etch adhesive, 2-step self-etch adhesive, or left uncoated. The specimens were immersed in a lactic acid solution and ion concentrations were measured in 4 days intervals for 32 days (atomic absorption spectrometry for calcium, UV–Vis spectrometry for phosphate, ion-selective electrode for fluoride, and pH-meter for pH values). The adhesive coating reduced ion release between 0.3 and 307 times, in a significantly material- and adhesive-dependent manner. Fluoride release was most highly impaired, with the reduction of up to 307 times, followed by phosphate and calcium release, which were reduced up to 90 and 45 times, respectively. The effect of different adhesive systems was most pronounced for phosphate release, with the following rankings: uncoated ≥ 2-step self-etch adhesive ≥ 1-step self-etch adhesive ≥ etch-and-rinse adhesive. The differences among adhesives were less pronounced for calcium and fluoride. It was concluded that the resinous adhesive layer can act as a barrier for ion release and diminish the beneficial effects of remineralizing restorative materials.
An antibacterial compound pyrimidomycin produced by Streptomyces sp. PSAA01 isolated from soil of Eastern Himalayan foothill
Authors: Das Prasenjit , Kundu Shampa , Maiti Pulak Kumar , Mandal Saurodeep , Sahoo Prithidipa , Mandal Sukhendu
Published: June 2022

Selective isolation of soil Actinobacteria was undertaken to isolate a new class of antibiotics and bioactive molecules. A Streptomyces sp. PSAA01 (= MTCC 13,157), isolated from soil of Eastern Himalaya foothill was cultivated on a large scale for the production of the antimicrobial SM02. It has been found that the maximum amount of SM02 produced while PSAA01 was grown in ISP-2 medium (pH 7.0) for 7 days at 30 °C in shaking (180 rpm) condition. A significant zone of inhibition against Staphylococcus aureus MTCC 96 has been found with the crude cell-free culture media (50 µL) of 7 days grown PSAA01. After the purification and chemical structural characterization, we found that SM02 is a new antimicrobial having 746 dalton molecular weight. The compound SM02 contains pyrimidine moiety in it and is produced by a species of Streptomyces and thus we have named this antibiotic pyrimidomycin. The antimicrobial spectrum of pyrimidomycin has been found to be restricted in Gram-positive organisms with a MIC of 12 µg/mL. SM02 was found active against Mycobacterium sp. and also multi-drug resistant Gram-positive bacteria with similar potency and found to disrupt the bacterial cell wall. Pyrimidomycin also showed significant impairment in the biofilm formation by S. aureus. Furthermore, pyrimidomycin showed synergy with the most used antibiotic like ampicillin, vancomycin and chloramphenicol. Pyrimidomycin did not have cytotoxicity towards human cell lines indicating its limited activity within bacteria.
Astodrimer sodium antiviral nasal spray for reducing respiratory infections is safe and well tolerated in a randomized controlled trial
Authors: Castellarnau Alex , Heery Graham P. , Seta Aynaz , Luscombe Carolyn A. , Kinghorn George R. , Button Peter , McCloud Philip , Paull Jeremy R. A.
Published: June 2022

Astodrimer sodium is a dendrimer molecule with antiviral and virucidal activity against SARS-CoV-2 and other respiratory viruses in vitro, and has previously been shown to be safe and well tolerated, and not systemically absorbed, when applied to the vaginal mucosa. To investigate its potential utility as a topical antiviral, astodrimer sodium has been reformulated for application to the nasal mucosa to help reduce viral load before or after exposure to respiratory infection. The current investigation assessed the safety, tolerability and absorption of astodrimer sodium 1% antiviral nasal spray. This was a single-centre, double-blinded, randomized, placebo-controlled, exploratory clinical investigation. Forty healthy volunteers aged 18 to 65 years with no clinically significant nasal cavity examination findings were randomized 3:1 to astodrimer sodium nasal spray (N = 30) or placebo (N = 10) at an Australian clinical trials facility. An initial cohort of participants (N = 12 astodrimer, N = 4 placebo) received a single application (one spray per nostril) to assess any acute effects, followed by a washout period, before self-administering the spray four times daily for 14 days to represent an intensive application schedule. Extent of absorption of astodrimer sodium via the nasal mucosa was also assessed in this cohort. A second cohort of participants (N = 18 astodrimer, N = 6 placebo) self-administered the spray four times daily for 14 days. The primary endpoint was safety, measured by frequency and severity of treatment emergent adverse events (TEAEs), including clinically significant nasal cavity examination findings, in the safety population (all participants randomized who administered any spray). Participants were randomized between 6 January 2021 and 29 March 2021. TEAEs occurred in 8/10 (80%) participants in the placebo arm and 19/30 (63.3%) participants in the astodrimer sodium arm; all were of mild intensity. TEAEs considered potentially related to study product occurred in 5/10 (50%) participants receiving placebo and 10/30 (33.3%) of participants receiving astodrimer sodium. No participants experienced serious AEs, or TEAEs leading to withdrawal from the study. No systemic absorption of astodrimer sodium via the nasal mucosa was detected. Astodrimer sodium nasal spray was well tolerated and is a promising innovation warranting further investigation for nasal administration to potentially reduce infection and spread of community acquired respiratory virus infections.

Trial Registration: ACTRN12620001371987, first registered 22-12-2020 (Australia New Zealand Clinical Trials Registry, https://anzctr.org.au/).
Progressive aortic stiffness in aging C57Bl/6 mice displays altered contractile behaviour and extracellular matrix changes
Authors: De Moudt Sofie , Hendrickx Jhana O. , Neutel Cédric , De Munck Dorien , Leloup Arthur , De Meyer Guido R. Y. , Martinet Wim , Fransen Paul
Published: June 2022

Aortic stiffness is a hallmark of cardiovascular disease, but its pathophysiology remains incompletely understood. This study presents an in-dept characterization of aortic aging in male C57Bl/6 mice (2–24 months). Cardiovascular measurements include echocardiography, blood pressure measurement, and ex vivo organ chamber experiments. In vivo and ex vivo aortic stiffness increases with age, and precede the development of cardiac hypertrophy and peripheral blood pressure alterations. Contraction-independent stiffening (due to extracellular matrix changes) is pressure-dependent. Contraction-dependent aortic stiffening develops through heightened α1-adrenergic contractility, aberrant voltage-gated calcium channel function, and altered vascular smooth muscle cell calcium handling. Endothelial dysfunction is limited to a modest decrease in sensitivity to acetylcholine-induced relaxation with age. Our findings demonstrate that progressive arterial stiffening in C57Bl/6 mice precedes associated cardiovascular disease. Aortic aging is due to changes in extracellular matrix and vascular smooth muscle cell signalling, and not to altered endothelial function.
Underload city conceptual approach extending ghost city studies
Authors: Zhang Xiuyuan , Du Shihong , Taubenböck Hannes , Wang Yi-Chen , Du Shouhang , Liu Bo , Feng Yuning
Published: June 2022

Global population growth and land development are highly imbalanced, marked by 43% of population increase but 150% of built-up area expansion from 1990 to 2018. This results in the widely concerned ghost city phenomenon and runs against the sustainable development goals. Existing studies identify ghost cities by population densities, but ignore the spatial heterogeneity of land carrying capacities (LCC). Accordingly, this study proposes a general concept termed underload city to define cities carrying fewer people and lower economic strength than their LCC. The underload city essentially describes imbalanced human-land relationship and is understood in a broader context than the usually applied ghost city. In this study, very high-resolution satellite images are analyzed to obtain land functional structures, and further combined with population and GDP data to derive LCC. We empirically identify eight underload cities among 81 major Chinese cities, differing from previous findings of ghost cities. Accordingly, the proposed underload city considers heterogeneous human-land relationships when assessing city loads and contributes to sustainable city developments.
An emission pathway classification reflecting the Paris Agreement climate objectives
Authors: Schleussner Carl-Friedrich , Ganti Gaurav , Rogelj Joeri , Gidden Matthew J.
Published: June 2022

The 2015 Paris Agreement sets the objectives of global climate ambition as expressed in its long-term temperature goal and mitigation goal. The scientific community has explored the characteristics of greenhouse gas emission reduction pathways in line with the Paris Agreement. However, when categorizing such pathways, the focus has been put on the temperature outcome and not on emission reduction objectives. Here we propose a pathway classification that aims to comprehensively reflect the climate criteria set out in the Paris Agreement. We show how such an approach allows for a fully consistent interpretation of the Agreement. For Paris Agreement compatible pathways, we report net zero CO2 and greenhouse gas emissions around 2050 and 2065, respectively. We illustrate how pathway design criteria not rooted in the Paris Agreement, such as the 2100 temperature level, result in scenario outcomes wherein about 6 - 24% higher deployment (interquartile range) of carbon dioxide removal is observed.
Nanotechnology for the Remediation of Plastic Wastes
Authors: Zheng Y. , Mao C. , Zhang Z. , Liu R. , Yan B.
Published: June 2022

Plastic wastes have been a global concern for several decades. Especially in recent years, microplastics and nanoplastics degraded from large plastic wastes are becoming emerging persistent pollutants worldwide, posing a serious threat to the environment and humans. To address the increasing environmental issues from plastic wastes and ensure sustainable development, biodegradable plastics have offered an effective solution to global plastic pollution due to their potential biodegradability and harmlessness. Moreover, benefiting from the remarkable development of nanotechnology, various nanomaterials with excellent physicochemical properties have significantly improved the performance of polymers. It also provides a promising way for remediation of plastic wastes. In this chapter, we summarize recent advances in the development of smart biodegradable plastics and progress in nanotechnologies for the degradation, conversion, and recycling of plastic wastes.
Proteolysis-targeting chimera (PROTAC) delivery system: advancing protein degraders towards clinical translation
Authors: Chen Yu , Tandon Ira , Heelan William , Wang Yixin , Tang Weiping , Hu Quanyin
Published: June 2022

This tutorial review discusses the convergence of drug delivery systems and PROTACs, surveys the burgeoning PROTAC delivery strategies, summarizes their design principles, clarifies their challenges, and outlooks future translational opportunities.
The Art in Science of MicroTAS 2020
Authors: Cooksey Gregory A.
Published: June 2022

Gregory A. Cooksey introduces this year's Art in Science award, presented at MicroTAS 2020.
A simple cost-effective paper-based electrochemical device for detection of adulterated sibutramine in slimming products
Authors: Sirivibulkovit Kitima , Wilairat Prapin , Nacapricha Duangjai , Wichit Sineewanlaya , Saetear Phoonthawee
Published: June 2022

The first report of a paper-based electrochemical device (ePAD) for detection and quantification of sibutramine adulteration. Non-surface modification on the ePAD is not required. Direct analysis of solid samples on ePAD shows tolerance to turbidity.
Stimuli-responsive assembly of bilingual peptide nucleic acids
Authors: Argueta-Gonzalez Hector S. , Swenson Colin S. , Song George , Heemstra Jennifer M.
Published: June 2022

“Bilingual” biopolymers comprised of γ-modified peptide nucleic acids can harness peptide and nucleic acid codes to direct assembly and recognition. Herein, we demonstrate stimuli-responsive assembly through a toehold-mediated displacement motif.
Novel cinnamic acid analogues: synthesis of aminotroponyl acrylates by Pd(ii)-catalysed C(sp2)–H olefination
Authors: Jena Chinmay K. , Sharma Nagendra K.
Published: June 2022

Cinnamic acid, a benzenoid scaffold, is a building block of various natural products.
Nickel-catalyzed 1,4-aryl rearrangement of aryl N-benzylimidates via C–O and C–H bond cleavage
Authors: Ogawa Satoshi , Tobisu Mamoru
Published: June 2022

We report herein that nickel-catalyzed reaction of aryl imidates bearing an N-benzyl group results in 1,4-migration of an O-aryl group via the cleavage of C–O and C–H bonds.
Total synthesis of pseudouridimycin and its epimer via Ugi-type multicomponent reaction
Authors: Okawa Ryotaro , Aldrich Courtney C. , Ichikawa Satoshi
Published: June 2022

A total synthesis of pseudouridimycin was accomplished featuring an unusual oxime Ugi-type multicomponent condensation to simultaneously construct the dipeptide moiety of this peptidyl nucleoside antibiotic.
Co-substitution in a Prussian blue analog with a hollow heterostructure for ultrahigh capacity and rate capability aqueous Zn2+ batteries
Authors: Su Zhihao , Huang Jionghao , Wang Runhao , Zhang Yufei , Liu Zili , Fan Haosen
Published: June 2022

Nickel and manganese co-substitution in a hollow Prussian blue nanocubes has been successfully carried out via utilizing a high-concentration polymer template, with an ultrahigh capacity of 138.4 mA h g−1 at 0.05 A g−1 in an aqueous zinc-ion battery.
Electro-elastic properties of a piezoelectric Te2O(PO4)2crystal
Authors: Dong Weimin , Liu Fuan , Sun Yingjie , Wang Biao , Zhu Mengqi , Li Jing , Xu Xinguang , Wang Jiyang
Published: June 2022

The introduction of distorted [TeO5] groups into phosphates is beneficial to improve the piezoelectric properties of phosphate crystals.