bluuebunny/crossref_metadata_2025 huggingface dataset:
Functionally distinct POMC-expressing neuron subpopulations in hypothalamus revealed by intersectional targeting
Authors: Biglari Nasim , Gaziano Isabella , Schumacher Jonas , Radermacher Jan , Paeger Lars , Klemm Paul , Chen Weiyi , Corneliussen Svenja , Wunderlich Claudia M. , Sue Michael , Vollmar Stefan , Klöckener Tim , Sotelo-Hitschfeld Tamara , Abbasloo Amin , Edenhofer Frank , Reimann Frank , Gribble Fiona M. , Fenselau Henning , Kloppenburg Peter , Wunderlich Frank T. , Brüning Jens C.
Published: May 2021

Pro-opiomelanocortin (POMC)-expressing neurons in the arcuate nucleus of the hypothalamus represent key regulators of metabolic homeostasis. Electrophysiological and single-cell sequencing experiments have revealed a remarkable degree of heterogeneity of these neurons. However, the exact molecular basis and functional consequences of this heterogeneity have not yet been addressed. Here, we have developed new mouse models in which intersectional Cre/Dre-dependent recombination allowed for successful labeling, translational profiling and functional characterization of distinct POMC neurons expressing the leptin receptor (Lepr) and glucagon like peptide 1 receptor (Glp1r). Our experiments reveal that POMCLepr+ and POMCGlp1r+ neurons represent largely nonoverlapping subpopulations with distinct basic electrophysiological properties. They exhibit a specific anatomical distribution within the arcuate nucleus and differentially express receptors for energy-state communicating hormones and neurotransmitters. Finally, we identify a differential ability of these subpopulations to suppress feeding. Collectively, we reveal a notably distinct functional microarchitecture of critical metabolism-regulatory neurons.
A network meta-analysis on the effectiveness and safety of acupuncture in treating patients with major depressive disorder
Authors: Zhichao Hu , Ching Lam Wai , Huijuan Li , Liang Yao , Zhiyu Wang , Weiyang Huang , Zhaoxiang Bian , Linda Zhong L. D.
Published: May 2021

Acupuncture is an important alternative therapy in treating major depressive disorder (MDD), but its efficacy and safety are still not well assessed. This study is the first network meta-analysis exploring the effectiveness and safety of acupuncture, common pharmacological treatments or other non-medication therapies for MDD. Eight databases including PubMed, Embase, Allied and Complementary Medicine Database, Cochrane Library, Wan Fang Data, China National Knowledge Infrastructure, China Biology Medicine disc, and Chongqing VIP Database were searched up to Jan 17, 2021. Articles were screened and selected by two reviewers independently. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the certainty of the evidence. A total of 71 eligible studies were included. The network analysis results indicated that the combined interventions of electro-acupuncture (EA) with selective serotonin reuptake inhibitors (SSRIs) and manual acupuncture (MA) with SSRIs were more effective in improving depression symptoms compared with acupuncture alone, pharmacological interventions alone, or other inactive groups. Among all the regimens, EA with SSRIs was found to have the highest effect in improving depression symptoms of MDD. In addition, there were slight differences in the estimations of the various treatment durations. The combination of acupuncture and serotonin-norepinephrine reuptake inhibitors (SNRIs) was found to be more effective than SNRIs alone. In conclusion, acupuncture and its combinations could be safe and effective interventions for MDD patients. EA with SSRIs seems to be the most effective intervention among the assessed interventions. Well-designed and large-scale studies with long-term follow-up should be conducted in the future.
Deciphering the laws of social network-transcendent COVID-19 misinformation dynamics and implications for combating misinformation phenomena
Authors: Cheng Mingxi , Yin Chenzhong , Nazarian Shahin , Bogdan Paul
Published: May 2021

The global rise of COVID-19 health risk has triggered the related misinformation infodemic. We present the first analysis of COVID-19 misinformation networks and determine few of its implications. Firstly, we analyze the spread trends of COVID-19 misinformation and discover that the COVID-19 misinformation statistics are well fitted by a log-normal distribution. Secondly, we form misinformation networks by taking individual misinformation as a node and similarity between misinformation nodes as links, and we decipher the laws of COVID-19 misinformation network evolution: (1) We discover that misinformation evolves to optimize the network information transfer over time with the sacrifice of robustness. (2) We demonstrate the co-existence of fit get richer and rich get richer phenomena in misinformation networks. (3) We show that a misinformation network evolution with node deletion mechanism captures well the public attention shift on social media. Lastly, we present a network science inspired deep learning framework to accurately predict which Twitter posts are likely to become central nodes (i.e., high centrality) in a misinformation network from only one sentence without the need to know the whole network topology. With the network analysis and the central node prediction, we propose that if we correctly suppress certain central nodes in the misinformation network, the information transfer of network would be severely impacted.
Dietary source of polyunsaturated fatty acids influences cell cytotoxicity in broiler chickens
Authors: Al-Khalaifah Hanan , Al-Nasser Afaf
Published: May 2021

The current study aims to investigate the effects of dietary source of n-3 polyunsaturated fatty acids (PUFA) on immune response in broiler chickens, represented by cytotoxic cell activity. A total of 255 one-day-old male Cobb 500 broiler chickens were fed on fish oil (FO)-, flaxseed oil-enriched diets at 50 and 19 g/kg, respectively, in addition to the soybean-based control diet. At slaughter, samples of blood and spleen were harvested from 20 birds/treatment (n = 20). The immune tissues' fatty acid profile was analyzed by gas chromatography, and the cytotoxic cell activity was investigated. The results showed that supplementing broiler chickens with diets rich in n-3 PUFA had a substantial effect on the broiler immune tissues' fatty acid profile. Cytotoxic cell activity was significantly higher in splenocytes and peripheral blood mononuclear cells (PBMCs) from broilers fed flaxseed oil than those provided FO and the soybean control diet. These results suggest that flaxseed oil may be used to enrich chickens with n-3 PUFA and improve the immune status of chicken flocks to resist diseases.
Dosimetry with gafchromic films based on a new micro-opto-electro-mechanical system
Authors: Guardiola C. , Márquez A. , Jiménez-Ramos M. C. , López J. García , Baratto-Roldán A. , Muñoz-Berbel X.
Published: May 2021

This work presents the first tests performed with radiochromic films and a new Micro‒Opto‒Electro-Mechanical system (MOEMS) for in situ dosimetry evaluation in radiotherapy in real time. We present a new device and methodology that overcomes the traditional limitation of time-delay in radiochromic film analysis by turning a passive detector into an active sensor. The proposed system consists mainly of an optical sensor based on light emitting diodes and photodetectors controlled by both customized electronic circuit and graphical user interface, which enables optical measurements directly. We show the first trials performed in a low‒energy proton cyclotron with this MOEMS by using gafchromic EBT3 films. Results show the feasibility of using this system for in situ dose evaluations. Further adaptation is ongoing to develop a full real‒time active detector by integrating MOEM multi‒arrays and films in flexible printed circuits. Hence, we point to improve the clinical application of radiochromic films with the aim to optimize radiotherapy treatment verifications.
LIPG endothelial lipase and breast cancer risk by subtypes
Authors: Gago-Dominguez Manuela , Redondo Carmen M. , Calaza Manuel , Matabuena Marcos , Bermudez Maria A. , Perez-Fernandez Roman , Torres-Español María , Carracedo Ángel , Castelao J. Esteban
Published: May 2021

Experimental data showed that endothelial lipase (LIPG) is a crucial player in breast cancer. However, very limited data exists on the role of LIPG on the risk of breast cancer in humans. We examined the LIPG-breast cancer association within our population-based case–control study from Galicia, Spain, BREOGAN (BREast Oncology GAlicia Network). Plasma LIPG and/or OxLDL were measured on 114 breast cancer cases and 82 controls from our case–control study, and were included in the present study. The risk of breast cancer increased with increasing levels of LIPG (multivariable OR for the highest category (95% CI) 2.52 (1.11–5.81), P-trend = 0.037). The LIPG-breast cancer association was restricted to Pre-menopausal breast cancer (Multivariable OR for the highest LIPG category (95% CI) 4.76 (0.94–28.77), P-trend = 0.06, and 1.79 (0.61–5.29), P-trend = 0.372, for Pre-menopausal and Post-menopausal breast cancer, respectively). The LIPG-breast cancer association was restricted to Luminal A breast cancers (Multivariable OR for the highest LIPG category (95% CI) 3.70 (1.42–10.16), P-trend = 0.015, and 2.05 (0.63–7.22), P-trend = 0.311, for Luminal A and non-Luminal A breast cancers, respectively). Subset analysis only based on HER2 receptor indicated that the LIPG-breast cancer relationship was restricted to HER2-negative breast cancers (Multivariable OR for the highest LIPG category (95% CI) 4.39 (1.70–12.03), P-trend = 0.012, and 1.10 (0.28–4.32), P-trend = 0.745, for HER2-negative and HER2-positive tumors, respectively). The LIPG-breast cancer association was restricted to women with high total cholesterol levels (Multivariable OR for the highest LIPG category (95% CI) 6.30 (2.13–20.05), P-trend = 0.018, and 0.65 (0.11–3.28), P-trend = 0.786, among women with high and low cholesterol levels, respectively). The LIPG-breast cancer association was also restricted to non-postpartum breast cancer (Multivariable OR for the highest LIPG category (95% CI) 3.83 (1.37–11.39), P-trend = 0.003, and 2.35 (0.16–63.65), P-trend = 0.396, for non-postpartum and postpartum breast cancer, respectively), although we lacked precision. The LIPG-breast cancer association was more pronounced among grades II and III than grade I breast cancers (Multivariable ORs for the highest category of LIPG (95% CI) 2.73 (1.02–7.69), P-trend = 0.057, and 1.90 (0.61–6.21), P-trend = 0.170, for grades II and III, and grade I breast cancers, respectively). No association was detected for OxLDL levels and breast cancer (Multivariable OR for the highest versus the lowest category (95% CI) 1.56 (0.56–4.32), P-trend = 0.457).
Resting state alpha oscillatory activity is a valid and reliable marker of schizotypy
Authors: Trajkovic Jelena , Di Gregorio Francesco , Ferri Francesca , Marzi Chiara , Diciotti Stefano , Romei Vincenzo
Published: May 2021

Schizophrenia is among the most debilitating neuropsychiatric disorders. However, clear neurophysiological markers that would identify at-risk individuals represent still an unknown. The aim of this study was to investigate possible alterations in the resting alpha oscillatory activity in normal population high on schizotypy trait, a physiological condition known to be severely altered in patients with schizophrenia. Direct comparison of resting-state EEG oscillatory activity between Low and High Schizotypy Group (LSG and HSG) has revealed a clear right hemisphere alteration in alpha activity of the HSG. Specifically, HSG shows a significant slowing down of right hemisphere posterior alpha frequency and an altered distribution of its amplitude, with a tendency towards a reduction in the right hemisphere in comparison to LSG. Furthermore, altered and reduced connectivity in the right fronto-parietal network within the alpha range was found in the HSG. Crucially, a trained pattern classifier based on these indices of alpha activity was able to successfully differentiate HSG from LSG on tested participants further confirming the specific importance of right hemispheric alpha activity and intrahemispheric functional connectivity. By combining alpha activity and connectivity measures with a machine learning predictive model optimized in a nested stratified cross-validation loop, current research offers a promising clinical tool able to identify individuals at-risk of developing psychosis (i.e., high schizotypy individuals).
The paradox of retained genetic diversity of Hippocampus guttulatus in the face of demographic decline
Authors: Stacy Rupert , Palma Jorge , Correia Miguel , Wilson Anthony B. , Andrade José Pedro , Castilho Rita
Published: May 2021

Genetic diversity is the raw foundation for evolutionary potential. When genetic diversity is significantly reduced, the risk of extinction is heightened considerably. The long-snouted seahorse (Hippocampus guttulatus) is one of two seahorse species occurring in the North-East Atlantic. The population living in the Ria Formosa (South Portugal) declined dramatically between 2001 and 2008, prompting fears of greatly reduced genetic diversity and reduced effective population size, hallmarks of a genetic bottleneck. This study tests these hypotheses using samples from eight microsatellite loci taken from 2001 and 2013, on either side of the 2008 decline. The data suggest that the population has not lost its genetic diversity, and a genetic bottleneck was not detectable. However, overall relatedness increased between 2001 to 2013, leading to questions of future inbreeding. The effective population size has seemingly increased close to the threshold necessary for the population to retain its evolutionary potential, but whether these results have been affected by sample size is not clear. Several explanations are discussed for these unexpected results, such as gene flow, local decline due to dispersal to other areas of the Ria Formosa, and the potential that the duration of the demographic decline too short to record changes in the genetic diversity. Given the results presented here and recent evidence of a second population decline, the precise estimation of both gene flow and effective population size via more extensive genetic screening will be critical to effective population management.
Male terminalia of Cercopidae (Hemiptera, Cicadomorpha): towards a consensus terminology
Authors: Le Cesne Maxime , Crispolon Elorde , Soulier-Perkins Adeline
Published: May 2021

The study of male genital appendages is often necessary to identify a species and to characterise the higher systematics ranks for the Cercopidae, a large family of Hemiptera. Therefore, many authors have used them in their work but without any clear consensus on the terms used for each part constituting the male terminalia. A standardised terminology is important for the quality of a taxonomic description but even more essential when we want to compare species and establish a primary homology between states of character and their use in the frame of phylogenetic analysis. The use of a consensus terminology should ensure that we are all observing, speaking and describing the same genital appendage and comparing homologous characters. In order to propose a consensus terminology, we have reviewed all the major works on the anatomy of terminalia for the family since the first description using those characters in 1922. We proposed the use of consensual terms, listed with their definitions. In addition we studied a diversified panel of male specimens, chosen in order to represent as many Cercopidae tribes as possible. We categorised five different groups of Cercopidae according to their male terminalia structures. This opens the reflection on the evolutionary patterns for these structures.
Catchment landscape components alter relationships between discharge and stream water nutrient ratios in the Xitiao River Basin China
Authors: Gao Changjun , Li Wei , Cui Lijuan , Ma Qiongfang , Cai Jian
Published: May 2021

The terrestrial environment of a watershed is a source of potential carbon (C), nitrogen (N), and phosphorus (P) exports, and the hydrological regime provides the mechanism to turn the potential exports into reality when water is available. However, the extent to which the terrestrial environment alters the strength and nature of streamflow in transporting stream water nutrient ratios remains largely unknown. This study combined monthly stream discharge data with synchronously sampled stream water C:N:P ratios in 14 catchment streams in the Xitiao River Basin (XRB) in Zhejiang Province, China. The transport effect of streamflow on C:N:P ratios varied depending on the nutrient element, flow condition, and terrestrial environment. In the lower reaches of the XRB, there were negative relationships between C:N ratios, C:P ratios and watershed discharge, and positive relationships between N:P ratios and watershed discharge in both high and low flow conditions. In the middle and upper reaches of the XRB, the C:N-discharge relationship changed from negative to positive when the streamflow conditions altered from low to high flow. The C:P- and N:P-discharge relationships were negative regardless of high or low flows, but the regression coefficient significantly decreased with increasing streamflow. The C:N-discharge correlation over the course of the year shifted from negative to positive, as urban areas expanded within the catchment. The C:P-discharge relationship altered from negative to positive with more cropland and wetland but from positive to negative with a greater forest percentage and mean percentage slope. Our results indicate that changes in the terrestrial environment (e.g., the proportion of a particular land cover within a watershed) generally produced a threshold flow above which the coupling relationships between element fluxes from the terrestrial to riverine ecosystem changed sharply.
Developmental and lifelong dioxin exposure induces measurable changes in cardiac structure and function in adulthood
Authors: de Gannes Matthew , Koch Sheryl E. , Puga Alvaro , Rubinstein Jack
Published: May 2021

Congenital heart disease (CHD) is the most common congenital abnormality. A precise etiology for CHD remains elusive, but likely results from interactions between genetic and environmental factors during development, when the heart adapts to physiological and pathophysiological conditions. Further, it has become clearer that early exposure to toxins that do not result in overt CHD may be associated with adverse cardiac outcomes that are not manifested until later life. Previously, interference with endogenous developmental functions of the aryl hydrocarbon receptor (AHR), either by gene ablation or by in utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent AHR ligand, was shown to cause structural, molecular and functional cardiac abnormalities and altered heart physiology in mouse embryos. Here, we show that continuous exposure to TCDD from fertilization throughout adulthood caused male mice to underperform at exercise tolerance tests compared to their control and female counterparts, confirming previous observations of a sexually dimorphic phenotype. Renin-angiotensin stimulation by angiotensin II (Ang II) caused measurable increases in blood pressure and left ventricle mass, along with decreased end diastolic volume and preserved ejection fraction. Interestingly, TCDD exposure caused measurable reductions in the myocardial hypertrophic effects of Ang II, suggesting that endogenous AHR signaling present in adulthood may play a role in the pathogenesis of hypertrophy. Overall, the findings reported in this pilot study highlight the complex systems underlying TCDD exposure in the development of cardiac dysfunction in later life.
El Niño-Southern Oscillation affects the water relations of tree species in the Yucatan Peninsula, Mexico
Authors: Palomo-Kumul Jorge , Valdez-Hernández Mirna , Islebe Gerald A. , Cach-Pérez Manuel J. , Andrade José Luis
Published: May 2021

We evaluated the effect of ENSO 2015/16 on the water relations of eight tree species in seasonally dry tropical forests of the Yucatan Peninsula, Mexico. The functional traits: wood density, relative water content in wood, xylem water potential and specific leaf area were recorded during the rainy season and compared in three consecutive years: 2015 (pre-ENSO conditions), 2016 (ENSO conditions) and 2017 (post-ENSO conditions). We analyzed tree size on the capacity to respond to water deficit, considering young and mature trees, and if this response is distinctive in species with different leaf patterns in seasonally dry tropical forests distributed along a precipitation gradient (700–1200 mm year−1). These traits showed a strong decrease in all species in response to water stress in 2016, mainly in the driest site. Deciduous species had lower wood density, higher predawn water potential and higher specific leaf area than evergreen species. In all cases, mature trees were more tolerant to drought. In the driest site, there was a significant reduction in water status, regardless of their leaf phenology, indicating that seasonally dry tropical forests are highly vulnerable to ENSO. Vulnerability of deciduous species is intensified in the driest areas and in the youngest trees.
Increased expression of Protein S in eyes with diabetic retinopathy and diabetic macular edema
Authors: Sugimoto Masahiko , Kondo Mineo , Yasuma Taro , D’Alessandro-Gabazza Corina N. , Toda Masaaki , Imai Hisanori , Nakamura Makoto , Gabazza Esteban C.
Published: May 2021

Protein S (PS) is a multifunctional glycoprotein that ameliorates the detrimental effects of diabetes mellitus (DM). The aim of this study was to evaluate the distribution of PS in diabetic retinopathy (DR) and diabetic macular edema (DME). This was a study of 50 eyes with DM (37 with DME, 6 with proliferative DR, and 7 with no DR) and 19 eyes without DM. The level of PS was measured by enzyme immunoassay and was compared between eyes with or without DM, with or without DME, and with severe DME (≥ 350 μm) or mild DME (< 350 μm). We also performed immunohistopathologic evaluations of post-mortem eyes and the cystoid lesions excised during surgery. The aqueous free PS was significantly higher with DM (7.9 ± 1.2 ng/ml, P < 0.01) than without DM (6.1 ± 0.7). The aqueous free PS was significantly elevated with DME (8.2 ± 1.2, P < 0.05) compared to proliferative DR (7.0 ± 1.0) and no DR (7.0 ± 0.7). Eyes with severe DME had significantly higher aqueous free PS than mild DME (8.5 ± 1.3 vs. 7.7 ± 1.0, P < 0.05). Immunohistochemistry showed PS in the outer plexiform layer of the retina and cystoid lesion. The higher expression of PS with DR and DME suggests that PS is involved in their pathogenesis.
Non-oxide precipitates in additively manufactured austenitic stainless steel
Authors: Upadhyay Manas Vijay , Slama Meriem Ben Haj , Gaudez Steve , Mohanan Nikhil , Yedra Lluis , Hallais Simon , Héripré Eva , Tanguy Alexandre
Published: May 2021

Precipitates in an austenitic stainless steel fabricated via any Additive Manufacturing (AM), or 3D printing, technique have been widely reported to be only Mn-Si-rich oxides. However, via Transmission Electron Microscopy (TEM) studies on a 316L stainless steel, we show that non-oxide precipitates (intermetallics, sulfides, phosphides and carbides) can also form when the steel is fabricated via Laser Metal Deposition (LMD)—a directed energy deposition-type AM technique. An investigation into their origin is conducted with support from precipitation kinetics and finite element heat transfer simulations. It reveals that non-oxide precipitates form during solidification/cooling at temperatures ≥ 0.75Tm (melting point) and temperature rates ≤ 105 K/s, which is the upper end of the maximum rates encountered during LMD but lower than those encountered during Selective Laser Melting (SLM)—a powder-bed type AM technique. Consequently, non-oxide precipitates should form during LMD, as reported in this work, but not during SLM, in consistency with existing literature.
A high-efficiency method for site-directed mutagenesis of large plasmids based on large DNA fragment amplification and recombinational ligation
Authors: Zhang Kewei , Yin Xiaomei , Shi Kaituo , Zhang Shihua , Wang Juan , Zhao Shasha , Deng Huan , Zhang Cheng , Wu Zihui , Li Yuan , Zhou Xiangyu , Deng Wensheng
Published: May 2021

Site-directed mutagenesis for large plasmids is a difficult task that cannot easily be solved by the conventional methods used in many laboratories. In this study, we developed an effective method for Site-directed Mutagenesis for Large Plasmids (SMLP) based on a PCR technique. The SMLP method combines several effective approaches, including a high-efficiency DNA polymerase for the large DNA amplification, two independent PCR reactions and a fast recombinational ligation. Using this method, we have achieved a variety of mutants for the filamin A gene (7.9 kb) cloned in the pcDNA (5.4 kb) or the pLV-U6-CMV-EGFP (9.4 kb) plasmids, indicating that this method can be applied to site-directed mutagenesis for the plasmids up to 17.3 kb. We show that the SMLP method has a greater advantage than the conventional methods tested in this study, and this method can be applied to substitution, deletion, and insertion mutations for both large and small plasmids as well as the assembly of three fragments from PCR reactions. Altogether, the SMLP method is simple, effective, and beneficial to the laboratories that require completing the mutagenesis of large plasmids.
End-tidal to arterial carbon dioxide gradient is associated with increased mortality in patients with traumatic brain injury: a retrospective observational study
Authors: Doppmann Pascal , Meuli Lorenz , Sollid Stephen J. M. , Filipovic Miodrag , Knapp Jürgen , Exadaktylos Aristomenis , Albrecht Roland , Pietsch Urs
Published: May 2021

Early definitive airway protection and normoventilation are key principles in the treatment of severe traumatic brain injury. These are currently guided by end tidal CO2 as a proxy for PaCO2. We assessed whether the difference between end tidal CO2 and PaCO2 at hospital admission is associated with in-hospital mortality. We conducted a retrospective observational cohort study of consecutive patients with traumatic brain injury who were intubated and transported by Helicopter Emergency Medical Services to a Level 1 trauma center between January 2014 and December 2019. We assessed the association between the CO2 gap—defined as the difference between end tidal CO2 and PaCO2—and in-hospital mortality using multivariate logistic regression models. 105 patients were included in this study. The mean ± SD CO2 gap at admission was 1.64 ± 1.09 kPa and significantly greater in non-survivors than survivors (2.26 ± 1.30 kPa vs. 1.42 ± 0.92 kPa, p < .001). The correlation between EtCO2 and PaCO2 at admission was low (Pearson's r = .287). The mean CO2 gap after 24 h was only 0.64 ± 0.82 kPa, and no longer significantly different between non-survivors and survivors. The multivariate logistic regression model showed that the CO2 gap was independently associated with increased mortality in this cohort and associated with a 2.7-fold increased mortality for every 1 kPa increase in the CO2 gap (OR 2.692, 95% CI 1.293 to 5.646, p = .009). This study demonstrates that the difference between EtCO2 and PaCO2 is significantly associated with in-hospital mortality in patients with traumatic brain injury. EtCO2 was significantly lower than PaCO2, making it an unreliable proxy for PaCO2 when aiming for normocapnic ventilation. The CO2 gap can lead to iatrogenic hypoventilation when normocapnic ventilation is aimed and might thereby increase in-hospital mortality.
Development and characterization of a monoclonal antibody blocking human TRPM4 channel
Authors: Low See Wee , Gao Yahui , Wei Shunhui , Chen Bo , Nilius Bernd , Liao Ping
Published: May 2021

TRPM4 is a calcium-activated non-selective monovalent cation channel implicated in diseases such as stroke. Lack of potent and selective inhibitors remains a major challenge for studying TRPM4. Using a polypeptide from rat TRPM4, we have generated a polyclonal antibody M4P which could alleviate reperfusion injury in a rat model of stroke. Here, we aim to develop a monoclonal antibody that could block human TRPM4 channel. Two mouse monoclonal antibodies M4M and M4M1 were developed to target an extracellular epitope of human TRPM4. Immunohistochemistry and western blot were used to characterize the binding of these antibodies to human TRPM4. Potency of inhibition was compared using electrophysiological methods. We further evaluated the therapeutic potential on a rat model of middle cerebral artery occlusion. Both M4M and M4M1 could bind to human TRPM4 channel on the surface of live cells. Prolonged incubation with TRPM4 blocking antibody internalized surface TRPM4. Comparing to M4M1, M4M is more effective in blocking human TRPM4 channel. In human brain microvascular endothelial cells, M4M successfully inhibited TRPM4 current and ameliorated hypoxia-induced cell swelling. Using wild type rats, neither antibody demonstrated therapeutic potential on stroke. Human TRPM4 channel can be blocked by a monoclonal antibody M4M targeting a key antigenic sequence. For future clinical translation, the antibody needs to be humanized and a transgenic animal carrying human TRPM4 sequence is required for in vivo characterizing its therapeutic potential.
Complement C5 is not critical for the formation of sub-RPE deposits in Efemp1 mutant mice
Authors: Garland Donita L. , Pierce Eric A. , Fernandez-Godino Rosario
Published: May 2021

The complement system plays a role in the formation of sub-retinal pigment epithelial (RPE) deposits in early stages of age-related macular degeneration (AMD). But the specific mechanisms that connect complement activation and deposit formation in AMD patients are unknown, which limits the development of efficient therapies to reduce or stop disease progression. We have previously demonstrated that C3 blockage prevents the formation of sub-RPE deposits in a mouse model of EFEMP1-associated macular degeneration. In this study, we have used double mutant Efemp1R345W/R345W:C5-/- mice to investigate the role of C5 in the formation of sub-RPE deposits in vivo and in vitro. The data revealed that the genetic ablation of C5 does not eliminate the formation of sub-RPE deposits. Contrarily, the absence of C5 in RPE cultures promotes complement dysregulation that results in increased activation of C3, which likely contributes to deposit formation even in the absence of EFEMP1-R345W mutant protein. The results also suggest that genetic ablation of C5 alters the extracellular matrix turnover through an effect on matrix metalloproteinases in RPE cell cultures. These results confirm that C3 rather than C5 could be an effective therapeutic target to treat early AMD.
The epidemiology of fracture-related infections in Germany
Authors: Walter Nike , Rupp Markus , Lang Siegmund , Alt Volker
Published: May 2021

The epidemiology of fracture-related infection (FRI) is unknown, which makes it difficult to estimate future demands and evaluate progress in infection prevention. Therefore, we aimed to determine the nationwide burden’s development over the last decade as a function of age group and gender. FRI prevalence as a function of age group and gender was quantified based on annual ICD-10 diagnosis codes from German medical institutions between 2008 through 2018, provided by the Federal Statistical Office of Germany (Destatis). The prevalence of FRI increased by 0.28 from 8.4 cases per 100,000 inhabitants to 10.7 cases per 100,000 inhabitants between 2008 and 2018. The proportion of fractures resulting in FRI increased from 1.05 to 1.23%. Gender distribution was equal. Patients aged 60–69 years and 70–79 years comprised the largest internal proportion with 20.2% and 20.7%, respectively, whereby prevalence increased with age group. A trend towards more diagnoses in older patients was observed with a growth rate of 0.63 for patients older than 90 years. Increasing rates of fracture-related infection especially in older patients indicate an upcoming challenge for stakeholders in health care systems. Newly emerging treatment strategies, prevention methods and interdisciplinary approaches are strongly required.
Author Correction: Interspecific interactions within a vector‑borne complex are influenced by a co‑occurring pathosystem
Authors: Cruzado-Gutiérrez Regina K. , Sadeghi Rohollah , Prager Sean M. , Casteel Clare L. , Parker Jessica , Wenninger Erik J. , Price William J. , Bosque-Pérez Nilsa A. , Karasev Alexander V. , Rashed Arash
Published: May 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Experimental pilot study for augmented reality-enhanced elbow arthroscopy
Authors: Yamamoto Michiro , Oyama Shintaro , Otsuka Syuto , Murakami Yukimi , Yokota Hideo , Hirata Hitoshi
Published: May 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Reducing Agents in Colloidal Nanoparticle Synthesis – an Introduction
Authors: Villaverde-Cantizano Gonzalo , Laurenti Marco , Rubio-Retama Jorge , Contreras-Cáceres Rafael
Published: May 2021

During the last four decades, the use of nanoparticles has become an important topic in the fields of nanotechnology. Their potential applications in high diversity areas of research make them practically irreplaceable tools in medicine, biomaterials, catalysis, etc. There are countless methods to afford nanoparticles; however, the reduction of ionic species into atomic material is probably one of the most used pathways to generate nanoparticles in a consistent and controlled manner. In the chemical and biological bottom–up approach, the soluble material is reduced to insoluble atomic clusters which grow until a nanoparticle dispersion occurs. For carrying out these kinds of processes, reagents from multiple sources and different intrinsic properties can be used, thanks to their redox potential. This introductory chapter aims to describe the main redox agents used for the colloidal nanoparticle synthesis, from the most classical to the newest chemistry pathways.
Gases
Authors: Yi D. , Chaudret B. , Soulantica K.
Published: May 2021

Dihydrogen and carbon monoxide have been used for many years for the reduction of metals from their ores. These are the two gaseous reducing agents of choice for the synthesis of metal nanoparticles starting from molecular precursors. Their drawbacks (flammability and/or toxicity, use of high pressures) are counterbalanced by an easy removal of the unreacted agents after reaction, and by the fact that they leave no or few residues after use. Apart from acting as reducing agents, they can act as shape-directing agents and surface-active species, which influences their structural features and their physical and chemical properties. Last but not least, since during the nanoparticle formation they are present in a large excess, they can be involved in homogeneous or heterogeneous catalytic reactions that take place on soluble metal compounds (precursors, intermediate species) or on the surface of the nascent nanoparticles, respectively. These catalytic reactions may influence the nanoparticle formation process and nanoparticle properties.
Amines and Amine-boranes
Authors: Yon A. Marjorie , Marty B. Jean-Daniel , Ciuculescu-Pradines C. Diana
Published: May 2021

This chapter provides a brief description of the use of amines and amine-borane complexes as reducing agents for the synthesis of metallic nanoparticles. The use of alkyl, aryl amines, hydrazine, amine-borane complexes and, finally, polymeric amines is discussed in relation to their ability to reduce different classes of metallic ions (noble, magnetic, semiconductor, metalloid, etc.). For each type of amine the main mechanisms of formation and stabilization of the formed nanoparticles will be described, based on the most outstanding examples in the literature.
Amino Acids and Peptides in Colloidal Nanoparticle Synthesis
Authors: Haldar Debasish
Published: May 2021

The synthesis of colloidal nanoparticles, having well-ordered structures in high yield, environmentally friendly methods and low cost, has drawn significant attention because of their diverse applications in material sciences, chemistry, biology and medicine. Generally, two distinct schools of thought, the “top-down” approach and the “bottom-up” method, have been used for the synthesis of colloidal nanoparticles. Chemical reduction is most frequently used for the synthesis of nanoparticles as stable, colloidal dispersions in solution. Among all reducing agents, amino acids, peptides and peptide mimetics are highly promising, owing to their structural diversity, self-assembly propensities, biocompatibility and biodegradability. The non-covalent interactions such as hydrogen bonding, hydrophobic, π-stacking and van der Waals interactions play a very important role in achieving the production of thermodynamically stable colloidal nanoparticles. Moreover, the balance between these non-covalent interactions can tune the shape, size and morphology of the colloidal nanoparticles. This chapter mainly focuses on the role of amino acids or small peptides as reducing agents or as a matrix to stabilize colloidal nanoparticles. Emphasis will be given on both advantages and limitations. Moreover, the chapter will compare amino acids with other reducing agents for the synthesis of colloidal nanoparticles. The recent advances and future scope in this area will be discussed briefly.
Biological Materials
Authors: Perotti Gustavo Frigi , Pereira da Costa Luiz
Published: May 2021

Nanoscience and nanotechnology (N&N) have aroused great interest in the past few decades due to their potential impact on several and different areas of knowledge, such as electronics, energy, and biomedicine. This technology allows for the manipulation of materials possessing very small size, with dimensions ranging from a few nanometers to less than 100 nanometers. Nanoparticles (NPs), especially metallic ones, have properties that are strongly dependent on size and morphology and are interesting for applications ranging from high-performance catalysts and excellent antimicrobial activity to biosensors and optics. Several methods of synthesis of metallic nanoparticles (MNPs) have been developed in order to control their size and shape, however the majority of them use substances that are potentially toxic and harmful to the environment. Currently, several studies seek the development of reliable, clean and eco-friendly experimental techniques for NP synthesis. An approach that has shown great potential is based on the biosynthesis of NPs using different biological components, such as plant derivatives (extract of leaves, fruits, and roots) and microorganisms (fungi, bacteria, yeast, etc.). The purpose of this chapter is, therefore, to present the current and reflect on the future perspectives of biological-based methods for MNP synthesis. Advantages and limitations of different branches of such an approach are herein discussed.
In vitrocoronal protein signatures and biological impact of silver nanoparticles synthesized with different natural polymers as capping agents
Authors: Srivastava Priyanka , Gunawan Cindy , Soeriyadi Alexander , Amal Rose , Hoehn Kyle , Marquis Christopher
Published: May 2021

Biopolymer-capped silver nanoparticle synthesis. Compositional and stability analysis of synthesised particles. Proteomic analysis of particles following serum exposure.In vitrohemolytic assays. Organ distribution following administration in mice.
Enhancing the enzymatic inhibition performance of Cu-based metal–organic frameworks by shortening the organic ligands
Authors: Xu Ming , Liang Hong , Meng Sha-Sha , Gu Zhi-Yuan
Published: May 2021

The shortest diazole ligand imidazole was utilized to create more active sites on the MOF surface and enhance the enzymatic inhibition performance of MOF.
Gadolinium-doped carbon dots with high-performance in dual-modal molecular imaging
Authors: Wang Le , Zhou Wenjie , Yang Dan , Zhe Hu , Mei Shiliang , Yuan Jun , Zhang Wanlu , Li Hui , Fan Hong , Xie Fengxian , Guo Ruiqian
Published: May 2021

Carbon dots (CDs), possessing unexpected advantages of photostability, biocompatibility and low toxicity, can be used for fluorescence (FL) and magnetic resonance (MR) imaging.
A novel red emission fluorescent probe for monitoring carbon monoxide in living cells and zebrafish
Authors: Chen Jie , Gan Yabing , Hong Sai , Yin Guoxing , Zhou Li , Wang Changze , Fu Yuchuan , Li Haitao , Yin Peng
Published: May 2021

Carbon monoxide (CO), a gaseous signal molecule, plays a crucial role in biological systems.
A dual-photoelectrode photofuel cell based self-powered aptasensor using a multimeter as a direct visual readout strategy
Authors: Zhang Meng , Zhang Zhenzhen , Wei Jie , Dai Zhen , Hao Nan , Wang Kun
Published: May 2021

Schematic illustration of the dual-photoelectrode photofuel cell typed self-powered aptasensor for SMZ detection combined with digital multimeter as the direct visual readout strategy.
Structure of ice confined in silica nanopores
Authors: Mohammed Sohaib , Asgar Hassnain , Benmore Chris J. , Gadikota Greeshma
Published: May 2021

Observed anomalous thermodynamic properties of confined water such as deviations in the melting point and freezing point motivate the determination of the structure of confined water as a function of pore size and temperature.
Improved efficiency and carrier dynamic transportation behavior in perovskite solar cells with CuInS2 quantum dots as hole-transport materials
Authors: Li Hong , Luo Donglian , Liu Liwang , Xiong Dehua , Peng Yong
Published: May 2021

The photoelectric conversion efficiency of perovskite solar cells was greatly improved from 2.83% to 12.33% utilizing CuInS2 quantum dots as HTMs.
Simultaneously enhancing redox kinetics and inhibiting the polysulfide shuttle effect using MOF-derived CoSe hollow sphere structures for advanced Li–S batteries
Authors: Hu Shunyou , Hu Yuanyuan , Liu Xiangli , Zhang Jiaheng
Published: May 2021

Raspberry-like CoSe/C HSs inhibit the “shuttle effect” and enhance the redox kinetics for high-performance Li–S batteries.
Ultralow-power flexible transparent carbon nanotube synaptic transistors for emotional memory
Authors: Wang Yarong , Huang Weihong , Zhang Ziwei , Fan Lingchong , Huang Qiuyue , Wang Jiaxin , Zhang Yiming , Zhang Min
Published: May 2021

The realized artificial flexible carbon nanotube synaptic transistors possess low operating voltage, quick response and ultra-low power consumption, indicating their high potential in biological systems and artificial intelligence systems.
Super resolution microscopy reveals DHA-dependent alterations in glioblastoma membrane remodelling and cell migration
Authors: Xu Xia , Wang Yixiong , Choi Won-Shik , Sun Xuejun , Godbout Roseline
Published: May 2021

FABP7 nanodomains on glioblastoma neural stem-like cell membranes are greatly reduced when cells are cultured in medium supplemented with the omega-3 polyunsaturated fatty acid DHA. Glioblastoma cell migration is also reduced under these conditions.
Transition-metal-free radical homocoupling polymerization to synthesize conjugated poly(phenylene butadiynylene) polymers
Authors: Liu Qingmin , Wang Xuepeng , Tan Bien , Jin Shangbin
Published: May 2021

A transition-metal-free radical polymerization method to synthesize conjugated poly(phenylene butadiynylene) polymers with high surface areas and high gas uptake abilities.
Synthesis and self-assembly of amphiphilic precision glycomacromolecules
Authors: Banger Alexander , Sindram Julian , Otten Marius , Kania Jessica , Wilms Dimitri , Strzelczyk Alexander , Miletic Sean , Marlovits Thomas C. , Karg Matthias , Hartmann Laura
Published: May 2021

Amphiphilic precision glycomacromolecules (APG) are synthesized using solid-phase synthesis and studied for their self-assembly behavior and as inhibitors of bacterial adhesion.
Biomaterial design strategies to address obstacles in craniomaxillofacial bone repair
Authors: Dewey Marley J. , Harley Brendan A. C.
Published: May 2021

There exist many challenges in the process of regenerating craniomaxillofacial bone defects, thus biomaterials must be designed to overcome these.
The effect of headgroup methylation on polymorphic phase behaviour in hydrated N-methylated phosphoethanolamine:palmitic acid membranes
Authors: Allen Matthew E. , Elani Yuval , Brooks Nicholas J. , Seddon John M.
Published: May 2021

Within this work we show that headgroup methylation greatly impacts polymorphic phase behaviour within palmitic acid:phospholipid mixtures.
Structural color from solid-state polymerization-induced phase separation
Authors: Sicher Alba , Ganz Rabea , Menzel Andreas , Messmer Daniel , Panzarasa Guido , Feofilova Maria , Prum Richard O. , Style Robert W. , Saranathan Vinodkumar , Rossi René M. , Dufresne Eric R.
Published: May 2021

Inspired by living organisms that exploit phase separation to assemble structurally colored materials from macromolecules, we show that solid-state polymerization-induced phase separation can produce stable structures at optical length scales.
Physics-informed constitutive modelling of hydrated biopolymer aerogel networks
Authors: Külcü İsmail Doğan , Rege Ameya
Published: May 2021

Hydration induces significant structural rearrangements in biopolymer aerogels, resulting in a completely different mechanical behaviour compared to the one in the dry state. A micro-mechanical constitutive model describing this effect is presented.
A novel eutectic solvent precursor for efficiently preparing N-doped hierarchically porous carbon nanosheets with unique surface functional groups and micropores towards dual-carbon lithium-ion capacitors
Authors: Zou Kaixiang , Deng Yuanfu , Wu Weijing , Zhang Shiwei , Chen Guohua
Published: May 2021

A novel eutectic solvent acts as a green and cheap precursor for the preparation of N-doped hierarchically porous carbon nanosheets with superior energy density for dual-carbon LICs.
Electron-interfered field-effect transistors as a sensing platform for detecting a delicate surface chemical reaction
Authors: Choi Giheon , Lee Kanghuck , Oh Seungtaek , Seo Jungyoon , Park Eunyoung , Park Yeong Don , Lee Jihoon , Lee Hwa Sung
Published: May 2021

Newly-designed electron-interfered field-effect transistors have the potential to be used in the field of electronic devices used to quantify surface chemical reactions.
Impact of chemical modifications on the luminescence properties of organic neutral radical emitters
Authors: Cho Eunkyung , Coropceanu Veaceslav , Brédas Jean-Luc
Published: May 2021

The hybridization of the charge-transfer (CT) state with both the ground state (GS) and local-excitation (LE) states is essential in order to describe accurately the radiative and non-radiative transition rates in TTM-based radicals.