bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glioma-derived LRIG3 interacts with NETO2 in tumor-associated macrophages to modulate microenvironment and suppress tumor growth
Authors: Li Youwei , Wang Wei , Hou Xiaoshuang , Huang Wenda , Zhang Po , He Yue , Wang Baofeng , Duan Qiuhong , Mao Feng , Guo Dongsheng 
Published: January 2023

AbstractTumor-associated macrophages (TAMs) account for 30–50% of glioma microenvironment. The interaction between glioma tumor cells and TAMs can promote tumor progression, but the intrinsic mechanisms remain unclear. Herein, we reported that soluble LRIG3 (sLRIG3) derived from glioma tumor cells can block the M2 polarization of TAMs via interacting with NETO2, thus suppressing GBM malignant progression. The expression or activity of ADAM17 in glioma cells was positively correlated with the expression of sLRIG3 in cell supernatant. Soluble LRIG3 can suppress the M2-like polarity transformation of TAMs and inhibit the growth of tumor. High expression of LRIG3 predicts a good prognosis in patients with glioma. Mass spectrometry and Co-immunoprecipitation showed that sLRIG3 interacts with the CUB1 domain of NETO2 in TAMs. Silencing or knockout of NETO2 could block the effect of sLRIG3, which inhibited the M2-like polarity transformation of TAMs and promoted GBM tumor growth. However, overexpressing His-target NETO2 with CUB1 deletion mutation does not fully recover the suppressive effects of sLRIG3 on the TAM M2-polarization in NETO2-Knockout TAMs. Our study revealed vital molecular crosstalk between GBM tumor cells and TAMs. Glioma cells mediated the M2 polarization of TAM through the sLRIG3-NETO2 pathway and inhibited the progression of GBM, suggesting that sLRIG3-NETO2 may be a potential target for GBM treatment.
Improving adeno-associated viral (AAV) vector-mediated transgene expression in retinal ganglion cells: comparison of five promoters
Authors: Nieuwenhuis Bart , Laperrousaz Elise , Tribble James R. , Verhaagen Joost , Fawcett James W. , Martin Keith R. , Williams Pete A. , Osborne Andrew 
Published: January 2023

AbstractRecombinant adeno-associated viral vectors (AAVs) are an effective system for gene transfer. AAV serotype 2 (AAV2) is commonly used to deliver transgenes to retinal ganglion cells (RGCs) via intravitreal injection. The AAV serotype however is not the only factor contributing to the effectiveness of gene therapies. Promoters influence the strength and cell-selectivity of transgene expression. This study compares five promoters designed to maximise AAV2 cargo space for gene delivery: chicken β-actin (CBA), cytomegalovirus (CMV), short CMV early enhancer/chicken β-actin/short β-globulin intron (sCAG), mouse phosphoglycerate kinase (PGK), and human synapsin (SYN). The promoters driving enhanced green fluorescent protein (eGFP) were examined in adult C57BL/6J mice eyes and tissues of the visual system. eGFP expression was strongest in the retina, optic nerves and brain when driven by the sCAG and SYN promoters. CBA, CMV, and PGK had moderate expression by comparison. The SYN promoter had almost exclusive transgene expression in RGCs. The PGK promoter had predominant expression in both RGCs and AII amacrine cells. The ubiquitous CBA, CMV, and sCAG promoters expressed eGFP in a variety of cell types across multiple retinal layers including Müller glia and astrocytes. We also found that these promoters could transduce human retina ex vivo, although expression was predominantly in glial cells due to low RGC viability. Taken together, this promoter comparison study contributes to optimising AAV-mediated transduction in the retina, and could be valuable for research in ocular disorders, particularly those with large or complex genetic cargos.
Multiple pkd and piezo gene family members are required for atrioventricular valve formation
Authors: Juan Thomas , Ribeiro da Silva Agatha , Cardoso Bárbara , Lim SoEun , Charteau Violette , Stainier Didier Y. R. 
Published: January 2023

AbstractCardiac valves ensure unidirectional blood flow through the heart, and altering their function can result in heart failure. Flow sensing via wall shear stress and wall stretching through the action of mechanosensors can modulate cardiac valve formation. However, the identity and precise role of the key mechanosensors and their effectors remain mostly unknown. Here, we genetically dissect the role of Pkd1a and other mechanosensors in atrioventricular (AV) valve formation in zebrafish and identify a role for several pkd and piezo gene family members in this process. We show that Pkd1a, together with Pkd2, Pkd1l1, and Piezo2a, promotes AV valve elongation and cardiac morphogenesis. Mechanistically, Pkd1a, Pkd2, and Pkd1l1 all repress the expression of klf2a and klf2b, transcription factor genes implicated in AV valve development. Furthermore, we find that the calcium-dependent protein kinase Camk2g is required downstream of Pkd function to repress klf2a expression. Altogether, these data identify, and dissect the role of, several mechanosensors required for AV valve formation, thereby broadening our understanding of cardiac valvulogenesis.
Cryo-EM structures of orphan GPR21 signaling complexes
Authors: Lin Xi , Chen Bo , Wu Yiran , Han Yingqi , Qi Ao , Wang Junyan , Yang Zhao , Wei Xiaohu , Zhao Tingting , Wu Lijie , Xie Xin , Sun Jinpeng , Zheng Jie , Zhao Suwen , Xu Fei 
Published: January 2023

AbstractGPR21 is a class-A orphan G protein-coupled receptor (GPCR) and a potential therapeutic target for type 2 diabetes and other metabolic disorders. This receptor shows high basal activity in coupling to multiple G proteins in the absence of any known endogenous agonist or synthetic ligand. Here, we present the structures of ligand-free human GPR21 bound to heterotrimeric miniGs and miniG15 proteins, respectively. We identified an agonist-like motif in extracellular loop 2 (ECL2) that occupies the orthosteric pocket and promotes receptor activation. A side pocket that may be employed as a new ligand binding site was also uncovered. Remarkably, G protein binding is accommodated by a flexible cytoplasmic portion of transmembrane helix 6 (TM6) which adopts little or undetectable outward movement. These findings will enable the design of modulators for GPR21 for understanding its signal transduction and exploring opportunity for deorphanization.
Complementing two-photon fluorescence detection with backscatter detection to decipher multiparticle dynamics inside a nonlinear laser trap
Authors: Devi Anita , Yadav Sumit , De Arijit K. 
Published: January 2023

AbstractUsing wide-field and point detection modalities, we show how optical trapping dynamics under femtosecond pulsed excitation can be explored by complementing detection of two-photon fluorescence with backscatter. Radial trajectories of trapped particles are mapped from correlated/anti-correlated fluctuations in backscatter pattern whereas temporal evolution of two-photon fluorescence is used to mark the onset of trapping involving multiple particles. Simultaneous confocal detection of backscatter and two-photon fluorescence estimates axial trap stiffness, delineating short-time trapping dynamics. When a second particle is being trapped an oscillatory signal is observed which is due to interference of backscatter amplitudes, revealing inter-particle interactions within the trap. These findings are crucial steps forward to achieve controlled manipulation by harnessing optical nonlinearity under femtosecond pulsed excitation.
Discovery of rafoxanide as a novel agent for the treatment of non-small cell lung cancer
Authors: Hu Ankang , Liu Jing , Wang Yonghui , Zhang Maoyin , Guo Yao , Qin Ying , Liu Tingya , Men Yanjuan , Chen Quangang , Liu Tingjun 
Published: January 2023

AbstractNon-small cell lung cancer (NSCLC), which accounts for approximately 85% of all lung cancer cases, is associated with a poor outcome. Rafoxanide is an anthelmintic drug that inhibits tumor growth in certain malignancies. However, its impact on NSCLC remains unknown. In this study, we examined the effect of rafoxanide on NSCLC and dissected the underlying mechanism. The results showed that rafoxanide significantly inhibited the growth, invasion, and migration of NSCLC cells. Besides, rafoxanide can induce NSCLC cell apoptosis and cell cycle arrest in a dose-dependent manner. RNA-seq analysis revealed that genes associated with endoplasmic reticulum stress (ER) stress responses were activated. Mechanistically, we found Rafoxanide can induce ER stress and activate the unfolded protein response (UPR). Apoptosis was activated by excessive ER stress, and autophagy was activated to partially alleviate ER stress. In vivo, we found that rafoxanide inhibited the growth of A549 and H1299 xenograft mouse models without severe side effects. Collectively, the present study indicates that rafoxanide may be a candidate drug for the treatment of NSCLC.
Domain motions, dimerization, and membrane interactions of the murine guanylate binding protein 2
Authors: Loschwitz Jennifer , Steffens Nora , Wang Xue , Schäffler Moritz , Pfeffer Klaus , Degrandi Daniel , Strodel Birgit 
Published: January 2023

AbstractGuanylate-binding proteins (GBPs) are a group of GTPases that are induced by interferon-$$\gamma$$
γ
and are crucial components of cell-autonomous immunity against intracellular pathogens. Here, we examine murine GBP2 (mGBP2), which we have previously shown to be an essential effector protein for the control of Toxoplasma gondii replication, with its recruitment through the membrane of the parasitophorous vacuole and its involvement in the destruction of this membrane likely playing a role. The overall aim of our work is to provide a molecular-level understanding of the mutual influences of mGBP2 and the parasitophorous vacuole membrane. To this end, we performed lipid-binding assays which revealed that mGBP2 has a particular affinity for cardiolipin. This observation was confirmed by fluorescence microscopy using giant unilamellar vesicles of different lipid compositions. To obtain an understanding of the protein dynamics and how this is affected by GTP binding, mGBP2 dimerization, and membrane binding, assuming that each of these steps are relevant for the function of the protein, we carried out standard as well as replica exchange molecular dynamics simulations with an accumulated simulation time of more than 30 μs. The main findings from these simulations are that mGBP2 features a large-scale hinge motion in its M/E domain, which is present in each of the studied protein states. When bound to a cardiolipin-containing membrane, this hinge motion is particularly pronounced, leading to an up and down motion of the M/E domain on the membrane, which did not occur on a membrane without cardiolipin. Our prognosis is that this up and down motion has the potential to destroy the membrane following the formation of supramolecular mGBP2 complexes on the membrane surface.
Heart rate variability responses to cognitive stress in fibromyalgia are characterised by inadequate autonomous system stress responses: a clinical trial
Authors: Zetterman Teemu , Markkula Ritva , Miettinen Teemu , Kalso Eija 
Published: January 2023

AbstractFibromyalgia (FM) is associated with sympathetically dominant dysautonomia, but the connection between dysautonomia and FM symptoms is unclear. Dysautonomia can be analysed with heart rate variability (HRV) and it has been proposed that FM patients comprise subgroups with differing profiles of symptom severity. In our study, 51 female FM patients aged 18 to 65 years and 31 age-matched healthy female controls followed a 20-min protocol of alternating relaxation and cognitive stress (mental arithmetic). Heart rates and electrocardiograms were registered. The HRV measures of heart rate (HR), mean interval between heart beats (RRmean), root mean squared interval differences of successive beats (RMSSD), and the standard deviation of intervals between normal heart beats (SDNN) were analysed with generalized linear modelling. Features in HRV reactivity which differed between FM patients and controls were used to cluster the FM patients and cluster characteristics were analysed. FM patients had higher baseline HR (72.3 [SD 12.7] vs 64.5 [7.80], p < 0.001) and lower RRmean (0.844 [0.134] vs 0.934 [0.118], p = 0.002), compared with controls. They also reacted to repeated cognitive stress with an attenuated rise in HR (− 4.41 [95% CI − 7.88 to − 0.93], p = 0.013) and attenuated decrease of RRmean (0.06 [95 CI 0.03 to 0.09], p < 0.001), compared with controls. Clustering of FM patients by HRV reactivity resulted in three clusters characterised by (1) normal levels of HRV and HRV reactivity with low levels of depressive mood and anxiety, (2) reduced levels of HRV and impaired HRV reactivity with increased levels of depressive mood and high levels of anxiety, and (3) lowest HRV and most impaired HRV reactivity with the highest scores for depressive mood and anxiety. Our results show that FM patients have lower HRV than healthy controls and their autonomous reactions to cognitive stress are attenuated. Dysautonomia in FM associates with mood disturbance.
Trial registration ClinicalTrials.gov (NCT03300635). Registered October 3 2017—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03300635.
Contrasting impacts of dry versus humid heat on US corn and soybean yields
Authors: Ting Mingfang , Lesk Corey , Liu Chunyu , Li Cuihua , Horton Radley M. , Coffel Ethan D. , Rogers Cassandra D. W. , Singh Deepti 
Published: January 2023

AbstractThe impact of extreme heat on crop yields is an increasingly pressing issue given anthropogenic climate warming. However, some of the physical mechanisms involved in these impacts remain unclear, impeding adaptation-relevant insight and reliable projections of future climate impacts on crops. Here, using a multiple regression model based on observational data, we show that while extreme dry heat steeply reduced U.S. corn and soy yields, humid heat extremes had insignificant impacts and even boosted yields in some areas, despite having comparably high dry-bulb temperatures as their dry heat counterparts. This result suggests that conflating dry and humid heat extremes may lead to underestimated crop yield sensitivities to extreme dry heat. Rainfall tends to precede humid but not dry heat extremes, suggesting that multivariate weather sequences play a role in these crop responses. Our results provide evidence that extreme heat in recent years primarily affected yields by inducing moisture stress, and that the conflation of humid and dry heat extremes may lead to inaccuracy in projecting crop yield responses to warming and changing humidity.
Incidence of muscle wasting in the critically ill: a prospective observational cohort study
Authors: Hrdy Ondrej , Vrbica Kamil , Kovar Marek , Korbicka Tomas , Stepanova Radka , Gal Roman 
Published: January 2023

AbstractLoss of muscle mass occurs rapidly during critical illness and negatively affects quality of life. The incidence of clinically significant muscle wasting in critically ill patients is unclear. This study aimed to assess the incidence of and identify predictors for clinically significant loss of muscle mass in this patient population. This was a single-center observational study. We used ultrasound to determine the rectus femoris cross-sectional area (RFcsa) on the first and seventh day of ICU stay. The primary outcome was the incidence of significant muscle wasting. We used a logistic regression model to determine significant predictors for muscle wasting. Ultrasound measurements were completed in 104 patients. Sixty-two of these patients (59.6%) showed ≥ 10% decreases in RFcsa. We did not identify any predictor for significant muscle wasting, however, age was of borderline significance (p = 0.0528). The 28-day mortality rate was higher in patients with significant wasting, but this difference was not statistically significant (30.6% versus 16.7%; p = 0.165). Clinically significant muscle wasting was frequent in our cohort of patients. Patient age was identified as a predictor of borderline significance for muscle wasting. The results could be used to plan future studies on this topic.Trial registration: ClinicalTrials.gov NCT03865095, date of registration: 06/03/2019.
Experimental study on the shear performance of an anchor cable with a C-shaped tube anchored flat structural plane
Authors: Tong Xiao , Shan Renliang , Liu Nan , Liu Dong , Wei Yonghui 
Published: January 2023

AbstractTo analyse the influence of normal stress (σn) and steel tube strength on an anchor cable with a C-shaped tube (ACC), we selected Q235 steel tubes and Q345 steel tubes as representative ACCs and carried out double shear tests of ACC-reinforced jointed rock masses. Based on the test results, the influence of the steel tube strength on the ACC axial force and shear force under different normal stresses, the characteristics of the shear force-shear displacement curve of the anchored flat structural plane (FSP) in the rock mass, and the ACC failure mode and contribution to the anchored concrete surface shear strength were studied. The test results show that under 2 ~ 10 MPa of σn, the failure angle varies between 28° and 40° due to the bending of the ACC near the structural plane and increases with increasing σn. Compared with Q235-ACC, Q345-ACC contributes more to the shear strength of the structural plane and can better exert its axial force when resisting the lateral shearing action of the structural plane. Additionally, we proved that σn is a main factor affecting the shear stiffness of the structural plane and that the Q345 C-shaped tube effectively improves the shear stiffness of an ACC-reinforced jointed rock mass and can more fully mobilize the anchor cable during shearing ductility in the tangential direction compared to the performance of the Q235 C-shaped tube. The research results can provide a reference for the further application of ACCs to roadways.
Aza-Wacker Cyclization Toward the Bridged Core of FR901483
Authors: Zhu Lili , Hong Ran , Shen Defeng , Xie Changmin , Ruan Zhuwei , Yang Chen , Huang Sha-Hua 
Published: January 2023

AbstractA nine-step synthetic route to access the tricyclic core of FR901483 is reported, featuring a key aza-Wacker cyclization step to construct an α-tertiary amine (ATA) in the bridged structure. The aza-Wacker protocol can tolerate both exocyclic and endocyclic double bonds, providing viable access to various bridged bicyclic rings bearing an ATA (e.g., 6-azabicyclo[3.2.1]octane, 7-azabicyclo[3.3.1]nonane, and 7-azabicyclo[4.2.1]nonane) in good to excellent yields. The synthetic studies presented herein enable structural derivatization of FR901483 to further exploit its compelling biological activities.
Extraction Site in Minimally Invasive Colorectal Surgery
Authors: Paruch Jennifer L. 
Published: January 2023

AbstractThe widespread adoption of minimally invasive colorectal surgery has led to improved patient recovery and outcomes. Specimen extraction sites remain a major source of pain and potential postoperative morbidity. Careful selection of the extraction site incision may allow surgeons to decrease postoperative pain, infectious complications, or rates of hernia formation. Options include midline, paramedian, transverse, Pfannenstiel, and natural orifice sites. Patient, disease, and surgeon-related factors should all be considered when choosing a site. This article will review different options for specimen extraction sites.
Techniques for Oxygenation and Ventilation in Coronavirus Disease 2019
Authors: Richards Guy A. , Smith Oliver 
Published: January 2023

AbstractThis paper discusses mechanisms of hypoxemia and interventions to oxygenate critically ill patients with COVID-19 which range from nasal cannula to noninvasive and mechanical ventilation. Noninvasive ventilation includes continuous positive airway pressure ventilation (CPAP) and high-flow nasal cannula (HFNC) with or without proning. The evidence for each of these modalities is discussed and thereafter, when to transition to mechanical ventilation (MV). Various techniques of MV, again with and without proning, and rescue strategies which would include extra corporeal membrane oxygenation (ECMO) when it is available and permissive hypoxemia where it is not, are discussed.
The Origins of Severe Acute Respiratory Syndrome-Coronavirus-2
Authors: Dwyer Dominic E. 
Published: January 2023

AbstractAn outbreak of severe pneumonia of unknown cause was identified in Wuhan, China in December 2019: the causative agent was a novel betacoronavirus, severe acute respiratory syndrome-cotonavirus-2 (SARS-CoV-2), a virus that joins a list of coronaviruses causing severe (e.g., SARS and Middle East respiratory syndrome) or milder (e.g., 229E, OC43, NL63, and HKU1) respiratory tract infection. The World Health Organization (WHO) classified the spreading outbreak as a pandemic on March 11, 2020. Many SARS-related coronaviruses (SARSr-CoVs) have been identified in bats, particularly in Rhinolophus horseshoe bats, animals that are common in southern China and Southeast Asia. Many of the features of SARS-CoV-2 that facilitate human infection—the furin cleavage site, the receptor binding domain that binds to the human ACE2 receptor—can be identified in SARSr-CoVs. Related coronaviruses can be detected in pangolins and other animals, and human SARS-CoV-2 itself can infect various animals, some of which can transmit SARS-CoV-2 back to humans. Investigation by the WHO and others pointed to the initial outbreak being centered on the Huanan wet market in Wuhan where wild and farmed animals were sold, and where environmental testing revealed widespread SARS-CoV-2 contamination. This supports the hypothesis that bats, probably via an intermediate animal, are the origin of SARS-CoV-2. Other possible origins have been postulated, such as an accidental or deliberate laboratory leak, or virus present in frozen foods, but evidence for these ideas has not surfaced. Study of the origins of SARS-CoV-2 have been complicated by intense media and political commentary, features that may slow the studies required to understand the viral origins. Such studies are complex and may be slow: international openness and co-operation is vital. Origins explanations are needed to predict or prevent future pandemics and support the “One Health” approach to disease.
A Rare Case of Migration of Hyaluronic Acid Gluteal Injection to the Medial Thigh Presenting as a Soft Lump
Authors: Saad Ahmed , Iyengar Karthikeyan P. , Davies A. Mark , Botchu Rajesh 
Published: January 2023

Abstract
Introduction Hyaluronic acid (HA) is a widely accepted agent most commonly used as a dermal filler in facial aesthetic/cosmetic medicine. More recently, HA has been utilized for gluteal augmentation. The common side effects of HA injection are often minor and self-limiting. HA migration is a very rare complication.
Case Report We describe a rare case of HA buttock injection migration in a transgender patient, appearing as a superficial lump on right thigh representing a diagnostic dilemma. We highlight the need of a clinical suspicion and discuss the appropriate investigations for guided management of such patients.
Conclusion It is essential for reporting radiologist to be aware of the commonly used injectable fillers, their complications, and imaging findings to avoid misdiagnosis and guide optimal patient management.