bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural basis of adhesion GPCR GPR110 activation by stalk peptide and G-proteins coupling
Authors: Zhu Xinyan , Qian Yu , Li Xiaowan , Xu Zhenmei , Xia Ruixue , Wang Na , Liang Jiale , Yin Han , Zhang Anqi , Guo Changyou , Wang Guangfu , He Yuanzheng 
Published: September 2022

AbstractAdhesion G protein-coupled receptors (aGPCRs) are keys of many physiological events and attractive targets for various diseases. aGPCRs are also known to be capable of self-activation via an autoproteolysis process that removes the inhibitory GAIN domain on the extracellular side of receptor and releases a stalk peptide to bind and activate the transmembrane side of receptor. However, the detailed mechanism of aGPCR activation remains elusive. Here, we report the cryo-electron microscopy structures of GPR110 (ADGRF1), a member of aGPCR, in complex with Gq, Gs, Gi, G12 and G13. The structures reveal distinctive ligand engaging model and activation conformations of GPR110. The structures also unveil the rarely explored GPCR/G12 and GPCR/G13 engagements. A comparison of Gq, Gs, Gi, G12 and G13 engagements with GPR110 reveals details of G-protein engagement, including a dividing point at the far end of the alpha helix 5 (αH5) of Gα subunit that separates Gq/Gs engagements from Gi/G12/G13 engagements. This is also where Gq/Gs bind the receptor through both hydrophobic and polar interaction, while Gi/G12/G13 engage receptor mainly through hydrophobic interaction. We further provide physiological evidence of GPR110 activation via stalk peptide. Taken together, our study fills the missing information of GPCR/G-protein engagement and provides a framework for understanding aGPCR activation and GPR110 signaling.
Systematic profiling of conditional degron tag technologies for target validation studies
Authors: Bondeson Daniel P. , Mullin-Bernstein Zachary , Oliver Sydney , Skipper Thomas A. , Atack Thomas C. , Bick Nolan , Ching Meilani , Guirguis Andrew A. , Kwon Jason , Langan Carly , Millson Dylan , Paolella Brenton R. , Tran Kevin , Wie Sarah J. , Vazquez Francisca , Tothova Zuzana , Golub Todd R. , Sellers William R. , Ianari Alessandra 
Published: September 2022

AbstractConditional degron tags (CDTs) are a powerful tool for target validation that combines the kinetics and reversible action of pharmacological agents with the generalizability of genetic manipulation. However, successful design of a CDT fusion protein often requires a prolonged, ad hoc cycle of construct design, failure, and re-design. To address this limitation, we report here a system to rapidly compare the activity of five unique CDTs: AID/AID2, IKZF3d, dTAG, HaloTag, and SMASh. We demonstrate the utility of this system against 16 unique protein targets. We find that expression and degradation are highly dependent on the specific CDT, the construct design, and the target. None of the CDTs leads to efficient expression and/or degradation across all targets; however, our systematic approach enables the identification of at least one optimal CDT fusion for each target. To enable the adoption of CDT strategies more broadly, we have made these reagents, and a detailed protocol, available as a community resource.
Small soluble α-synuclein aggregates are the toxic species in Parkinson’s disease
Authors: Emin Derya , Zhang Yu P. , Lobanova Evgeniia , Miller Alyssa , Li Xuecong , Xia Zengjie , Dakin Helen , Sideris Dimitrios I. , Lam Jeff Y. L. , Ranasinghe Rohan T. , Kouli Antonina , Zhao Yanyan , De Suman , Knowles Tuomas P. J. , Vendruscolo Michele , Ruggeri Francesco S. , Aigbirhio Franklin I. , Williams-Gray Caroline H. , Klenerman David 
Published: September 2022

AbstractSoluble α-synuclein aggregates varying in size, structure, and morphology have been closely linked to neuronal death in Parkinson’s disease. However, the heterogeneity of different co-existing aggregate species makes it hard to isolate and study their individual toxic properties. Here, we show a reliable non-perturbative method to separate a heterogeneous mixture of protein aggregates by size. We find that aggregates of wild-type α-synuclein smaller than 200 nm in length, formed during an in vitro aggregation reaction, cause inflammation and permeabilization of single-liposome membranes and that larger aggregates are less toxic. Studying soluble aggregates extracted from post-mortem human brains also reveals that these aggregates are similar in size and structure to the smaller aggregates formed in aggregation reactions in the test tube. Furthermore, we find that the soluble aggregates present in Parkinson’s disease brains are smaller, largely less than 100 nm, and more inflammatory compared to the larger aggregates present in control brains. This study suggests that the small non-fibrillar α-synuclein aggregates are the critical species driving neuroinflammation and disease progression.
Smart soft contact lenses for continuous 24-hour monitoring of intraocular pressure in glaucoma care
Authors: Zhang Jinyuan , Kim Kyunghun , Kim Ho Joong , Meyer Dawn , Park Woohyun , Lee Seul Ah , Dai Yumin , Kim Bongjoong , Moon Haesoo , Shah Jay V. , Harris Keely E. , Collar Brett , Liu Kangying , Irazoqui Pedro , Lee Hyowon , Park Shin Ae , Kollbaum Pete S. , Boudouris Bryan W. , Lee Chi Hwan 
Published: September 2022

AbstractContinuous monitoring of intraocular pressure, particularly during sleep, remains a grand challenge in glaucoma care. Here we introduce a class of smart soft contact lenses, enabling the continuous 24-hour monitoring of intraocular pressure, even during sleep. Uniquely, the smart soft contact lenses are built upon various commercial brands of soft contact lenses without altering their intrinsic properties such as lens power, biocompatibility, softness, transparency, wettability, oxygen transmissibility, and overnight wearability. We show that the smart soft contact lenses can seamlessly fit across different corneal curvatures and thicknesses in human eyes and therefore accurately measure absolute intraocular pressure under ambulatory conditions. We perform a comprehensive set of in vivo evaluations in rabbit, dog, and human eyes from normal to hypertension to confirm the superior measurement accuracy, within-subject repeatability, and user comfort of the smart soft contact lenses beyond current wearable ocular tonometers. We envision that the smart soft contact lenses will be effective in glaucoma care.
Hydrothermal synthesis of CuO@MnO2 on nitrogen-doped multiwalled carbon nanotube composite electrodes for supercapacitor applications
Authors: Kakani Vijay , Ramesh Sivalingam , Yadav H. M. , Bathula Chinna , Basivi Praveen Kumar , Palem Ramasubba Reddy , Kim Heung Soo , Pasupuletti Visweswara Rao , Lee Handol , Kim Hakil 
Published: September 2022

AbstractNitrogen-doped multiwalled carbon nanotubes (N-MWCNTs) have been used to fabricate nanostructured materials for various energy devices, such as supercapacitors, sensors, batteries, and electrocatalysts. Nitrogen-doped carbon-based electrodes have been widely used to improve supercapacitor applications via various chemical approaches. Based on previous studies, CuO@MnO2and CuO@MnO2/N-MWCNT composites were synthesized using a sonication-supported hydrothermal reaction process to evaluate their supercapacitor properties. The structural and morphological properties of the synthesized composite materials were characterized via Raman spectroscopy, XRD, SEM, and SEM–EDX, and the morphological properties of the composite materials were confirmed by the nanostructured composite at the nanometer scale. The CuO@MnO2and CuO@MnO2/N-MWCNT composite electrodes were fabricated in a three-electrode configuration, and electrochemical analysis was performed via CV, GCD, and EIS. The composite electrodes exhibited the specific capacitance of ~ 184 F g−1at 0.5 A g−1in the presence of a 5 M KOH electrolyte for the three-electrode supercapacitor application. Furthermore, it exhibited significantly improved specific capacitances and excellent cycling stability up to 5000 GCD cycles, with a 98.5% capacity retention.
Incidence and risk factors of metabolic syndrome among Royal Thai Army personnel
Authors: Sakboonyarat Boonsub , Rangsin Ram , Mittleman Murray A. 
Published: September 2022

AbstractMetabolic Syndrome is a clustering of obesity, hyperglycemia/insulin resistance, dyslipidemia, and hypertension. We aimed to determine the incidence of metabolic syndrome among Royal Thai Army (RTA) personnel and its risk factors. We conducted a retrospective cohort study using data from 2017 to 2021. Metabolic syndrome was defined by NCEP ATP III (2005 Revision). A total of 98,264 participants were enrolled in the present study. The overall incidence rate of metabolic syndrome was 3.7 per 100 person-year (95% CI 3.7–3.8). The statistically significant risk factors for metabolic syndrome included male sex (aHR 1.40; 95% CI 1.29–1.51), age > 35 years, current alcohol consumption, and no exercise. When stratified by sex, the incidence rate of metabolic syndrome among participants aged ≥ 45 years was higher than those aged < 35 years with aHR 6.34; 95% CI 6.01–6.70 for males and aHR 9.59; 95% CI 7.55–12.19 for females. Our data demonstrated that metabolic syndrome is a common health issue, especially among RTA personnel over 35 years. Alcohol consumption and sedentary behavior played an essential role in facilitating metabolic syndrome in this study population and are potential targets for intervention to enhance primary prevention of the sequelae of metabolic syndrome.
Evaluation of ecological quality in southeast Chongqing based on modified remote sensing ecological index
Authors: Ye Xi , Kuang Honghai 
Published: September 2022

AbstractRocky desertification is a serious ecological and environmental problem in Southwest China. Quickly and scientifically reveal the distribution and changes of ecological environment quality in rocky desertification areas, which is of great significance to rocky desertification restoration, ecological environment governance and sustainable development. Based on the remote sensing ecological index (RSEI), in addition to greenness, humidity, dryness, and heat, combined with the degree of rocky desertification, this study used the principal component analysis (PCA) method to construct a modified remote sensing ecological index (MRSEI). Then, the temporal and spatial variation characteristics and imaging factors of the ecological environment quality in the typical rocky desertification region of southeastern Chongqing from 2001 to 2021 were explored. The results revealed that the greenness and humidity indicators had a positive effect on the ecological quality, while the indicators of dryness, heat and rocky desertification had the opposite impact. From 2001 to 2021, the ecological environment quality in southeastern Chongqing showed a trend of gradual improvement, and the improvement area accounted for about 70% of the total area. The elevation, slope, monthly average precipitation, and land use pattern were the main factors influencing the quality of the ecological environment in the region.
Identification and characterization of a novel cell binding and cross-reactive region on spike protein of SARS-CoV-2
Authors: Wang Hanlu , Yang Tiantian , Jiang Wenhong , Qin Meng , Sun Ziyong , Dai Wei , Jiang Yongping 
Published: September 2022

AbstractGiven that COVID-19 continues to wreak havoc around the world, it is imperative to search for a conserved region involved in viral infection so that effective vaccines can be developed to prevent the virus from rapid mutations. We have established a twelve-fragment library of recombinant proteins covering the entire region of spike protein of both SARS-CoV-2 and SARS-CoV from Escherichia coli. IgGs from murine antisera specifically against 6 spike protein fragments of SARS-CoV-2 were produced, purified, and characterized. We found that one specific IgG against the fusion process region, named COVID19-SF5, serologically cross-reacted with all twelve S-protein fragments. COVID19-SF5, with amino acid sequences from 880 to 1084, specifically bound to VERO-E6 and BEAS-2B cells, with Kd values of 449.1 ± 21.41 and 381.9 ± 31.53 nM, and IC50 values of 761.2 ± 28.2 nM and 862.4 ± 32.1 nM, respectively. In addition, COVID19-SF5 greatly enhanced binding of the full-length CHO cell-derived spike protein to the host cells in a concentration-dependent manner. Furthermore, COVID19-SF5 and its IgGs inhibited the infection of the host cells by pseudovirus. The combined data from our studies reveal that COVID19-SF5, a novel cell-binding fragment, may contain a common region(s) for mediating viral binding during infection. Our studies also provide valuable insights into how virus variants may evade host immune recognition. Significantly, the observation that the IgGs against COVID19-SF5 possesses cross reactivity to all other fragments of S protein, suggesting that it is possible to develop universal neutralizing monoclonal antibodies to curb rapid mutations of COVID-19.
SGLT2 inhibitors attenuate nephrin loss and enhance TGF-β1 secretion in type 2 diabetes patients with albuminuria: a randomized clinical trial
Authors: Tian Yuan , Chen Xiao-min , Liang Xian-ming , Wu Xiao-bin , Yao Chun-meng 
Published: September 2022

AbstractTo evaluate the effect of SGLT2 inhibitor (SGLT2i) on albuminuria, nephrin (NPH) and transforming-growth-factor-beta1 (TGF-β1) levels in urine and low-grade inflammation in type 2 diabetes (T2D) patients. A randomized, blank-controlled clinical trial included 68 T2D patients and 10 controls. Based on the urinary albumin-to-creatinine ratio (UACR), 68 diabetic patients were stratified into three levels, UACR < 30 mg/g, UACR ≧ 30 mg/g to ≦ 300 mg/g and UACR ˃ 300 mg/g, who were randomized (1:1:1) to receive SGLT2i treatment for 12 weeks. The concentrations of NPH and TGF-β1 in urine were measured as indications of podocyte injury and renal fibrosis. Low-grade inflammation was assessed by the levels of IL-6, TNFα and hsCRP. After 12 weeks of SGLT2i treatment, the levels of UACR and NPH decreased, UTGF-β1 increased in the T2D with microalbuminuria and macroalbuminuria groups, NPH (1.12 [0.59, 1.29] vs. 0.71 [0.41, 1.07] µg/ml, P = 0.022) and (1.29 [0.99, 1.96] vs. 0.93 [0.57, 1.31] µg/ml, P = 0.002), UTGF-β1 (4.88 ± 1.31 vs. 7.27 ± 1.21 pg/ml, P < 0.001) and (4.30 ± 1.34 vs. 6.78 ± 2.59 pg/ml, P < 0.001), respectively. The changes in NPH were positively correlated with the UACR and negatively correlated with UTGF-β1 in T2D with albuminuria. SGLT2i alleviate nephrin loss and enhance TGF-β1 excretion in urine in T2DM with albuminuria. The anti-albuminuric effect of SGLT2i could be attributed to mitigating podocyte apoptosis and attenuating renal fibrosis.Trial registration This clinical trial was registered on 15/10/2019, in ClinicalTrials.gov, and the registry number is NCT04127084.
Towards understanding various influences on mass balance of the Hoksar Glacier in the Upper Indus Basin using observations
Authors: Romshoo Shakil Ahmad , Murtaza Khalid Omar , Abdullah Tariq 
Published: September 2022

AbstractMass balance is a good indicator of glacier health and sensitivity to climate change. The debris-covered Hoksar Glacier (HG) in the Upper Indus Basin (UIB) was studied using direct and geodetic mass balances. During the 5-year period from 2013 to 2018, the glacier’s mean in situ mass balance (MB) was − 0.95 ± 0.39 m w.e. a−1. Similarly, the glacier’s mean geodetic MB from 2000 to 2012 was − 1.20 ± 0.35 m w.e. a−1. The continuously negative MB observations indicated that the HG is losing mass at a higher rate than several other Himalayan glaciers. The glacier showed increased mass loss with increasing altitude, in contrast to the typical decreasing MB with increasing elevation, due to the existence of thick debris cover in the ablation zone, which thins out regularly towards the accumulation zone. Rising temperatures, depleting snowfall and increasing black carbon concentration in the region, indicators of climatic change, have all contributed to the increased mass loss of the HG. During the lean period, when glacier melt contributes significantly to streamflow, the mass loss of glaciers has had a considerable impact on streamflow. Water availability for food, energy, and other essential economic sectors would be adversely affected, if, glaciers in the region continued to lose mass due to climatic change. However, long-term MB and hydro-meteorological observations are required to gain a better understanding of glacier recession in the region as climate changes in the UIB.
Effect of PbO-nanoparticles on dimethyl polysiloxane for use in radiation shielding applications
Authors: El-Khatib Ahmed M. , Abbas Mahmoud I. , Hammoury Sabbah I. , Gouda Mona M. , Zard Kareman , Elsafi Mohamed. 
Published: September 2022

AbstractIn this work, morphological and attenuation parameters of gamma ray protection were studied. Dimethyl polysiloxane (Silicon Rubber) Mixed with micro-size and nano-size lead oxide particles at different weight percentage were prepared. The morphological structure of PbO/SR composites was investigated by SEM test, according to SEM images the nano PbO particles are more uniform micro PbO particles. The radiation attenuation test was carried out using 3ʺ × 3ʺ NaI (TI) detector for (Am-241), (Cs-137), (Co-60), (Ba-133), and (Eu-152). The effect on attenuation property of SR-PbO shown that the increase of PbO filler significantly increases the linear attenuation coefficient and improve the other radiation protection parameters especially at low gamma energy. It's found that a significant agreement between the experimental result and theoretical result from Xcom program. In this study it's found matrix filled with nano-PbO have higher gamma shielding ability compared to micro-PbO matrix at the same filler concentration. It can say that SR-nano PbO has a higher radiation protection than SR-micro PbO compositions.
Structural design and effect analysis on a new type of hydraulic oscillator driven with double valve groups
Authors: Lingxia Hou , Qiaolei Sun , Long Deng , Yuwei Liu , Ding Feng 
Published: September 2022

AbstractA new hydraulic oscillator was designed, which was able to adjust pressure fluctuations through two sets of dynamic and fixed valves. Hydraulic oscillators can meet the frequency and axial force requirements of drilling at lower drilling fluid flow than general hydraulic oscillators. Oscillator structure was described in detail and over-flow area between the two sets of dynamic and fixed valves was calculated. Based on drilling fluid flow difference, the influence of different fluid flows on oscillator pressure drops was analyzed, its influence law was determined by the finite element software Fluent, and its effect was verified by numerical simulations. The related research is of great significance in the selection of dynamic and fixed valves and provides the theoretical basis for the optimization of the structural parameters of double-valve hydraulic oscillators.
Culexarchaeia, a novel archaeal class of anaerobic generalists inhabiting geothermal environments
Authors: Kohtz Anthony J , Jay Zackary J , Lynes Mackenzie M , Krukenberg Viola , Hatzenpichler Roland 
Published: September 2022

Abstract
Geothermal environments, including terrestrial hot springs and deep-sea hydrothermal sediments, often contain many poorly understood lineages of archaea. Here, we recovered ten metagenome-assembled genomes (MAGs) from geothermal sediments and propose that they constitute a new archaeal class within the TACK superphylum, “Candidatus Culexarchaeia”, named after the Culex Basin in Yellowstone National Park. Culexarchaeia harbor distinct sets of proteins involved in key cellular processes that are either phylogenetically divergent or are absent from other closely related TACK lineages, with a particular divergence in cell division and cytoskeletal proteins. Metabolic reconstruction revealed that Culexarchaeia have the capacity to metabolize a wide variety of organic and inorganic substrates. Notably, Culexarchaeia encode a unique modular, membrane associated, and energy conserving [NiFe]-hydrogenase complex that potentially interacts with heterodisulfide reductase (Hdr) subunits. Comparison of this [NiFe]-hydrogenase complex with similar complexes from other archaea suggests that interactions between membrane associated [NiFe]-hydrogenases and Hdr may be more widespread than previously appreciated in both methanogenic and non-methanogenic lifestyles. The analysis of Culexarchaeia further expands our understanding of the phylogenetic and functional diversity of lineages within the TACK superphylum and the ecology, physiology, and evolution of these organisms in extreme environments.
Serum metabolome alterations in patients with early nonalcoholic fatty liver disease
Authors: Wang Xuemei , Rao Benchen , Wang Haiyu , Liu Chao , Ren Zhigang , Yu Zujiang 
Published: September 2022

Abstract
Background: Although metabolomic analysis for patients with nonalcoholic fatty liver disease (NAFLD) was a promising approach to identify novel biomarkers as targets for the diagnosis of NAFLD, the serum metabolomics profile of early-stage NAFLD patients from central China remain unknown. Objective: The aim of the present study was to explore the metabolic characteristics of patients with early-stage NAFLD based on the ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) technology, to identify differential metabolites and perform functional analysis, and especially, to establish a novel early NAFLD clinical diagnostic tool. Results: Compared with healthy controls, serum metabolite species increased significantly in early stage NAFLD patients. Expression of 88 metabolites including 1-naphthylmethanol, rosavin, and theophylline were up-regulated in early NAFLD, while 68 metabolites including 2-hydroxyphenylacetic acid and lysophosphatidylcholine (24:1(15Z)) were down-regulated. The early NAFLD classifier achieved a strong diagnostic efficiency in the discovery phases (80.99%) and was successfully verified in the validation phases (75.23%). Conclusions: These results advance our understanding about the composition and biological functions of serum metabolites of early NAFLD. In addition, serum metabolic markers can serve as an efficient diagnostic tool for the early-stage NAFLD.
The antioxidant and anti-inflammatory effects of Eremina desertorum snail mucin on experimentally induced intestinal inflammation and testicular damage
Authors: Ibrahim Amina M. , Morad Mostafa Y. , El-Khadragy Manal F. , Hammam Olfat A. 
Published: September 2022

Abstract
Eremina desertorum snail mucin antioxidant and anti-inflammatory effects were investigated against carbon tetrachloride (CCl4)-intestinal inflammation and testes damage. Male albino mice were intraperitoneally injected with 0.5 ml/kg b.wt of 40% CCl4, twice a week for 8 weeks. The treated groups were treated orally with mucin (after 8 weeks of CCl4 intoxication, twice a week for 4 weeks). CCl4 caused significant increases in C-reactive protein, lipid peroxidation, interleukin-2 levels and caspase-3, while decreasing the total proteins levels, activities of catalase, superoxide dismutase, and glutathione reductase contents, testosterone and 17β estradiol levels compared with the control mice. The improvements of these parameters occurred after treatment with E. desertorum mucin, where all the biochemical measurements tended to restore to the normal values. Histopathologically, CCl4 caused ulceration in the columnar mucin secreting cells that lined the ileal mucosa, partial loss of goblet cells, abnormal villous/crypt ratio, and submucosal infiltrate of the inflammatory cells. Also, sections of testis showed alterations in the developmental spermatogenic arrangement of the same seminiferous tubules, with no spermatozoa in the center. Improvements in these architectures occurred after administration of mucin, where sections showed almost normal histological structure. In conclusion, E. desertorum mucin could be used as a supplementary material as it has antioxidant and anti-inflammatory effects; besides it has low cost.