bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated analyses of the intestinal microbiome and transcriptome in NingXiang piglets
Authors: Hu Zhenguo , Yao Yuezhou , Chen Feiyue , Feng Luya , Yuan Zian , Deng Junhao , Huang Lang , Yin Yulong , Tang Xiongzhuo 
Published: April 2024

Abstract

NingXiang (NX) pig has been recognized as one of the most famous Chinese indigenous breeds due to its characteristics in high fertility and stress resistance. However, the global intestinal gene expression profiling and the feature of gut microorganisms in NX piglets have not been studied. Here, we compared the intestinal microbiome and transcriptome between NX and Duroc × Landrace × Large white (DLY) piglets and found the high enrichment of several colonic Bacteroides, Prevotella and Clostridium species in NX piglets than DLY piglets. Further functional analyses of these microbes revealed their predominant function in methane, glycolysis and gluconeogenesis metabolism. Our mRNA-sequencing data unraveled the distinct colonic gene expression between these two pig breeds. In particular, NX piglets exhibited improved intestinal barrier function and cellulose digestibility, as well as varied immune features than DLY piglets. Finally, by integrating metagenomic and transcriptomic analyses, we further showed that the improved intestinal function in NX piglets may be determined by intestinal genes through modulating the composition of the gut microbes. Together, our study revealed the intestinal characteristics of NX piglets, providing their potential application in improving breeding strategies and developing dietary interventions.
Data-driven Network Connectivity Analysis: An Underestimated Metric
Authors: Xu Junxiang , Nair Divya Jayakumar 
Published: April 2024

Abstract

In network structure analysis, metrics such as Isolated Node Ratio (INR), Network Efficiency (NE), Network Clustering Coefficient (NCC), Betweenness Centrality (BC), and Closeness Centrality (CC) are used as quantitative tools to measure network connectivity. However, there is another metric that is often easily overlooked and underestimated, i.e., the Relative Size of Largest Connected Component (RSLCC), we do not find any literature that analyzed RSLCC in a separate study. However, through the research in this paper, we not only prove that this metric is underestimated, but also design 7 methods to predict the value of this metric, with a Deep Neural Network (DNN) prediction accuracy of more than 99%. This research results can be applied to any network, and in a disaster scenario, whether it is a physical entity network or a virtual abstract network, the approximate network connectivity value can be predicted simply by knowing the number of connected edges in the pre-disaster network and the number of connected edges in the post-disaster network.
Uptake of alpha-synuclein preformed fibrils is suppressed by inflammation and induces an aberrant phenotype in human microglia
Authors: Niskanen Jonna , Peltonen Sanni , Ohtonen Sohvi , Fazaludeen Mohammad Feroze , Luk Kelvin C. , Giudice Luca , Koistinaho Jari , Malm Tarja , Goldsteins Gundars , Albert Katrina , Lehtonen Šárka 
Published: April 2024

Abstract

Microglia are brain resident immune cells that maintain proteostasis and cellular homeostasis. Recent findings suggest that microglia dysfunction could contribute to the pathogenesis of Parkinson’s disease. One of the hallmarks of Parkinson’s disease is the aggregation and accumulation of alpha-synuclein into Lewy bodies inside nerve cells. Microglia may worsen the neuronal microenvironment by persistent inflammation, resulting in deficient clearing of aggregated alpha-synuclein. To model microglial behavior in Parkinson’s disease, we utilized human induced pluripotent stem cells to generate functionally active microglia. We studied the microglial uptake of alpha-synuclein preformed fibrils (PFFs) and the effect of pro-inflammatory stimulation by interferon gamma. We demonstrate that combined exposure disrupts the phagosome maturation pathway while inflammatory stimuli suppress chaperone mediated autophagy and mitochondrial function. Furthermore, inflammatory stimulation impairs PFF uptake in microglia and increases cytokine production. Moreover, excessive PFF uptake by microglia results in induction of iNOS. Taken together, we demonstrate that this model is valuable for investigating the behavior of microglia in Parkinson’s disease and provide new insights on how human microglia process aggregated alpha-synuclein.
Bringing Together Synthesis and Simulations: Advancing Intercalation Strategies in Layered Hybrid Perovskites
Authors: Payne Julia , Yang Linjie , Xuan Wenye , Henda Sara , Wang Shaoyang , Rajendran Sai Kiran , Cordes David , Miller David , Slawin Alexandra , Jagadamma Lethy Krishnan , Ohadi Hamid , Chen Hsin-Yi Tiffany , Dyer Matthew 
Published: April 2024

Abstract

Finding new, innovative ways to modify the electronic structure of halide perovskites is desireable as they have applications in a variety of devices, from photovoltaics to LEDs. Additionally, designing new, functional materials can be facilitated through the use of computation. Here, we have used a combination of synthesis and computation to screen for new, intercalated, layered hybrid perovskites. 54 compositions were screened and five compounds containing intercalated halogens were prepared as single crystals. A further compound, which was not screened and contained IBr, was prepared. We computationally identified an intercalated layered hybrid perovskite with a low bandgap and prepared it as a thin-film. Through examination of single crystal X-ray diffraction data, we provide some design guidelines for intercalation. The conformational flexibility in the organic ammonium cation allows rotations in the carbon backbone which change upon intercalation. Optoelectronic properties were studied using photoluminescence spectroscopy and preliminary photovoltaic device testing.
Evaluation and optimization of electrocoagulation process parameters for the treatment of oil industry drilling site wastewater
Authors: Kumar Pramod , Nawaz Tabish , Singh Swatantra P. 
Published: April 2024

Abstract

The effluent from the oil drilling site is a complex mixture of hazardous chemicals that causes environmental impacts on its disposal. The treatment of oil drill-site wastewater has not been explored much and requires understanding its characteristics and optimizing the treatment process. In the present study, we have optimized the electrocoagulation process with aluminum electrodes for drill-site wastewater treatment. A multi-level factorial center composite design using response surface methodology (RSM) is applied to optimize the effect of current density, pH, and inter-electrode distance (IED) on COD removal. The increasing current density shows a significant increase in COD removal, and a similar trend was observed with a decrease in pH. It was found that with current density and inter-electrode distance, the maximum COD removal achieved was 70% at the CD of 19.04 mA cm-2 and IED 2.6 cm. By varying pH and current density, the COD removal reached up to 90% at pH 6 and CD 19.04 mA cm-2. The study shows that the current density is the dominant factor for the process's energy consumption and operating cost, followed by pH. This study's findings could be effectively used for developing large-scale treatment processes through the electrocoagulation process.
Novel anthraquinone amino derivatives as anticancer agents targeting the human serine/threonine kinase PAK4
Authors: Hasan Hamad M. , Koua Faisal H. M. , Beit Hajer A. , Ebrahim Reem M. A. , Ismail Amar Mohamed 
Published: April 2024

Abstract

Recently, anthraquinone scaffolds have attracted increasing amounts of attention as sources for effective drug synthesis for the treatment of various diseases. Here, we demonstrate the potential of nine anthraquinone amino-derivatives (AADs) as anticancer agents. We synthesized nine Schiff bases (1-9) using an anthraquinone scaffold and amino acids. We applied in silico analysis by performing molecular docking against the anticancer drug target human serine/threonine p21-activated kinase 4 (PAK4) and compared them with the recently developed PAK4 inhibitor PF-3758309. Compounds 5and 8 showed docking properties comparable to that of PF-3758309 at two binding sites located in the C-terminal domain of PAK4. Compound 5, a tryptophan-based anthraquinone derivative, had docking scores of -9.3 and -8.7 kcal/mol at two different identified cavities, cav-1 and cav-4, respectively, exceeding that of the control PF-3758309 for both cavities. Additional optimization of the indole moiety of 5gave rise to 5b, resulting in high drug likeness (0.74) and comparable binding properties to cav-1 (-8.6 kcal/mol) and the highest achievable binding affinity to cav-4, with an average of -9.7 kcal/mol, indicating a potential allosteric inhibitory effect via cav-4. Our molecular dynamics simulation analysis of the top hits and the control compound provides important insights into the mechanism of action of these drug candidates. Additionally, all the compounds exhibited promising pharmacokinetic and toxicity properties, as revealed by the ADMET profiles, urging the need for comprehensive in vitro and in vivo antitumor characterization. Our results also indicate that cav-4 may serve as a target for designing specific allosteric inhibitors against PAK4-overexpressing cancer cells, suggesting its potential application in adjuvant cancer treatment.
Investigating the effect of TIG welding process variables on the mechanical properties of stainless steel-304 pipe welded joints
Authors: Yeshanew Dessalegn Ahmed , Yeshanew Dessalegn Ahmed , Mana Labena Manza 
Published: April 2024

Abstract

Stainless steel weld joint quality optimization research has become necessary due to the rise in sudden welded pipe joint failure. The mechanical characteristics and weld quality are greatly influenced by the combined effect of controllable process parameters. This study sought to determine the ideal parameters and examine how tungsten inert gas welding process factors affected the mechanical characteristics of the stainless pipe weld joint. Welded features such as bead shape, size, and mechanical properties were studied related to the weld controllable factors in order to achieve the desired weld quality. Austenitic stainless-steel samples (AISI 304) having 90mm outer diameter and 5mm thick pipe was used for the study. Data were studied using analysis of variance to evaluate the effect of each factor and validated the model's suitability. The results show that the rate of gas flow had the greatest impact on the tensile strength and hardness, whereas the welding current had the main influential factor on the bending strength. Weld parameters were optimized by applying response surface methodology technic and validated using laboratory tests. According to the experiment, optimum weld parameters were 121.30amp, 14 Lit/min, and 2mm for current, gas flow, and root gap respectively. As a result of these parameters combination, optimized mechanical properties were determined including tensile strength of 1402.601N/mm2, hardness of 61.372HRA, and bending strength of 826.022Nm. The optimized parameters evolved from this research can be utilized in the fabrication process of TIG welding at the industries.
Alterations in genes associated with cytosolic RNA sensing in whole blood are associated with coronary microvascular disease in SLE
Authors: Huo Lihong , Montano Erica , Tumurkhuu Gantseg , Bose Moumita , Berman Daniel S. , Wallace Daniel , Wei Janet , Ishimori Mariko , Merz C. Noel Bairey , Jefferies Caroline 
Published: April 2024

Abstract

Systemic lupus erythematosus (SLE) patients are 90% women and over three times more likely to die of cardiovascular disease than women in the general population. Chest pain with no obstructive cardiac disease is associated with coronary microvascular disease (CMD), where narrowing of the small blood vessels can lead to ischemia, and frequently reported by SLE patients. Using whole blood RNA samples, we asked whether gene signatures discriminate SLE patients with coronary microvascular dysfunction (CMD) on cardiac MRI (n=4) from those without (n=7) and whether any signaling pathway is linked to the underlying pathobiology of SLE CMD. RNA-seq analysis revealed 143 differentially expressed (DE) genes between the SLE and healthy control (HC) groups, with virus defense and interferon (IFN) signaling being the key pathways identified as enriched in SLE as expected. We next conducted a comparative analysis of genes differentially expressed in SLE-CMD and SLE-non-CMD relative to HC samples. Our analysis highlighted differences in IFN signaling, RNA sensing and ADP-ribosylation pathways between SLE-CMD and SLE-non-CMD. This is the first study to investigate possible gene signatures associating with CMD in SLE, and our data strongly suggests that distinct molecular mechanisms underly vascular changes in CMD and non-CMD involvement in SLE.
Influence of electrodeposition parameters on the fabrication of Ni-Co/SiC+TiN composite films through pulse current electrodeposition
Authors: Cui Tianqi , Cao Mengyu 
Published: April 2024

Abstract

In this investigation, pulsed current electro-deposition (PCE) was used to prefabricate Ni-Co/SiC + TiN composite films (NCSTCFs) on mild steel surfaces. The research focused on the influence of two electrodeposition parameters, pulse frequency (PF) and duty cycle (DC), on NCSTCF features including microscopic surface morphology, crystal orientation, grain size, microhardness, SiC and TiN nanoparticles (NPs), deposition quantity, and corrosion resistance properties. The results indicated that NCSTCFs produced under a 10% DC showed minimal SiC and TiN contents with a percent volume of just 5.6 v/v% and 5.4 v/v% respectively under the fixed condition of 60 Hz PF. However, the three-dimensional surface diagram indicated that the Ni-Co/SiC + TiN composite film deposited at 50% DC and 10 Hz PF displayed the highest SiC and TiN contents (11.6 v/v% and 11.7 v/v%) among all the films. Furthermore, NCSTCFs deposited under 50% DC and 10 Hz PF had peak microhardness at 667.4 kg/mm2, while the composite film achieved a microhardness of 514.1 kg/mm2 when prepared using 10% DC and 60 Hz PF. Moreover, when the DC and PF were at 50% and 10 Hz respectively, the Ni-Co/SiC + TiN composite film presented the maximum charge transfer resistance (4915.7-4927.2 Ω·cm2), indicating an excellent corrosion resistance.
GFPT2 controls immune evasion in EGFR-mutated non-small cell lung cancer
Authors: Liu Jiali , Ao Luyao , Jia Wenjing , Gong Qixing , Cui Jiawen , Wang Jun , Yu Ying , Fu Chenghao , Li Haobin , Wei Jia , Wang Ruiqi , Wang Feiyi , Shang Xin , Li Yantong , Fang Shencun , Wang Guangji , Zhou Fang 
Published: April 2024

Abstract

In the evolving field of cancer immunotherapy, EGFR-mutated non-small cell lung cancer (NSCLC) poses a significant obstacle due to its inherent resistance to conventional treatments. The development of an effective strategy to overcome this resistance remains a challenge. Here we have identified glutamine fructose-6-phosphate transaminase 2 (GFPT2) as a prime architect in the immune evasion phenotype induced by EGFR mutations. Mechanistically, in the presence of EGFR mutations, the expression of GFPT2, typically low in normal tissues, is significantly upregulated via the EGFR/IRE1α/Xbp1s signaling pathway. This results in a significant increase in intracellular UDP-GlcNAc levels, altering N-glycosylation profiles extensively. GFPT2 escalates the expression and glycosylation of PD-L1, PVR and CD276, bolstering their interactions with CD8+T cells, and also amplifies CD73 glycosylation to intensify adenosine-mediated suppression of CD8+T cells. These actions collectively reduce tumor cell vulnerability to CD8+T cell-mediated death. Moreover, GFPT2 also hinders the infiltration of CD8+T cells into tumors by regulating EGFR glycosylation and subsequent secretion of CXCL10 and VEGF. The validation of this GFPT2-mediated immune evasion phenotype is substantiated by compelling clinical evidence. We further identified a GFPT2 isoform-specific inhibitor that can enhance the efficacy of PD-1 blockade therapy beyond current strategies, as evidenced by results in xenograft models and patient-derived organoids. Taken together, our results highlight the potential of GFPT2 as a metabolic checkpoint in controlling immune escape in EGFR-mutated NSCLC, offering an innovative and druggable target to bolster immunotherapy outcomes in NSCLC with EGFR mutations.
Rapid and accurate prediction of protein homo-oligomer symmetry with Seq2Symm
Authors: Kshirsagar Meghana , Meller Artur , Humphreys Ian , Sledzieski Samuel , Xu Yixi , Dodhia Rahul , Horvitz Eric , Berger Bonnie , Bowman Gregory , Ferres Juan Lavista , Baker David , Baek Minkyung 
Published: April 2024

Abstract

The majority of proteins must form higher-order assemblies to perform their biological functions. Despite the importance of protein quaternary structure, there are few machine learning models that can accurately and rapidly predict the symmetry of assemblies involving multiple copies of the same protein chain. Here, we address this gap by training several classes of protein foundation models, including ESM-MSA, ESM2, and RoseTTAFold2, to predict homo-oligomer symmetry. Our best model named Seq2Symm, which utilizes ESM2, outperforms existing template-based and deep learning methods. It achieves an average PR-AUC of 0.48 and 0.44 across homo-oligomer symmetries on two different held-out test sets compared to 0.32 and 0.23 for the template-based method. Because Seq2Symm can rapidly predict homo-oligomer symmetries using a single sequence as input (~ 80,000 proteins/hour), we have applied it to 5 entire proteomes and ~ 3.5 million unlabeled protein sequences to identify patterns in protein assembly complexity across biological kingdoms and species.
Gipc3 Mutation Might Cause Sensorineural Hearing Loss by Inhibiting Mitophagy in Inner Ear Hair Cells
Authors: Li Xinxin , Wang Jing , Shi Lin , Wang Liang 
Published: April 2024

Abstract

Sensory hearing loss (SNHL) has a high degree of genetic heterogeneity, and there are many mutated genes that cause deafness. GIPC3 gene is one of the mutated genes that can cause congenital hearing loss found in recent years, but the mechanism of its cause is still unclear. Mitophagy is the process of selectively encapsulating and lysing damaged or dysfunctional mitochondria in order to prevent accumulation of damaged mitochondria from damaging the cells and is of great importance in the maintenance of homeostasis in the inner ear. The aim of this paper is to observe the effect of Gipc3 expression on mitochondrial metabolism and autophagy in inner ear hair cells, and to explore the possible mechanism of sensorineural hearing loss caused by Gipc3 mutations. In this study, The House Ear Institute Organ of Corti 1(HEI-OC1) cells and cochlear explants were cultured to change the expression level of Gipc3 by transfection, and the knockdown efficiency was examined by quantitative polymerase chain reaction (qPCR) and Western Blot. Knockdown of Gipc3 inhibited cell viability and its proliferation ability. When t-BHP was used to induce oxidative stress injury and knockdown of Gipc3, inner ear hair cells had weakened ability to resist oxidative stress injury, mitochondrial metabolism was altered, and there was accumulation of reactive oxygen species and reduction of mitochondrial membrane potential. Immunofluorescence and Western Blot techniques revealed that the mitochondrial autophagy-related proteins, LC3B and P62, showed autophagy disorders. A PH domain, leucine zipper motif 1(APPL1) mediates early endosome-dependent mitophagy, and deletion of APPL1 impairs mitochondrial autophagy. We found that fluorescence co-localization exists between Gipc3 and APPL1, and that they interact with each other, with positive correlation in their trends. In summary, Gipc3 mutation may lead to decreased mitochondrial function by inhibiting the APPL1-mediated mitochondrial autophagy process, out of which impaired oxidative metabolism in hair cells may occur, which is a possible mechanism for the inhibition of mitochondrial autophagy by Gipc3 mutation.
Bexarotene promotes neuroblastoma SH-SY5Y cells differentiation to mature neurons with decreased proliferation
Authors: Zhang Fan , Gao Kai , Zhang Junjiao , Wang Jingmin , Wu Ye , Jiang Yuwu , Wu Congying 
Published: April 2024

Abstract

Bexarotene is an retinoid X receptor (RXR) pharmacological agonist that has been demonstrated to treat cutaneous T-cell lymphoma and promising therapeutic potential for neurological diseases. But it still remains unclear whether bexarotene participates in regulation of neuroblastoma. Human neuroblastoma SH-SY5Y cells were used as a model to investigate the neuronal differentiation impact of bexarotene. Bexarotene-cultured SH-SY5Y cells showed changes in cell morphology, adopting pyramidal shapes and extending neurites, increased expression of neuronal marker β-tubulin III and mature neurons marker Neurofilament M and upregulation of neuronal differentiation markers including growth associated protein 43 (GAP43) and synaptophysin (SYP). SH-SY5Y cells induced by bexarotene increased the mRNA expression of glutamatergic marker glutamate-ammonia ligase (GLUL), GABAergic marker glutamate decarboxylase (GAD1) and dopaminergic marker TH, but not cholinergic marker solute carrier family 18 member 1 (SLC18A1). Functional enrichment analysis of RNAseq data revealed that the PI3K-AKT axis is the dominant signaling pathway promoting the differentiation of SH-SY5Y cells into mature and functional neurons in response to bexarotene. Additionally, we observed that SH-SY5Y cells show reduced proliferation rates accompanied by decreased expression of cyclin dependent kinase 6 (CDK6) and increased expression of cyclin dependent kinase 1 (CDK1) following 7-day exposure to bexarotene, suggesting bexarotene induces a quiescent state in SH-SY5Y cells. SH-SY5Y cells can be induced to mature neurons with decreased proliferation induced by bexarotene via PI3K-AKT axis. It indicates bexarotene has the potential to treat neuroblastoma.
Extended Postoperative Ciprofloxacin Prophylaxis for Post-Phacoemulsification Endophthalmitis
Authors: Ciftci Suleyman 
Published: April 2024

Abstract

Purpose: This study investigated the efficacy of extended oral ciprofloxacin prophylaxis in reducing the incidence of endophthalmitis after cataract surgery.
Setting: Single-center study conducted at a tertiary health facility.
Design: This was a retrospective observational study.
Methods: This study was conducted on patients who underwent uncomplicated phacoemulsification surgery. Two cohorts were analyzed: one receiving oral ciprofloxacin twice daily for one week post-surgery and another not receiving ciprofloxacin. The patients who did not receive ciprofloxacin were operated on between June 2013 and October 2019, while the others underwent surgery between June 2011 and April 2021. Endophthalmitis incidence, patient demographics, and surgical variables were assessed between the two groups. Statistical analyses included chi-square tests, Fisher’s exact tests, logistic regression, and Kaplan‒Meier estimates.
Results: Out of 1172 eyes (1015 patients), 548 received ciprofloxacin, and 624 did not. The ciprofloxacin group reported a 0% incidence of endophthalmitis compared to 0.8% in the non ciprofloxacin group. While the chi-square test revealed significant differences (p=0.036), Fisher’s exact test did not reach significance at values less than <0.05. The efficacy of oral ciprofloxacin in preventing endophthalmitis was 100%. The odds ratios for sex, age, and unilateral/bilateral surgery were not significant. Challenges in achieving statistical significance, attributable to zero events in the ciprofloxacin group, were acknowledged.
Conclusion: Oral administration of two 750 mg tablets of ciprofloxacin per day for one week after phacoemulsification surgery is superior to a single intracameral antibiotic injection as an additional treatment.