bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting SOD1 via RNAi with PEGylated graphene oxide nanoparticles in platinum-resistant ovarian cancer
Authors: Szénási Attila , Sivasudhan Enakshi , Du Hong , Zhang Peizhuo , Huang Jie , Zhang Zhijun , Rocha Sonia , Wang Mu 
Published: August 2023

AbstractAcquired platinum resistance poses a significant therapeutic impediment to ovarian cancer patient care, accounting for more than 200,000 deaths annually worldwide. We previously identified that overexpression of the antioxidant superoxide dismutase 1 (SOD1) in ovarian cancer is associated with a platinum-resistant phenotype via conferring oxidative stress resistance against platinum compounds. We further demonstrated that enzymatic inhibition using small-molecule inhibitors or silencing of SOD1 via RNA interference (RNAi) increased cisplatin sensitivity and potency in vitro. We launched this study to explore the potential therapeutic applications of SOD1 silencing in vivo in order to reverse cisplatin resistance using a graphene-based siRNA delivery platform. PEGylated graphene oxide (GO) polyethyleneimine (GOPEI-mPEG) nanoparticle was complexed with SOD1 siRNA. GOPEI-mPEG-siSOD1 exhibited high biocompatibility, siRNA loading capacity, and serum stability, and showed potent downregulation of SOD1 mRNA and protein levels. We further observed that cisplatin and PEI elicited mitochondrial dysfunction and transcriptionally activated the mitochondrial unfolded protein response (UPRmt) used as a reporter for their respective cytotoxicities. SOD1 silencing was found to augment cisplatin-induced cytotoxicity resulting in considerable tumour growth inhibition in cisplatin-sensitive A2780 and cisplatin-resistant A2780DDP subcutaneous mouse xenografts. Our study highlights the potential therapeutic applicability of RNAi-mediated targeting of SOD1 as a chemosensitizer for platinum-resistant ovarian cancers.
m5C-methylated lncRNA NR_033928 promotes gastric cancer proliferation by stabilizing GLS mRNA to promote glutamine metabolism reprogramming
Authors: Fang Lang , Huang Hongxin , Lv Jialun , Chen Zetian , Lu Chen , Jiang Tianlu , Xu Penghui , Li Ying , Wang Sen , Li Bowen , Li Zheng , Wang Weizhi , Xu Zekuan 
Published: August 2023

AbstractAbnormal 5-methylcytosine (m5C) methylation has been proved to be closely related to gastric carcinogenesis, progression, and prognosis. Dysregulated long noncoding RNAs (lncRNAs) participate in a variety of biological processes in cancer. However, to date, m5C-methylated lncRNAs are rarely researched in gastric cancer (GC). Here, we found that RNA cytosine-C(5)-methyltransferase (NSUN2) was upregulated in GC and high NSUN2 expression was associated with poor prognosis. NR_033928 was identified as an NSUN2-methylated and upregulated lncRNA in GC. Functionally, NR_033928 upregulated the expression of glutaminase (GLS) by interacting with IGF2BP3/HUR complex to promote GLS mRNA stability. Increased glutamine metabolite, α-KG, upregulated NR_033928 expression by enhancing its promoter 5-hydroxymethylcytosine (hm5C) demethylation. In conclusion, our results revealed that NSUN2-methylated NR_033928 promoted GC progression and might be a potential prognostic and therapeutic target for GC.
Methionine orchestrates the metabolism vulnerability in cisplatin resistant bladder cancer microenvironment
Authors: Yang Chen , Ou Yuxi , Zhou Quan , Liang Yingchun , Li Weijian , Chen Yiling , Chen Wensun , Wu Siqi , Chen Yifan , Dai Xiyu , Chen Xinan , Chen Tian , Jin Shengming , Liu Yufei , Zhang Limin , Liu Shenghua , Hu Yun , Zou Lujia , Mao Shanhua , Jiang Haowen 
Published: August 2023

AbstractMetabolism vulnerability of cisplatin resistance in BCa cells remains to be discovered, which we applied integrated multi-omics analysis to elucidate the metabolism related regulation mechanism in bladder cancer (BCa) microenvironment. Integrated multi-omics analysis of metabolomics and proteomics revealed that MAT2A regulated methionine metabolism contributes to cisplatin resistance in BCa cells. We further validated MAT2A and cancer stem cell markers were up-regulated and circARHGAP10 was down-regulated through the regulation of MAT2A protein stability in cisplatin resistant BCa cells. circARHGAP10 formed a complex with MAT2A and TRIM25 to accelerate the degradation of MAT2A through ubiquitin-proteasome pathway. Knockdown of MAT2A through overexpression of circARHGAP10 and restriction of methionine up-take was sufficient to overcome cisplatin resistance in vivo in immuno-deficiency model but not in immuno-competent model. Tumor-infiltrating CD8+ T cells characterized an exhausted phenotype in tumors with low methionine. High expression of SLC7A6 in BCa negatively correlated with expression of CD8. Synergistic inhibition of MAT2A and SLC7A6 could overcome cisplatin resistance in immuno-competent model in vivo. Cisplatin resistant BCa cells rely on methionine for survival and stem cell renewal. circARHGAP10/TRIM25/MAT2A regulation pathway plays an important role in cisplatin resistant BCa cells while circARHGAP10 and SLC7A6 should be evaluated as one of the therapeutic target of cisplatin resistant BCa.
Nanoparticles carrying paclitaxel and anti-miR-221 for breast cancer therapy triggered by ultrasound
Authors: Zhang Libo , Ren Zhen , Lü Jinhui , Mo Xinhai , Lin Jie , Li Ya , Ma Wenjing , Liu Pengfei , Shen Yajing , Zhao Qian , Qian Lu , Cheng Xiaoxin , Yu Zuoren , Zhang Bo 
Published: August 2023

AbstractNanomaterials have been well demonstrated to have the potential to be used for tumor cell-targeted drug delivery. Targeted inhibition of miR-221 was proved to promote the sensitivity of triple genitive breast cancer (TNBC) cells to chemo-drugs. In order to improve the chemotherapeutic effect in TNBC, herein, we developed a novel kind of nanoparticles shelled with PLGA and loaded with perfluoropentane (PFP), paclitaxel (PTX), and anti-miR-221 inhibitor, which was named PANP. Ultrasound-triggered vaporization of PFP in PANPs was utilized for real-time imaging track of the nanoparticles in vivo. In addition, macrophages were applied for the internalization of PANPs to form RAW-PANP with strong chemotaxis to accumulate around cancer cells. Nanoparticles with different contents did not cause M2 polarization compared with the control group but caused polarization toward M1. We compared the inherent tumor-homing behavior of macrophages containing different contents with that of normal macrophages and no significant abnormalities were observed. After injection into the tumor-burden mice, RAW-PANPs showed enrichment within tumor tissues. Upon the ultrasound cavitation-triggered burst, PTX was released in the tumor. Meanwhile, the release of anti-miR-221 improved the sensitivity of tumor cells to PTX. As a result, RAW-PANPs showed high efficiency in suppressing TNBC cell proliferation in vitro and inhibiting tumor growth and progression in vivo. The treatments did not induce liver, heart, or kidney injury. In conclusion, the current study not only developed a macrophage-carried, ultrasound-triggered, cancer cell-targeted chemotherapeutic system, but also demonstrated a miRNA-based technique to promote drug sensitivity of cancer cells, which holds strong potential to treat patients with TNBC, especially for those suffering drug-resistance. The innovation of this study is to use macrophages to deliver nanoparticles to the tumors and then use ultrasound locally to burst the nanoparticles to release the miRNA and PTX.
NeuroD4 converts glioblastoma cells into neuron-like cells through the SLC7A11-GSH-GPX4 antioxidant axis
Authors: Wang Hao , Zhao Peiqi , Zhang Ying , Chen Zhen , Bao Han , Qian Wenqi , Wu Jian , Xing Zhenqiu , Hu Xiaowei , Jin Kunlin , Zhuge Qichuan , Yang Jianjing 
Published: August 2023

AbstractCell fate and proliferation ability can be transformed through reprogramming technology. Reprogramming glioblastoma cells into neuron-like cells holds great promise for glioblastoma treatment, as it induces their terminal differentiation. NeuroD4 (Neuronal Differentiation 4) is a crucial transcription factor in neuronal development and has the potential to convert astrocytes into functional neurons. In this study, we exclusively employed NeuroD4 to reprogram glioblastoma cells into neuron-like cells. In vivo, the reprogrammed glioblastoma cells demonstrated terminal differentiation, inhibited proliferation, and exited the cell cycle. Additionally, NeuroD4 virus-infected xenografts exhibited smaller sizes compared to the GFP group, and tumor-bearing mice in the GFP+NeuroD4 group experienced prolonged survival. Mechanistically, NeuroD4 overexpression significantly reduced the expression of SLC7A11 and Glutathione peroxidase 4 (GPX4). The ferroptosis inhibitor ferrostatin-1 effectively blocked the NeuroD4-mediated process of neuron reprogramming in glioblastoma. To summarize, our study demonstrates that NeuroD4 overexpression can reprogram glioblastoma cells into neuron-like cells through the SLC7A11-GSH-GPX4 signaling pathway, thus offering a potential novel therapeutic approach for glioblastoma.
Fast kernel-based association testing of non-linear genetic effects for biobank-scale data
Authors: Fu Boyang , Pazokitoroudi Ali , Sudarshan Mukund , Liu Zhengtong , Subramanian Lakshminarayanan , Sankararaman Sriram 
Published: August 2023

AbstractOur knowledge of non-linear genetic effects on complex traits remains limited, in part, due to the modest power to detect such effects. While kernel-based tests offer a versatile approach to test for non-linear relationships between sets of genetic variants and traits, current approaches cannot be applied to Biobank-scale datasets containing hundreds of thousands of individuals. We propose, FastKAST, a kernel-based approach that can test for non-linear effects of a set of variants on a quantitative trait. FastKAST provides calibrated hypothesis tests while enabling analysis of Biobank-scale datasets with hundreds of thousands of unrelated individuals from a homogeneous population. We apply FastKAST to 53 quantitative traits measured across ≈ 300 K unrelated white British individuals in the UK Biobank to detect sets of variants with non-linear effects at genome-wide significance.
A sex-specific thermogenic neurocircuit induced by predator smell recruiting cholecystokinin neurons in the dorsomedial hypothalamus
Authors: Jovanovic Predrag , Pool Allan-Hermann , Morones Nancy , Wang Yidan , Novinbakht Edward , Keshishian Nareg , Jang Kaitlyn , Oka Yuki , Riera Celine E. 
Published: August 2023

AbstractOlfactory cues are vital for prey animals like rodents to perceive and evade predators. Stress-induced hyperthermia, via brown adipose tissue (BAT) thermogenesis, boosts physical performance and facilitates escape. However, many aspects of this response, including thermogenic control and sex-specific effects, remain enigmatic. Our study unveils that the predator odor trimethylthiazoline (TMT) elicits BAT thermogenesis, suppresses feeding, and drives glucocorticoid release in female mice. Chemogenetic stimulation of olfactory bulb (OB) mitral cells recapitulates the thermogenic output of this response and associated stress hormone corticosterone release in female mice. Neuronal projections from OB to medial amygdala (MeA) and dorsomedial hypothalamus (DMH) exhibit female-specific cFos activity toward odors. Cell sorting and single-cell RNA-sequencing of DMH identify cholecystokinin (CCK)-expressing neurons as recipients of predator odor cues. Chemogenetic manipulation and neuronal silencing of DMHCCK neurons further implicate these neurons in the propagation of predator odor-associated thermogenesis and food intake suppression, highlighting their role in female stress-induced hyperthermia.
Spatial transcriptomics reveal markers of histopathological changes in Duchenne muscular dystrophy mouse models
Authors: Heezen L.G.M. , Abdelaal T. , van Putten M. , Aartsma-Rus A. , Mahfouz A. , Spitali P. 
Published: August 2023

AbstractDuchenne muscular dystrophy is caused by mutations in the DMD gene, leading to lack of dystrophin. Chronic muscle damage eventually leads to histological alterations in skeletal muscles. The identification of genes and cell types driving tissue remodeling is a key step to developing effective therapies. Here we use spatial transcriptomics in two Duchenne muscular dystrophy mouse models differing in disease severity to identify gene expression signatures underlying skeletal muscle pathology and to directly link gene expression to muscle histology. We perform deconvolution analysis to identify cell types contributing to histological alterations. We show increased expression of specific genes in areas of muscle regeneration (Myl4, Sparc, Hspg2), fibrosis (Vim, Fn1, Thbs4) and calcification (Bgn, Ctsk, Spp1). These findings are confirmed by smFISH. Finally, we use differentiation dynamic analysis in the D2-mdx muscle to identify muscle fibers in the present state that are predicted to become affected in the future state.
Optical blood-brain-tumor barrier modulation expands therapeutic options for glioblastoma treatment
Authors: Cai Qi , Li Xiaoqing , Xiong Hejian , Fan Hanwen , Gao Xiaofei , Vemireddy Vamsidhara , Margolis Ryan , Li Junjie , Ge Xiaoqian , Giannotta Monica , Hoyt Kenneth , Maher Elizabeth , Bachoo Robert , Qin Zhenpeng 
Published: August 2023

AbstractThe treatment of glioblastoma has limited clinical progress over the past decade, partly due to the lack of effective drug delivery strategies across the blood-brain-tumor barrier. Moreover, discrepancies between preclinical and clinical outcomes demand a reliable translational platform that can precisely recapitulate the characteristics of human glioblastoma. Here we analyze the intratumoral blood-brain-tumor barrier heterogeneity in human glioblastoma and characterize two genetically engineered models in female mice that recapitulate two important glioma phenotypes, including the diffusely infiltrative tumor margin and angiogenic core. We show that pulsed laser excitation of vascular-targeted gold nanoparticles non-invasively and reversibly modulates the blood-brain-tumor barrier permeability (optoBBTB) and enhances the delivery of paclitaxel in these two models. The treatment reduces the tumor volume by 6 and 2.4-fold and prolongs the survival by 50% and 33%, respectively. Since paclitaxel does not penetrate the blood-brain-tumor barrier and is abandoned for glioblastoma treatment following its failure in early-phase clinical trials, our results raise the possibility of reevaluating a number of potent anticancer drugs by combining them with strategies to increase blood-brain-tumor barrier permeability. Our study reveals that optoBBTB significantly improves therapeutic delivery and has the potential to facilitate future drug evaluation for cancers in the central nervous system.
Improved figure of merit (z) at low temperatures for superior thermoelectric cooling in Mg3(Bi,Sb)2
Authors: Chen Nan , Zhu Hangtian , Li Guodong , Fan Zhen , Zhang Xiaofan , Yang Jiawei , Lu Tianbo , Liu Qiulin , Wu Xiaowei , Yao Yuan , Shi Youguo , Zhao Huaizhou 
Published: August 2023

AbstractThe low-temperature thermoelectric performance of Bi-rich n-type Mg3(Bi,Sb)2 was limited by the electron transport scattering at grain boundaries, while removing grain boundaries and bulk crystal growth of Mg-based Zintl phases are challenging due to the volatilities of elemental reactants and their severe corrosions to crucibles at elevated temperatures. Herein, for the first time, we reported a facile growth of coarse-grained Mg3Bi2-xSbx crystals with an average grain size of ~800 μm, leading to a high carrier mobility of 210 cm2 · V−1 · s−1 and a high z of 2.9 × 10−3 K−1 at 300 K. A $$\Delta$$
Δ
T of 68 K at Th of 300 K, and a power generation efficiency of 5.8% below 450 K have been demonstrated for Mg3Bi1.5Sb0.5- and Mg3Bi1.25Sb0.75-based thermoelectric modules, respectively, which represent the cutting-edge advances in the near-room temperature thermoelectrics. In addition, the developed grain growth approach can be potentially extended to broad Zintl phases and other Mg-based alloys and compounds.
Screening of immunogenic proteins and evaluation of vaccine candidates against Mycoplasma synoviae
Authors: Zhang Guihua , Han Lejiabao , Li Zewei , Chen Yifei , Li Quan , Wang Shifeng , Shi Huoying 
Published: August 2023

AbstractMycoplasma synoviae (M. synoviae) is a serious avian pathogen that causes significant economic losses to chicken and turkey producers worldwide. The currently available live attenuated and inactivated vaccines provide limited protection. The objective of this study was to identify potential subunit vaccine candidates using immunoproteomics and reverse vaccinology analyses and to evaluate their preliminary protection. Twenty-four candidate antigens were identified, and five of them, namely RS01790 (a putative sugar ABC transporter lipoprotein), BMP (a substrate-binding protein of the BMP family ABC transporter), GrpE (a nucleotide exchange factor), RS00900 (a putative nuclease), and RS00275 (an uncharacterized protein), were selected to evaluate their immunogenicity and preliminary protection. The results showed that all five antigens had good immunogenicity, and they were localized on the M. synoviae cell membrane. The antigens induced specific humoral and cellular immune responses, and the vaccinated chickens exhibited significantly greater body weight gain and lower air sac lesion scores and tracheal mucosal thicknesses. Additionally, the vaccinated chickens had lower M. synoviae loads in throat swabs than non-vaccinated chickens. The protective effect of the RS01790, BMP, GrpE, and RS00900 vaccines was better than that of the RS00275 vaccine. In conclusion, our study demonstrates the potential of subunit vaccines as a new approach to developing M. synoviae vaccines, providing new ideas for controlling the spread of M. synoviae worldwide.
Ranking routes in semiconductor wafer fabs
Authors: Gupta Shreya , Hasenbein John J. , Kim Byeongdong 
Published: August 2023

AbstractWe develop a method to estimate the quality of processing routes in a wafer fabrication process. Ranking such routes can be useful for identifying the “best” and “worst” routes when making adjustments to recipes. Route categorization is also useful in developing efficient scheduling algorithms. In particular, we propose a method for ranking routes based on count-based metrics such as the number of defects on a wafer. We start with a statistical model to produce a “local” ranking of a tool and then build a “global” ranking via a heuristic procedure. Creating a fully statistical procedure for ranking routes in semiconductor fabrication plants is virtually impossible, given the number of possible routes and the limited data available. Nonetheless, our discussions with working engineers indicate that even approximate rankings are useful for making better operational decisions.
Computations of volumes in five candidates elections
Authors: Bruns Winfried , Ichim Bogdan 
Published: August 2023

AbstractWe describe several analytical (i.e., precise) results obtained in five candidates social choice elections under the assumption of the Impartial Anonymous Culture. These include the Condorcet and Borda paradoxes, as well as the Condorcet efficiency of plurality, negative plurality and Borda voting, including their runoff versions. The computations are done by Normaliz. It finds precise probabilities as volumes of polytopes in dimension 119, using its recent implementation of the Lawrence algorithm.
Pathological analysis and antimicrobial susceptibility of Chryseobacterium balustinum RTFCP 298 isolated from diseased rainbow trout, Oncorhynchus mykiss
Authors: Mallik Sumanta Kumar , Pathak Richa , Shahi Neetu , Kala Krishna , Chandra Suresh , Das Partha , Singh Bhupendra , Singh Mohan , Giri Abhay Kumar , Tandel Ritesh Shantilal , Sarma Debajit , Pandey Pramod Kumar 
Published: August 2023

AbstractIn this study, six isolates of Chryseobacterium balustinum were characterized from diseased rainbow trout fingerlings. The virulence characteristics, pathogenicity, and antimicrobial susceptibility pattern of these isolates were investigated. The bacterium showed positive results for catalase, cytochrome oxidase, and aesculin hydrolysis, while negative results were obtained for DNase, gelatinase, methyl red, Voges-Proskauer's reaction, Simon citrate, Hydrogen sulphide, and starch hydrolysis. Amino acid metabolism analysis revealed the inability to metabolize arginine, lysine, and ornithine decarboxylase. Molecular characterization (16S rRNA) and phylogenetic analysis revealed the test isolates as C. balustinum, closely related to strain WLT (99.85% similarity) and C. balustinum P-27 (99.77%). Virulence assay indicated haemolytic activity and biofilm formation by the test bacterium. The challenge test confirmed moderate pathogenicity in rainbow trout and established Koch's postulates. The clinical manifestations of infection included fin erosion, eye and body surface haemorrhage, exophthalmia, and organ liquefaction. The minimum inhibitory concentrations of various antimicrobials ranged from 1 to > 256 µg mL−1. The novel synthetic antimicrobial peptides exhibited MICs of 8 to > 256 µg mL−1, suggesting a potential control method. These findings suggest that C. balustinum is an opportunistic pathogen with moderate pathogenicity in rainbow trout. Further research on the host–pathogen relationship is necessary to understand virulence characteristics and pathogenicity in aquaculture.
Propionic acid induces alterations in mitochondrial morphology and dynamics in SH-SY5Y cells
Authors: Buchanan Erin , Mahony Caitlyn , Bam Sophia , Jaffer Mohamed , Macleod Sarah , Mangali Asandile , van der Watt Mignon , de Wet Sholto , Theart Rensu , Jacobs Caron , Loos Ben , O’Ryan Colleen 
Published: August 2023

AbstractPropionic acid (PPA) is used to study the role of mitochondrial dysfunction in neurodevelopmental conditions like autism spectrum disorders. PPA is known to disrupt mitochondrial biogenesis, metabolism, and turnover. However, the effect of PPA on mitochondrial dynamics, fission, and fusion remains challenging to study due to the complex temporal nature of these mechanisms. Here, we use complementary quantitative visualization techniques to examine how PPA influences mitochondrial ultrastructure, morphology, and dynamics in neuronal-like SH-SY5Y cells. PPA (5 mM) induced a significant decrease in mitochondrial area (p < 0.01), Feret's diameter and perimeter (p < 0.05), and in area2 (p < 0.01). Mitochondrial event localiser analysis demonstrated a significant increase in fission and fusion events (p < 0.05) that preserved mitochondrial network integrity under stress. Moreover, mRNA expression of cMYC (p < 0.0001), NRF1 (p < 0.01), TFAM (p < 0.05), STOML2 (p < 0.0001), and OPA1 (p < 0.01) was significantly decreased. This illustrates a remodeling of mitochondrial morphology, biogenesis, and dynamics to preserve function under stress. Our data provide new insights into the influence of PPA on mitochondrial dynamics and highlight the utility of visualization techniques to study the complex regulatory mechanisms involved in the mitochondrial stress response.