bluuebunny/crossref_metadata_2025_split huggingface dataset:
Research progress of electronic nose technology in exhaled breath disease analysis
Authors: Li Ying , Wei Xiangyang , Zhou Yumeng , Wang Jing , You Rui 
Published: October 2023

AbstractExhaled breath analysis has attracted considerable attention as a noninvasive and portable health diagnosis method due to numerous advantages, such as convenience, safety, simplicity, and avoidance of discomfort. Based on many studies, exhaled breath analysis is a promising medical detection technology capable of diagnosing different diseases by analyzing the concentration, type and other characteristics of specific gases. In the existing gas analysis technology, the electronic nose (eNose) analysis method has great advantages of high sensitivity, rapid response, real-time monitoring, ease of use and portability. Herein, this review is intended to provide an overview of the application of human exhaled breath components in disease diagnosis, existing breath testing technologies and the development and research status of electronic nose technology. In the electronic nose technology section, the three aspects of sensors, algorithms and existing systems are summarized in detail. Moreover, the related challenges and limitations involved in the abovementioned technologies are also discussed. Finally, the conclusion and perspective of eNose technology are presented.
A concerted ATPase cycle of the protein transporter AAA-ATPase Bcs1
Authors: Pan Yangang , Zhan Jingyu , Jiang Yining , Xia Di , Scheuring Simon 
Published: October 2023

AbstractBcs1, a homo-heptameric transmembrane AAA-ATPase, facilitates folded Rieske iron-sulfur protein translocation across the inner mitochondrial membrane. Structures in different nucleotide states (ATPγS, ADP, apo) provided conformational snapshots, but the kinetics and structural transitions of the ATPase cycle remain elusive. Here, using high-speed atomic force microscopy (HS-AFM) and line scanning (HS-AFM-LS), we characterized single-molecule Bcs1 ATPase cycling. While the ATP conformation had ~5600 ms lifetime, independent of the ATP-concentration, the ADP/apo conformation lifetime was ATP-concentration dependent and reached ~320 ms at saturating ATP-concentration, giving a maximum turnover rate of 0.17 s−1. Importantly, Bcs1 ATPase cycle conformational changes occurred in concert. Furthermore, we propose that the transport mechanism involves opening the IMS gate through energetically costly straightening of the transmembrane helices, potentially driving rapid gate resealing. Overall, our results establish a concerted ATPase cycle mechanism in Bcs1, distinct from other AAA-ATPases that use a hand-over-hand mechanism.
Defense against phytopathogens relies on efficient antimicrobial protein secretion mediated by the microtubule-binding protein TGNap1
Authors: Bhandari Deepak D. , Ko Dae Kwan , Kim Sang-Jin , Nomura Kinya , He Sheng Yang , Brandizzi Federica 
Published: October 2023

AbstractPlant immunity depends on the secretion of antimicrobial proteins, which occurs through yet-largely unknown mechanisms. The trans-Golgi network (TGN), a hub for intracellular and extracellular trafficking pathways, and the cytoskeleton, which is required for antimicrobial protein secretion, are emerging as pathogen targets to dampen plant immunity. In this work, we demonstrate that tgnap1-2, a loss-of-function mutant of Arabidopsis TGNap1, a TGN-associated and microtubule (MT)-binding protein, is susceptible to Pseudomonas syringae (Pst DC3000). Pst DC3000 infected tgnap1-2 is capable of mobilizing defense pathways, accumulating salicylic acid (SA), and expressing antimicrobial proteins. The susceptibility of tgnap1-2 is due to a failure to efficiently transport antimicrobial proteins to the apoplast in a partially MT-dependent pathway but independent from SA and is additive to the pathogen-antagonizing MIN7, a TGN-associated ARF-GEF protein. Therefore, our data demonstrate that plant immunity relies on TGNap1 for secretion of antimicrobial proteins, and that TGNap1 is a key immunity element that functionally links secretion and cytoskeleton in SA-independent pathogen responses.
Structural basis of promiscuous substrate transport by Organic Cation Transporter 1
Authors: Zeng Yi C. , Sobti Meghna , Quinn Ada , Smith Nicola J. , Brown Simon H. J. , Vandenberg Jamie I. , Ryan Renae M. , O’Mara Megan L. , Stewart Alastair G. 
Published: October 2023

AbstractOrganic Cation Transporter 1 (OCT1) plays a crucial role in hepatic metabolism by mediating the uptake of a range of metabolites and drugs. Genetic variations can alter the efficacy and safety of compounds transported by OCT1, such as those used for cardiovascular, oncological, and psychological indications. Despite its importance in drug pharmacokinetics, the substrate selectivity and underlying structural mechanisms of OCT1 remain poorly understood. Here, we present cryo-EM structures of full-length human OCT1 in the inward-open conformation, both ligand-free and drug-bound, indicating the basis for its broad substrate recognition. Comparison of our structures with those of outward-open OCTs provides molecular insight into the alternating access mechanism of OCTs. We observe that hydrophobic gates stabilize the inward-facing conformation, whereas charge neutralization in the binding pocket facilitates the release of cationic substrates. These findings provide a framework for understanding the structural basis of the promiscuity of drug binding and substrate translocation in OCT1.
A low-power vertical dual-gate neurotransistor with short-term memory for high energy-efficient neuromorphic computing
Authors: Xu Han , Shang Dashan , Luo Qing , An Junjie , Li Yue , Wu Shuyu , Yao Zhihong , Zhang Woyu , Xu Xiaoxin , Dou Chunmeng , Jiang Hao , Pan Liyang , Zhang Xumeng , Wang Ming , Wang Zhongrui , Tang Jianshi , Liu Qi , Liu Ming 
Published: October 2023

AbstractNeuromorphic computing aims to emulate the computing processes of the brain by replicating the functions of biological neural networks using electronic counterparts. One promising approach is dendritic computing, which takes inspiration from the multi-dendritic branch structure of neurons to enhance the processing capability of artificial neural networks. While there has been a recent surge of interest in implementing dendritic computing using emerging devices, achieving artificial dendrites with throughputs and energy efficiency comparable to those of the human brain has proven challenging. In this study, we report on the development of a compact and low-power neurotransistor based on a vertical dual-gate electrolyte-gated transistor (EGT) with short-term memory characteristics, a 30 nm channel length, a record-low read power of ~3.16 fW and a biology-comparable read energy of ~30 fJ. Leveraging this neurotransistor, we demonstrate dendrite integration as well as digital and analog dendritic computing for coincidence detection. We also showcase the potential of neurotransistors in realizing advanced brain-like functions by developing a hardware neural network and demonstrating bio-inspired sound localization. Our results suggest that the neurotransistor-based approach may pave the way for next-generation neuromorphic computing with energy efficiency on par with those of the brain.
Structure-guided inhibition of the cancer DNA-mutating enzyme APOBEC3A
Authors: Harjes Stefan , Kurup Harikrishnan M. , Rieffer Amanda E. , Bayarjargal Maitsetseg , Filitcheva Jana , Su Yongdong , Hale Tracy K. , Filichev Vyacheslav V. , Harjes Elena , Harris Reuben S. , Jameson Geoffrey B. 
Published: October 2023

AbstractThe normally antiviral enzyme APOBEC3A is an endogenous mutagen in human cancer. Its single-stranded DNA C-to-U editing activity results in multiple mutagenic outcomes including signature single-base substitution mutations (isolated and clustered), DNA breakage, and larger-scale chromosomal aberrations. APOBEC3A inhibitors may therefore comprise a unique class of anti-cancer agents that work by blocking mutagenesis, slowing tumor evolvability, and preventing detrimental outcomes such as drug resistance and metastasis. Here we reveal the structural basis of competitive inhibition of wildtype APOBEC3A by hairpin DNA bearing 2′-deoxy-5-fluorozebularine in place of the cytidine in the TC substrate motif that is part of a 3-nucleotide loop. In addition, the structural basis of APOBEC3A’s preference for YTCD motifs (Y = T, C; D = A, G, T) is explained. The nuclease-resistant phosphorothioated derivatives of these inhibitors have nanomolar potency in vitro and block APOBEC3A activity in human cells. These inhibitors may be useful probes for studying APOBEC3A activity in cellular systems and leading toward, potentially as conjuvants, next-generation, combinatorial anti-mutator and anti-cancer therapies.
Small-scale layered structures at the inner core boundary
Authors: Zhang Baolong , Ni Sidao , Wu Wenbo , Shen Zhichao , Wang Wenzhong , Sun Daoyuan , Wu Zhongqing 
Published: October 2023

AbstractThe fine-scale seismic features near the inner core boundary (ICB) provide critical insights into the thermal, chemical, and geodynamical interactions between liquid and solid cores, and may shed light on the evolution mechanism of the Earth’s core. Here, we utilize a dataset of pre-critical PKiKP waveforms to constrain the fine structure at the ICB, considering the influence of various factors such as source complexity, structural anomalies in the mantle, and properties at the ICB. Our modeling suggests a sharp ICB beneath Mongolia and most of Northeast Asia, but a locally laminated ICB structure beneath Central Asia, Siberia, and part of Northeast Asia. The complex ICB structure might be explained by either the existence of a kilometer-scale thickness of mushy zone, or the localized coexistence of bcc and hcp iron phase at the ICB. We infer that there may be considerable lateral variations in the dendrites growing process at ICB, probably due to the complicated thermochemical and geodynamical interaction between the outer and inner core.
Technical aspects of a new approach to intraoperative pelvic neuromonitoring during robotic rectal surgery
Authors: Schuler Ramona , Marquardt Christoph , Kalev Georgi , Langer Andreas , Konschake Marko , Schiedeck Thomas , Bandura Julia , Goos Matthias 
Published: October 2023

AbstractIt has been found that rectal surgery still leads to high rates of postoperative urinary, fecal, or sexual dysfunction, which is why nerve-sparing surgery has gained increasing importance. To improve functional outcomes, techniques to preserve pelvic autonomic nerves by identifying anatomic landmarks and implementing intraoperative neuromonitoring methods have been investigated. The objective of this study was to transfer a new approach to intraoperative pelvic neuromonitoring based on bioimpedance measurement to a clinical setting. Thirty patients (16 male, 14 female) involved in a prospective clinical investigation (German Clinical Trials Register DRKS00017437, date of first registration 31/03/2020) underwent nerve-sparing rectal surgery using a new approach to intraoperative pelvic neuromonitoring based on direct nerve stimulation and impedance measurement on target organs. Clinical feasibility of the method was outlined in 93.3% of the cases. Smooth muscle contraction of the urinary bladder and/ or the rectum in response to direct stimulation of innervating functional nerves correlated with a change in tissue impedance compared with the pre-contraction state. The mean amplitude (Amax) of positive signal responses was Amax = 3.8%, negative signal responses from a control tissue portion with no stimulation-induced impedance change had an amplitude variation of 0.4% on average. The amplitudes of positive and negative signal responses differed significantly (statistical analysis using two-sided t-test), allowing the nerves to be identified and preserved. The results indicate a reliable identification of pelvic autonomic nerves during rectal surgery.
Effect of (poly)phenol-rich ‘Daux Belan’ apple supplementation on diet-induced obesity and glucose intolerance in C57BL/6NCrl mice
Authors: Yu Cindy H. J. , Kienesberger Petra C. , Pulinilkunnil Thomas , Rupasinghe H. P. Vasantha 
Published: October 2023

AbstractObesity is a state of metabolic dysfunction that can lead to dyslipidemia and impaired glucose homeostasis. Apple polyphenols have been shown to ameliorate dyslipidemia/metabolic dysfunction in humans. The influence of apple (poly)phenols on energy metabolism in high-fat (HF) diet-induced obese mice remains controversial. This study examined the effect of dietary supplementation of (poly)phenol-rich ‘Daux Belan’ apple (DB; 6.2 mg gallic acid equivalence (GAE)/mouse/day; 0.15% (poly)phenol) in the form of freeze-dried powder on glucose and lipid metabolism in male HF-fed C57BL/6NCrl mice, in comparison to low-(poly)phenol-containing ‘Zestar’ apple (Z; 0.4 mg GAE/mouse/day). Obesity, glucose intolerance, hypertriglyceridemia, and hepatic lipid vacuolation were induced by HF feeding while circulating cholesterol levels remained unchanged. DB apple supplementation did not protect against HF-induced body weight gain, hyperglycemia, hepatic triglyceride level elevation, and hepatic lipid vacuolation at the tested dosage. Future studies should be conducted with increased DB dosage and employ apple (poly)phenols supplemented in the form of extracts or sugar-free powder.
Trimetallic CuO/Ag/NiO supported with silica nanoparticles based composite materials for green hydrogen production
Authors: Naikoo Gowhar A. , Bano Mustri , Hassan Israr U. , Ayyub Mohd Monis , Zamani Pedram Mona 
Published: October 2023

AbstractProduction and utilization of grey and blue hydrogen is responsible for emission of millions of tons of carbon dioxide (CO2) across the globe. This increased emission of CO2 has severe repercussions on the planet earth and in particular on climate change. Here in, we explored advance bimetallic (BM) CuO/Ag and trimetallic (TM) CuO/Ag/NiO based nanoporous materials supported with silica nanoparticles (SiNPs) via sol–gel route. The explored nanocatalysts were characterized by Powder X-ray diffraction (P-XRD), scanning electron microscopy (SEM), transmittance electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), energy dispersive X-ray spectroscopy (EDX), and Raman spectroscopic techniques. These advance nanocatalysts were evaluated for the green hydrogen production through electrocatalysis and photocatalysis. The catalysts exhibited an exceptional catalytic performance, the onset potential for hydrogen evolution reaction (HER) was determined to be − 0.9 V BMSiNPs-GCE and − 0.7 V (vs Ag/AgCl) for TMSiNPs-GCE, whereas η@10 for BMSiNPs-GCE and TMSiNPs-GCE is − 1.26 and − 1.00 V respectively. Significantly, the TMSiNPs composite and the BMSiNPs composite exhibited superior photochemical H2 evolution rates of 1970.72 mmol h−1 g−1 and 1513.97 mmol h−1 g−1, respectively. The TMSiNPs catalyst presents a highly promising material for HER. This study reveals a cost-effective approach to develop sustainable and resourceful electrocatalysts for HER.
Development of scalable and generalizable machine learned force field for polymers
Authors: Mohanty Shaswat , Stevenson James , Browning Andrea R. , Jacobson Leif , Leswing Karl , Halls Mathew D. , Afzal Mohammad Atif Faiz 
Published: October 2023

AbstractUnderstanding and predicting the properties of polymers is vital to developing tailored polymer molecules for desired applications. Classical force fields may fail to capture key properties, for example, the transport properties of certain polymer systems such as polyethylene glycol. As a solution, we present an alternative potential energy surface, a charge recursive neural network (QRNN) model trained on DFT calculations made on smaller atomic clusters that generalizes well to oligomers comprising larger atomic clusters or longer chains. We demonstrate the validity of the polymer QRNN workflow by modeling the oligomers of ethylene glycol. We apply two rounds of active learning (addition of new training clusters based on current model performance) and implement a novel model training approach that uses partial charges from a semi-empirical method. Our developed QRNN model for polymers produces stable molecular dynamics (MD) simulation trajectory and captures the dynamics of polymer chains as indicated by the striking agreement with experimental values. Our model allows working on much larger systems than allowed by DFT simulations, at the same time providing a more accurate force field than classical force fields which provides a promising avenue for large-scale molecular simulations of polymeric systems.
Blood biomarker-based classification study for neurodegenerative diseases
Authors: Kelly Jack , Moyeed Rana , Carroll Camille , Luo Shouqing , Li Xinzhong 
Published: October 2023

AbstractAs the population ages, neurodegenerative diseases are becoming more prevalent, making it crucial to comprehend the underlying disease mechanisms and identify biomarkers to allow for early diagnosis and effective screening for clinical trials. Thanks to advancements in gene expression profiling, it is now possible to search for disease biomarkers on an unprecedented scale.Here we applied a selection of five machine learning (ML) approaches to identify blood-based biomarkers for Alzheimer's (AD) and Parkinson's disease (PD) with the application of multiple feature selection methods. Based on ROC AUC performance, one optimal random forest (RF) model was discovered for AD with 159 gene markers (ROC-AUC = 0.886), while one optimal RF model was discovered for PD (ROC-AUC = 0.743). Additionally, in comparison to traditional ML approaches, deep learning approaches were applied to evaluate their potential applications in future works. We demonstrated that convolutional neural networks perform consistently well across both the Alzheimer's (ROC AUC = 0.810) and Parkinson's (ROC AUC = 0.715) datasets, suggesting its potential in gene expression biomarker detection with increased tuning of their architecture.
A novel monoclonal antibody reveals the enrichment of NADPH oxidase 5 in human splenic endothelial cells
Authors: Szeles Zsolt , Petheő Gábor L. , Szikora Bence , Kacskovics Imre , Geiszt Miklós 
Published: October 2023

AbstractMembers of the NOX/DUOX family of NADPH oxidases are responsible for regulated ROS production in diverse cells and tissues. Detection of NOX/DUOX proteins at the protein level remains an important challenge in the field. Here we report the development and characterization of a novel anti-NOX5 monoclonal antibody, which recognizes the human NOX5 protein in both Western blot, immunocytochemistry, and histochemistry applications. With the help of the antibody we could successfully detect both heterologously and endogenously expressed NOX5 in mammalian cells. Furthermore, we could also detect NOX5 protein in the human spleen, testis, and ovary. Immunohistochemical studies on human testis revealed that NOX5 localized to spermatogenic cells. This expression pattern was also supported by the result of in silico analysis of single-cell RNA sequencing data that indicated that NOX5 protein is present in developing spermatids and spermatocytes. Mature spermatozoa, however, did not contain detectable NOX5. In the human ovary, both immunostaining and single-cell RNA sequencing suggest that NOX5 is expressed in interstitial fibroblasts and theca cells. We also analyzed vascular cells for the presence of NOX5 and we found that NOX5 expression is a fairly specific feature of splenic endothelial cells.
Immunoglobulin superfamily member 3 is required for the vagal neural crest cell migration and enteric neuronal network organization
Authors: Tanjore Ramanathan Jayendrakishore , Zárybnický Tomáš , Filppu Pauliina , Monzo Hector J , Monni Outi , Tervonen Topi A , Klefström Juha , Kerosuo Laura , Kuure Satu , Laakkonen Pirjo 
Published: October 2023

AbstractThe immunoglobulin (Ig) superfamily members are involved in cell adhesion and migration, complex multistep processes that play critical roles in embryogenesis, wound healing, tissue formation, and many other processes, but their specific functions during embryonic development remain unclear. Here, we have studied the function of the immunoglobulin superfamily member 3 (IGSF3) by generating an Igsf3 knockout (KO) mouse model with CRISPR/Cas9-mediated genome engineering. By combining RNA and protein detection methodology, we show that during development, IGSF3 localizes to the neural crest and a subset of its derivatives, suggesting a role in normal embryonic and early postnatal development. Indeed, inactivation of Igsf3 impairs the ability of the vagal neural crest cells to migrate and normally innervate the intestine. The small intestine of Igsf3 KO mice shows reduced thickness of the muscularis externa and diminished number of enteric neurons. Also, misalignment of neurons and smooth muscle cells in the developing intestinal villi is detected. Taken together, our results suggest that IGSF3 functions contribute to the formation of the enteric nervous system. Given the essential role of the enteric nervous system in maintaining normal gastrointestinal function, our study adds to the pool of information required for further understanding the mechanisms of gut innervation and etiology behind bowel motility disorders.
Comparison of adjuvant capecitabine plus oxaliplatin (CAPOX) versus S-1 after gastrectomy: a population-based cohort study using a nationwide claims database
Authors: Maeng Chi Hoon , Kim Hoseob , Kim Mina 
Published: October 2023

AbstractAlthough both capecitabine plus oxaliplatin (CAPOX) and S-1 are accepted as adjuvant chemotherapy following gastrectomy for gastric cancer, the better option between the two is still controversial. We conducted a retrospective nationwide cohort study using data from the National Health Insurance Service of Korea. We included patients who underwent gastrectomy for a primary diagnosis of gastric cancer between January 1, 2013, and December 31, 2018. The study compared the survival outcomes of patients who received postoperative chemotherapy based on S-1 (Arm S) vs. CAPOX (Arm C), as well as other relevant clinical variables such as comorbidity and completion of planned treatment. A total of 6602 patients were included in the analysis, with 4199 in Arm S and 2403 in Arm C. After propensity score matching, the final study population consisted of 2067 patients in each arm. Arm C showed statistically inferior 5-year overall survival (OS) and disease-free survival (DFS) rates compared to Arm S (84.0% vs. 90.0%; p < 0.0001; and 78.4% vs. 86.1%; p < 0.0001). Age (65 ≥ vs. < 65) and the incomplete planned treatment also had a significant negative effect on both OS and DFS. In the multivariable analysis, Arm C still showed worse OS (hazard ratio [HR], 1.609; 95% confidence intervals [CI], 1.339–1.934; p < 0.0001) and DFS (HR, 1.552; 95% CI 1.333–1.807; p < 0.0001) than Arm S. Both S-1 and CAPOX showed excellent efficacy, but this nationwide cohort study suggests that S-1 may be a better option in certain clinical situations.