bluuebunny/crossref_metadata_2025 huggingface dataset:
Cell Division Cycle-Associated Protein 8 in Pan-Cancer: A Comprehensive Prognostic and Immune Infiltration Investigation
Authors: Zheng Wanrong , Zhong Chengqian , Lai Fobao
Published: October 2023

The Cell Division Cycle-Associated Protein 8 (CDCA8) protein is a vital player in the process of cell division and can influence numerous physiological and pathological events in the body by triggering certain proteins such as cell cycle-controlling proteins, transcription factors, and signal transmission molecules. Despite numerous studies indicating that dysregulation of CDCA8 is prevalent in human cancers, no systematic pan-cancer analysis has been conducted. In this study, we used The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA), and Gene Expression Omnibus (GEO) datasets, and several bioinformatics tools to investigate the role of CDCA8 in 33 different tumor types. The results showed that Patients with malignancies that overexpressed CDCA8, such as adrenocortical carcinoma, kidney renal clear cell carcinoma, and liver hepatocellular carcinoma, typically had poor overall survival (OS). We also found that CDCA8 expression was favorably correlated with immune cell infiltration levels in numerous human cancer types. Furthermore, GSEA results showed that overexpression of CDCA8 in human malignancies may accelerate the development of cancer by triggering a number of oncogenic signaling pathways. In conclusion, our comprehensive assessment of the oncogenic activity of CDCA8 in several human cancer types suggests that CDCA8 can be used as a potential therapeutic target and prognostic biomarker in various human cancer types.
Polydatin combined with hawthorn flavonoids alleviate high fat diet induced atherosclerosis by remodeling the gut microbiota and glycolipid metabolism
Authors: Li Dan , Li Yujuan , Yang Shengjie , Zhang Xiaonan , Cao Yu , Zhao Ran , Zhao Yixi , Jin Xiao , Lu Jing , Wang Xinyue , Liu Longtao , Wu Min
Published: October 2023

Background
Atherosclerosis is a widely studied pathophysiological foundation of cardiovascular diseases. The gut microbiota and their metabolites are considered independent risk factors for atherosclerosis. Polydatin combined with hawthorn flavonoids (PH), as the extracts of Polygonum cuspidatum Sieb. et Zucc. (P. cuspidatum) and Crataegus pinnatifida Bunge (C. pinnatifida), have shown excellent cardiovascular protective effects. However, the underlying mechanism requires further investigation. Our study aimed to explore the anti-atherosclerotic mechanism of PH through gut microbiota and their metabolites.
Methods
ApoE−/− mice were fed either a normal-chow diet or a high-fat diet. The PH group received varied doses of polydatin and hawthorn flavonoids: a high dose (polydatin 200 mg/kg daily; hawthorn flavonoids 100 mg/kg daily), a medium dose (polydatin 100 mg/kg daily; hawthorn flavonoids 50 mg/kg daily), and a low dose (polydatin 50 mg/kg daily; hawthorn flavonoids 25 mg/kg daily). The control and model groups were administered distilled water (0.2 mL daily). The experiment lasted for 24 weeks.
Results
PH administration significantly reduced lipid and inflammatory cytokine levels, meanwhile, the atherosclerotic lesions in a high-fat diet-induced ApoE−/− mice were significantly decreased. Additionally, PH also inhibited the enhancement of trimethylamine N-oxide (TMAO), trimethylamine (TMA) levels of HFD-induced ApoE−/− mice by regulating the expression of hepatic flavin-containing enzyme monooxygenase 3 (FMO3). 16S rRNA sequencing results demonstrated that high-dose PH treatment reduced Firmicutes/Bacteroidetes ratio, increased the abundance of Actinobacteriota, Atopobiaceae and Coriobacteriaea_UCG-002, and decreased the abundance of Desulfobacterota. Norank_f_Muribaculaceae was enriched in the medium-dose PH and simvastatin groups, and Lactobacillus was mainly increased in the simvastatin and the low-dose PH groups. According to the metagenetic results, functional annotations also suggested that the biological processes of each group mainly focused on metabolism-related processes. Specifically, PH may regulate the abundance of TMA-producing bacteria (Coriobacteriaceae, Desulfovibrio, Muribaculum, and Clostridium) and related enzymes in glycolipid metabolic pathways to exert an important effect on the prevention of atherosclerosis.
Conclusions
Our results suggested that PH could regulate the glucolipid metabolism-related pathway, attenuate inflammatory cytokine levels, and reduce atherosclerotic plaques by remodeling gut microbiota.
Trial registration:
Not applicable.
The effect of pacing at different sites on cardiac function ： A network analysis
Authors: Li Han , Zhang Qian , Wang Qing-Yi , Yang Li-Hong , Xu Jin-Yi
Published: October 2023

Background: The slow arrhythmia caused by sick sinus syndrome and conduction disorder is mainly manifested in palpitation, dizziness, and even syncope. If not treated in time, it will lead to heart failure, shock, and even endanger the life of patients, posing a great threat to the life and health of patients.At present, the most effective treatment is pacemaker implantation.Pacemaker can help excite the patient's heart according to the patient's own heart rate, thus treating bradyarrhythmia.The ventricular pacing electrode can be placed at multiple locations. Pacing at different locations in the medium and long term may have different effects on the heart function of patients[1]。
Objective: To investigate the effects of right ventricular middle septum (RVMS), right ventricular high septum (RVHS), right ventricular septum (RVS), right ventricular outflow tract (RVOT), right ventricle (RVA) and His bundle (HB) pacemakers on left ventricular function 6 to 36 months after implantation.
Methods PubMed, Embase, Cochrane and Wanfang databases were searched through computer retrieval databases. The retrieval time was up to June 2022. Clinical studies on the effects of pacing at different sites on left ventricular function were collected, and the effects of pacing at different sites on left ejection fraction (LVEF), 6-minute walk test (6MWT), NT proBNP, and QRS duration were compared.
Results: A total of 14 randomized controlled trials were included in our research;All trials were reported postoperative LVEF, 7 trials were reported 6MWT, 5 trials were reported NT proBNP, and 8 trials were reported QRS duration;The results of reticular meta-analysis showed that in terms of LVEF, HB group was superior to other groups in SMD-0.82 (95% CI-1.28, -0.37) in RVS group and SMD-0.77 (95% CI-1.34, -0.19) in RVB group. There was no statistical difference between RVHS group, RVMS group, RVOT group and each group.In 7 articles about the study of 6MWT after pacemaker implantation, the HB group was superior to the RVA group SMD-0.51 (95% CI-0.99, -0.03), and there was no statistical significance between other groups.The SUCRA scores were HB (92.9)>RVS (72.5)>RVHS (30.7)>RVMS (24.6).Five articles related to the study of NT proBNP after pacemaker implantation, HB group was better than RVA group SMD 0.42 (95% CI 0.06,0.79);SMD 0.67 (95% CI 0.13,1.21) in RVS group;SMD 0.69 (95% CI 0.24,1.13) in RVHS group was not significantly different from that in RVMS group.There was no statistical significance between the RVMS group and each group. The HB group was the best, and the SUCRA score was 97.8 for HB.In 8 articles about the study of QRS duration after pacemaker implantation, the HB group was superior to the RVA group SMD1.79 (95% CI 0.32,3.27).There was no statistical significance among other groups.HB group was the best, and the SUCRA score was 85.8.
Conclusion: His bundle pacing is the best in hemodynamics and ventricular synchrony.
Dexmedetomidine versus midazolam for conscious sedation during blind nasotracheal intubation with bispectral index monitoring: a randomized and controlled clinical trial
Authors: Li Zhengyu , Wang Man , Jin Bi , Hou Nina , Yang Heng , Luo Hong , Zhang Yuwei
Published: October 2023

Objective
Despite the rapid progress of tracheal intubation visualization techniques, blind nasotracheal intubation remains a significant approach for difficult airway management, requiring satisfactory conscious sedation. The purpose of this study was to evaluate and compare the efficacy and safety of dexmedetomidine (DEX) and midazolam (MID) for conscious sedation during blind nasotracheal intubation under bispectral index (BIS) monitoring.
Methods
This study included 60 patients undergoing elective oral and maxillofacial surgery who were randomized into two groups: the DEX group (dexmedetomidine, 1.0 µg/kg, continuous infusion for 15 minutes) and the MID group (midazolam, 0.02 mg/kg). Under BIS monitoring, the primary outcome, time of intubation, was recorded. Additionally, changes in vital signs and stress hormone levels were measured before and after intubation. Intraoperative sufentanil consumption was determined, and such parameters as the end-tidal carbon dioxide partial pressure (PETCO2) after intubation as well as pain and satisfaction scores were assessed. Also, postoperatively, the incidence of adverse events associated with nasotracheal intubation was assessed in both groups.
Results
All patients successfully intubated. The DEX group had a shorter intubation time (P < 0.05) when compared to the MID group. In comparison to pre-induction values, BIS, heart rate (HR) and mean arterial pressure (MAP) were significantly decreased after induction of anesthesia in both groups (P < 0.05), with BIS (P < 0.001) and HR (P = 0.001) being significantly lower in the DEX group than the MID group. BIS, MAP and pulse oximeter oxygen saturation (SpO2) immediately after intubation were significantly lower in both groups than before the induction.HR was significantly lower in DEX group than that in the MID group (P < 0.05). The levels of epinephrine (E), and beta-endorphin (β-EP) were significantly reduced at three and fifteen minutes after intubation in the MID group compared to pre-induction values (P < 0.05). Similarly, compared to pre-induction, at three and fifteen minutes after intubation, cortisol (Cor), norepinephrine (NE), E, and β-EP were significantly lower in both groups (P < 0.05). Moreover, the DEX group had lower PETCO2 post-intubation, lower sufentanil consumption, lower postoperative pain scores, and higher patient satisfaction scores (P < 0.05).
Conclusion
Although, using BIS monitoring, both DEX and MID have shown safe and effective conscious sedation for blind nasotracheal intubation, the efficacy of DEX is greater than that of MID.
Trial registration:
This study was registered on the China Clinical Trial Registry website (https://www.chictr.org.cn/index.html) on 26/05/2023 (Registration number: ChiCTR2300071838).
A Novel Pathogenic Tau Conformer Playing Part in Tau Pathology in Human Neurons Upon Aging Stress
Authors: Tofigh Nahid , Agahi Sadaf , Riazi Gholam , Pakdaman Hossein , Moazzam Mahboobeh Ghalamkar , Shahpasand koorosh
Published: October 2023

Alzheimer’s disease (AD), is the most prevalent cause of dementia, with no effective treatment thus far. It is clear that tau protein hyperphosphorylation is the major pathogenic process, leading to neurodegeneration upon AD. It has been previously shown that tau phosphorylation at Thr231 is of crucial importance in tauopathy process. It was reported that pT231-tau in the cis conformation is the early driver of tau pathogenicity in the tauopathy mouse models. In this study, we identified gauche P-tau pathology (a novel P-tau conformer) in human postmortem brain tissue and as well as induced pluripotent stem cell (iPSC) derived neurons from AD patients as the neurotoxic pT231-tau conformer. We observed gauche P-tau levels dramatically increase in neurons under aging stress which disrupts the microtubule network, propagates to other neurons, and ultimately leads to apoptosis and cell death. Moreover, while cis p-tau depletion using respective monoclonal antibody suppressed neurodegeneration in mouse neurons, gauche p-tau elimination using respective monoclonal antibody stopped neurodegeneration in the human AD cultured neurons. Taken these together, we concluded that gauche p-tau is the leading cause of neuronal cell death in human neurons, and the anti gauche p-tau antibody could be introduced as an efficient therapeutic for blocking neurodegeneration upon AD.
Sweat lactate sensor for detecting anaerobic threshold in heart failure: a prospective clinical trial (LacS-001)
Authors: Katsumata Yoshinori , Muramoto Yuki , Ishida Noriyuki , Takemura Ryo , Nagashima Kengo , Ikoma Takenori , Kawamatsu Naoto , Araki Masaru , Goda Ayumi , Okawara Hiroki , Sawada Tomonori , Ichihara　Kawakubo Yumiko , Hattori Osamu , Yamaoka Koki , Seki Yuta , Ryuzaki Toshinobu , Ikura Hidehiko , Nakashima Daisuke , Nagura Takeo , Nakamura Masaya , Sato Kazuki , Shiraishi Yasuyuki
Published: October 2023

Background
A simple method for determining the anaerobic threshold in patients with heart failure (HF) is needed. This prospective clinical trial (LacS-001) investigated the safety of a sweat lactate-monitoring sensor and the correlation between lactate threshold in sweat (sLT) and ventilatory threshold (VT).
Methods
We recruited 50 patients with HF and New York Heart Association functional classification I–II (mean age: 63.5 years, interquartile range: 58.0–72.0 years). Incremental exercise tests were conducted while monitoring sweat lactate levels using our sensor. sLT was defined as the first steep increase in lactate levels from baseline. Primary outcome measures were a correlation coefficient of ≥ 0.6 between sLT and VT, similarities as assessed by the Bland–Altman analysis, and standard deviation of the difference within 15 W.
Results
A correlation coefficient of 0.651 (95% confidence interval, 0.391–0.815) was achieved in 32/50 cases. The difference between sLT and VT was − 4.9 ± 15.0 W. No comparative error was noted in the Bland–Altman plot. No device-related adverse events were reported among the registered patients.
Conclusions
Our sweat lactate sensor is safe and accurate for detecting VT in patients with HF in clinical settings, thereby offering valuable additional information for treatment.
Clinical characteristics and prognostic factors of patients with intraocular foreign bodies from a Tertiary Eye Center in North China
Authors: Xing XiaoLi , Liu Fang , Qi Yan , Li Jun , Yu Bin , Wan Lei
Published: October 2023

Background
This study aims to describe the epidemiology and clinical features of patients with intraocular foreign bodies (IOFBs) and analyze the prognostic factors influencing final vision.
Methods
We retrospectively reviewed medical records of 159 patients (159 eyes) with IOFBs admitted to Qingdao Eye Hospital of Shandong First Medical University between January 1, 2014, and December 31, 2021. Demographic characteristics, clinical features, and prognostic factors were analyzed.
Results
This study analyzed 159 patients (159 eyes) with IOFBs. The mean age of the patients was 41.58 ± 11.97 years, with 151 (95.0%) being males. The most common age group was 40–49 years. Based on discharge and follow-up results, IOFB removal was performed through pars plana incision in 105 (67.9%) eyes, corneoscleral limbus incision in 24 (15.1%) eyes, and original wound in 27 (17.0%) eyes. Of these, 44 eyes underwent IOFB removal without vitrectomy, while 55 eyes were treated with silicone oil. Post-vitrectomy, three cases showed secondary macular membrane, five cases exhibited retinal detachment, and enucleation was necessary in three cases. The final best corrected visual acuity (BCVA, logMAR) was 1.65 ± 0.87, significantly better than preoperative visual acuity of 1.06 ± 0.88 (t = 8.21, p < 0.01). Multi-factor logistic regression analysis indicated that wound length, IOFB size, initial presenting visual acuity (VA), and macular lesions were prognostic factors for postoperative vision after intraocular foreign body surgery (p < 0.05).
Conclusions
In a tertiary eye center in northern China, IOFBs predominantly affected the working-age group, particularly males. Factors such as wound length, IOFB size, initial presenting VA, and macular lesions might impact the final visual outcome.
A signal-on electrochemical aptasensor for rapid detection of methylamphetamine based on competition with complementary DNA
Authors: Chang Wenzhuo Chang , Zheng Zhixiang , Ma Yongjun , Du Yongling , Shi Xuezhao , Wang Chunming
Published: October 2023

A simple and rapid electrochemical sensing method with high sensitivity and specificity of aptamers was developed for the detection of methylamphetamine (MAMP).A short anti-MAMP thiolated aptamer (Apt) with a methylene blue (MB) probe at 3’-end was immobilized on the surface of a gold electrode (MB-Apt-S/GE). The electrochemical signal appeared when MAMP presenting in the sample solution competed with cDNA for binding with MB-Apt-S. Under optimized conditions, the liner range of this signal-on electrochemical aptasensor for the detection of MAMP achieved from 1.0 to 10.0 nmol/L and 10.0 to 400 nmol/L. Satisfactory spiked recoveries of saliva and urine were also obtained. In this method, only 5 minutes were needed to incubate before the square wave voltammetry (SWV) analysis, which was much more rapid than other electrochemical sensors, leading to a bright and broad prospect for the detection of MAMP in biological sample. This method can be used for on-site rapid detection on special occasions, such as drug driving scenes, entertainment venues suspected of drug use, etc.
PHB2 Promotes SHIP2 Ubiquitination via the E3 ligase NEDD4 to Regulate AKT Signaling in Gastric Cancer
Authors: Xu Liang , Xiang Wanying , Yang Jiezhen , Gao Jing , Wang Xinyue , Meng Li , Ye Kaihong , Zhao Xiao Hong , Zhang Xu Dong , Jin Lei , Ye Yan
Published: October 2023

Background:
Prohibitin 2 (PHB2) exhibits opposite functions of promoting or inhibiting tumour across various cancer types; nevertheless, its involvement in gastric cancer (GC) remains predominantly unexplored.
Method:
PHB2 protein expression levels in GC and normal tissues were examined using western blot and Immunohistochemistry. PHB2 expression level associations with patient outcomes were examined through Kaplan-Meier plotter analysis utilizing GEO datasets (GSE14210 and GSE29272). The biological role of PHB2 and its subsequent regulatory mechanisms were elucidated in vitro and in vivo. GC cell proliferation was assessed using MTT cell viability analysis, clonogenic assays, and BrdU incorporation assays, while the growth of GC xenografted tumors was measured via IHC staining of Ki-67. The interaction among PHB2 and SHIP2, as well as between SHIP2 and NEDD4, was identified through co-immunoprecipitation, GST pull-down assays, and deletion-mapping experiments. SHIP2 ubiquitination and degradation were assessed using Cycloheximide treatment, plasmid transfection and co-immunoprecipitation, followed by western blot analysis.
Results:
Our analysis revealed a substantial increase in PHB2 expression in GC tissues compared to adjacent normal tissues. Notably, higher PHB2 levels correlated with poorer patient outcomes, suggesting its clinical relevance. Functionally, silencing PHB2 in GC cells significantly reduced cell proliferation and retarded GC tumour growth, whereas overexpression of PHB2 further enhanced GC cell proliferation. Mechanistically, PHB2 physically interacted with Src homology 2-containing inositol 5-phosphatase 2 (SHIP2) in the cytoplasm of GC cells, thus leading to SHIP2 degradation via its novel E3 ligase NEDD4. It subsequently activated the PI3K/Akt signaling pathway and thus promoted GC cell proliferation.
Conclusion:
Our findings highlight the importance of PHB2 upregulation in driving GC progression and its association with adverse patient outcomes. Understanding the functional impact of PHB2 on GC growth contributes valuable insights into the molecular underpinnings of GC and may pave the way for the development of targeted therapies to improve patient outcomes.
Factors associated with medical students’ career choice in different specialties: a multiple cross-sectional questionnaire study at a German medical school
Authors: Leutritz Tobias , Krauthausen Maike , Simmenroth Anne , König Sarah
Published: October 2023

Background: Given the shortage and unequal distribution of physicians across specialties, we aimed to evaluate factors associated with medical students’ career choices, including background, personality traits, educational experience, personal interests, lifestyle considerations, and the awareness of work requirements.
Methods: We conducted multiple cross-sectional surveys of students; a 159-item online questionnaire was designed and students from three different stages of the six-year medical degree course (outset, clinical phase, and on graduation) were invited to complete the survey. Data were collected between May 2021 and April 2023.
Results: The questionnaire was sent to 1406 students, of whom 683 replied (49%); 481 respondents were female (70%). The top specialty choices across the respondents were internal medicine, surgery, and general practice, with anaesthesiology, paediatric and adolescent medicine (ranging 11-15%), and obstetrics and gynaecology also receiving interest, with 6% undecided. In particular, female students lost interest in surgery during the course of study in favour of the other options. The choice of general practice was associated with more vocational training, prior positive experiences with the specialty, and lower grades in the university entry examination. Clinical clerkships in a specific (freely chosen) specialty aligned with career choice, while the final practical year did not have an impact on career decision-making. All students highly desired regulated working hours and work-life-balance; however, students choosing surgery rated these items as less important. Willingness to work in a hospital environment was highly associated with choosing anaesthesiology and surgery, whereas rural areas and practices were associated with general practice. Higher scores at agreeableness were associated with choosing paediatric and adolescent medicine by more female students, whereas lower neuroticism values were associated with the choice of anaesthesiology.
Conclusions: The results highlight the intricate nature of decision-making and shed light on various aspects that contribute to the process of selecting a specialty. By identifying and addressing influencing factors, we can develop targeted interventions and policies to enhance diversity and distribution across medical specialisations and to aim for high-quality and equitable healthcare that matches the specific needs of both individuals and the population as a whole.
Reproducible Method for 1-methylcylopropene (1-MCP) Application and Quantitation for Post-harvest Research
Authors: Stowe Evan , Mattinson D. Scott , Blauer Jacob , Dhingra Amit
Published: October 2023

Background: Actively combating post-harvest food spoilage and waste can dramatically increase the efficiency of food utilization worldwide. In climacteric fruits, treatment with 1-MCP effectively reduces post-harvest spoilage and waste by inhibiting the fruit’s ability to perceive ethylene. 1-MCP treatment is increasingly being used to explore the complex nature of ripening physiology at a fundamental level; however, differences in application and quantitation methods create difficulties in comparing conclusions across studies.
Results Here, we report an effective and reproducible 1-MCP application and quantitation method to enable research investigations. The highly volatile and elusive 1-MCP molecule can be identified and quantified by gas chromatography by using surrogate alkenes 1-butene and cis-2-butene to develop standard curves.
Conclusions. It is hoped that the methodology outlined here can help standardize consistent 1-MCP application for post-harvest research without excessive investment in specialized equipment.
Electrocardiogram Prediction Based on Variational Modal Decomposition and Convolutional Recurrent Gate Unit
Authors: Wang Hongbo , Wang Yizhe , Liu Yu , Yao Yuejuan
Published: October 2023

Electrocardiogram (ECG) prediction is of great significance in compressing and storing heart signals and reminding of potential health hazards. In order to improve the duration and accuracy of ECG prediction on the basis of noise filtering, a new algorithm based on Variational Mode Decomposition (VMD) and Convolutional Recurrent Gate Unit (ConvGRU) was proposed, named VMD-ConvGRU. VMD can directly remove noise such as the baseline drift without manual interventions, which greatly improves the usability of the model, and the combination with ConvGRU improves the prediction time and accuracy. The proposed algorithm was compared with three related algorithms (PSR-NN, VMD-NN and TS Fuzzy) on MIT-BIH, an internationally recognized arrhythmia database. Experiments show that VMD-ConvGRU not only has better prediction accuracy than the above three algorithms, but also has a considerable advantage in the prediction time. In addition, the prediction experiments on both MIT-BIH and EDB have shown better generalization performance of VMD-ConvGRU.
A Novel Signature Model Based on Ferroptosis-Related Genes for Predicting the Prognosis of Colorectal Carcinoma.
Authors: Wei Jingjing , Deng Cini , Zeng Zhiwu , Fu Dongmei , Han Jianglong , Fu Zhenming , Liu Li
Published: October 2023

Colorectal carcinoma (CRC) is a prevalent malignant tumour worldwide, and understanding its prognosis is crucial for effective treatment. The purpose of this work was to use genes linked to ferroptosis to create a prognostic prediction model for CRC. The GEO and TCGA databases were used to obtain data from CRC patients, and the Ferroptosis Gene Database was used to gather information on genes associated with ferroptosis. To discover prognostic markers and build the prognostic model, LASSO regression analysis was utilized. We assessed the prognostic significance of the model by employing Kaplan-Meier analysis and ROC curve evaluation. We utilised the CIBERSORT tool to investigate the possible link between ferroptosis-related genes and immune cells. In this research, a prognostic model comprising 11 ferroptosis-related genes was developed. This model demonstrates a high level of accuracy in predicting outcomes and assessing immune responses in CRC. Based on the analysis of the receiver operating characteristic curve, patients belonging to the high-risk group exhibited an unfavourable prognosis. The model achieved area under the curve values of 0.756, 0.774, and 0.782 at 1-, 3-, and 5-years, respectively. The ferroptosis-related gene biomarkers identified in this study may serve as independent predictors of CRC. The examination of differentially expressed genes in enrichment showed significant immune function differences between high-risk and low-risk groups. This suggests that immune-related mechanisms affect CRC prognosis. This research proposes a prediction model employing 11 ferroptosis-related genes that may help personalise treatment and evaluate CRC patients' prognoses.
The mechanism underlying correlation of particulate matter-induced ferroptosis with inflammasome activation and iron accumulation in macrophages
Authors: Lee Seon-Jin , Park Minkyung , Park Sujeong , Choi Yumin , Cho Young-Lai , Kim Min Jeong , Park Young-Jun , Chung Su Wol , Lee Heedoo
Published: October 2023

Particulate matter (PM) is a global environmental hazard, which affects human health through free radical production, cell death induction, and immune responses. PM activates inflammasomes leading to an excessive inflammatory response, and induces ferroptosis, a type of cell death. Despite ongoing research on the correlation among PM-induced ferroptosis, immune response, and inflammasomes, the underlying mechanism of this relationship has not been elucidated. In this study, we demonstrated the levels of PM-induced cell death and immune responses in murine macrophages, J774A.1 and RAW264.7, depending on the size and composition of particulate matter. PM2.5, with extraction ions, induced significant levels of cell death and immune responses; it induces lipid peroxidation, iron accumulation, and reactive oxygen species (ROS) production, which characterize ferroptosis. In addition, inflammasome-mediated cell death occurred owing to the excessive activation of inflammatory responses. PM-induced iron accumulation activates ferroptosis and inflammasome formation through ROS production; similar results were observed in vivo. These results suggest that the link between ferroptosis and inflammasome formation induced by PM, especially PM2.5 with extraction ions, is established through the iron-ROS axis. Moreover, this study can effectively facilitate the development of a new therapeutic strategy for PM-induced immune and respiratory diseases.
On multifaceted inhibitory control in betel-quid-dependent chewers
Authors: Chang Tzu-Yi , Ho Ming-Chou
Published: October 2023

Background: Betel-quid (BQ) is regarded as a human carcinogen by the World Health Organization. We asked whether BQ chewers have worse inhibitory control, in terms of three separate inhibitory control functions: propotent response inhibition, resistance to distractor interference, and resistance to proactive interference (PI).
Methods: The antisaccade task, the flanler task and the recent-probe task are employed to measure the three inhibition functions, respectively. BQ dependent chewers with concurrent use of tobacco and alcohol (BQD), tobacco and alcohol user controls (TAC), and healthy controls (HC) were included.
Results: We found that the BQD group did not differ from TAC and HC in prepotent response inhibition, measured by the antisaccade task, and resistance to distractor interference, measured by the flanker task. Finally, the BQD group had a worse resistance to PI than the two control groups, measured by the recent-probe task.
Conclusions: When discussing from the perspective of multifacted inhibitory control, we can fully understand the inhibitory control ability of BQ chewers.
Structure elucidation of a human melanocortin-4 receptor specific orthosteric nanobody agonist
Authors: Menet Christel , Laeremans Toon , Fontaine Thomas , Busch Andreas , De Cesco Stéphane , Triest Sarah , Dekeyzer Lies , Samyn Noor , Loeys Nicolas , Perneel Lisa , Debaere Melanie , virmani richa , skieterska kamila , staelens stephanie , Roy maarten Van , Liang Yi-Lynn , Jaakola Veli-Pekka , Sands Zara , Masiulis Simonas , Martini Murielle , Barroco Rosa
Published: October 2023

The melanocortin receptor 4 (MC4R) belongs to the melanocortin receptor family of G-protein coupled receptors and is a key switch in the leptin-melanocortin molecular axis that controls hunger and satiety. Brain-produced hormones such as α-melanocyte-stimulating hormone (agonist) and agouti-related peptide (inverse agonist) regulate the molecular communication of the MC4R axis but are promiscuous for melanocortin receptor subtypes and induce a wide array of biological effects. Using a conformation-selective ConfoBody, the use of active state-stabilized MC4R facilitated efficient de novo discovery of a sequence diverse panel of MC4R-specific, potent and full agonistic nanobodies. We solved the active state MC4R structure in complex with the full agonistic nanobody pN162 at 3.4 Å resolution. The structure shows a unique interaction with pN162 binding deeply in the orthosteric pocket of MC4R and lacking the structural interactions of MC4R agonists reported to date. MC4R peptide agonists, such as the marketed setmelanotide, lack receptor selectivity and show off-target effects. In contrast, the agonistic nanobody is highly specific and hence can be a more suitable agent for anti-obesity therapeutic intervention via MC4R.
Midregional pro atrial naturetic peptide (MRproANP) and copeptin (COPAVP) as predictors of all- cause mortality in early COPD – Results from COSYCONET
Authors: Fähndrich Sebastian , Herr Christian , Teuteberg Sebastian , Alter Peter , Söhler Sandra , Soriano Daniel , Classen Johanna , Adams Julia , Weinhold Victoria , Watz Henrik , Waschki Benjamin , Zeller Tanja , Eichenlaub Martin , Trudzinski Franziska C , Michels Julia D , Omlor Albert , Seiler Frederik , Moneke Isabelle , Biertz Frank , Stolz Daiana , Welte Tobias , Kauczor Hans-Ulrich , Kahnert Kathrin , Jörres Rudolf A , vogelmeier claus , bals robert , group COSYCONET study
Published: October 2023

Background: A number of prognostic markers of mortality are known in chronic obstructive pulmonary disease (COPD) but less so for early and mild stages of the disease. We thus analyzed several biomarkers as potential predictors of mortality in early COPD.
Methods: The blood biomarkers considered were copeptin (COPAVP), midregional adrenomedullin (MRproADM), midregional pro atrial naturetic peptide (MRproANP), and fibrinogen. Analyses were performed in patients with stable “early COPD” defined by GOLD grades 0-2 and diagnosis of COPD ≤5 years prior to inclusion into the COSYCONET cohort (COPD and Systemic Consequences - Comorbidities Network), using Cox regression analysis with stepwise adjustment for multiple COPD characteristics, comorbidities, troponin and NT-proBNP.
Results: 655 patients with early COPD were included. In the initial regression model, 43 of 655 patients died during the 6-year follow-up, in the final model 27 of 487. Regression analyses with adjustment for confounders identified COPAVP and MRproANP as statistically robust biomarkers (p<0.05 each) of all-cause mortality, while MRproADM and fibrinogen were not. The fourth quartile of MRproANP (97 pmol/L) was associated with a hazard ratio of 4.5 (95%CI: 1.6; 12.8), and the fourth quartile of COPAVP (9.2 pmol/L) with 3.0 (1.1; 8.0). The results for MRproANP were confirmed in the total cohort of grade 0-4 (n=1470 finally).
Conclusion: In patients with early COPD, elevated values of COPVP and in particular MRproANP were robust, independent biomarkers for all-cause mortality risk after adjustment for multiple other factors. This suggests that these markers might be considered in the risk assessment of early COPD.
Machine Intelligence Accelerated Design of Conductive MXene Aerogels with Programmable Properties
Authors: Chen Po-Yen , Shrestha Snehi , Barvenik Kieran , Chen Tianle , Yang Haochen , Li Yang , Kesavan Meera , Little Joshua , Tubaldi Eleonora
Published: October 2023

Designing ultralight conductive aerogels with tailored electrical and mechanical properties is critical for various applications. Conventional approaches rely on iterative optimization experiments, which are time-consuming when exploring a vast parameter space. Herein, an integrated workflow is developed to combine collaborative robotics with machine learning to accelerate the design of conductive aerogels with programmable electrical and mechanical properties. First, an automated pipetting robot is operated to prepare 264 mixtures using four building blocks at different ratios/loadings (including Ti3C2Tx MXene, cellulose nanofibers, gelatin, glutaraldehyde). After freeze-drying, the structural integrity of conductive aerogels is evaluated to train a support vector machine classifier. Through 8 active learning cycles with data augmentation, 162 kinds of conductive aerogels are fabricated/characterized via robotics-automated platforms, enabling the construction of an artificial neural network prediction model. The prediction model can conduct two-way design tasks: (1) predicting the physicochemical properties of conductive aerogels from fabrication parameters and (2) automating the inverse design of conductive aerogels for specific property requirements. The combined use of model interpretation and finite element simulations validates a pronounced correlation between aerogel density and its compressive strength. The model-suggested conductive aerogels with high electrical conductivity, customized compression resilience, and pressure insensitivity allow for compression-stable Joule heating for wearable thermal management. The fusion of robotics-accelerated experimentation, machine intelligence, and simulation tools expedites the tailored design and scalable production of conductive aerogels.
Head-to-tail plume shrinking contributes to the Hawaiian-Emperor Bend and plume zonation
Authors: Wang Zhensheng , Wang Qin , He Xiaobo , Wen Bin , Kusky Timothy
Published: October 2023

The Hawaiian-Emperor Bend (HEB) is traditionally attributed to the motion of the Pacific plate over a fixed or drifting mantle plume. Yet, the role of the plume's evolving radius in this process remains unexplored. We incorporate a shrinking plume head into plate reconstructions to investigate the formation of the HEB. Initially, the plume transported magma near the Kula-Pacific plate boundary, ~1500 km away from the plume axis. During 80-47 Ma, the shrinking plume head compelled newly formed craters to move from the mid-ocean ridge toward the mantle plume axis, forming an age-progressive volcanic chain on the moving plate and with decreased asthenospheric material signatures. After 47 Ma, seamounts approached the plume axis, causing the later island chain to align more parallel to the plate motion and exhibit more distinct plume signatures. Our model thus provides a new mechanism that contributed to the migration and compositional change of the Hawaiian-Emperor seamounts during the plume-plate interaction.
PM2.5 Source apportionment and health effects in urban districts of Hanoi: inter-comparison of source apportionment results
Authors: Bui Thi Hieu , Nguyen Thi Phuong Mai
Published: October 2023

Comparison results obtained by different models with different physical assumptions and constraints for source apportionment is important for better understanding the sources of the pollutants. Source apportionment of PM2.5 measured at three sites located in inner urban districts of Hanoi was performed using two receptor models, UNMIX and principal component analysis with absolute principle component score (PCA/APCS). A total of 78 daily samples were collected consecutively during the dry and wet seasons in 2019 and 2020. Both UNMIX and PCA/APCS expressed comparable ability to reproduce measured PM2.5 concentrations. Additionally, both models distinguished 4 potential sources of PM2.5 including traffic-related emission, scrap metal recycling villages, crustal mixed with construction sources, coal combustion mixed with industry, and biomass burning. Both UNMIX and PCA/APCS confirmed that traffic-related emission was the most influential PM2.5 with a high percentage contribution (59% and 55.97%, respectively). All the HQ and Cr values for both children and adults of toxic elements apportioned by both UNMIX and PCA/APCS in every source were within the acceptable range.
Transcriptomic Analysis Pipeline (TAP) for quality control and functional assessment of transcriptomes
Authors: Boyd Joseph , Nadeau Emily A.W. , Kogut Sophie , Rodriguez Princess , Munteneau Daniel , O’Leary Thomas , Filler Sara , Lockwood Brent , Cahan Sara Helms , Frietze Seth
Published: October 2023

Background
RNA-sequencing (RNA-seq) has revolutionized the exploration of biological mechanisms, shedding light on the roles of non-coding RNAs, including long non-coding RNAs (lncRNAs), across various biological processes, including stress responses. Despite these advancements, there remains a gap in our understanding of the implications of different RNA-seq library protocols on comprehensive lncRNA expression analysis, particularly in non-mammalian organisms.
Results
In this study, we sought to bridge this knowledge gap by investigating lncRNA expression patterns in Drosophila melanogaster under thermal stress conditions. To achieve this, we conducted a comparative analysis of two RNA-seq library protocols: polyA + RNA capture and rRNA-depletion. Our approach involved the development and application of a Transcriptome Analysis Pipeline (TAP) designed to systematically assess both the technical and functional dimensions of RNA-seq, facilitating a robust comparison of these library protocols. Our findings underscore the efficacy of the polyA + protocol in capturing the majority of expressed lncRNAs within the Drosophila melanogaster transcriptome. In contrast, rRNA-depletion exhibited limited advantages in the context of D. melanogaster studies. Notably, the polyA + protocol demonstrated superior performance in terms of usable read yield and the accurate detection of splice junctions.
Conclusions
Our study introduces a versatile transcriptomic analysis pipeline, TAP, designed to uniformly process RNA-seq data from any organism with a reference genome. It also highlights the significance of selecting an appropriate RNA-seq library protocol tailored to the specific research context.
Dynamic mechanical response and crack evolution law of raw coal loaded by dynamic-static coupling under three-dimensional constraints
Authors: Zhao ShunKun , Wei ShanYang , Zhang Lin , Tian Xianggui , Yang XingZhuan , Wang Xing
Published: October 2023

Investigation of the dynamic mechanical properties of coal rock under complex stress conditions at depth. In this work, based on the improved Separate Hopkinson Pressure Bar Test System, 15 groups of coal samples were used to perform dynamic impact tests under different conditions. The changing rules of dynamic strength, crushing, fractal dimension and damage modes of coal under different stress conditions were analyzed. And 9 groups of coal specimens were selected for numerical simulation using ANSYS/LS-DYNA. The results show that: (1) The stress-strain curves of coal specimens under different strain rates, different circumferential pressures and axial pressures basically have the same trend of a bimodal phenomenon. (2) The peak dynamic stress of the coal specimens increased linearly with the increase of strain rate and confining pressure, and the ambient pressure limited the expansion of the internal cracks of the coal specimens under impact loading. And based on the experimental and simulation data, the maximum relative errors between the two are derived as (Group A: 2.9578%, Group B: 6.177%, Group C:6.382%) (3) The damage modes of the coal specimens under the three-dimensional dynamic-static combined loading were mainly "X" type and "conical" shear damage modes. The fractal dimension increases with the increase of strain rate, decreases with the increase of circumferential pressure, and first decreases and then increases with the increase of axial pressure.
CT Radiogenomics for Differentiating KIT Exon 11 from non-KIT Exon 11 Gene Mutations in Small Intestinal Gastrointestinal Stromal Tumors
Authors: Yang Cai-Wei , Yin Xiao-Nan , Che Feng , Zhao Lian , Song Bin , Li Zheng-Yan , Liu Xi-Jiao
Published: October 2023

Backgroud
This study aimed to explore the non-invasive differentiation of gene mutational subtypes of KIT exon 11 from non-KIT exon 11 in small intestinal gastrointestinal stromal tumors (siGISTs) using radiogenomics based on the contrast-enhanced CT (CECT) images.
Materials and Methods
Patients with primary siGISTs diagnosed by surgery and pathology at our hospital from May 2010 to December 2022 were retrospectively evaluated. The patients were randomly divided into a training set and a validation set with a ratio of 7:3. The synthetic minority oversampling technique algorithm was used by screening radiomics features and constructing models. Then, CECT, radiomics, and combined models are established. The performance of the three models was evaluated by the area under the curve (AUC) of the receiver operating characteristic (ROC) curve.
Results
This study included 91 siGISTs, including 59 (64.8%) with KIT exon 11 mutations and 32 (35.2%) with non-KIT exon 11 mutations. The diagnostic performance of the CECT model and radiomics model were sufficient, with the AUC values of its ROC curve being 0.746 and 0.869 in the training set, and 0.676 and 0.787 in the validation set, respectively. Additionally, the combined model composed of CECT and radiomics features has good performance, with AUC values of 0.882 (95% confidence interval [CI]: 0.828–0.937) and 0.618 (95% CI: 0.373–0.862), respectively.
Conclusions
The combined radiogenomics model based on CECT has the value of non-invasive differentiating KIT exon 11 from non-KIT exon 11 mutations in patients with siGISTs.
Headache is a predictive and prognostic protective factor for COVID-19: a retrospective study
Authors: Wu Linguangjin , Sun Yuting , Liu Changya , Zhang Wen , Xu Xiangru , Fang Bangjiang
Published: October 2023

Background
With the SARS-CoV-2 virus epidemic in these years, people have become accustomed to living with the virus. However, many people have been infected at least once. Therefore, the early warning factors before repeated infection play a vital role. The aim of this study is to investigate the relationship between headache factors and the occurrence and prognosis of COVID-19, as there is a clinical need to identify predictive indicators related to the disease.
Methods
This retrospective study analyzed routine epidemiological and clinical data on 298 COVID-19 patients at the Mobile Cabin Hospital in Shanghai, China from 3 April to 1 June 2022. The primary observations of interest were the viral load shedding time, including the time to first re-negative nucleic acid results and the time to two consecutive negative nucleic acid results.
Results
Of the 298 patients, 149 experienced headache symptoms, while the other 149 did not. Using advanced statistical methods, a significant effect of headache factor (p < 0.001) and disease severity (p < 0.001) on patients' load-shedding time was found. Moreover, patients in the headache group were able to reduce their viral load (p < 0.001) and stop the virus from multiplying. The prognostic index of the patients was also calculated, revealing a significant difference in PI for patients in the headache and non-headache groups.
Conclusion
There was a significant protective effect of headache factors in predicting infection in COVID-19 patients and the prognostic level of patient recovery.
Complementarity behind tree-level trait expression and variation: soil conditions modify species diversity effects
Authors: Davrinche Andréa , Haider Sylvia
Published: October 2023

Examples of positive effects of biodiversity on ecosystem functions have kept accumulating in the last two decades, and functional traits are considered suitable tools to explain their underlying mechanisms. However, traits are rarely studied at the scale where these mechanisms (e.g., complementarity) are likely to originate, that is, between two interacting individuals. In a greenhouse experiment, we investigated how species diversity (i.e., monospecific or heterospecific tree pairs) affects within-individual leaf traits expression and variation and how this effect is modified by soil conditions. While resource addition through phosphorus fertilization partly strengthened the diversity effects, inoculation of soil microbiota (potentially leading to increased resource accessibility) resulted in counter effects. Hence, in contrast to our expectations, we did not find synergistic effects of the two soil treatments, but we found distinct effects on species following an acquisitive or conservative growth strategy. Overall, our study showed that the effect of species diversity on trees’ adaptability and resource-use strategy needs to be considered alongside soil biotic and abiotic aspects. The influence of soil conditions on species diversity effects is essential to understand mechanisms behind complementarity at the individual level, which ultimately translate to the community scale.