bluuebunny/crossref_metadata_2025 huggingface dataset:
A unified in vitro to in vivo fluorescence lifetime screening platform yields amyloid β aggregation inhibitors
Authors: Collins Suil , Vliet Liisa van , Gielen Fabrice , Janeček Matej , Valladolid Sara Wagner , Poudel Chetan , Fusco Giuliana , De Simone Alfonso , Michel Claire , Kaminski Clemens , Spring David , Hollfelder Florian , Schierle Gabriele S Kaminski
Published: April 2022

Inhibiting the aggregation of amyloid β (1-42) is a promising strategy for the development of disease-modifying Alzheimer’s disease therapeutics. To date, however, no sufficiently efficacious inhibitors have been identified, despite the best efforts of >200 advanced drug development campaigns. This failure can be attributed to limitations in current compound screening and in vivo validation assays. Here, we report an in vitro to in vivo screening platform based on the use of a fluorescence lifetime aggregation sensor. The microfluidic “nanoFLIM” assay developed circumvents issues that plague conventional assays, such as lack of reproducibility, high cost and artefactual false read-outs. The fluorescence lifetime sensor can also dynamically monitor peptide aggregation in cellular and Caenorhabditis elegans disease models, providing directly comparable aggregation kinetics, which is not achievable by any other method. The power of this unified system for accelerating hit-to-lead strategies, lowering attrition rates and expediting in vivo screening, was demonstrated with a pilot screening campaign of 445 compounds, revealing a new inhibitor that can inhibit amyloid β self-assembly in vitro as well as in cellular and whole organism disease models.
Tryptophan Metabolism is a Physiological Integrator Regulating Circadian Rhythms
Authors: Petrus Paul , Cervantes Marlene , Samad Muntaha , Sato Tomoki , Chao Alina , Sato Shogo , Koronowski Kevin , Park Grace , Alam Yasmine , Mejhert Niklas , Seldin Marcus , Kuhn Jose Monroy , Dyar Kenneth , Lutter Dominik , Baldi Pierre , Kaiser Peter , Jang Cholsoon , Sassone-Corsi Paolo
Published: April 2022

The circadian clock aligns physiology with the 24-hour rotation of Earth. Light and food are the main environmental cues (zeitgebers) regulating circadian rhythms in mammals. Yet, little is known about the interaction between specific dietary components and light in coordinating circadian homeostasis. Herein, we focused on essential amino acids and identified tryptophan as a key circadian modulator. Through a multi-omics approach and combinatory diet/light interventions, we demonstrated that tryptophan metabolism modulates temporal regulation of metabolism and transcription programs by buffering photic cues. Specifically, tryptophan metabolites regulate central circadian functions of the suprachiasmatic nucleus and the core clock machinery in the liver. Taken together, our findings propose tryptophan metabolism as a potential point for pharmacologic intervention to modulate phenotypes associated with disrupted circadian rhythms.
Microvascular Changes After Scleral Buckling For Rhegmatogenous Retinal Detachment: An Optical Coherence Tomography Angiography Study
Authors: Fallico Matteo , Longo Antonio , Avitabile Teresio , Alosi Pietro , Grillo Marco , Castellino Niccolò , Bonfiglio Vincenza , Reibaldi Michele , Russo Andrea
Published: April 2022

This retrospective study aimed at investigating macular microvascular alterations after successful scleral buckling (SB) for rhegmatogenous retinal detachment (RRD). Nine-teen eyes with macula-on RRD and 18 eyes with macula-off RRD were included. In all cases an encircling band was placed. Optical coherence tomography angiography (OCTA) was performed at baseline and postoperatively. Changes in foveal avascular zone (FAZ) area and vessel density (VD) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) were the primary outcome. Correlations between OCTA findings and clinical variables were considered as secondary outcome. In both macula-on and macula-off groups, FAZ area was comparable with controls. In the macula-on group, VD in the whole SCP was lower compared with controls at both baseline (P < 0.001) and 6 months (P = 0.03), but showed a significant increase after surgery (P = 0.004). In the macula-off group, postoperative VD in both whole SCP and whole DCP was lower compared with controls (P < 0.001). In the macula-on group, there was an inverse correlation between axial length increase and SCP VD change (r=-0.508;P = 0.03). These findings demonstrated microvascular alterations after SB for RRD. However, VD impairment seems to mitigate after the surgery. A greater increase in postoperative axial length was associated with a poorer VD outcome.
Predicted diversity in water contents of Earth-like rocky exoplanets orbiting M dwarfs
Authors: Kimura Tadahiro , Ikoma Masahiro
Published: April 2022

A majority of stars in the solar neighbourhood are M dwarfs with subsolar mass and luminosity. Recent exoplanet surveys around M dwarfs have detected a growing number of exoplanets with Earth-like insolation. Those exoplanets are expected to include habitable planets with temperate climates. Climatology, however, indicates that planetary habitability requires not only moderate stellar insolation but also an appropriate amount of seawater. Previous models of planetary population synthesis predict that terrestrial planets orbiting in the habitable zone around M dwarfs have no water or too much water, leading to a discouraging conclusion that habitable planets are pretty rare around M dwarfs. Here we develop a new planetary population synthesis model, introducing updated theories for several components of the planet formation process and the effects of water vapour enrichment in the primordial atmosphere of nebular origin; such enrichment can occur through water production by oxidation of the atmospheric hydrogen with rocky materials from incoming planetesimals and the magma ocean. Our state-of-the-art model of planetary population synthesis yields rocky planets with a wide range of water content. In particular, the water production in the primordial atmosphere is found to significantly impact the occurrence of Earth-like aqua planets. Our results suggest that aqua planets with appropriate amounts of seawater for temperate climates will be normally found around M dwarfs, encouraging efforts of M dwarf habitable planet search, in contrast to the prediction of the previous models.
Comparative developmental toxicity of 3-5 ringed polycyclic aromatic hydrocarbons to zebrafish embryos and the possible reason
Authors: Xu Ke , Zhang Ying , Zheng Jingyan , Wang Chonggang , Chen Rong
Published: April 2022

Polycyclic aromatic hydrocarbons (PAHs) are pervasive pollutants in the environment. To compare the developmental toxicity of PAHs with different ring numbers to fish embryos, benzo(a)pyrene (BaP), pyrene (Pyr) and phenanthrene (Phe) were selected as the representatives of 3, 4 and 5-ringed PAHs, and fertilized embryos of zebrafish (Danio rerio) were exposed to 5 nM PAHs for 72h. The PAH-treated embryos showed cardiac abnormalities and dysfunction and defects in craniofacial cartilage. The order of toxicity to the development of craniofacial cartilage and heart rate was Phe > Pyr > BaP. The transcription of genes related to cardiac development was up-regulated, while the transcription of genes related to the development of craniofacial cartilage was downregulated. The GC-MS/MS detection showed that bioaccumulation of BaP in the exposed embryos was two orders of magnitude lower than that of Phe and Pyr. The activity of ethoxyresorcinol-o-deethyl enzyme was activated by the three PAHs, but glutathione-S-transferases activity was significantly induced in the Phe and Pyr treatments. It is suggested that the more uptake and accumulation of Phe and Pyr could be one of the reasons for their greater toxicity to development in early stage embryos.
Mass spectral molecular networking to decode the chemical space of biostimulant Bacillus strains
Authors: Nephali Lerato , Steenkamp Paul , Burgess Karl , Huyser Johan , Brand Margaretha , Hooft Justin van der , Tugizimana Fidele
Published: April 2022

Beneficial soil microbes like plant growth-promoting rhizobacteria (PGPR) significantly contribute to plant growth and development through various mechanisms activated by plant-PGPR interactions. However, decoding this belowground chemical intercommunication is still enigmatic, thus hindering the use of PGPR formulations for sustainable agriculture. Therefore, we report the application of mass spectrometry (MS)-based untargeted metabolomics and molecular networking (MN) to interrogate and profile the intracellular chemical space of PGPR Bacillus strains: B. laterosporus, B. amyloliquefaciens, B. licheniformis 1001 and B. licheniformis M017 and their consortium. The results revealed differential and diverse chemistries in the four Bacillus strains when grown separately, and also differing from when grown as a consortium. MolNetEnhancer networks revealed 11 differential molecular families that are comprised of lipids and lipid-like molecules, benzenoids, nucleotide-like, and organic acids and derivatives. Consortium and B. amyloliquefaciens were characterized by the high abundance of surfactins, whereas B. licheniformis strains were characterized by the unique presence of lichenysins. Thus, this work demonstrates that the application of metabolome mining tools offers unique opportunities to map the microbial chemical space, thus providing unprecedented access and insights to molecular information of microbial systems. Such fundamental knowledge is essential for the informed future formulation of PGPR-based biostimulants.
Dissimilar Joining of UHWMPE and PP Using Friction Stir Welding (FSW), and Mechanical Properties Evaluation.
Authors: MIRANDA Mario Alberto SANCHEZ , ALMARAZ Gonzalo Mariano DOMINGUEZ , LOPEZ Juan Jesús VILLALON , DOMINGUEZ Aymeric Edouard , VILCHEZ Julio Adrían RUIZ , JUAREZ Julio Cesar VERDUZCO
Published: April 2022

This work presents the results of the Friction Stir Welding (FSW) for two dissimilar thermoplastic polymers: Polypropylene (PP) and ultra-high molecular weight polyethylene (UHMWPE), under butt welding position. The preliminary results show poor welding, consequently, bad mechanical properties; nevertheless, introducing a self-designed and constructed fixed aluminum shoulder and determination of the best FSW parameters, such as advance speed, rotation speed, preheating or no preheating, leads to an improvement on the welding results. Tensile tests for the welded dissimilar specimens PP-UHMWPE, have revealed as high as 80% of welding efficiency in regard the original base materials. Furthermore, measures of microhardness along the welded zone and around were performed; together with the analysis of fracture behavior under tensile tests, in order to deduce the generalities of effect-cause in the improvement of mechanical properties, which are related to the glassy transition temperature of both thermoplastics, the molecular diffusion in liquid state and the process parameters.
Perineal ultrasound to assess the urethral spatial movement in stress urinary incontinence in women
Authors: Dong Binbin , Shi Yingqiu , Chen Yin , Liu Ming , Lu Xiaoming , Liu Yadong
Published: April 2022

Background: To evaluate characteristics of the urethral mobility with perineal ultrasonography.Methods: A total of 136 female patients with stress urinary incontinence and 44 controls were enrolled. Stress urinary incontinence was diagnosed using the International Consultation on Incontinence Questionnaire Short Form, medical history and physical examination, and severity was assessed using a 1-hour pad test. We described the mobility of four equidistant points (A to D) located along the urethra length. The retrovesical and urethral rotation angles were measured using perineal ultrasonography at rest and during the maximal Valsalva maneuver. Results: Patients with stress urinary incontinence showed a more significant vertical movement at Points A and B than controls. The mean variations in the retrovesical angle were significantly larger in patients with stress urinary incontinence at rest and during the Valsalva maneuver than in controls (21.0±16.5° vs. 14.7±20.1°, respectively). The cut-off value for the retrovesical angle variation was 10.7° with 72% sensitivity and 54% specificity. There was a receiver-operating characteristic curve area of 0.73 and 0.72 for Points A and B, respectively. A cut-off of 10.8 mm, and 9.4 mm provided 71% sensitivity and 68% specificity and 67% sensitivity and 75% specificity, respectively. Conclusions: The horizontal and vertical direction movement of the bladder neck and proximal urethra, and variations in the retrovesical angle may be correlated with clinical symptoms and facilitate to the assessment of SUI.
Assessing mental health of elderly outpatients, to screen only dementia or depression will have a strong bias
Authors: Lin Yen-Kuang , Lee Yao-Tung , Lee Hsin-Chien , Huang Li-Kai , Chao Shu-Ping , Lin Yi-Jung , Chi Mei-Ju
Published: April 2022

Background: Dementia and depression have emerged as two of the major mental health concerns for elderly people, which are likely to substantially affect public health in the coming decades. Both dementia and geriatric depression are associated with increased morbidity, health care utilization, and mortality. Early detection and treatment initiation are some of the best strategies to minimize the ill effects of dementia and depression on the elderly people. To this end, large-scale screening may be the first step.Methods: Screening of individuals ≥65 years old was conducted in the outpatient department of a university hospital. Ascertainment of dementia 8 (AD8) and five-item Brief Symptom Rating Scale (BSRS-5) were used to screen for cognitive decline and depression, respectively.Findings: In total, 3079 elderly people completed both AD8 and BSRS-5. Patients tested positive for cognitive impairment and depression were 28.2% and 15%, respectively. However, 7% were tested positive by both AD8 and BSRS-5 and with statistical significance.Interpretation: The high ratio of suspected dementia and suspected depression suggested the needs and cost-effect of screening among the elderly outpatients. However, the statistically significant overlap implied potential bias when screening only one condition. Future screening program of geriatric mental health needs to consider this.
A flexible and stretchable photonic crystal sensor for biosensing and tactile sensing
Authors: Peng Wang , Huang Bing , Huang Xuanxuan , Song Han , Liao Qingxi
Published: April 2022

A flexible and stretchable photonic crystal that can be used for biosensing and tactile sensing is designed and demonstrated. The nanograting of a flexible and stretchable photonic crystal was fabricated using the nanoreplica molding method with a Si master wafer. The flexible and stretchable photonic crystal consists of PDMS (Polydimethylsiloxane) as the substrate and TiO2 as the high refractive index (RI) layer. The flexible and stretchable photonic crystal was used for strain sensing and biosensing. When the flexible and stretchable photonic crystal was stretched by 0.1%, the peak resonance wavelength shifted 0.4 nm. Also, a refractive index sensitivity of 93 nm/RIU was obtained for biosensing. The proposed flexible and stretchable photonic-crystal-based sensor can be used in the areas of tactile sensing and biosensing in the future.
Safety/feasibility study of pedicle screws coated with a fibroblast growth factor-2-calcium phosphate composite layer for posterior cervical fusion surgery
Authors: Nagashima Katsuya , Hara Yuki , Mutsuzaki Hirotaka , Totoki Yasukazu , Okano Eriko , Mataki Kentaro , Matsumoto Yukei , Yanagisawa Yohei , Noguchi Hiroshi , Sogo Yu , Ito Atsuo , Koda Masao , Yamazaki Masashi
Published: April 2022

To solve the instrument loosening problem, we developed a fibroblast growth factor-2-calcium phosphate composite layer as a novel coating material to improve screw fixation strength. The primary aim of the present study was to demonstrate the safety and feasibility of screws coated with the FGF-2-calcium phosphate composite layer for posterior instrumented surgery of the cervical spine. The trial design was a single-arm, open-label, safety and feasibility study. Patients receiving fusion of the cervical spine from C2 (or C3) to C7 (or T1) were recruited. The primary endpoint to confirm safety was any screw-related adverse events. Seven patients who underwent posterior fusion surgery of the cervical spine were enrolled in the present study. The coated pedicle screws were inserted bilaterally into the lowest instrumented vertebrae. There was only one severe adverse event unrelated with the coated screw”. Three out of the 14 coated screws showed loosening. The present results prove the safety and feasibility of pedicle screws coated with the FGF-2-calcium phosphate composite layer for fusion surgery in the cervical spine. This is the first step to apply this novel surface coating in the field of spine surgery.
Right atrial function index is an independent predictor of functional status in patients with pulmonary hypertension
Authors: Li Yi-dan , Guo Di-chen , Hu Hui-min , Zhang Xin-yuan , Yang Yuan-hua , Gong Juan-ni , Lu Xiu-zhang
Published: April 2022

Objectives: Right atrium (RA) plays an essential role in modulating right ventricular (RV) function. RA dysfunction is associated with poor survival in patients with pulmonary hypertension (PH). Right atrial function index (RAFI) which is defined as (RAEF×RVOT-VTI)/(RAVmax index) represents an easily obtainable echocardiographic variable of RA function assessment, synthesizing expressions of RA size, RA reservoir function and cardiac output. The purpose of our study was to evaluate RAFI and explore its association with functional status in PH subjects.Methods: A total of 63 PH patients were retrospectively studied. Patients were classified into high RAFI group and low RAFI group based on the median of RAFI. Echocardiography parameters of right heart dimension, RV overload, RV function and RA strain were assessed. Patients’ data of clinical characteristics were documented.Results: Elevated pulmonary arterial pressure, dilated RV dimension, RV overload and worsen cardiac function were observed in low RAFI group (P < 0.05). RAFI was significantly correlated with clinical and echocardiographic indices of pulmonary arterial pressure, pulmonary vascular resistance, RV dimension, RV overload and cardiac function (P < 0.05). In multivariable binary logistic regression analysis, RAFI independently predicted World Heart Organization functional class (WHO FC) III or IV (odds ratio = 0.847; 95% confidence interval, 0.722-0.994; P = 0.041). RAFI < 9.7 was the best cutoff to identify patients with WHO FC III or IV, with sensitivity of 70% and specificity of 79% (area under the curve = 0.777; 95% confidence interval, 0.660-0.894).Conclusions: RAFI provided an easy and valid alternative approach to evaluating RA function. RAFI showed correlation with most clinical and echocardiographic indices of right heart. RAFI was the independent determinant of WHO FC III or IV implying clinical deterioration.
Evidence of communication between heat-stressed and unheat-stressed Caenorhabditis elegans via volatile stress signal
Authors: chen Liangwen , wang Yun , Zhou Xiuhong , Wang Ting , Zhan Huimin , Wu Fei , Li Haolan , Bian Po , Xie Zhongwen
Published: April 2022

Our research group has recently described that radiation-induced airborne stress signals can be communicated between Caenorhabditis elegans (C. elegans). This paper addresses the question of whether heat stress can also induce emission of airborne stress signal to alert neighboring C. elegans and elicit their subsequent stress response. Here, we report that heat-stressed C. elegans produces volatile stress signal(s) that trigger an increase in radiation resistance in neighboring unheat-stressed C. elegans. When several loss-of-function mutations affecting the thermosensory neuron (AFD), heat shock factor-1 (HSF-1), and small heat-shock proteins (HSPs) were used as the heat-stressed C. elegans, we found that the production of the volatile stress signal(s) were blocked, demonstrating the heat shock response as a role in controlling the production of the volatile stress signal(s). It can be found that the mutations affecting DNA damage response (DDR) could inhibit the increasing of radiation resistance in neighboring unheat-stressed C. elegans having received the volatile stress signal(s), which indicate that the DDR might contribute to RAR induction by the volatile stress signal(s). Together, this study demonstrates that heat-stressed nematodes could communicate with unheat-stressed nematodes via volatile stress signal. In addition, the regulating pattern of signal production and action are preliminarily clarified.
Different host plants alter structure, diversity, and function of gut bacterial communities in larval instars of Spodoptera frugiperda
Authors: Wang Yanping , Yi Chunyan , Chen Xingyu , Guo Jingwei , Liu Changhua , Zhang Cuicui , Chen Qingdong , Chen Song , Liu Hongling , Liu Xu
Published: April 2022

Insect gut microbes have important roles in host feeding, digestion, immunity, and growth and development. The fall armyworm, Spodoptera frugiperda, is a major migratory agricultural pest worldwide, effects of host plants on its communities of gut bacteria remain to be investigated. Therefore, differences in gut bacterial communities were examined in S. frugiperda 5th and 6th instar larvae fed leaves of different host plants (corn, sorghum, highland barley, citrus). Metagenomic DNA was extracted from larval intestines, and abundance and diversity of gut bacteria were determined using 16S rDNA full-length amplification and sequencing. Highest richness and diversity of gut bacteria were in corn-fed 5th instar larvae; whereas in 6th instar larvae, richness and diversity were higher when larvae were fed other crops. Firmicutes and Proteobacteria were dominant phyla in gut bacterial communities of 5th and 6th instar larvae. According to LEfSe analysis, host plant had important effects on structure of gut bacterial communities in S. frugiperda. In an analysis using PICRUSt2 software, most predicted functional categories were associated with metabolism. Thus, the plant species attacked by S. frugiperda larvae affects their gut bacterial communities, and such changes are likely important in adaptation to a host plant.
Water decontamination in terms of Hg (II) over thiol immobilized magnesium ferrite – Gum Arabic biosorbent: Response surface optimization, kinetic, isotherm and comparing study
Authors: Nowroozi Mostafa , Alijani Hassan , Beyki Mostafa Hossein , yadaei Hassan , Shemirani Farzaneh
Published: April 2022

Mercury thrown even at a low concentrations in water resources causes a severe threat to ecosystem hence the presented work describes a low cost and environmentally friendly clean up platform for decontamination of water in terms of mercury ions. For this purpose MgFe2O4 – Gum Arabic composite was prepared with a simple ultrasound assisted precipitation route and further modified with L-cysteine as a thiol resource to improve its adsorption characteristic. The structure of biosorbent was characterized with XRD, FESEM, VSM, EDX, and BET techniques. Effective parameters on mercury adsorption were optimized with response surface methodology (RSM) using Box-Behnken design (BBD). Maximum removal efficiency was obtained at pH of 5, contact time of 15 min and adsorbent dosage of 19 mg by magnetic GA. After thiol functionalization optimum variables changed to pH of 2, time of 15 min and dosage of 5 mg. Isotherm study indicated that mercury biosorption onto the magnetic Gum Arabic and thiol immobilized sorbent followed Langmuir and Freundlich model with adsorption capacity of 96 and 250 mg g-1, respectively. Results for kinetic study revealed that mercury adsorption followed pseudo – second order model. To study the ability of biosorbent as a reusable compound a mixture of HCl (0.5 mol L-1) and thiourea (2%) was employed to release the adsorbed ions from the sorbent surface moreover, it showed 90% removal efficiency after three cycles of sorption and desorption which confirmed the presented composite is a reusable biosorbent.
Diagnostic value of tissue motion annular displacement in sepsis-induced cardiomyopathy: a single-center retrospective observational study
Authors: Song Jieqiong , Yao Yao , Lin Shilong , He Yizhou , Zhu Duming , Zhong Ming
Published: April 2022

Background
Currently, there is no formal diagnostic criterion for sepsis-induced cardiomyopathy (SICM). The classic approach has been to use left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) to define SICM. In this regard, tissue motion annular displacement (TMAD) is a novel speckle tracking indicator to quickly assess LV longitudinal systolic function. This study aimed to evaluate the feasibility and application value of TMAD in the diagnosis of SICM in septic patients.
Methods
We conducted a single-center retrospective observational study in sepsis or septic shock patients who underwent echocardiography examination within the first 24h after admission. Basic clinical information and conventional echocardiographic data were collected. Based on speckle tracking echocardiography (STE), GLS and TMAD were respectively performed offline. The correlations between TMAD and other LV systolic function parameters, as well as the diagnostic value of TMAD for SICM, were assessed. Data of 28d and in-hospital mortality were compared between SICM and non-SICM patients.
Results
A total of 143 patients were enrolled in this study. The incidence of SICM according to GLS or TMAD criteria was significantly higher than that according to LVEF criteria (32.9% vs. 18.2%, p = 0.006; 38.5% vs. 18.2%, p < 0.001). The 28d and in-hospital mortality of SICM patients were significantly higher than the non-SICM patients according to any of the diagnostic criteria (all p < 0.05). Significant correlations between TMAD and other LV systolic function echocardiographic parameters, including LVEF, GLS, mitral annular plane systolic excursion (MAPSE), and maximal lateral systolic mitral annular tissue velocity (MA Smax), were detected (all p < 0.001). According to the AUROC value, TMADMid had an excellent diagnostic value for SICM (AUROC > 0.9). Compared with LVEF and GLS, TMAD had the highest intra-observer and inter-observer reliability. The mean time for off-line analyses with TMAD was significantly shorter than that with LVEF or GLS (p < 0.05).
Conclusion
STE-based TMAD is a feasible, reliable, and time-saving option to assess the LV systolic function. Overall, this approach shows an excellent diagnostic value for SICM in septic patients.
KRCC1, a novel modulator of the DNA damage response
Authors: Neizer-Ashun Fiifi , Dwivedi Shailendra , Dey Anindya , Thavathiru Elangovan , Berry William , Lees-Miller Susan , Mukherjee Priyabrata , Bhattacharya Resham
Published: April 2022

The lysine rich coiled-coil 1 (KRCC1) protein is overexpressed in multiple malignancies including ovarian cancer and overexpression correlates with poor overall survival. Despite a potential role in cancer progression, the biology of KRCC1 remains elusive. Here we characterize the biology of KRCC1 and define its role in the DNA damage response and in cell cycle progression. We demonstrate that KRCC1 associates with the checkpoint kinase 1 (CHK1) upon DNA damage and regulates the CHK1-mediated checkpoint. KRCC1 facilitates RAD51 recombinase (RAD51) foci formation and augments homologous recombination repair. Furthermore, KRCC1 is required for proper S-phase progression and subsequent mitotic entry. Our findings uncover a novel component of the DNA damage response and a potential link between cell cycle, associated damage response, and DNA repair.
Myometrial Oxidative Stress Drives MED12 Mutations for Leiomyoma development
Authors: Li Yinuo , Xu Xiuhua , Asif Huma , Feng Yue , Kohrn Brendan F. , Kennedy Scott R. , Kim J Julie , Wei Jian-Jun
Published: April 2022

Background

More than 70% of leiomyomas (LM) harbor MED12 mutations, primarily in exon 2 at c.130-131(GG). The cause of MED12 mutations in myometrial cells remains largely unknown. We hypothesized that increased ROS promotes MED12 mutations in myometrial cells through the oxidation of guanine nucleotides followed by misrepair.

Methods

Genomic oxidative burden (8-OHdG) was evaluated in vitro and in vivo by immunohistochemistry. MED12 mutations were examined by Sanger sequencing and deep sequencing. Transcriptome examined by RNA-seq was performed in myometrium with and without LM, in primary myometrial cells treated with ROS. 8-OHdG mediated misrepair was analyzed by CRISPR/Cas9.

Results

Uteri with high LM burden had a significantly higher rate of MED12 mutations than uteri with low LM burden. Compelling data suggest that the uterus normally produces reactive oxidative species (ROS) in response to stress, and ROS levels in LM are elevated due to metabolic defects. We demonstrated that genomic oxidized guanine (8-OHdG) was found at a significantly higher level in the myometrium of uteri that had multiple LM compared to myometrium without LM. Transcriptome and pathway analyses detected ROS stress in myometrium with LM. Targeted replacement of guanine with 8-OHdG at MED12 c.130 by CRISPR/Cas9 significantly increased the misrepair of G>T. Exposure of primary myometrial cells to oxidative stress in vitro increased misrepair/mutations as detected by duplex sequencing.

Conclusions

Together, our data identified a clear connection between increased myometrial oxidative stress and a high rate of MED12 mutations that may underlie the risk of LM development and severity in women of reproductive age.
Synthesis of porous hollow spheres Co@TiO 2-x -carbon composites for highly efficient lithium-ion batteries
Authors: Liang Chunyong , Huang Zhongliang , Chen Lu , Wang Hongshui , Yang Tai , Liu Ning , Liao Tingdi , Wang Feng
Published: April 2022

The hollow TiO2 anode material has received great attention for next-generation LIBs because of its excellent stability, environmental friendly, and low volume change during lithiation/delithiation. Nevertheless, the current anatase TiO2 anode materials are unable to be energy storage system owing to low lithium ion diffusivity and poor reversible theoretical capacities. The introduction of defects has been turned out to be a significant and effective method to improve electronic conductivity, especially oxygen vacancies (OVs). In this paper, a facile hydrothermal reaction and subsequent chemical vapor deposition method were successfully used to fabricate Co@TiO2-x-carbon hollow nanospheres. These results suggest that the synthesized product exhibits good rate performance and superior cycling stability.
Improving and further analysis of eCPDP (EarlyCross-Project Defect Prediction)
Authors: Kwon Sunjae , Ryu Duksan , Baik Jongmoon
Published: April 2022

Abstract Context Cross-project Defect Prediction (CPDP) utilizes other finished project (i.e., source project) data to predict defects of the current working project. Transfer Learning (TL) has been mainly applied at CPDP to improve prediction performance by alleviating the data distribution discrepancy between different projects. However, existing TL-based CPDP techniques are not applicable at the unit testing phase since they require the entire historical target project data. As a result, they lose the chance to increase the product’s reliability in the early phase by applying the prediction results.Objective To increase the product’s reliability in the early phase by proposing a novel TL-based CPDP technique applicable at the unit testing phase (i.e., eCPDP).Method We utilize Singular Value Decomposition (SVD) that only requires source project data for TL. Result eCPDP shows similar or better performance than the 5 state-of-the- art TL-based CPDP techniques on 9 different performance metrics over 24 projects.Conclusion 1) We show that eCPDP is an applicable CPDP model at the unit testing phase. 2) It can help practitioners find and fix defects in an earlier phase than other TL-based CPDP techniques.
KMT2D mutations promoted tumor progression in diffuse large B-cell lymphoma through altering tumor-induced regulatory T cell trafficking via FBXW7-NOTCH-MYC/TGF-β1 axis
Authors: Liu Qing-Xiao , Zhu Yue , Yi Hong-Mei , Shen Yi-Ge , Wang Li , Cheng Shu , Xu Peng-Peng , Xu Hai-Min , Zhou Lu-Ting , Huang Yao-Hui , Huang Chuan-Xin , Fu Di , Ji Meng-Meng , Wang Chao-Fu , Zhao Wei-Li
Published: April 2022

Background Histone methyltransferase KMT2D is one of the most frequently mutated genes in diffuse large B-cell lymphoma (DLBCL) and has been identified as an important pathogenic factor and prognostic marker. However, the biological relevance of KMT2D mutations on tumor microenvironment remains to be determined.Methods KMT2D mutations were assessed by whole-genome/exome sequencing (WGS/WES) in 334 patients and by targeted sequencing in 427 patients with newly diagnosed DLBCL. Their correlation with clinical outcomes and immune cell characteristics were evaluated. Underlying molecular mechanisms on tumor microenvironment were investigated both in vitro and in vivo.Results Among all 761 DLBCL patients, somatic mutations in KMT2D were observed in 143 (18.79%) patients and significantly associated with advanced Ann Arbor stage and MYC expression ≥ 40%, as well as inferior progression-free survival and overall survival. In B-lymphoma cells, the mutation or knockdown of KMT2D inhibited methylation of lysine 4 on histone H3 (H3K4), downregulated FBXW7 expression, activated NOTCH signaling pathway and downstream MYC/TGF-β1, resulting in alterations of tumor-induced regulatory T cell trafficking. In B-lymphoma murine models established with subcutaneous injection of SU-DHL-4 cells, xenografted tumors bearing KMT2D mutation presented lower H3K4 methylation, higher regulatory T cell recruitment, thereby provoking rapid tumor growth compared with wild-type KMT2D via FBXW7-NOTCH-MYC/TGF-β1 axis. Conclusions Our work thus contributed to the better understanding of aberrant histone methylation on tumor microenvironment as an alternative mechanism of tumor progression in DLBCL.
Antimalarial potential of Gymnema inodorum leaf extract and dihydroartemisinin combination against Plasmodium berghei infected mice
Authors: Somsak Voravuth , Ounjaijean Sakaewan
Published: April 2022

Chemotherapy plays a crucial role in malaria control. However, the main obstacle to treatment has been the rise of parasite resistance to most antimalarial drugs. Artemisinin-based combination therapies (ACTs) remain today’s most effective antimalarial therapies. However, malaria parasite tolerance to ACTs is now increasingly prevalent, especially in Southeast Asia. Consequently, this creates the need for effective alternative antimalarials. Interestingly, the effectiveness of Gymnema inodorum leaf extract (GIE) as an antimalarial candidate was reported earlier. Therefore, this study sought to evaluate the antimalarial potential of dihydroartemisinin (DHA) based combination therapy with GIE against Plasmodium berghei in a mouse model. Drug assessment was carried out on P. berghei ANKA (PbANKA) using the standard 4-day test for determination of fifty percent effective dose (ED50) of DHA and GIE individually. Moreover, the combination of DHA and GIE was also evaluated based on fixed-ratio strategy, 100/0, 80/20, 60/40, 40/60, 20/80, and 0/100 of ED50 of DHA and GIE, respectively. Overall, 2 mg/kg and 100 mg/kg of DHA and GIE resulted in ED50 against PbANKA. In combination, the ratio of 60/40 (DHA/GIE) had a considerable the highest antimalarial activity significantly (p < 0.001) against PbANKA with 88.95% inhibition that indicated a synergism efficacy (CI value = 0.68695). Additionally, this ratio was protected PbANKA infected mice from BW loss and PCV reduction with prolonged survival time throughout the 30 day follow up. This study points to better efficacy of GIE as an alternative drug partner in combination to enhance antimalarial efficacy of DHA against PbANKA infected mice.
Rubber–Ice friction
Authors: Persson Bo , Tada T. , Kawasaki S. , Shimizu R. , Persson B.N.J.
Published: April 2022

We study the friction when a rectangular tire tread rubber block is slid on an ice surface at different temperatures ranging from −38○C to −2○C, and sliding speeds ranging from 3 µm/s to 1 cm/s. At low temperatures and low sliding speeds we propose that an important contribution to the friction force is due to slip between the ice surface and ice fragments attached to the rubber surface. At temperatures above −10○C or for high enough sliding speeds a thin premelted water film occur on the ice surface and the contribution to the friction from shearing the area of real contact is small. In this case the dominant contribution to the friction force comes from viscoelastic deformations of the rubber by the ice asperities.
Evolution of work ability, quality of life and self-rated health in a police department after remodelling shift schedule
Authors: Velasco-Garrido Marcial , Herold Robert , Rohwer Elisabeth , Mache Stefanie , Terschüren Claudia , Preisser Alexandra M. , Harth Volker
Published: April 2022

Background: There exists a great diversity of schedules concerning the way shift work is organized and implemented with ample agreement regarding recommendable features of a shift system. In order to adapt the shift schedule of a metropolitan police department to current recommendations, a remodelled shift schedule was introduced in 2015. The aim of this study was to evaluate the potential associations between the remodelled shift schedule and work ability, quality of life and self-rated health after one and five years.Methods: A controlled before-and- after study were conducted during the piloting phase (2015-2016) as well as a 5-year follow-up using paper questionnaires. Outcome parameters included work ability, quality of life and self-rated health.Results: Work ability, quality of life and self-rated health improved after the first year of the newly implemented shift schedule among police officers working in the piloting police stations compared to those working according to the former schedule. In 5-year follow-up differences between indicators diminished.Conclusions: The implementation of a remodelled shift schedule including more 12-hours shifts accompanied by more days off and a coherent weekend off duty was not associated with detrimental effects to work ability, quality of life or self-reported health among police officers.
Non-invasive transdermal delivery of biomacromolecules with fluorocarbon-modified chitosan for melanoma immunotherapy and transdermal vaccines
Authors: Zhu Wenjun , Wei Ting , Jin Qiutong , Lu Jiaqi , Xu Jun , Chen Muchao , Zhu Jiafei , Chao Yu , Chen Qian , Liu Zhuang
Published: April 2022

Transdermal drug delivery has been regarded as an alternative to oral delivery and subcutaneous injection for its non-invasiveness, improved patient compliance and avoidance of the first-pass effect. However, needleless transdermal delivery of biomacromolecules remains a challenge. Herein, a transdermal delivery platform is developed to achieve highly efficient non-invasive transdermal delivery of biomacromolecules. In this system, fluorocarbon modified chitosan (FCS) is optimized as an effective yet biocompatible transdermal carrier to assemble with different proteins including immune checkpoint blockade (ICB) antibodies, and antigens such as the spike (S) protein of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The formed FCS-containing nanocomplexes exhibited rather effective transdermal penetration ability via both intercellular and transappendageal routes. Interestingly, non-invasive transdermal delivery of ICB antibodies by FCS induced stronger immune responses to treat mouse melanoma compared to intravenous injection of free antibodies, while presenting reduced systemic toxicity. Moreover, transdermal delivery of SARS-CoV-2 vaccine using FCS-containing nanocomplexes resulted in comparable humoral immunity as well as improved cell immunity and immune memory compared to that achieved with subcutaneous vaccine injection. Thus, FCS-based transdermal delivery systems may provide a compelling opportunity to overcome the skin barrier for efficient transdermal delivery of biomacromolecules, widening the range of therapeutics that can be topically administered.
Contribution of histone acetylation to the serotonin-mediated long-term synaptic plasticity in terrestrial snails
Authors: Zuzina Alena B. , Balaban Pavel M.
Published: April 2022

Serotonin plays a decisive role in long-term synaptic plasticity and long-term memory in mollusks. Previously, we demonstrated that histone acetylation is a critical regulatory mechanism of long-term memory in terrestrial snail. At the behavioral level, many studies were done in Helix to elucidate the role of histone acetylation and serotonin. However, the impact of histone acetylation on long-term potentiation of synaptic efficiency in electrophysiological studies in Helix has been studied only in one paper. Here we investigated effects of serotonin, histone deacetylases inhibitors sodium butyrate and trichostatin A, and a serotonergic receptor inhibitor methiothepin on long-term potentiation of synaptic responses in vitro. We demonstrated that long-term potentiation was suppressed by methiothepin but rescued by co-application of histone deacetylase inhibitors sodium butyrate or trichostatin A. Increased histone acetylation compensated the loss of serotonergic activation. We showed that single serotonin application in combination with histone deacetylase blockade could mimic the effect of repeated serotonin applications and be enough for sustained long-lasting synaptic changes. The data obtained demonstrated that histone deacetylases blockade ameliorated deficits in synaptic plasticity induced by different paradigms (methiothepin treatment, the weak training protocol with single application of serotonin), suggesting that histone acetylation contributes to the serotonin-mediated synaptic plasticity.
Enhanced stent visualization system for percutaneous coronary intervention in patients with chronic kidney disease: effects on contrast media volume and radiation exposure
Authors: Tian Yunpeng , Zhao Xiangdong , Yang Yang , Cai Xiaoshu , Jian Lian , Guo Suzhen , Xia Dasheng , Chen Xin , Li Chao , Guo Qianyu , Chen Bingwei , Lu Chengzhi
Published: April 2022

Objective: We aimed to assess the impact of using enhanced stent visualization (ESV) systems on contrast media volume and radiation dose in percutaneous coronary intervention (PCI), especially for patients with chronic kidney disease (CKD). Background: Coronary heart disease (CHD) is associated with chronic kidney disease (CKD) as they share the similar pathological pathway. In addition, the iodinated contrast media used for angiography is a risk factor for contrast-associated acute kidney injury (CA-AKI), which could aggravate the progression of CKD. We hypothesized that ESV systems have the potential to reduce the use of contrast media as well as radiation dose, however, few study reported the impact on contrast media with use of ESV systems. Methods: We retrospectively collected 124 patients with acute coronary syndromes underwent PCI from May 2020 to July 2021. Patients were divided into ESV-guided group (n = 64) and angiography-guided group (n = 60). Procedural parameters including contrast media volume, radiation exposure (in Air Kerma), number of cines, cine frames, fluoroscopy and procedure time were recorded and analyzed.Results: Groups were comparable for patient characteristics. A significant reduction in contrast media volume (179.41 ± 16.76 ml vs. 114.5 ± 13.56ml, p = 0.0001), radiation exposure (693.99 ± 351.04 mGy vs. 1439.45 ± 973.01 mGy, p = 0.001) and procedure time (47.75 ± 15.43 min vs. 65.88 ± 23.81 min, p = 0.029) with the use of ESV systems. Similar results were observed in the subgroup analysis for the patients with CKD.Conclusion: This study suggested that the use of ESV is associated with reduced contrast media usage, radiation dose and procedure time during PCI. The same results were observed in subgroup analysis in patients with CKD, which is of great significance in decreasing the occurrence of contrast-induced nephropathy and mitigating the progression of CKD and CHD.
Evaluation of the effectiveness of androgenetic alopecia treatment in men us- ing platelet-rich plasma: A systematic review of randomized, placebo-con- trolled trials
Authors: Borowiecka Julia Maria , Pałka Łukasz
Published: April 2022

Platelet-Rich Plasma becomes more and more popular treatment alternative or additional method in androgen alopecia (AGA). AGA is a multifactorial disease, in which testosterone plays a significant role in influencing hair growth. The aim was to evaluate the effectiveness of PRP treatment in androgenetic alopecia affecting men. The research was performed using the following databases: PubMed, Embase, and Cochrane Library. The effects were measured with a Tricho-Scan and the measure of the effect was the difference between the initial and final hair density. A significant difference was observed between the areas of the scalp where PRP injections were made and those where saline was administered. Compared to conventional minoxidil 5% topical platelet-rich plasma therapy PRP is more effective in male-pattern baldness treatment. A beneficial effect of combining PRP Therapy with minoxidil 5% was observed, therefore PRP is not only an excellent alternative for patients in whom the minoxidil 5% topical monotherapy did not bring the expected effect or experienced unacceptable side effects, but also can be used as a complementary therapy.
Ecological scheme of cyanobacterial responses to hydrogen peroxide and antioxidant enzymes against diurnal light intensity
Authors: Asaeda Takashi , Rahman Mizanur , Matsuo Akihiko , Abeynayaka H. Damitha L.
Published: April 2022

Diurnal variations of the oxidative stress condition of cyanobacteria were measured by field observations and laboratory experiments. In the field experiment, on clear summer days, transparent bottles, filled with surface water, were set up near the water surface, and several depths to 1 m deep. One bottle from each depth was collected every three hours together with the measurement of the photosynthetically active radiation (PAR). In the laboratory experiment, two cyanobacterial species were exposed to gradually increasing then decreasing light intensities. The samples were analyzed with the hydrogen peroxide (H2O2) concentration, the catalase activities (CAT), protein and chlorophyll a (Chl-a) contents. Regardless of difference in cyanobacterial species, similar diurnal trends were obtained. Protein contents did not change for one day experiments. Biologically generated H2O2 increased following the PAR intensity variation, with the delay of a few hours. The H2O2 concentration per protein was given as an increasing function of the exposure period (T) to the PAR. The amount of Chl-a content declined with the H2O2 per protein value. The model was developed to estimate the H2O2 per protein value, elucidating that the effect of the cyanobacterial biomass and the surface layer mixing on the oxidative stress and mortality.