bluuebunny/crossref_metadata_2025 huggingface dataset:
The loss of SHMT2 mediates 5-fluorouracil chemoresistance in colorectal cancer by upregulating autophagy
Authors: Chen Jian , Na Risi , Xiao Chao , Wang Xiao , Wang Yupeng , Yan Dongwang , Song Guohe , Liu Xueni , Chen Jiayi , Lu Huijun , Chen Chunyan , Tang Huamei , Zhuang Guohong , Fan Guangjian , Peng Zhihai
Published: May 2021

5-Fluorouracil (5-FU)-based chemotherapy is the first-line treatment for colorectal cancer (CRC) but is hampered by chemoresistance. Despite its impact on patient survival, the mechanism underlying chemoresistance against 5-FU remains poorly understood. Here, we identified serine hydroxymethyltransferase-2 (SHMT2) as a critical regulator of 5-FU chemoresistance in CRC. SHMT2 inhibits autophagy by binding cytosolic p53 instead of metabolism. SHMT2 prevents cytosolic p53 degradation by inhibiting the binding of p53 and HDM2. Under 5-FU treatment, SHMT2 depletion promotes autophagy and inhibits apoptosis. Autophagy inhibitors decrease low SHMT2-induced 5-FU resistance in vitro and in vivo. Finally, the lethality of 5-FU treatment to CRC cells was enhanced by treatment with the autophagy inhibitor chloroquine in patient-derived and CRC cell xenograft models. Taken together, our findings indicate that autophagy induced by low SHMT2 levels mediates 5-FU resistance in CRC. These results reveal the SHMT2–p53 interaction as a novel therapeutic target and provide a potential opportunity to reduce chemoresistance.
Decentering as a core component in the psychological treatment and prevention of youth anxiety and depression: a narrative review and insight report
Authors: Bennett Marc P. , Knight Rachel , Patel Shivam , So Tierney , Dunning Darren , Barnhofer Thorsten , Smith Patrick , Kuyken Willem , Ford Tamsin , Dalgleish Tim
Published: May 2021

Decentering is a ubiquitous therapeutic concept featuring in multiple schools of psychological intervention and science. It describes an ability to notice to day-to-day psychological stressors (negative thoughts, feelings, and memories) from an objective self-perspective and without perseverating on the themes they represent. Thus, decentering dampens the impact and distress associated with psychological stressors that can otherwise increase mental ill health in vulnerable individuals. Importantly, the strengthening of decentering-related abilities has been flagged as a core component of psychological interventions that treat and prevent anxiety and depression. We provide an in-depth review evidence of the salutary effects of decentering with a special focus on youth mental health. This is because adolescence is a critical window for the development of psychopathology but is often under-represented in this research line. A narrative synthesis is presented that integrates and summarizes findings on a range of decentering-related abilities. Section 1 reviews extant conceptualizations of decentering and data-driven approaches to characterize its characteristic. A novel definition is then offered to guide future empirical research. Section 2 overviews laboratory-based research into the development of decentering as well as its relationship with anxiety and depression. Section 3 examines the role decentering-related skills play in psychological interventions for anxiety and depression. Critically, we review evidence that treatment-related increases in decentering predict latter reductions in anxiety and depression severity. Each section highlights important areas for future research. The report concludes by addressing the vital questions of whether, how, why and when decentering alleviates youth anxiety and depression.
Tumor- and osteoclast-derived NRP2 in prostate cancer bone metastases
Authors: Polavaram Navatha Shree , Dutta Samikshan , Islam Ridwan , Bag Arup K. , Roy Sohini , Poitz David , Karnes Jeffrey , Hofbauer Lorenz C. , Kohli Manish , Costello Brian A. , Jimenez Raffael , Batra Surinder K. , Teply Benjamin A. , Muders Michael H. , Datta Kaustubh
Published: May 2021

Understanding the role of neuropilin 2 (NRP2) in prostate cancer cells as well as in the bone microenvironment is pivotal in the development of an effective targeted therapy for the treatment of prostate cancer bone metastasis. We observed a significant upregulation of NRP2 in prostate cancer cells metastasized to bone. Here, we report that targeting NRP2 in cancer cells can enhance taxane-based chemotherapy with a better therapeutic outcome in bone metastasis, implicating NRP2 as a promising therapeutic target. Since, osteoclasts present in the tumor microenvironment express NRP2, we have investigated the potential effect of targeting NRP2 in osteoclasts. Our results revealed NRP2 negatively regulates osteoclast differentiation and function in the presence of prostate cancer cells that promotes mixed bone lesions. Our study further delineated the molecular mechanisms by which NRP2 regulates osteoclast function. Interestingly, depletion of NRP2 in osteoclasts in vivo showed a decrease in the overall prostate tumor burden in the bone. These results therefore indicate that targeting NRP2 in prostate cancer cells as well as in the osteoclastic compartment can be beneficial in the treatment of prostate cancer bone metastasis.
Cephalomannine inhibits hypoxia-induced cellular function via the suppression of APEX1/HIF-1α interaction in lung cancer
Authors: Ullah Asmat , Leong Sze Wei , Wang Jingjing , Wu Qing , Ghauri Mohsin Ahmad , Sarwar Ammar , Su Qi , Zhang Yanmin
Published: May 2021

Lung cancer (LC) is one of the leading causes of cancer-related death. As one of the key features of tumor microenvironment, hypoxia conditions are associated with poor prognosis in LC patients. Upregulation of hypoxic-induced factor-1α (HIF-1α) leads to the activation of various factors that contribute to the increased drug resistance, proliferation, and migration of tumor cells. Apurinic/apyrimidinic endonuclease-1 (APEX1) is a multi-functional protein that regulates several transcription factors, including HIF-1α, that contribute to tumor growth, oxidative stress responses, and DNA damage. In this study, we explored the mechanisms underlying cell responses to hypoxia and modulation of APEX1, which regulate HIF-1α and downstream pathways. We found that hypoxia-induced APEX1/HIF-1α pathways regulate several key cellular functions, including reactive oxygen species (ROS) production, carbonic anhydrase 9 (CA9)-mediated intracellular pH, migration, and angiogenesis. Cephalomannine (CPM), a natural compound, exerted inhibitory effects in hypoxic LC cells via the inhibition of APEX1/HIF-1α interaction in vitro and in vivo. CPM can significantly inhibit cell viability, ROS production, intracellular pH, and migration in hypoxic LC cells as well as angiogenesis of HUVECs under hypoxia through the inhibition of APEX1/HIF-1α interaction. Taken together, CPM could be considered as a promising compound for LC treatment.
The endoribonuclease N4BP1 prevents psoriasis by controlling both keratinocytes proliferation and neutrophil infiltration
Authors: Gou Chenliang , Ni Wenkai , Ma Panpan , Zhao Fengbo , Wang Zhou , Sun Rong , Wu Yingcheng , Wu Yuanyuan , Chen Miaomiao , Chen Hao , Zhang Jie , Shen Yu , Xiao Mingbing , Lu Cuihua , Mao Renfang , Fan Yihui
Published: May 2021

Psoriasis is a common chronic skin disease, characterized by abnormal interplay between hyperproliferative epidermal keratinocytes and self-reactive immune cells with not fully addressed molecular mechanism. N4BP1 (NEDD4-binding protein 1) is considered as an immune regulator for a long time but its physiological role is not determined yet. Here, we found that the expression of N4BP1 in skin was highest among all 54 tested tissues, and its expression was further upregulated in psoriatic skin. N4BP1-deficient mice exhibited normal grossly, but developed severe and prolonged IMQ-induced psoriasis-like disease comparing to controls. N4BP1 mainly expressed in keratinocytes and located on nucleus. Up- but not downregulated genes in N4BP1-deficient skin were specifically enriched in keratinocyte proliferation and differentiation. The proliferation of N4BP1-deficient primary keratinocytes was faster compared to that of controls. The upregulated genes upon ablation of N4BP1 were highly enriched in targets of AP-1 transcription factor. Knocking out N4BP1 resulted in upregulation of JunB and FosB, and conversely, overexpression of N4BP1 greatly reduced their expression. Furthermore, N4BP1 binds with JunB and FosB encoding mRNAs and greatly reduces their stability. In addition, with a high expression in neutrophils, N4BP1 limits survival of neutrophils in blood and infiltration of neutrophils in psoriatic skin by targeting CXCL1, CCL20, and S100A8. These findings demonstrate that N4BP1 controls the proper function of keratinocytes and neutrophils by negatively regulating JunB, FosB, and CXCL1, respectively, and that is critical for psoriasis prevention.
Single cell RNA sequencing for breast cancer: present and future
Authors: Ren Lili , Li Junyi , Wang Chuhan , Lou Zheqi , Gao Shuangshu , Zhao Lingyu , Wang Shuoshuo , Chaulagain Anita , Zhang Minghui , Li Xiaobo , Tang Jing
Published: May 2021

Breast cancer is one of the most common malignant tumors in women. It is a heterogeneous disease related to genetic and environmental factors. Presently, the treatment of breast cancer still faces challenges due to recurrence and metastasis. The emergence of single-cell RNA sequencing (scRNA-seq) technology has brought new strategies to deeply understand the biological behaviors of breast cancer. By analyzing cell phenotypes and transcriptome differences at the single-cell level, scRNA-seq reveals the heterogeneity, dynamic growth and differentiation process of cells. This review summarizes the application of scRNA-seq technology in breast cancer research, such as in studies on cell heterogeneity, cancer cell metastasis, drug resistance, and prognosis. scRNA-seq technology is of great significance to deeply analyze the mechanism of breast cancer occurrence and development, identify new therapeutic targets and develop new therapeutic approaches for breast cancer.
3D particle averaging and detection of macromolecular symmetry in localization microscopy
Authors: Heydarian Hamidreza , Joosten Maarten , Przybylski Adrian , Schueder Florian , Jungmann Ralf , Werkhoven Ben van , Keller-Findeisen Jan , Ries Jonas , Stallinga Sjoerd , Bates Mark , Rieger Bernd
Published: May 2021

Single molecule localization microscopy offers in principle resolution down to the molecular level, but in practice this is limited primarily by incomplete fluorescent labeling of the structure. This missing information can be completed by merging information from many structurally identical particles. In this work, we present an approach for 3D single particle analysis in localization microscopy which hugely increases signal-to-noise ratio and resolution and enables determining the symmetry groups of macromolecular complexes. Our method does not require a structural template, and handles anisotropic localization uncertainties. We demonstrate 3D reconstructions of DNA-origami tetrahedrons, Nup96 and Nup107 subcomplexes of the nuclear pore complex acquired using multiple single molecule localization microscopy techniques, with their structural symmetry deducted from the data.
The effect of levodopa on bilateral coordination and gait asymmetry in Parkinson’s disease using inertial sensor
Authors: Son Minji , Han Seung Hwan , Lyoo Chul Hyoung , Lim Joo Ae , Jeon Jeanhong , Hong Kee-Bum , Park Hoon
Published: May 2021

This study aimed to evaluate the effect of levodopa on the phase coordination index (PCI) and gait asymmetry (GA) of patients with Parkinson’s disease (PD) and to investigate correlations between the severity of motor symptoms and gait parameters measured using an inertial sensor. Twenty-six patients with mild-to-moderate-stage PD who were taking levodopa participated in this study. The Unified Parkinson’s Disease Rating Scale part III (UPDRS III) was used to assess the severity of motor impairment. The Postural Instability and Gait Difficulty (PIGD) subscore was calculated from UPDRS III. Patients were assessed while walking a 20-m corridor in both “OFF” and “ON” levodopa medication states, and gait analysis was performed using inertial sensors. We investigated the changes in gait parameters after taking levodopa and the correlations between UPDRS III, PIGD, and gait parameters. There was a significant improvement in PCI after taking levodopa. No significant effect of levodopa on GA was found. In “OFF” state, PCI and GA were not correlated with UPDRS III and PIGD. However, in “ON” state, PCI was the only gait parameter correlating with UPDRS III, and it was also highly correlated with PIGD compared to other gait parameters. Significant improvement in bilateral-phase coordination was identified in patients with PD after taking levodopa, without significant change in gait symmetricity. Considering the high correlation with UDPRS III and PIGD in “ON” states, PCI may be a useful and quantitative parameter to measure the severity of motor symptoms in PD patients who are on medication.
Association of asthma with low serum vitamin D and its related musculoskeletal and psychological symptoms in adults: a case-control study
Authors: Alkhatatbeh Mohammad J. , Almomani Haneen S. , Abdul-Razzak Khalid K. , Samrah Shaher
Published: May 2021

There are complex potential inter-relationships between the chronic inflammation of asthma and poor control, vitamin D deficiency, musculoskeletal pain and anxiety and depression. The aim was to investigate associations between vitamin D and these possible co-morbidities. This case-controlled study involved 75 adults with asthma and 75 controls. Serum 25-hydroxyvitamin D (25(OH)D) was measured, levels of anxiety, depression, musculoskeletal pain, and asthma control were assessed. Participants with asthma had lower 25(OH)D and higher anxiety scores and higher measures of musculoskeletal pain compared to controls. Binary logistic regression showed that asthma was associated with decreased 25(OH)D (Odds ratio (OR) = 0.86), general weakness (OR = 13.29), complaint of musculoskeletal pain (OR = 13.73), and increased intensity of musculoskeletal pain (OR = 0.61) and number of painful sites (OR = 2.58). Asthma was not associated with anxiety or depression. Further studies are required to investigate if vitamin D supplementation can improve asthma symptoms and musculoskeletal pain.
Single-shot detection of 8 unique monochrome fringe patterns representing 4 distinct directions via multispectral fringe projection profilometry
Authors: Omidi Parsa , Najiminaini Mohamadreza , Diop Mamadou , Carson Jeffrey J. L.
Published: May 2021

Spatial resolution in three-dimensional fringe projection profilometry is determined in large part by the number and spacing of fringes projected onto an object. Due to the intensity-based nature of fringe projection profilometry, fringe patterns must be generated in succession, which is time-consuming. As a result, the surface features of highly dynamic objects are difficult to measure. Here, we introduce multispectral fringe projection profilometry, a novel method that utilizes multispectral illumination to project a multispectral fringe pattern onto an object combined with a multispectral camera to detect the deformation of the fringe patterns due to the object. The multispectral camera enables the detection of 8 unique monochrome fringe patterns representing 4 distinct directions in a single snapshot. Furthermore, for each direction, the camera detects two π-phase shifted fringe patterns. Each pair of fringe patterns can be differenced to generate a differential fringe pattern that corrects for illumination offsets and mitigates the effects of glare from highly reflective surfaces. The new multispectral method solves many practical problems related to conventional fringe projection profilometry and doubles the effective spatial resolution. The method is suitable for high-quality fast 3D profilometry at video frame rates.
Predictive SNPs for β0-thalassemia/HbE disease severity
Authors: Munkongdee Thongperm , Tongsima Sissades , Ngamphiw Chumpol , Wangkumhang Pongsakorn , Peerapittayamongkol Chayanon , Hashim Hafizah Binti , Fucharoen Suthat , Svasti Saovaros
Published: May 2021

β-Thalassemia/HbE disease has a wide spectrum of clinical phenotypes ranging from asymptomatic to dependent on regular blood transfusions. Ability to predict disease severity is helpful for clinical management and treatment decision making. A thalassemia severity score has been developed from Mediterranean β-thalassemia patients. However, different ethnic groups may have different allele frequency and linkage disequilibrium structures. Here, Thai β0-thalassemia/HbE disease genome-wild association studies (GWAS) data of 487 patients were analyzed by SNP interaction prioritization algorithm, interacting Loci (iLoci), to find predictive SNPs for disease severity. Three SNPs from two SNP interaction pairs associated with disease severity were identifies. The three-SNP disease severity risk score composed of rs766432 in BCL11A, rs9399137 in HBS1L-MYB and rs72872548 in HBE1 showed more than 85% specificity and 75% accuracy. The three-SNP predictive score was then validated in two independent cohorts of Thai and Malaysian β0-thalassemia/HbE patients with comparable specificity and accuracy. The SNP risk score could be used for prediction of clinical severity for Southeast Asia β0-thalassemia/HbE population.
A numerical study on capillary-evaporation behavior of porous wick in electronic cigarettes
Authors: Gao Yihan , Li Dian , Ru Jiexiong , Yang Muyun , Lu Lehua , Lu Li , Wu Jinlu , Huang Zhonghui , Xie Yan , Gao Naiping
Published: May 2021

A mathematical model based on heat and mass transfer processes in the porous wick of electronic cigarettes was established to describe the atomization of e-liquids according to max liquid temperature, vaporization rate and thermal efficiency in a single puff. Dominant capillary-evaporation effects were defined in the model to account for the effects of electrical power, e-liquid composition and porosity of the wick material on atomization and energy transmission processes. Liquid temperature, vaporization rate, and thermal efficiency were predicted using the mathematical model in 64 groups, varying with electrical power, e-liquid composition and wick porosity. Experimental studies were carried out using a scaled-model test bench to validate the model’s prediction. A higher PG/VG ratio in the e-liquid promoted energy transfer for vaporization, and the e-liquid temperature was comparatively reduced at a relatively high power, which was helpful to avoid atomizer overheating. Compared with the other factors, wick porosity affected the thermal efficiency more significantly. The vaporization rate increased with a higher wick porosity in a certain range. The modelling results suggested that a greater wick porosity and a higher PG ratio in e-liquids helped to improve the overall thermal efficiency.
EGR1 as a potential marker of prognosis in extranodal NK/T-cell lymphoma
Authors: Lee Ji Yun , Kim Joo Hyun , Bang Heejin , Cho Junhun , Ko Young Hyeh , Kim Seok Jin , Kim Won Seog
Published: May 2021

Extranodal natural killer T-cell lymphoma (ENKTL) is an aggressive malignancy with a dismal prognosis. In the present study, gene expression profiling was performed to provide more information on ENKTL molecular signature and offer a rationale for further investigation of prognostic markers in ENKTL. NanoString nCounter Analysis encompassing 133 target genes was used to compare gene expression levels of 43 ENKTL tumor samples. The majority of the patients were under 60 years of age (79.1%); 32 (74.4%) patients had nasal type ENKTL and 23 patients (53.5%) had intermediate/high risk ENKTL based on the prognostic index for natural killer cell lymphoma (PINK). The median follow-up was 15.9 months and the median overall survival (OS) was 16.1 months (95% CI 13.0–69.8). EGR1 upregulation was consistently identified in the localized stage with a low risk of prognostic index based on the PINK. Among the six significantly relevant genes for EGR1 expression, high expression levels of genes, including CD59, GAS1, CXCR7, and RAMP3, were associated with a good survival prognosis. The in vitro test showed EGR1 modulated the transcriptional activity of the target genes including CD59, GAS1, CXCR7, and RAMP3. Downregulation of EGR1 and its target genes significantly inhibited apoptosis and decreased chemosensitivity and attenuated radiation-induced apoptosis. The findings showed EGR1 may be a candidate for prognostic markers in ENKTL. Considerable additional characterization may be necessary to fully understand EGR1.
Adalimumab biosimilars, ABP501 and SB5, are equally effective and safe as adalimumab originator
Authors: Cingolani Linda , Barberio Brigida , Zingone Fabiana , Ferronato Antonio , Bertani Lorenzo , Costa Francesco , Bodini Giorgia , Demarzo Maria Giulia , Melatti Piera , Gubbiotti Alessandro , Massimi Davide , Casadei Cesare , D’Incà Renata , Savarino Edoardo Vincenzo
Published: May 2021

To date, data on effectiveness and safety of Adalimumab (ADA) biosimilars in inflammatory bowel diseases (IBDs) are lacking. Therefore, we aimed to verify the ability of ABP501 and SB5 to maintain the clinical and biochemical response induced by the ADA originator, after switching to them. We prospectively analyzed data collected from 55 patients with IBD who switched to ABP501, and 25 patients with IBD who switched to SB5, from ADA originator at four IBD Units between 2018 and 2020. In addition, we included an age and sex-matched control group (n = 38) who continued ADA originator for at least two years and who did not switch to a biosimilar drug. Clinical and biochemical data (C-Reactive Protein (CRP), fecal calprotectin (FC)), concomitant steroid and/or immunosuppressant therapy at the time of the switch and after six months were collected. At six months, in the ABP501 group, we did not observe statistically significant modifications in clinical activity of disease (p = 0.09) and FC values (p = 0.90). Some patients (n = 8) needed to add steroids at six months after switching (p = 0.01), however the need for optimization was not significant between the two timepoints (p = 0.70). Finally, 14.5% patients stopped therapy after six months. Similarly, in the SB5 group we observed a stability of clinical activity and FC values (p = 0.90 and p = 0.20), and a concomitant statistically significant decrease in CRP (p = 0.03). There were no differences in steroids/immunosuppressants need or optimizing biological therapy in this group. Finally, drug survival curves of patients who switched from originator to ABP501 and those who continued ADA originator were similar (p = 0.20). Overall, biosimilar drugs seem to be as effective and safe as the originator. Further larger and longer studies are mandatory to understand the clinical implications of these findings.
Impact of selenium addition to the cadmium-zinc-telluride matrix for producing high energy resolution X-and gamma-ray detectors
Authors: Roy Utpal N. , Camarda Giuseppe S. , Cui Yonggang , Yang Ge , James Ralph B.
Published: May 2021

Both material quality and detector performance have been steadily improving over the past few years for the leading room temperature radiation detector material cadmium-zinc-telluride (CdZnTe). However, although tremendous progress being made, CdZnTe still suffers from high concentrations of performance-limiting defects, such as Te inclusions, networks of sub-grain boundaries and compositional inhomogeneity due to the higher segregation coefficient of Zn. Adding as low as 2% (atomic) Se into CdZnTe matrix was found to successfully mitigate many performance-limiting defects and provide improved compositional homogeneity. Here we report record-high performance of Virtual Frisch Grid (VFG) detector fabricated from as-grown Cd0.9Zn0.1Te0.98Se0.02 ingot grown by the Traveling Heater Method (THM). Benefiting from superior material quality, we achieved superb energy resolution of 0.77% at 662 keV (as-measured without charge-loss correction algorithms) registered at room temperature. The absence of residual thermal stress in the detector was revealed from white beam X-ray topographic images, which was also confirmed by Infra-Red (IR) transmission imaging under cross polarizers. Furthermore, neither sub-grain boundaries nor their networks were observed from the X-ray topographic image. However, large concentrations of extrinsic impurities were revealed in as-grown materials, suggesting a high likelihood for further reduction in the energy resolution after improved purification of the starting material.
A randomized clinical trial evaluating the short-term results of ureteral stent encrustation in urolithiasis patients undergoing ureteroscopy: micro-computed tomography evaluation
Authors: Yoshida Takashi , Takemoto Kuniko , Sakata Yoshiko , Matsuzaki Tomoaki , Koito Yuya , Yamashita Shimpei , Hara Isao , Kinoshita Hidefumi , Matsuda Tadashi
Published: May 2021

Although many ureteral stents are commercially available, the actuality of encrustation is yet to be elucidated in humans. This study compared the Tria Ureteral Stent with PercuShield and the Polaris Ultra Ureteral Stent with HydroPlus Coating for short-term encrustation formation. Eighty-four patients, who required ureteral stent placement after ureteroscopy, were randomized into two stent groups. After stent removal on postoperative day 14, the encrustation volume on the stent surface was measured by micro-computed tomography. The primary outcome was the inner luminal encrustation volume. Secondary outcomes were encrustation volume on the outer or total surfaces and occurrence of adverse events. Clinical factors related to encrustation were also assessed as a post-hoc analysis. Finally, of the 82 patients analyzed, 75 (91.5%) had encrustation in the inner lumen of the stent. The difference in median inner encrustation volume between the Tria and Polaris Ultra stents was comparable (0.56 vs. 0.37 mm3,P = 0.183). There was no difference observed in the encrustation volume on the outer/total surfaces and stent-related adverse events. In both ureteral stents, the shaft body showed significant inner luminal encrustation compared to the proximal or distal loop (all,P < 0.05). Dyslipidemia (P = 0.027), elevated urine pH (P = 0.046), and crystalluria (P = 0.010) were associated with encrustation formation. The Tria and Polaris Ultra stents had similar efficacy for preventing encrustation in the short-term. Further studies are required to compare their long-term patency.
Gliadin-mediated green preparation of hybrid zinc oxide nanospheres with antibacterial activity and low toxicity
Authors: Wang Qun , Ji Peng , Yao Yansheng , Liu Yi , Zhang Yajie , Wang Xianglong , Wang Yuhang , Wu Jinyan
Published: May 2021

The development of inorganic antibacterial agents that impart antibacterial properties to biomaterials has attracted wide attention. The paper introduced a kind of hybrid nanosphere antibacterial agent composed of wheat gliadin (WG) and zinc oxide (ZnO), with antibacterial efficacy and low toxicity. The ZnO/WG hybrid nanospheres were environment-friendly integrated by molecular self-assembly co-precipitating and freeze-drying transformation, and were characterized using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), atomic absorption spectroscopy (AAS), specific surface and pore size analysis, bacteriostasis test, reactive oxygen species (ROS) determination and safety evaluation. It was found that the prepared hybrid nanospheres were composed of two components, WG and ZnO, with a diameter scope of 100–200 nm; the content of ZnO in the hybrid nanospheres can reach 46.9–70.2% (w/w); the bacteriostasis tests proved that the prepared ZnO/WG nanospheres generating ROS, have a significant inhibitory effect on E. coli and S. aureus; furthermore, the ZnO/WG nanospheres are relatively safe and highly biocompatible in cells and mice. Therefore, the prepared novel ZnO/WG hybrid nanospheres were supposed to apply in the preparation of anti-infective wound dressings, tissue engineering skin scaffold materials, food, and cosmetics preservatives, and so on.
Radioactivity and radionuclides in deciduous teeth formed before the Fukushima-Daiichi Nuclear Power Plant accident
Authors: Takahashi Atsushi , Chiba Mirei , Tanahara Akira , Aida Jun , Shimizu Yoshinaka , Suzuki Toshihiko , Murakami Shinobu , Koarai Kazuma , Ono Takumi , Oka Toshitaka , Ikeyama Joji , Kaneko Osamu , Unno Makoto , Hirose Kimiharu , Ohno Takashi , Kino Yasushi , Sekine Tsutomu , Osaka Ken , Sasaki Keiichi , Shinoda Hisashi
Published: May 2021

The Fukushima-Daiichi Nuclear Power Plant (FNPP) accident in March of 2011 released substantial amounts of radionuclides into the environment. We collected 4,957 deciduous teeth formed in children before the Fukushima accident to obtain precise control data for teeth formed after the accident. Radioactivity was measured using imaging plates (IP) and epidemiologically assessed using multivariate regression analysis. Additionally, we measured 90Sr, 137Cs, and natural radionuclides which might be present in teeth. Epidemiological studies of IP showed that the amount of radioactivity in teeth from Fukushima prefecture was similar to that from reference prefectures. We found that artificial radionuclides of 90Sr and 137Cs, which were believed to have originated from past nuclear disasters, and natural radionuclides including 40 K and daughter nuclides in the 238U and 232Th series contributed to the generation of radioactivity in teeth. We also found no evidence to suggest that radionuclides originating from the FNPP accident significantly contaminated pre-existing teeth. This is the first large-scale investigation of radioactivity and radionuclides in teeth. The present findings will be indispensable for future studies of teeth formed after the FNPP accident, which will fall out over the next several years and might be more contaminated with radionuclides.
Ab initio prediction of semiconductivity in a novel two-dimensional Sb2X3 (X= S, Se, Te) monolayers with orthorhombic structure
Authors: Bafekry A. , Mortazavi B. , Faraji M. , Shahrokhi M. , Shafique A. , Jappor H. R. , Nguyen C. , Ghergherehchi M. , Feghhi S. A. H.
Published: May 2021

$$\hbox {Sb}_2\hbox {S}_3$$

Sb
2

S
3

and $$\hbox {Sb}_2\hbox {Se}_3$$

Sb
2

Se
3

are well-known layered bulk structures with weak van der Waals interactions. In this work we explore the atomic lattice, dynamical stability, electronic and optical properties of $$\hbox {Sb}_2\hbox {S}_3$$

Sb
2

S
3

, $$\hbox {Sb}_2\hbox {Se}_3$$

Sb
2

Se
3

and $$\hbox {Sb}_2\hbox {Te}_3$$

Sb
2

Te
3

monolayers using the density functional theory simulations. Molecular dynamics and phonon dispersion results show the desirable thermal and dynamical stability of studied nanosheets. On the basis of HSE06 and PBE/GGA functionals, we show that all the considered novel monolayers are semiconductors. Using the HSE06 functional the electronic bandgap of $$\hbox {Sb}_2\hbox {S}_3$$

Sb
2

S
3

, $$\hbox {Sb}_2\hbox {Se}_3$$

Sb
2

Se
3

and $$\hbox {Sb}_2\hbox {Te}_3$$

Sb
2

Te
3

monolayers are predicted to be 2.15, 1.35 and 1.37 eV, respectively. Optical simulations show that the first absorption coefficient peak for $$\hbox {Sb}_2\hbox {S}_3$$

Sb
2

S
3

, $$\hbox {Sb}_2\hbox {Se}_3$$

Sb
2

Se
3

and $$\hbox {Sb}_2\hbox {Te}_3$$

Sb
2

Te
3

monolayers along in-plane polarization is suitable for the absorption of the visible and IR range of light. Interestingly, optically anisotropic character along planar directions can be desirable for polarization-sensitive photodetectors. Furthermore, we systematically investigate the electrical transport properties with combined first-principles and Boltzmann transport theory calculations. At optimal doping concentration, we found the considerable larger power factor values of 2.69, 4.91, and 5.45 for hole-doped $$\hbox {Sb}_{{2}}\hbox {S}_{{3}}$$

Sb
2

S
3

, $$\hbox {Sb}_{{2}}\hbox {Se}_{{3}}$$

Sb
2

Se
3

, and $$\hbox {Sb}_{{2}}\hbox {Te}_{{3}}$$

Sb
2

Te
3

, respectively. This study highlights the bright prospect for the application of $$\hbox {Sb}_2\hbox {S}_3$$

Sb
2

S
3

, $$\hbox {Sb}_2\hbox {Se}_3$$

Sb
2

Se
3

and $$\hbox {Sb}_2\hbox {Te}_3$$

Sb
2

Te
3

nanosheets in novel electronic, optical and energy conversion systems.
Resolving few-layer antimonene/graphene heterostructures
Authors: Gupta Tushar , Elibol Kenan , Hummel Stefan , Stöger-Pollach Michael , Mangler Clemens , Habler Gerlinde , Meyer Jannik C. , Eder Dominik , Bayer Bernhard C.
Published: May 2021

Two-dimensional (2D) antimony (Sb, “antimonene”) is of interest in electronics and batteries. Sb however exhibits a large allotropic structural diversity, which is also influenced by its support. Thus, Sb heterostructure formation is key in 2D Sb integration. Particularly, 2D Sb/graphene interfaces are important. We thus study here few-layered 2D Sb/graphene heterostructures with atomic resolution (scanning) transmission electron microscopy. We find two Sb morphologies to coexist: first, a 2D morphology of layered β-Sb with β-Sb(001)||graphene(001) texture. Second, one-dimensional Sb nanowires which can be matched to β-Sb[2-21]⊥graphene(001) and are closely related to cubic Sb(001)||graphene(001). Importantly, both Sb morphologies show rotational van-der-Waals epitaxy with graphene. Both are resilient against oxidation, although superficial Sb-oxide formation merits consideration, including epitaxial Sb2O3(111)/β-Sb(001) heterostructures. Exact Sb growth behavior depends on processing and substrate properties including, notably, the support underneath the graphene. Our work elucidates the rich phase and epitaxy landscape in 2D Sb and 2D Sb/graphene heterostructures.
Magnetic order and critical temperature of substitutionally doped transition metal dichalcogenide monolayers
Authors: Tiwari Sabyasachi , Van de Put Maarten L. , Sorée Bart , Vandenberghe William G.
Published: May 2021

Using first-principles calculations, we investigate the magnetic order in two-dimensional (2D) transition-metal-dichalcogenide (TMD) monolayers: MoS2, MoSe2, MoTe2, WSe2, and WS2 substitutionally doped with period four transition-metals (Ti, V, Cr, Mn, Fe, Co, Ni). We uncover five distinct magnetically ordered states among the 35 distinct TMD-dopant pairs: the non-magnetic (NM), the ferromagnetic with out-of-plane spin polarization (Z FM), the out-of-plane polarized clustered FMs (clustered Z FM), the in-plane polarized FMs (X–Y FM), and the anti-ferromagnetic (AFM) state. Ni and Ti dopants result in an NM state for all considered TMDs, while Cr dopants result in an anti-ferromagnetically ordered state for all the TMDs. Most remarkably, we find that Fe, Mn, Co, and V result in an FM ordered state for all the TMDs, except for MoTe2. Finally, we show that V-doped MoSe2 and WSe2, and Mn-doped MoS2, are the most suitable candidates for realizing a room-temperature FM at a 16–18% atomic substitution.
Topological vectors as a fingerprinting system for 2D-material flake distributions
Authors: Santos Joyce C. C. , Prado Mariana C. , Morais Helane L. O. , Sousa Samuel M. , Silva-Pinto Elisangela , Cançado Luiz G. , Neves Bernardo R. A.
Published: May 2021

The production of 2D material flakes in large quantities is a rapidly evolving field and a cornerstone for their industrial applicability. Although flake production has advanced in a fast pace, its statistical characterization is somewhat slower, with few examples in the literature which may lack either modelling uniformity and/or physical equivalence to actual flake dimensions. The present work brings a methodology for 2D material flake characterization with a threefold target: (i) propose a set of morphological shape parameters that correctly map to actual and relevant flake dimensions; (ii) find a single distribution function that efficiently describes all these parameter distributions; and (iii) suggest a representation system—topological vectors—that uniquely characterizes the statistical flake morphology within a given distribution. The applicability of such methodology is illustrated via the analysis of tens of thousands flakes of graphene/graphite and talc, which were submitted to different production protocols. The richness of information unveiled by this universal methodology may help the development of necessary standardization procedures for the imminent 2D-materials industry.
Graphene-based 3D XNOR-VRRAM with ternary precision for neuromorphic computing
Authors: Alimkhanuly Batyrbek , Sohn Joon , Chang Ik-Joon , Lee Seunghyun
Published: May 2021

Recent studies on neural network quantization have demonstrated a beneficial compromise between accuracy, computation rate, and architecture size. Implementing a 3D Vertical RRAM (VRRAM) array accompanied by device scaling may further improve such networks’ density and energy consumption. Individual device design, optimized interconnects, and careful material selection are key factors determining the overall computation performance. In this work, the impact of replacing conventional devices with microfabricated, graphene-based VRRAM is investigated for circuit and algorithmic levels. By exploiting a sub-nm thin 2D material, the VRRAM array demonstrates an improved read/write margins and read inaccuracy level for the weighted-sum procedure. Moreover, energy consumption is significantly reduced in array programming operations. Finally, an XNOR logic-inspired architecture designed to integrate 1-bit ternary precision synaptic weights into graphene-based VRRAM is introduced. Simulations on VRRAM with metal and graphene word-planes demonstrate 83.5 and 94.1% recognition accuracy, respectively, denoting the importance of material innovation in neuromorphic computing.
High-throughput sequencing defines donor and recipient HLA B-cell epitope frequencies for prospective matching in transplantation
Authors: Tran Jenny N. , Günther Oliver P. , Sherwood Karen R. , Fenninger Franz , Allan Lenka L. , Lan James , Sapir-Pichhadze Ruth , Duquesnoy Rene , Claas Frans , Marsh Steven G. E. , McMaster W. Robert , Keown Paul A. ,   Genome Canada Transplant Consortium,   Canada Working Group, Bryan Stirling , Caulfield Timothy , Ragoussis Ioannis , Oualkacha Karim , Tinckam Kathryn , Liwski Robert , Campbell Patricia , Cardinal Heloise , De Serres Sacha A. , Saw Chee Loong , Mengel Michael , Sis Banu , Wagner Eric , Berka Noureddine , McManus Bruce , Hebert Marie-Josée , Foster Leonard J. , Rossi Fabio , Borchers Christoph H. , Piccirillo Ciriaco A. , Polychronakos Constantin , Ng Raymond , Jevnikar Anthony , Cullis Pieter , Filler Guido , Wong Harvey , Foster Bethany , Gill John , Kim S. Joseph , Tibbles Lee Anne , Humar Atul , Shechter Steven , Chaudhury Prosanto , Fernandez Nicolas , Fowler Elizabeth , Kiberd Bryce , Gill Jagbir , Fortin Marie-Chantal , Klarenbach Scott , Balshaw Robert , Mital Seema , Mucsi Istvan , Ostrow David , Stiller Calvin , Parekh Rulan S. , Richard Lucie , Senecal Lynne , Blydt-Hansen Tom ,   United States Working Group, Erlich Henry , Gebel Howard , Weimer Eric , Kaplan Bruce , Burckart Gilbert ,   United Kingdom Working Group, Middleton Derek , Marsh Steven G. E. ,   Netherlands Working Group, Tilanus Marcel , van Gelder Teun ,   Germany Working Group, Opelz Gerhard , Oellerich Michael ,   France Working Group, Marquet Pierre ,   New Zealand Working Group, Marra Carlo ,   Hungary Working Group, Kaló Zoltán
Published: May 2021

Compatibility for human leukocyte antigen (HLA) genes between transplant donors and recipients improves graft survival but prospective matching is rarely performed due to the vast heterogeneity of this gene complex. To reduce complexity, we have combined next-generation sequencing and in silico mapping to determine transplant population frequencies and matching probabilities of 150 antibody-binding eplets across all 11 classical HLA genes in 2000 ethnically heterogeneous renal patients and donors. We show that eplets are more common and uniformly distributed between donors and recipients than the respective HLA isoforms. Simulations of targeted eplet matching shows that a high degree of overall compatibility, and perfect identity at the clinically important HLA class II loci, can be obtained within a patient waiting list of approximately 250 subjects. Internal epitope-based allocation is thus feasible for most major renal transplant programs, while regional or national sharing may be required for other solid organs.
G-protein coupled receptor 35 (GPR35) regulates the colonic epithelial cell response to enterotoxigenic Bacteroides fragilis
Authors: Boleij Annemarie , Fathi Payam , Dalton William , Park Ben , Wu Xinqun , Huso David , Allen Jawara , Besharati Sepideh , Anders Robert A. , Housseau Franck , Mackenzie Amanda E. , Jenkins Laura , Milligan Graeme. , Wu Shaoguang , Sears Cynthia L.
Published: May 2021

G protein-coupled receptor (GPR)35 is highly expressed in the gastro-intestinal tract, predominantly in colon epithelial cells (CEC), and has been associated with inflammatory bowel diseases (IBD), suggesting a role in gastrointestinal inflammation. The enterotoxigenic Bacteroides fragilis (ETBF) toxin (BFT) is an important virulence factor causing gut inflammation in humans and animal models. We identified that BFT signals through GPR35. Blocking GPR35 function in CECs using the GPR35 antagonist ML145, in conjunction with shRNA knock-down and CRISPRcas-mediated knock-out, resulted in reduced CEC-response to BFT as measured by E-cadherin cleavage, beta-arrestin recruitment and IL-8 secretion. Importantly, GPR35 is required for the rapid onset of ETBF-induced colitis in mouse models. GPR35-deficient mice showed reduced death and disease severity compared to wild-type C57Bl6 mice. Our data support a role for GPR35 in the CEC and mucosal response to BFT and underscore the importance of this molecule for sensing ETBF in the colon.
Imbalanced social-communicative and restricted repetitive behavior subtypes of autism spectrum disorder exhibit different neural circuitry
Authors: Bertelsen Natasha , Landi Isotta , Bethlehem Richard A. I. , Seidlitz Jakob , Busuoli Elena Maria , Mandelli Veronica , Satta Eleonora , Trakoshis Stavros , Auyeung Bonnie , Kundu Prantik , Loth Eva , Dumas Guillaume , Baumeister Sarah , Beckmann Christian F. , Bölte Sven , Bourgeron Thomas , Charman Tony , Durston Sarah , Ecker Christine , Holt Rosemary J. , Johnson Mark H. , Jones Emily J. H. , Mason Luke , Meyer-Lindenberg Andreas , Moessnang Carolin , Oldehinkel Marianne , Persico Antonio M. , Tillmann Julian , Williams Steve C. R. , Spooren Will , Murphy Declan G. M. , Buitelaar Jan K. ,   the EU-AIMS LEAP group, Ahmad Jumana , Ambrosino Sara , Banaschewski Tobias , Bours Carsten , Brammer Michael , Brandeis Daniel , Brogna Claudia , de Bruijn Yvette , Chakrabarti Bhismadev , Chatham Chris , Cornelissen Ineke , Crawley Daisy , Dell’Acqua Flavio , Faulkner Jessica , Frouin Vincent , Garcés Pilar , Goyard David , Ham Lindsay , Hayward Hannah , Hipp Joerg , Holt Rosemary J. , D’ardhuy Xavier Liogier , Lythgoe David J. , Mandl René , Marquand Andre , Mennes Maarten , Mueller Nico , Oakley Bethany , O’Dwyer Laurence , Oranje Bob , Pandina Gahan , Persico Antonio M. , Ruggeri Barbara , Ruigrok Amber N. V. , Sabet Jessica , Sacco Roberto , Cáceres Antonia San José , Simonoff Emily , Toro Roberto , Tost Heike , Waldman Jack , Williams Steve C. R. , Wooldridge Caroline , Zwiers Marcel P. , Baron-Cohen Simon , Lai Meng-Chuan , Lombardo Michael V.
Published: May 2021

Social-communication (SC) and restricted repetitive behaviors (RRB) are autism diagnostic symptom domains. SC and RRB severity can markedly differ within and between individuals and may be underpinned by different neural circuitry and genetic mechanisms. Modeling SC-RRB balance could help identify how neural circuitry and genetic mechanisms map onto such phenotypic heterogeneity. Here, we developed a phenotypic stratification model that makes highly accurate (97–99%) out-of-sample SC = RRB, SC > RRB, and RRB > SC subtype predictions. Applying this model to resting state fMRI data from the EU-AIMS LEAP dataset (n = 509), we find that while the phenotypic subtypes share many commonalities in terms of intrinsic functional connectivity, they also show replicable differences within some networks compared to a typically-developing group (TD). Specifically, the somatomotor network is hypoconnected with perisylvian circuitry in SC > RRB and visual association circuitry in SC = RRB. The SC = RRB subtype show hyperconnectivity between medial motor and anterior salience circuitry. Genes that are highly expressed within these networks show a differential enrichment pattern with known autism-associated genes, indicating that such circuits are affected by differing autism-associated genomic mechanisms. These results suggest that SC-RRB imbalance subtypes share many commonalities, but also express subtle differences in functional neural circuitry and the genomic underpinnings behind such circuitry.
Malfunctioning CD106-positive, short-term hematopoietic stem cells trigger diabetic neuropathy in mice by cell fusion
Authors: Katagi Miwako , Terashima Tomoya , Ohashi Natsuko , Nakae Yuki , Yamada Akane , Nakagawa Takahiko , Miyazawa Itsuko , Maegawa Hiroshi , Okano Junko , Suzuki Yoshihisa , Fujino Kazunori , Eguchi Yutaka , Kojima Hideto
Published: May 2021

Diabetic neuropathy is an incurable disease. We previously identified a mechanism by which aberrant bone marrow-derived cells (BMDCs) pathologically expressing proinsulin/TNF-α fuse with residential neurons to impair neuronal function. Here, we show that CD106-positive cells represent a significant fraction of short-term hematopoietic stem cells (ST-HSCs) that contribute to the development of diabetic neuropathy in mice. The important role for these cells is supported by the fact that transplantation of either whole HSCs or CD106-positive ST-HSCs from diabetic mice to non-diabetic mice produces diabetic neuronal dysfunction in the recipient mice via cell fusion. Furthermore, we show that transient episodic hyperglycemia produced by glucose injections leads to abnormal fusion of pathological ST-HSCs with residential neurons, reproducing neuropathy in nondiabetic mice. In conclusion, we have identified hyperglycemia-induced aberrant CD106-positive ST-HSCs underlie the development of diabetic neuropathy. Aberrant CD106-positive ST-HSCs constitute a novel therapeutic target for the treatment of diabetic neuropathy.
Molecular basis for the disruption of Keap1–Nrf2 interaction via Hinge & Latch mechanism
Authors: Horie Yuta , Suzuki Takafumi , Inoue Jin , Iso Tatsuro , Wells Geoffrey , Moore Terry W. , Mizushima Tsunehiro , Dinkova-Kostova Albena T. , Kasai Takuma , Kamei Takashi , Koshiba Seizo , Yamamoto Masayuki
Published: May 2021

The Keap1-Nrf2 system is central for mammalian cytoprotection against various stresses and a drug target for disease prevention and treatment. One model for the molecular mechanisms leading to Nrf2 activation is the Hinge-Latch model, where the DLGex-binding motif of Nrf2 dissociates from Keap1 as a latch, while the ETGE motif remains attached to Keap1 as a hinge. To overcome the technical difficulties in examining the binding status of the two motifs during protein-protein interaction (PPI) simultaneously, we utilized NMR spectroscopy titration experiments. Our results revealed that latch dissociation is triggered by low-molecular-weight Keap1-Nrf2 PPI inhibitors and occurs during p62-mediated Nrf2 activation, but not by electrophilic Nrf2 inducers. This study demonstrates that Keap1 utilizes a unique Hinge-Latch mechanism for Nrf2 activation upon challenge by non-electrophilic PPI-inhibiting stimuli, and provides critical insight for the pharmacological development of next-generation Nrf2 activators targeting the Keap1-Nrf2 PPI.