bluuebunny/crossref_metadata_2025 huggingface dataset:
A SARS-CoV-2-specific CAR-T-cell model identifies felodipine, fasudil, imatinib, and caspofungin as potential treatments for lethal COVID-19
Authors: Xia Lin , Yuan Lun-zhi , Hu Ya-hong , Liu Jun-yi , Hu Guo-sheng , Qi Ruo-yao , Zhang Tian-ying , Xiong Hua-long , Zheng Zao-zao , Lin Hong-wei , Zhang Jia-mo , Yu Chao , Zhou Ming , Ma Jian , Cheng Tong , Chen Ri-rong , Guan Yi , Xia Ning-shao , Liu Wen
Published: March 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced cytokine storm is closely associated with coronavirus disease 2019 (COVID-19) severity and lethality. However, drugs that are effective against inflammation to treat lethal COVID-19 are still urgently needed. Here, we constructed a SARS-CoV-2 spike protein-specific CAR, and human T cells infected with this CAR (SARS-CoV-2-S CAR-T) and stimulated with spike protein mimicked the T-cell responses seen in COVID-19 patients, causing cytokine storm and displaying a distinct memory, exhausted, and regulatory T-cell phenotype. THP1 remarkably augmented cytokine release in SARS-CoV-2-S CAR-T cells when they were in coculture. Based on this “two-cell” (CAR-T and THP1 cells) model, we screened an FDA-approved drug library and found that felodipine, fasudil, imatinib, and caspofungin were effective in suppressing the release of cytokines, which was likely due to their ability to suppress the NF-κB pathway in vitro. Felodipine, fasudil, imatinib, and caspofungin were further demonstrated, although to different extents, to attenuate lethal inflammation, ameliorate severe pneumonia, and prevent mortality in a SARS-CoV-2-infected Syrian hamster model, which were also linked to their suppressive role in inflammation. In summary, we established a SARS-CoV-2-specific CAR-T-cell model that can be utilized as a tool for anti-inflammatory drug screening in a fast and high-throughput manner. The drugs identified herein have great potential for early treatment to prevent COVID-19 patients from cytokine storm-induced lethality in the clinic because they are safe, inexpensive, and easily accessible for immediate use in most countries.
Reciprocal causation mixture model for robust Mendelian randomization analysis using genome-scale summary data
Authors: Liu Zipeng , Qin Yiming , Wu Tian , Tubbs Justin D. , Baum Larry , Mak Timothy Shin Heng , Li Miaoxin , Zhang Yan Dora , Sham Pak Chung
Published: March 2023

Mendelian randomization using GWAS summary statistics has become a popular method to infer causal relationships across complex diseases. However, the widespread pleiotropy observed in GWAS has made the selection of valid instrumental variables problematic, leading to possible violations of Mendelian randomization assumptions and thus potentially invalid inferences concerning causation. Furthermore, current MR methods can examine causation in only one direction, so that two separate analyses are required for bi-directional analysis. In this study, we propose a ststistical framework, MRCI (Mixture model Reciprocal Causation Inference), to estimate reciprocal causation between two phenotypes simultaneously using the genome-scale summary statistics of the two phenotypes and reference linkage disequilibrium information. Simulation studies, including strong correlated pleiotropy, showed that MRCI obtained nearly unbiased estimates of causation in both directions, and correct Type I error rates under the null hypothesis. In applications to real GWAS data, MRCI detected significant bi-directional and uni-directional causal influences between common diseases and putative risk factors.
Cell surface protein aggregation triggers endocytosis to maintain plasma membrane proteostasis
Authors: Paul David , Stern Omer , Vallis Yvonne , Dhillon Jatinder , Buchanan Andrew , McMahon Harvey
Published: March 2023

The ability of cells to manage consequences of exogenous proteotoxicity is key to cellular homeostasis. While a plethora of well-characterised machinery aids intracellular proteostasis, mechanisms involved in the response to denaturation of extracellular proteins remain elusive. Here we show that aggregation of protein ectodomains triggers their endocytosis via a macroendocytic route, and subsequent lysosomal degradation. Using ERBB2/HER2-specific antibodies we reveal that their cross-linking ability triggers specific and fast endocytosis of the receptor, independent of clathrin and dynamin. Upon aggregation, canonical clathrin-dependent cargoes are redirected into the aggregation-dependent endocytosis (ADE) pathway. ADE is an actin-driven process, which morphologically resembles macropinocytosis. Physical and chemical stress-induced aggregation of surface proteins also triggers ADE, facilitating their degradation in the lysosome. This study pinpoints aggregation of extracellular domains as a trigger for rapid uptake and lysosomal clearance which besides its proteostatic function has potential implications for the uptake of pathological protein aggregates and antibody-based therapies.
Dietary restriction of cysteine and methionine sensitizes gliomas to ferroptosis and induces alterations in energetic metabolism
Authors: Upadhyayula Pavan S. , Higgins Dominique M. , Mela Angeliki , Banu Matei , Dovas Athanassios , Zandkarimi Fereshteh , Patel Purvi , Mahajan Aayushi , Humala Nelson , Nguyen Trang T. T. , Chaudhary Kunal R. , Liao Lillian , Argenziano Michael , Sudhakar Tejaswi , Sperring Colin P. , Shapiro Benjamin L. , Ahmed Eman R. , Kinslow Connor , Ye Ling F. , Siegelin Markus D. , Cheng Simon , Soni Rajesh , Bruce Jeffrey N. , Stockwell Brent R. , Canoll Peter
Published: March 2023

Ferroptosis is mediated by lipid peroxidation of phospholipids containing polyunsaturated fatty acyl moieties. Glutathione, the key cellular antioxidant capable of inhibiting lipid peroxidation via the activity of the enzyme glutathione peroxidase 4 (GPX-4), is generated directly from the sulfur-containing amino acid cysteine, and indirectly from methionine via the transsulfuration pathway. Herein we show that cysteine and methionine deprivation (CMD) can synergize with the GPX4 inhibitor RSL3 to increase ferroptotic cell death and lipid peroxidation in both murine and human glioma cell lines and in ex vivo organotypic slice cultures. We also show that a cysteine-depleted, methionine-restricted diet can improve therapeutic response to RSL3 and prolong survival in a syngeneic orthotopic murine glioma model. Finally, this CMD diet leads to profound in vivo metabolomic, proteomic and lipidomic alterations, highlighting the potential for improving the efficacy of ferroptotic therapies in glioma treatment with a non-invasive dietary modification.
In-situ forming dynamic covalently crosslinked nanofibers with one-pot closed-loop recyclability
Authors: Wang Sheng , Wang Nannan , Kai Dan , Li Bofan , Wu Jing , YEO Jayven Chee Chuan , Xu Xiwei , Zhu Jin , Loh Xian Jun , Hadjichristidis Nikos , Li Zibiao
Published: March 2023

Polymeric nanofibers are attractive nanomaterials owing to their high surface-area-to-volume ratio and superior flexibility. However, a difficult choice between durability and recyclability continues to hamper efforts to design new polymeric nanofibers. Herein, we integrate the concept of covalent adaptable networks (CANs) to produce a class of nanofibers ⎯ referred to dynamic covalently crosslinked nanofibers (DCCNFs) via electrospinning systems with viscosity modulation and in-situ crosslinking. The developed DCCNFs possess homogeneous morphology, flexibility, mechanical robustness, and creep resistance, as well as good thermal and solvent stability. Moreover, to solve the inevitable issues of performance degradation and crack of nanofibrous membranes, DCCNF membranes can be one-pot closed-loop recycled or welded through thermal-reversible Diels-Alder reaction. This study may unlock strategies to fabricate the next generation nanofibers with recyclable features and consistently high performance via dynamic covalent chemistry for intelligent and sustainable applications.
Genomic and immune landscape Of metastatic pheochromocytoma and paraganglioma
Authors: Calsina Bruna , Piñeiro-Yáñez Elena , Martínez-Montes Ángel M. , Caleiras Eduardo , Fernández-Sanromán Ángel , Monteagudo María , Torres-Pérez Rafael , Fustero-Torre Coral , Pulgarín-Alfaro Marta , Gil Eduardo , Letón Rocío , Jiménez Scherezade , García-Martín Santiago , Martin Maria Carmen , Roldán-Romero Juan María , Lanillos Javier , Mellid Sara , Santos María , Díaz-Talavera Alberto , Rubio Ángeles , González Patricia , Hernando Barbara , Bechmann Nicole , Dona Margo , Calatayud María , Guadalix Sonsoles , Álvarez-Escolá Cristina , Regojo Rita M. , Aller Javier , Del Olmo-Garcia Maria Isabel , López-Fernández Adrià , Fliedner Stephanie M. J. , Rapizzi Elena , Fassnacht Martin , Beuschlein Felix , Quinkler Marcus , Toledo Rodrigo A. , Mannelli Massimo , Timmers Henri J. , Eisenhofer Graeme , Rodríguez-Perales Sandra , Domínguez Orlando , Macintyre Geoffrey , Currás-Freixes Maria , Rodríguez-Antona Cristina , Cascón Alberto , Leandro-García Luis J. , Montero-Conde Cristina , Roncador Giovanna , García-García Juan Fernando , Pacak Karel , Al-Shahrour Fátima , Robledo Mercedes
Published: March 2023

The mechanisms triggering metastasis in pheochromocytoma/paraganglioma are unknown, hindering therapeutic options for patients with metastatic tumors (mPPGL). Herein we show by genomic profiling of a large cohort of mPPGLs that high mutational load, microsatellite instability and somatic copy-number alteration burden are associated with ATRX/TERT alterations and are suitable prognostic markers. Transcriptomic analysis defines the signaling networks involved in the acquisition of metastatic competence and establishes a gene signature related to mPPGLs, highlighting CDK1 as an additional mPPGL marker. Immunogenomics accompanied by immunohistochemistry identifies a heterogeneous ecosystem at the tumor microenvironment level, linked to the genomic subtype and tumor behavior. Specifically, we define a general immunosuppressive microenvironment in mPPGLs, the exception being PD-L1 expressing MAML3-related tumors. Our study reveals canonical markers for risk of metastasis, and suggests the usefulness of including immune parameters in clinical management for PPGL prognostication and identification of patients who might benefit from immunotherapy.
Unintended consequences of combating desertification in China
Authors: Wang Xunming , Ge Quansheng , Geng Xin , Wang Zhaosheng , Gao Lei , Bryan Brett A. , Chen Shengqian , Su Yanan , Cai Diwen , Ye Jiansheng , Sun Jimin , Lu Huayu , Che Huizheng , Cheng Hong , Liu Hongyan , Liu Baoli , Dong Zhibao , Cao Shixiong , Hua Ting , Chen Siyu , Sun Fubao , Luo Geping , Wang Zhenting , Hu Shi , Xu Duanyang , Chen Mingxing , Li Danfeng , Liu Fa , Xu Xinliang , Han Dongmei , Zheng Yang , Xiao Feiyan , Li Xiaobin , Wang Ping , Chen Fahu
Published: March 2023

Since the early 2000s, China has carried out extensive “grain-for-green” and grazing exclusion practices to combat desertification in the desertification-prone region (DPR). However, the environmental and socioeconomic impacts of these practices remain unclear. We quantify and compare the changes in fractional vegetation cover (FVC) with economic and population data in the DPR before and after the implementation of these environmental programmes. Here we show that climatic change and CO2 fertilization are relatively strong drivers of vegetation rehabilitation from 2001-2020 in the DPR, and the declines in the direct incomes of farmers and herders caused by ecological practices exceed the subsidies provided by governments. To minimize economic hardship, enhance food security, and improve the returns on policy investments in the DPR, China needs to adapt its environmental programmes to address the potential impacts of future climate change and create positive synergies to combat desertification and improve the economy in this region.
Allelic variation of TaWD40-4B.1 contributes to drought tolerance by modulating catalase activity in wheat
Authors: Tian Geng , Wang Shubin , Wu Jianhui , Wang Yanxia , Wang Xiutang , Liu Shuwei , Han Dejun , Xia Guangmin , Wang Mengcheng
Published: March 2023

Drought drastically restricts wheat production, so to dissect allelic variations of drought tolerant genes without imposing trade-offs between tolerance and yield is essential to cope with the circumstance. Here, we identify a drought tolerant WD40 protein encoding gene TaWD40-4B.1 of wheat via the genome-wide association study. The full-length allele TaWD40-4B.1C but not the truncated allele TaWD40-4B.1T possessing a nonsense nucleotide variation enhances drought tolerance and grain yield of wheat under drought. TaWD40-4B.1C interacts with canonical catalases, promotes their oligomerization and activities, and reduces H2O2 levels under drought. The knock-down of catalase genes erases the role of TaWD40-4B.1C in drought tolerance. TaWD40-4B.1C proportion in wheat accessions is negatively correlative with the annual rainfall, suggesting this allele may be selected during wheat breeding. The introgression of TaWD40-4B.1C enhances drought tolerance of the cultivar harboring TaWD40-4B.1T. Therefore, TaWD40-4B.1C could be useful for molecular breeding of drought tolerant wheat.
Codon-specific KRAS mutations predict survival benefit of trifluridine/tipiracil in metastatic colorectal cancer
Authors: van de Haar Joris , Ma Xuhui , Ooft Salo N. , van der Helm Pim W. , Hoes Louisa R. , Mainardi Sara , Pinato David J. , Sun Kristi , Salvatore Lisa , Tortora Giampaolo , Zurlo Ina Valeria , Leo Silvana , Giampieri Riccardo , Berardi Rossana , Gelsomino Fabio , Merz Valeria , Mazzuca Federica , Antonuzzo Lorenzo , Rosati Gerardo , Stavraka Chara , Ross Paul , Rodriquenz Maria Grazia , Pavarana Michele , Messina Carlo , Iveson Timothy , Zoratto Federica , Thomas Anne , Fenocchio Elisabetta , Ratti Margherita , Depetris Ilaria , Cergnul Massimiliano , Morelli Cristina , Libertini Michela , Parisi Alessandro , De Tursi Michele , Zanaletti Nicoletta , Garrone Ornella , Graham Janet , Longarini Raffaella , Gobba Stefania Maria , Petrillo Angelica , Tamburini Emiliano , La Verde Nicla , Petrelli Fausto , Ricci Vincenzo , Wessels Lodewyk F. A. , Ghidini Michele , Cortellini Alessio , Voest Emile E. , Valeri Nicola
Published: March 2023

Genomics has greatly improved how patients with cancer are being treated; however, clinical-grade genomic biomarkers for chemotherapies are currently lacking. Using whole-genome analysis of 37 patients with metastatic colorectal cancer (mCRC) treated with the chemotherapy trifluridine/tipiracil (FTD/TPI), we identified KRAS codon G12 (KRASG12) mutations as a potential biomarker of resistance. Next, we collected real-world data of 960 patients with mCRC receiving FTD/TPI and validated that KRASG12 mutations were significantly associated with poor survival, also in analyses restricted to the RAS/RAF mutant subgroup. We next analyzed the data of the global, double-blind, placebo-controlled, phase 3 RECOURSE trial (n = 800 patients) and found that KRASG12 mutations (n = 279) were predictive biomarkers for reduced overall survival (OS) benefit of FTD/TPI versus placebo (unadjusted interaction P = 0.0031, adjusted interaction P = 0.015). For patients with KRASG12 mutations in the RECOURSE trial, OS was not prolonged with FTD/TPI versus placebo (n = 279; hazard ratio (HR) = 0.97; 95% confidence interval (CI) = 0.73–1.20; P = 0.85). In contrast, patients with KRASG13 mutant tumors showed significantly improved OS with FTD/TPI versus placebo (n = 60; HR = 0.29; 95% CI = 0.15–0.55; P < 0.001). In isogenic cell lines and patient-derived organoids, KRASG12 mutations were associated with increased resistance to FTD-based genotoxicity. In conclusion, these data show that KRASG12 mutations are biomarkers for reduced OS benefit of FTD/TPI treatment, with potential implications for approximately 28% of patients with mCRC under consideration for treatment with FTD/TPI. Furthermore, our data suggest that genomics-based precision medicine may be possible for a subset of chemotherapies.
A promising approach using Fibonacci sequence-based optimization algorithms and advanced computing
Authors: Tran-Ngoc H. , Le-Xuan T. , Khatir S. , De Roeck G. , Bui-Tien T. , Abdel Wahab Magd
Published: March 2023

In this paper, the feasibility of Structural Health Monitoring (SHM) employing a novel Fibonacy Sequence (FS)-based Optimization Algorithms (OAs) and up-to-date computing techniques is investigated for a large-scale railway bridge. During recent decades, numerous metaheuristic intelligent OAs have been proposed and immediately gained a lot of momentum. However, the major concern is how to employ OAs to deal with real-world problems, especially the SHM of large-scale structures. In addition to the requirement of high accuracy, a high computational cost is putting up a major barrier to the real application of OAs. Therefore, this article aims at addressing these two aforementioned issues. First, we propose employing the optimal ability of the golden ratio formulated by the well-known FS to remedy the shortcomings and improve the accuracy of OAs, specifically, a recently proposed new algorithm, namely Salp Swarm Algorithm (SSA). On the other hand, to deal with the high computational cost problems of OAs, we propose employing an up-to-date computing technique, termed superscalar processor to conduct a series of iterations in parallel. Moreover, in this work, the vectorization technique is also applied to reduce the size of the data. The obtained results show that the proposed approach is highly potential to apply for SHM of real large-scale structures.
Comparative phylogenomic insights of KCS and ELO gene families in Brassica species indicate their role in seed development and stress responsiveness
Authors: Khan Uzair Muhammad , Rana Iqrar Ahmad , Shaheen Nabeel , Raza Qasim , Rehman Hafiz Mamoon , Maqbool Rizwana , Khan Iqrar Ahmad , Atif Rana Muhammad
Published: March 2023

Very long-chain fatty acids (VLCFAs) possess more than twenty carbon atoms and are the major components of seed storage oil, wax, and lipids. FAE (Fatty Acid Elongation) like genes take part in the biosynthesis of VLCFAs, growth regulation, and stress responses, and are further comprised of KCS (Ketoacyl-CoA synthase) and ELO (Elongation Defective Elongase) sub-gene families. The comparative genome-wide analysis and mode of evolution of KCS and ELO gene families have not been investigated in tetraploid Brassica carinata and its diploid progenitors. In this study, 53 KCS genes were identified in B. carinata compared to 32 and 33 KCS genes in B. nigra and B. oleracea respectively, which suggests that polyploidization might has impacted the fatty acid elongation process during Brassica evolution. Polyploidization has also increased the number of ELO genes in B. carinata (17) over its progenitors B. nigra (7) and B. oleracea (6). Based on comparative phylogenetics, KCS, and ELO proteins can be classified into eight and four major groups, respectively. The approximate date of divergence for duplicated KCS and ELO genes varied from 0.03 to 3.20 million years ago (MYA). Gene structure analysis indicated that the maximum number of genes were intron-less and remained conserved during evolution. The neutral type of selection seemed to be predominant in both KCS and ELO genes evolution. String-based protein-protein interaction analysis suggested that bZIP53, a transcription factor might be involved in the activation of transcription of ELO/KCS genes. The presence of biotic and abiotic stress-related cis-regulatory elements in the promoter region suggests that both KCS and ELO genes might also play their role in stress tolerance. The expression analysis of both gene family members reflect their preferential seed-specific expression, especially during the mature embryo development stage. Furthermore, some KCS and ELO genes were found to be specifically expressed under heat stress, phosphorus starvation, and Xanthomonas campestris infection. The current study provides a basis to understand the evolution of both KCS and ELO genes in fatty acid elongation and their role in stress tolerance.
A new method for ferroresonance suppression in an IEEE 33-bus distribution system integrated with multi distributed generation
Authors: Abdel-hamed Alaa M. , El-Shafhy Mohamed M. , Badran Ebrahim A.
Published: March 2023

Although integrating a distributed generation (DG) into a distribution system (DS) has several benefits, it may be accompanied by some issues, such as ferroresonance. Therefore, ferroresonance investigations in an integrated DS with multi-DGs have been identified as a research gap. To this end, this paper presents a new method to mitigate ferroresonance in distribution networks, after which ferroresonance in an IEEE-33 bus radial DS integrated with multi-DGs was investigated. Here the RLC shunt limiter is introduced as a method for mitigating ferroresonance, including a design approach for adjusting its dimensions to fit the system. Investigations revealed that this shunt relied on the negative sequence detector to connect it to the system during ferroresonance. Finally, the effectiveness and superiority of the proposed method have been demonstrated by comparing its result with those obtained using other existing ferroresonance mitigation methods used in the literature.
Pediatric chronic graft-versus-host disease-related dry eye disease and the diagnostic association of potential clinical findings
Authors: Yagi Hitomi , Shimizu Eisuke , Yagi Ryuichiro , Uchino Miki , Kamoi Mizuka , Asai Kazuki , Tsubota Kazuo , Negishi Kazuno , Ogawa Yoko
Published: March 2023

Pediatric graft-versus-host-disease (GVHD)-related dry eye disease (DED) is often overlooked due to a lack of subjective symptoms and reliable testing, leading to irreversible corneal damage. To study the clinical findings contributing to the accurate detection of pediatric GVHD-related DED, a retrospective study of pediatric patients treated with hematopoietic stem cell transplantation (HSCT) at Keio University Hospital between 2004 and 2017 was conducted. Association and diagnostic values of ophthalmological findings for DED were analyzed. Twenty-six patients who had no ocular complications before HSCT were included in the study. Eleven (42.3%) patients developed new-onset DED. The cotton thread test showed excellent diagnostic accuracy in detecting DED (area under the receiver operating curve, 0.96; sensitivity, 0.95; specificity, 0.85) with a cut-off of 17 mm, which was higher than the conventional threshold of 10 mm. Additionally, the presence of filamentary keratitis (FK) and pseudomembranous conjunctivitis (PC) were significantly associated with the diagnosis of DED (p value, 0.003 and 0.001 for FK and PC, respectively) and displayed good diagnostic performance (sensitivity, 0.46 and 0.54; specificity, 0.97 and 0.97 for FK and PC, respectively). In conclusion, the cotton thread test with a new threshold, the presence of PC and FK, could be helpful for promptly detecting pediatric GVHD-related DED.
Efficacy and safety of angiogenesis inhibitors plus immune checkpoint inhibitors in advanced soft tissue sarcoma: a real-world, single-center study
Authors: Liu Zengjun , Xu Jing , Liu Mengyao , Hu Wenyu , Xu Ni , Zhu Dongyuan
Published: March 2023

Angiogenesis inhibitors (AIs) and immune checkpoint inhibitors (ICIs) are new treatment options for advanced soft tissue sarcoma (STS) patients. This study evaluated the efficacy and safety of AIs plus ICIs in patients with advanced STS. A retrospective cohort study was performed on STS patients treated with AIs and ICIs at Shandong Cancer Hospital and Institute between August 2020 and December 2021. The primary endpoint was objective response rate (ORR); secondary endpoints included progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and adverse events. Thirty-three patients were enrolled; 27 were evaluable for objective response. The ORR and DCR were 48.1% (95% CI 30.7–66.0%) and 85.2% (95% CI 67.5–94.1%). With a median follow-up of 7.6 months (range, 0.8–25.5), the median PFS for all 33 patients was 8.90 months (95% CI 5.98–11.82). The median OS was not reached. The most common treatment-related adverse events (TRAEs) of any grade were hypertension (50.0%), ECG T-wave abnormality (30.0%), hypothyroidism (26.7%), elevated alanine aminotransferase or aspartate aminotransferase (23.3%), elevated thyroid-stimulating hormone (23.3%), and fatigue (16.7%). The most common grade 3–4 TRAE was hypertension (27.3%). Three serious TRAEs (two myocarditis and one rapid atrial fibrillation) were recorded. This study suggests that adding AIs to ICIs is beneficial in STS.
The role of dung beetle species in nitrous oxide emission, ammonia volatilization, and nutrient cycling
Authors: García Carlos C. V. , Dubeux José C. B. , Martini Xavier , Conover Derick , Santos Erick R. S. , Homem Bruno G. C. , Ruiz-Moreno Martin , da Silva Izabela A. G. , Abreu Daciele S. , Queiroz Luana M. D. , van Cleef Flavia O. S. , Santos Mércia V. F. , Fracetto Giselle G. M.
Published: March 2023

This study evaluated the role of dung beetle species alone or associated under different species on nitrous oxide (N2O) emission, ammonia volatilization, and the performance of pearl millet [Pennisetum glaucum(L.)]. There were seven treatments, including two controls (soil and soil + dung without beetles), single species ofOnthophagus taurus[Shreber, 1759] (1),Digitonthophagus gazella[Fabricius, 1787] (2), orPhanaeus vindex[MacLeay, 1819] (3); and their assemblages (1 + 2 and 1 + 2 + 3). Nitrous oxide emission was estimated for 24 days, when pearl millet was planted in sequence to assess growth, nitrogen yield (NY), and dung beetle activity. Dung beetle species presented greater N2O flow of dung on the 6th day (80 g N2O-N ha−1 day−1) compared to soil and dung (2.6 g N2O-N ha−1 day−1). Ammonia emissions varied with the presence of dung beetles (P < 0.05), andD. gazellahad less NH3−N on days 1, 6, and 12 with averages of 2061, 1526, and 1048 g ha−1 day−1, respectively. The soil N content increased with dung + beetle application. Dung application affected pearl millet herbage accumulation (HA) regardless of dung beetle presence, and averages ranged from 5 to 8 g DM bucket−1. A PCA analysis was applied to analyze variation and correlation to each variable, but it indicated a low principal component explanation (less than 80%), not enough to explain the variation in findings. Despite the greater dung removal, the largest species,P. vindexand their species combination, need to be more studied to get a better understanding about their contribution on greenhouse gases. The presence of dung beetles prior to planting improved pearl millet production by enhancing N cycling, although assemblages with the three beetle species enhanced N losses to the environment via denitrification.
Astragalus-cultivated soil was a suitable bed soil for nurturing Angelica sinensis seedlings from the rhizosphere microbiome perspective
Authors: An Zhi-Gang , Guo Feng-Xia , Chen Yuan , Bai Gang , Guo Ai-Feng
Published: March 2023

Angelica sinensis (Oliv.) Diels is an important Chinese medicinal plant. A. sinensis seedlings are grown on an undisturbed alpine meadow soil to ensure the high-quality seedlings, but these soils are disappearing year after year. Thus, selecting a suitable bed soil for A. sinensis seedlings could ensure their long-term sustainability. Using HiSeq sequencing of 16S and 18S marker genes, we investigated the rhizosphere bacterial and fungal microbiotas of the seedlings grown in wheat, astragalus, potato, and angelica-cultivated soils at a geo-authentic habitat. Co-occurrence network analysis, canonical correspondence analysis, Mantel test, and Envfit test were used to examine the relationship between the microbiotas and the surrounding factors. Astragalus-cultivated soils exhibited the following properties: the highest plant weight, the highest neighborhood connectivity in the bacterial network, the highest ratio of positive/negative relationship in both bacterial and fungal networks, the highest relative abundance of the arbuscular mycorrhizal fungi and the ectomycorrhizal fungi, the lowest relative abundance of Rhizoctonia solani, the suitable soil pH, and the close relationship between the rhizosphere microbiotas and the ecological factors. Moreover, each growth stage has its own major drivers in all crop-cultivated soils. Climate temperature and soil pH at 56 days after planting, precipitation at 98 days, and plant weight as well as microbial biomass C and N at 129 days were the major drivers of the bacterial and fungal microbiotas. Overall, the astragalus-cultivated soil was a suitable bed soil for nurturing A. sinensis seedlings to replace the undisturbed alpine meadow soils.
Elevated serum levels of bone morphogenetic protein-9 are associated with better outcome in AQP4-IgG seropositive NMOSD
Authors: Masuda Hiroki , Mori Masahiro , Uzawa Akiyuki , Uchida Tomohiko , Muto Mayumi , Ohtani Ryohei , Aoki Reiji , Kuwabara Satoshi
Published: March 2023

Lymphatic drainage in the central nervous system is regulated by meningeal lymphatic vasculature, and recurrent neuroinflammation alters lymphatic vessel remodeling. Patients with aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4 + NMOSD) were reported to demonstrate worse outcomes compared with patients with anti-myelin oligodendrocyte glycoprotein-associated disorders (MOGAD). This study aimed to investigate the serum cytokines relevant to vascular remodeling after attacks and their prognostic role in patients with AQP4 + NMOSD. This study measured the serum levels of 12 cytokines relevant to vascular remodeling, including bone morphogenetic protein-9 (BMP-9) and leptin, in 20 patients with AQP4 + NMOSD and 17 healthy controls (HCs). Disease controls included 18 patients with MOGAD. Serum and cerebrospinal fluid interleukin-6 levels were also measured. Clinical severity was evaluated with Kurtzke’s Expanded Disability Status Scale (EDSS). Compared with HCs, patients with AQP4 + NMOSD showed higher BMP-9 (median; 127 vs. 80.7 pg/mL; P = 0.0499) and leptin levels (median; 16,081 vs. 6770 pg/mL; P = 0.0224), but not those with MOGAD. Better improvement in EDSS at 6 months was associated with baseline BMP-9 levels in patients with AQP4 + NMOSD (Spearman’s rho =  − 0.47; P = 0.037). Serum BMP-9 is upregulated at relapse and may contribute to vascular remodeling in AQP4 + NMOSD. Serum BMP-9 levels could predict clinical recovery 6 months after the attack.
Prognosis after discontinuing renin angiotensin aldosterone system inhibitor for heart failure with restored ejection fraction after acute myocardial infarction
Authors: Lee Seung Hun , Rhee Tae-Min , Shin Doosup , Hong David , Choi Ki Hong , Kim Hyun Kuk , Park Taek Kyu , Yang Jeong Hoon , Song Young Bin , Hahn Joo-Yong , Choi Seung-Hyuck , Chae Shung Chull , Cho Myeong-Chan , Kim Chong Jin , Kim Ju Han , Kim Hyo-Soo , Gwon Hyeon-Cheol , Jeong Myung Ho , Lee Joo Myung ,   The KAMIR-NIH Investigators, Lee Seung Hun , Rhee Tae-Min , Shin Doosup , Hong David , Choi Ki Hong , Kim Hyun Kuk , Park Taek Kyu , Yang Jeong Hoon , Song Young Bin , Hahn Joo-Yong , Choi Seung-Hyuck , Chae Shung Chull , Cho Myeong-Chan , Kim Chong Jin , Kim Ju Han , Kim Hyo-Soo , Gwon Hyeon-Cheol , Jeong Myung Ho , Lee Joo Myung
Published: March 2023

Prognostic effect of discontinuing renin–angiotensin–aldosterone-system-inhibitor (RAASi) for patients with heart failure (HF) after acute myocardial infarction (AMI) whose left ventricular (LV) systolic function was restored during follow-up is unknown. To investigate the outcome after discontinuing RAASi in post-AMI HF patients with restored LV ejection fraction (EF). Of 13,104 consecutive patients from the nationwide, multicenter, and prospective Korea Acute Myocardial Infarction-National Institutes of Health (KAMIR-NIH) registry, HF patients with baseline LVEF < 50% that was restored to ≥ 50% at 12-month follow-up were selected. Primary outcome was a composite of all-cause death, spontaneous MI, or rehospitalization for HF at 36-month after index procedure. Of 726 post-AMI HF patients with restored LVEF, 544 maintained RAASi (Maintain-RAASi) beyond 12-month, 108 stopped RAASi (Stop-RAASi), and 74 did not use RAASi (RAASi-Not-Used) at baseline and follow-up. Systemic hemodynamics and cardiac workloads were similar among groups at baseline and during follow-up. Stop-RAASi group showed elevated NT-proBNP than Maintain-RAASi group at 36-month. Stop-RAASi group showed significantly higher risk of primary outcome than Maintain-RAASi group (11.4% vs. 5.4%; adjusted hazard ratio [HRadjust] 2.20, 95% confidence interval [CI] 1.09–4.46, P = 0.028), mainly driven by increased risk of all-cause death. The rate of primary outcome was similar between Stop-RAASi and RAASi-Not-Used group (11.4% vs. 12.1%; HRadjust 1.18 [0.47–2.99], P = 0.725). In post-AMI HF patients with restored LV systolic function, RAASi discontinuation was associated with significantly increased risk of all-cause death, MI, or rehospitalization for HF. Maintaining RAASi will be necessary for post-AMI HF patients, even after LVEF is restored.
Analysis of contact pressure in a 3D model of dual-mobility hip joint prosthesis under a gait cycle
Authors: Tauviqirrahman Mohammad , Ammarullah Muhammad Imam , Jamari J. , Saputra Eko , Winarni Tri Indah , Kurniawan Febri Dwi , Shiddiq Shidnan Amir , van der Heide Emile
Published: March 2023

Hip joint prostheses are used to replace hip joint function in the human body. The latest dual-mobility hip joint prosthesis has an additional component of an outer liner that acts as a cover for the liner component. Research on the contact pressure generated on the latest model of a dual-mobility hip joint prosthesis under a gait cycle has never been done before. The model is made of ultrahigh molecular weight polyethylene (UHMWPE) on the inner liner and 316L stainless steel (SS 316L) on the outer liner and acetabular cup. Simulation modeling using the finite element method is considered static loading with an implicit solver for studying the geometric parameter design of dual-mobility hip joint prostheses. In this study, simulation modeling was carried out by applying varying inclination angles of 30°, 40°, 45°, 50°, 60°, and 70° to the acetabular cup component. Three-dimensional loads were placed on femoral head reference points with variations of femoral head diameter used at 22 mm, 28 mm, and 32 mm. The results in the inner surface of the inner liner, the outer surface of the outer liner, and the inner surface of the acetabular cup showed that the variations in inclination angle do not have a major effect on the maximum contact pressure value on the liner component, where the acetabular cup with an inclination angle of 45° can reduce contact pressure more than the other studied inclination angle variations. In addition, it was found that the 22 mm diameter of the femoral head increases the contact pressure. The use of a larger diameter femoral head with an acetabular cup configuration at a 45° inclination can minimize the risk of implant failure due to wear.
Systemic immune modulation by stereotactic radiotherapy in early-stage lung cancer
Authors: Gkika Eleni , Firat Elke , Adebahr Sonja , Graf Erika , Popp Ilinca , Radicioni Gianluca , Lo Simon S. , Nestle Ursula , Nicolay Nils H. , Niedermann Gabriele , Duda Dan G. , Grosu Anca-L.
Published: March 2023

We performed a prospective study of circulating immune cell changes after stereotactic body radiotherapy (SBRT) in 50 early-stage NSCLC patients. We found no significant increase in CD8+ cytotoxic T lymphocytes at first follow-up (the primary endpoint) but detected a significant increase in expanding Ki-67+CD8+ and Ki-67+CD4+ T-cell fractions in patients treated with 10 Gy or less per fraction. SBRT can induce significant expansion in circulating effector T-cells immediately post-treatment.
Downregulation of KEAP1 in melanoma promotes resistance to immune checkpoint blockade
Authors: Fox Douglas B. , Ebright Richard Y. , Hong Xin , Russell Hunter C. , Guo Hongshan , LaSalle Thomas J. , Wittner Ben S. , Poux Nicolas , Vuille Joanna A. , Toner Mehmet , Hacohen Nir , Boland Genevieve M. , Sen Debattama R. , Sullivan Ryan J. , Maheswaran Shyamala , Haber Daniel A.
Published: March 2023

Immune checkpoint blockade (ICB) has demonstrated efficacy in patients with melanoma, but many exhibit poor responses. Using single cell RNA sequencing of melanoma patient-derived circulating tumor cells (CTCs) and functional characterization using mouse melanoma models, we show that the KEAP1/NRF2 pathway modulates sensitivity to ICB, independently of tumorigenesis. The NRF2 negative regulator, KEAP1, shows intrinsic variation in expression, leading to tumor heterogeneity and subclonal resistance.
PARP1 allows proper telomere replication through TRF1 poly (ADP-ribosyl)ation and helicase recruitment
Authors: Maresca C. , Dello Stritto A. , D’Angelo C. , Petti E. , Rizzo A. , Vertecchi E. , Berardinelli F. , Bonanni L. , Sgura A. , Antoccia A. , Graziani G. , Biroccio A. , Salvati E.
Published: March 2023

Telomeres are nucleoprotein structures at eukaryotic chromosome termini. Their stability is preserved by a six-protein complex named shelterin. Among these, TRF1 binds telomere duplex and assists DNA replication with mechanisms only partly clarified. Here we found that poly (ADP-ribose) polymerase 1 (PARP1) interacts and covalently PARylates TRF1 in S-phase modifying its DNA affinity. Therefore, genetic and pharmacological inhibition of PARP1 impairs the dynamic association of TRF1 and the bromodeoxyuridine incorporation at replicating telomeres. Inhibition of PARP1 also affects the recruitment of WRN and BLM helicases in TRF1 containing complexes during S-phase, triggering replication-dependent DNA-damage and telomere fragility. This work unveils an unprecedented role for PARP1 as a “surveillant” of telomere replication, which orchestrates protein dynamics at proceeding replication fork.
Engineering cation vacancies in high-entropy layered double hydroxides for boosting the oxygen evolution reaction
Authors: Yao Junchuan , Wang Fangqing , He Wenjun , Li Ying , Liang Limin , Hao Qiuyan , Liu Hui
Published: March 2023

High-entropy FeCoNiCuZn LDHs nanoneedle arrays with rich cation vacancies exhibit excellent OER catalytic activity and stability.
Nanoscale characterization of the heterogeneous interfacial oxidation layer of graphene/Cu based on a SEM electron beam induced reduction effect
Authors: Feng Panpan , Zhang Dan , Zhang Peng , Wang You , Gan Yang
Published: March 2023

This method was developed based on SEM image contrast reversal caused by EBI induced reduction of interfacial oxides. It realizes multi-length scale characterization in a rather short time and map nanoscale heterogeneously oxidized interface of Gr/Cu.
Preparation, photoluminescence and excited state properties of the homoleptic cluster cation [(W6I8)(CH3CN)6]4+
Authors: Pachel Florian , Frech Philipp , Ströbele Markus , Enseling David , Romao Carl P. , Jüstel Thomas , Scheele Marcus , Meyer Hans-Jürgen
Published: March 2023

Cluster compounds containing the [(W6I8)(CH3CN)6]4+ ion were established. Photophysical properties of [(W6I8)(CH3CN)6](BF4)4 are compared to those of compounds featuring the [(W6I8)L6]2− ion.
Using laser-induced breakdown spectroscopy to characterize the surface mechanical properties of soft materials
Authors: Li Xiaolong , Liu Xueqi , Gong Shuhang , Li Yaju , Chen Liangwen , Qian Dongbin , Zhang Shaofeng , Ma Xinwen
Published: March 2023

The ratio of ionic to atomic lines with surface rigidity implying the feasibility of characterizing soft surface mechanical properties using LIBS.
Insights into the regioselectivity and diastereoselectivity of the Nazarov cyclization of 3-alkenyl-2-indolylmethanol with tryptophol
Authors: Cheng Qi , Yan Wenxin , Li Tian , Jiao Yinchun , Tang Zilong
Published: March 2023

Density functional theory calculations of Nazarov cyclizations showed that 3-alkenyl-2-indolylmethanol and tryptophol formed binary and ternary complexes, respectively, in the presence and absence of H2O to produce C–N and C–C products.
NIR-II semiconducting polymers forin vivohigh-resolution imaging and theranostics
Authors: Kang Xiaoying , Yin Shuai , Song Jianwen , Zhang Yuan , Qi Ji
Published: March 2023

This review summarizes the recent advances in semiconducting polymers with NIR-II fluorescence emission forin vivohigh-resolution imaging and theranostics.
Electrostatic assemblies of molecularly imprinted polymers on the surface of electrospun nanofiber membranes for the point-of-care detection of thiodiglycol, a sulfur mustard poisoning metabolic marker
Authors: Luo Yu Jie , Ye Qi Chao , Xie Tian Jin , Tian Li Li , Yan Yuan , Lei Zhan , Wang Dong Mei , Huang Cheng Zhi , Li Yuan Fang , Zhen Shu Jun
Published: March 2023

In this study, a new method for the point-of-care testing of thiodiglycol (TDG) using molecularly imprinted polymer (MIP)-coated electrospun nanofiber membranes is reported.
Highlights from Faraday Discussion on Nanoalloys: recent developments and future perspectives, London, UK
Authors: Roncaglia Cesare , Swaminathan Swathi , Farris Riccardo , El koraychy El yakout
Published: March 2023

A Faraday Discussion meeting was held on the topic of ‘Nanoalloys: recent developments and future perspectives’. This report covers the highlights of this meeting, including brief summaries of the papers discussed.
Diversity at the nanoscale: laser-oxidation of single-layer graphene affects Fmoc-phenylalanine surface-mediated self-assembly
Authors: Schirmer Johanna , Chevigny Romain , Emelianov Aleksei , Hulkko Eero , Johansson Andreas , Myllyperkiö Pasi , Sitsanidis Efstratios D. , Nissinen Maija , Pettersson Mika
Published: March 2023

The secondary organization level of self-assembled Fmoc-phenylalanine is affected at the nanoscale by laser-oxidation of the graphene surface.
Excited state potential energy surfaces of N-phenylpyrrole upon twisting: reference values and comparison between BSE/GW and TD-DFT
Authors: Knysh Iryna , Letellier Kelvine , Duchemin Ivan , Blase Xavier , Jacquemin Denis
Published: March 2023

The many-body Green’s function Bethe–Salpeter equation formalism provides an accurate evolution upon twisting of the N-PP excited state surfaces with almost no dependency on the starting exchange-correlation functional contrary to TD-DFT.
1,3-Dioxolane compounds (DOXs) as biobased reaction media
Authors: Melchiorre Massimo , Budzelaar Peter H. M. , Cucciolito Maria E. , Esposito Roberto , Santagata Emanuela , Ruffo Francesco
Published: March 2023

1,3-dioxolanes are proposed as green polar aprotic solvents that could replace more traditional solvents and hence reduce the environmental impact of fine-chemical processes.
Controlling simonkolleite crystallisation via metallic Zn oxidation in a betaine hydrochloride solution
Authors: Qu Shaoqing , Hadjittofis Eftychios , Malaret Francisco , Hallett Jason , Smith Rachel , Campbell Kyra Sedransk
Published: March 2023

Zinc oxide nanoparticles, with a hexagonal flake structure, are of significant interest across a range of applications including photocatalysis and biomedicine.
Understanding the partitioning behavior of single-walled carbon nanotubes using an aqueous two-phase extraction system composed of non-ionic surfactants and polymers
Authors: Tiwari Pranjala , Podleśny Błażej , Krzywiecki Maciej , Milowska Karolina Z. , Janas Dawid
Published: March 2023

In this work, we decipher the mechanism of the aqueous two-phase extraction (ATPE) method, which has considerable application potential for purifying many types of nanomaterials.
Interfacial electronic properties and tunable band offset in graphyne/MoSe2 heterostructure with high carrier mobility
Authors: Zhang Siyu , Yun Jiangni , Zeng Liru , Yao Linwei , Bi Zhisong , Mai Chunwei , Kang Peng , Yan Junfeng , Zhang Zhiyong
Published: March 2023

A novel vertical graphyne/MoSe2 heterostructure with intrinsic type-I band alignment, high carrier mobility and tunable band offset.
Highly parallel stateful Boolean logic gates based on aluminum-doped self-rectifying memristors in a vertical crossbar array structure
Authors: Park Taegyun , Kim Seung Soo , Lee Byeol Jun , Park Tae Won , Kim Hae Jin , Hwang Cheol Seong
Published: March 2023

Aluminum-doped self-rectifying memristors in vertical arrays enable in-memory computing that can synthesize multi-layered Boolean logic functions in parallel, suppressing the sneak current.
C3-selective C–H thiolation of quinolines via an N-arylmethyl activation strategy
Authors: Li Shun , Tang Juan , Fu Yi-Hua , Zheng Xue-Li , Yuan Mao-Lin , Li Rui-Xiang , Su Zhi-Shan , Fu Hai-Yan , Chen Hua
Published: March 2023

Metal-free selective C–H thiolation of quinoline, including trifluoromethyl thiolation, aryl thiolation, alkyl thiolation and phenyl selenylation, using N-arylmethyl activation strategies is reported and is applicable to quinoline-based biologically active complex molecules.
Fast neutron fluence estimation by measurement of93mNb and93Mo
Authors: Ichikawa Masashi , Tanaka Shigeaki , Chatani Kazuhiro
Published: March 2023

The possibility for estimation of fast neutron fluence from93mNb produced from Nb contained in structural component materials of nuclear power plants was investigated as an evaluation tool for extending plant operating lifetime. First, to establish a measurement method for93mNb in structural component materials, chemical separations and measurements of93mNb were carried out using specimens of fast neutron-irradiated XM-19 and X-750 alloy; these are used as structural component materials and contain Nb as a component. The93mNb activities obtained from the measurements of both XM-19 and X-750 alloy agreed well with the calculated values of93mNb, which were simply calculated from the evaluated fast neutron fluence. On the other hand, in the case of type 316L stainless steel, which contains Mo, Mo derived93mNb presents a problem, so an approach was used that estimates the amount of Mo derived93mNb based on93Mo measurements with the third specimen, neutron-irradiated type 316L stainless steel. The difference between the measured and calculated93mNb values was about two-fold, indicating that the estimation method for93mNb produced from Mo needs to be improved.
Radiologic staging of peritoneal and retroperitoneal disease
Authors: Glockzin Gabriel , Helmberger Thomas
Published: March 2023

Peritoneal and retroperitoneal tumors consist of a heterogenous group of benign and malignant lesions of different origin. Due to often complex multidisciplinary treatment concepts in patients with peritoneal surface malignancies radiological imaging plays a pivotal role regarding the therapeutic options. Moreover, tumor entity, abdominal tumor distribution and common as well as rare differential diagnoses have to be taken into account. Using different radiological modalities non-invasive pretherapeutic diagnostics might be significantly improved.

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