bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting the cholesterol-RORα/γ axis inhibits colorectal cancer progression through degrading c-myc
Authors: Wang Ying-Nan , Ruan Dan-Yun , Wang Zi-Xian , Yu Kai , Rong Dai-Lin , Liu Ze-Xian , Wang Feng , Hu Jia-Jia , Jin Ying , Wu Qi-Nian , Pu Heng-Ying , Wang Min , Xu Rui-Hua , Zeng Zhao-Lei
Published: October 2022

Dysregulated cholesterol metabolism is a hallmark of colorectal cancer (CRC). However, the usage of cholesterol-lowering agents seemed to have no benefit in CRC patients. In this study, we focused on the cholesterol-nuclear receptors (NRs) axis as a strategy. Cholesterol and its derivatives work as ligands for different nuclear receptors, thus promoting cancer progression. The key NR downstream of cholesterol in CRC is unknown. Here, we treated CRC cells with a cholesterol-lowering agent and lipoprotein-depleted conditioned medium, and then detected the change of the putative NRs. The results revealed that RORα/γ (Retinoic acid receptor-related Orphan Receptor α/γ) levels exhibited the most obvious increases in CRC cells subjected them to cholesterol deprivation. RORα/γ agonists significantly inhibited CRC cells proliferation and migration in vitro and in vivo. Also, RORα/γ overexpression repressed CRC cells proliferation and migration in vitro and in vivo and RORα/γ knockdown promoted it. Mechanistically, RORα/γ agonists promoted c-myc degradation by activating the transcription of the ubiquitinase NEDD4. Intriguingly, the combination of RORα/γ agonists and atorvastatin had a synergistic effect on inhibiting CRC cells. These findings demonstrate that the cholesterol- RORα/γ axis is important for maintaining c-myc protein levels. Combination therapy with atorvastatin and RORα/γ agonist is a promising therapeutic strategy for CRC.
CUR5g, a novel autophagy inhibitor, exhibits potent synergistic anticancer effects with cisplatin against non-small-cell lung cancer
Authors: Chen Jingxuan , Shen Yunpeng , Wu Bowen , Yang Peichang , Sun Gangchun , Liu Xiaoting , Qiang Pengfei , Gao Yamei , Sha Fangfang , Li Zirui , Zhang Lu
Published: October 2022

Autophagy, a highly conserved degradation process of eukaryotic cells, has been proven to be closely related to chemoresistance and metastasis of non-small-cell lung cancer (NSCLC). Autophagy inhibitors, such as chloroquine (CQ) and its derivative hydroxychloroquine (HCQ), has been shown to mediate anticancer effects in preclinical models, especially when combined with chemotherapy. However, the vast majority of autophagy inhibitors, including CQ and HCQ, actually disrupt lysosomal or/and possibly non-lysosomal processes other than autophagy. It is therefore of great significance to discover more specific autophagy inhibitors. In this study, after screening a series of curcumin derivatives synthesized in our laboratory, we found that (3E,5E)-1-methyl-3-(4-hydroxybenzylidene)-5-(3-indolymethylene)-piperidine-4-one (CUR5g) selectively inhibited autophagosome degradation in cancer cells by blocking autophagosome-lysosome fusion. CUR5g did not affect the lysosomal pH and proteolytic function, nor did it disturb cytoskeleton. CUR5g blocked the recruitment of STX17, a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein, to autophagosomes via a UVRAG-dependent mechanism, resulting in the inability of autophagosomes to fuse with lysosomes. CUR5g alone did not induce apoptosis and necrosis of A549 cells, but significantly inhibited the mobility and colony formation of A549 cells. More excitingly, CUR5g showed no obvious toxicity to normal HUVECs in vitro or mice in vivo. CUR5g enhances the cisplatin sensitivity of A549 cells and effectively inhibited autophagy in tumor tissues in vivo. Collectively, our study identified a new late-stage autophagy inhibitor and provided a novel option for NSCLC treatment, particular when combined with cisplatin.
DNAJA1- and conformational mutant p53-dependent inhibition of cancer cell migration by a novel compound identified through a virtual screen
Authors: Nishikawa Shigeto , Kaida Atsushi , Parrales Alejandro , Ranjan Atul , Alalem Mohamed , Ren Hongyi , Schoenen Frank J. , Johnson David K. , Iwakuma Tomoo
Published: October 2022

Cancers are frequently addicted to oncogenic missense mutant p53 (mutp53). DNAJA1, a member of heat shock protein 40 (HSP40), also known as J-domain proteins (JDPs), plays a crucial role in the stabilization and oncogenic activity of misfolded or conformational mutp53 by binding to and preventing mutp53 from proteasomal degradation. However, strategies to deplete mutp53 are not well-established, and no HSP40/JDPs inhibitors are clinically available. To identify compounds that bind to DNAJA1 and induce mutp53 degradation, we performed an in silico docking study of ~10 million of compounds from the ZINC database for the J-domain of DNAJA1. A compound 7-3 was identified, and its analogue A11 effectively reduced the levels of DNAJA1 and conformational mutp53 with minimal effects on the levels of wild-type p53 and DNA-contact mutp53. A11 suppressed migration and filopodia formation in a manner dependent on DNAJA1 and conformational mutp53. A mutant DNAJA1 with alanine mutations at predicted amino acids (tyrosine 7, lysine 44, and glutamine 47) failed to bind to A11. Cells expressing the mutant DNAJA1 became insensitive to A11-mediated depletion of DNAJA1 and mutp53 as well as A11-mediated inhibition of cell migration. Thus, A11 is the first HSP40/JDP inhibitor that has not been previously characterized for depleting DNAJA1 and subsequently conformational mutp53, leading to inhibition of cancer cell migration. A11 can be exploited for a novel treatment against cancers expressing conformational mutp53.
Characterization of EGFR-reprogrammable temozolomide-resistant cells in a model of glioblastoma
Authors: Gong Lingli , Yin Ying , Chen Cheng , Wan Quan , Xia Die , Wang Mei , Pu Zhening , Zhang Bo , Zou Jian
Published: October 2022

Temozolomide (TMZ) resistance is a major clinical challenge for glioblastoma (GBM). O6-methylguanine-DNA methyltransferase (MGMT) mediated DNA damage repair is a key mechanism for TMZ resistance. However, MGMT-null GBM patients remain resistant to TMZ, and the process for resistance evolution is largely unknown. Here, we developed an acquired TMZ resistant xenograft model using serial implantation of MGMT-hypermethylated U87 cells, allowing the extraction of stable, TMZ resistant (TMZ-R) tumors and primary cells. The derived tumors and cells exhibited stable multidrug resistance both in vitro and in vivo. Functional experiments, as well as single-cell RNA sequencing (scRNA-seq), indicated that TMZ treatment induced cellular heterogeneity including quiescent cancer stem cells (CSCs) in TMZ-R tumors. A subset of these were labeled by NES+/SOX2+/CADM1+ and demonstrated significant advantages for drug resistance. Further study revealed that Epidermal Growth Factor Receptor (EGFR) deficiency and diminished downstream signaling may confer this triple positive CSCs subgroup’s quiescent phenotypes and chemoresistance. Continuous EGF treatment improved the chemosensitivity of TMZ-R cells both in vitro and in vivo, mechanically reversing cell cycle arrest and reduced drug uptake. Further, EGF treatment of TMZ-R tumors favorably normalized the response to TMZ in combination therapy. Here, we characterize a unique subgroup of CSCs in MGMT-null experimental glioblastoma, identifying EGF + TMZ therapy as a potential strategy to overcome cellular quiescence and TMZ resistance, likely endowed by deficient EGFR signaling.
Translation and natural selection of micropeptides from long non-canonical RNAs
Authors: Patraquim Pedro , Magny Emile G. , Pueyo José I. , Platero Ana Isabel , Couso Juan Pablo
Published: October 2022

Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides but lacking canonical coding sequences. Apparently unable to produce peptides, lncRNA function seems to rely only on RNA expression, sequence and structure. Here, we exhaustively detect in-vivo translation of small open reading frames (small ORFs) within lncRNAs using Ribosomal profiling during Drosophila melanogaster embryogenesis. We show that around 30% of lncRNAs contain small ORFs engaged by ribosomes, leading to regulated translation of 100 to 300 micropeptides. We identify lncRNA features that favour translation, such as cistronicity, Kozak sequences, and conservation. For the latter, we develop a bioinformatics pipeline to detect small ORF homologues, and reveal evidence of natural selection favouring the conservation of micropeptide sequence and function across evolution. Our results expand the repertoire of lncRNA biochemical functions, and suggest that lncRNAs give rise to novel coding genes throughout evolution. Since most lncRNAs contain small ORFs with as yet unknown translation potential, we propose to rename them “long non-canonical RNAs”.
Exploring species-level infant gut bacterial biodiversity by meta-analysis and formulation of an optimized cultivation medium
Authors: Alessandri Giulia , Fontana Federico , Mancabelli Leonardo , Lugli Gabriele Andrea , Tarracchini Chiara , Argentini Chiara , Longhi Giulia , Viappiani Alice , Milani Christian , Turroni Francesca , van Sinderen Douwe , Ventura Marco
Published: October 2022

In vitro gut cultivation models provide host-uncoupled, fast, and cost-efficient solutions to investigate the effects of intrinsic and extrinsic factors impacting on both composition and functionality of the intestinal microbial ecosystem. However, to ensure the maintenance and survival of gut microbial players and preserve their functions, these systems require close monitoring of several variables, including oxygen concentration, pH, and temperature, as well as the use of a culture medium satisfying the microbial nutritional requirements. In this context, in order to identify the macro- and micro-nutrients necessary for in vitro cultivation of the infant gut microbiota, a meta-analysis based on 1669 publicly available shotgun metagenomic samples corresponding to fecal samples of healthy, full-term infants aged from a few days to three years was performed to define the predominant species characterizing the “infant-like” gut microbial ecosystem. A subsequent comparison of growth performances was made using infant fecal samples that contained the most abundant bacterial taxa of the infant gut microbiota, when cultivated on 18 different culture media. This growth analysis was performed by means of flow cytometry-based bacterial cell enumeration and shallow shotgun sequencing, which allowed the formulation of an optimized growth medium, i.e., Infant Gut Super Medium (IGSM), which maintains and sustains the infant gut microbial biodiversity under in vitro growth conditions. Furthermore, this formulation was used to evaluate the in vitro effect of two drugs commonly used in pediatrics, i.e., acetaminophen and simethicone, on the taxonomic composition of the infant gut microbiota.
Regulation of viable/inactivated/lysed probiotic Lactobacillus plantarum H6 on intestinal microbiota and metabolites in hypercholesterolemic mice
Authors: Li Yue , Chen Mengling , Ma Yuxuan , Yang Yue , Cheng Ying , Ma Huijing , Ren Dayong , Chen Ping
Published: October 2022

Evidence suggests that probiotic interventions reduce non-communicable diseases (NCDs) risk. However, its therapeutic effect and mechanism are still unclear. To evaluate the hypocholesterolemic effect of Lactobacillus plantarum H6 (L.p H6), a new commercial patent strain capable of preventing hypercholesterolemia, and its mechanism in depth, three states of the strain were prepared, namely, viable (vH6), heat-inactivated (iH6), and ultrasonically-lysed (uH6) bacteria cells. The results showed that v/i/uH6 cells could lower serum and liver blood lipid levels, alleviate liver damage and improve glucose tolerance test (GTT) and insulin tolerance test (ITT) indexes. v/i/uH6 cells improved the gut microbial composition and significantly reduced the Firmicutes to Bacteroidetes ratio (F/B ratio) in feces. In particular, Muribaculaceae may be a potential biomarker for effective cholesterol reduction. Also, the recovery of these biochemical indices and gut microbiome was found following fecal microbiota transplantation (FMT) using stool from vH6 treated mice. The v/i/uH6 cells increased the intestinal flora metabolism of vitamins-cofactors, as well as amino acids, while decreasing the relative content of primary bile acids. The Pearson correlation analysis showed that norank_f__Muribaculaceae and Lactobacillus had a negative correlation with blood lipid levels. Overall, v/i/uH6 cells were effective in improving hypercholesterolemia in mice, and this effect was attributed partly to the regulation of intestinal microbiota and metabolites related to lipid metabolism. Our findings provided a theoretical basis for the industrial development of probiotics and postbiotics and the treatment of cholesterol diseases.
Admixture has obscured signals of historical hard sweeps in humans
Authors: Souilmi Yassine , Tobler Raymond , Johar Angad , Williams Matthew , Grey Shane T. , Schmidt Joshua , Teixeira João C. , Rohrlach Adam , Tuke Jonathan , Johnson Olivia , Gower Graham , Turney Chris , Cox Murray , Cooper Alan , Huber Christian D.
Published: October 2022

The role of natural selection in shaping biological diversity is an area of intense interest in modern biology. To date, studies of positive selection have primarily relied on genomic datasets from contemporary populations, which are susceptible to confounding factors associated with complex and often unknown aspects of population history. In particular, admixture between diverged populations can distort or hide prior selection events in modern genomes, though this process is not explicitly accounted for in most selection studies despite its apparent ubiquity in humans and other species. Through analyses of ancient and modern human genomes, we show that previously reported Holocene-era admixture has masked more than 50 historic hard sweeps in modern European genomes. Our results imply that this canonical mode of selection has probably been underappreciated in the evolutionary history of humans and suggest that our current understanding of the tempo and mode of selection in natural populations may be inaccurate.
Millennial-scale climate variability over land overprinted by ocean temperature fluctuations
Authors: Hébert R. , Herzschuh U. , Laepple T.
Published: October 2022

Variations in regional temperature have widespread implications for society, but our understanding of the amplitude and origin of long-term natural variability is insufficient for accurate regional projections. This is especially the case for terrestrial temperature variability, which is currently thought to be weak over long timescales. By performing spectral analysis on climate reconstructions, produced using sedimentary pollen records from the Northern Hemisphere over the last 8,000 years, coupled with instrumental data, we provide a comprehensive estimate of regional temperature variability from annual to millennial timescales. We show that short-term random variations are overprinted by strong ocean-driven climate variability on multi-decadal and longer timescales. This may cause substantial and potentially unpredictable regional climatic shifts in the coming century, in contrast to the relatively muted and homogeneous warming projected by climate models. Due to the marine influence, regions characterized by stable oceanic climate at sub-decadal timescales experience stronger long-term variability, and continental regions with higher sub-decadal variability show weaker long-term variability. This fundamental relationship between the timescales provides a unique insight into the emergence of a marine-driven low-frequency regime governing terrestrial climate variability and sets the basis to project the amplitude of temperature fluctuations on multi-decadal timescales and longer.
Observation of vortices and vortex stripes in a dipolar condensate
Authors: Klaus Lauritz , Bland Thomas , Poli Elena , Politi Claudia , Lamporesi Giacomo , Casotti Eva , Bisset Russell N. , Mark Manfred J. , Ferlaino Francesca
Published: October 2022

Quantized vortices are a prototypical feature of superfluidity that have been observed in multiple quantum gas experiments. But the occurrence of vortices in dipolar quantum gases—a class of ultracold gases characterized by long-range anisotropic interactions—has not been reported yet. Here we exploit the anisotropic nature of the dipole–dipole interaction of a dysprosium Bose–Einstein condensate to induce angular symmetry breaking in an otherwise cylindrically symmetric pancake-shaped trap. Tilting the magnetic field towards the radial plane deforms the cloud into an ellipsoid, which is then set into rotation. At stirring frequencies approaching the radial trap frequency, we observe the generation of dynamically unstable surface excitations, which cause angular momentum to be pumped into the system through vortices. Under continuous rotation, the vortices arrange into a stripe configuration along the field, in close agreement with numerical simulations.
An all-Africa dataset of energy model “supply regions” for solar photovoltaic and wind power
Authors: Sterl Sebastian , Hussain Bilal , Miketa Asami , Li Yunshu , Merven Bruno , Ben Ticha Mohammed Bassam , Elabbas Mohamed A. Eltahir , Thiery Wim , Russo Daniel
Published: October 2022

With solar and wind power generation reaching unprecedented growth rates globally, much research effort has recently gone into a comprehensive mapping of the worldwide potential of these variable renewable electricity (VRE) sources. From a perspective of energy systems analysis, the locations with the strongest resources may not necessarily be the best candidates for investment in new power plants, since the distance from existing grid and road infrastructures and the temporal variability of power generation also matter. To inform energy planning and policymaking, cost-optimisation models for energy systems must be fed with adequate data on potential sites for VRE plants, including costs reflective of resource strength, grid expansion needs and full hourly generation profiles. Such data, tailored to energy system models, has been lacking up to now. In this study, we present a new open-source and open-access all-Africa dataset of “supply regions” for solar photovoltaic and onshore wind power to feed energy models and inform capacity expansion planning.
Exploration of various roles of hypoxia genes in osteosarcoma
Authors: Ma Jimin , Guo Ziming , Yang Xuefei , Zhu Yakun
Published: October 2022

Osteosarcoma is a primary malignant tumor that often metastasizes in orthopedic diseases. Although multi-drug chemotherapy and surgical treatment have significantly improved the survival and prognosis of patients with osteosarcoma, the survival rate is still very low due to frequent metastases in patients with osteosarcoma. In-depth exploration of the relationship between various influencing factors of osteosarcoma is very important for screening promising therapeutic targets. This study used multivariate COX regression analysis to select the hypoxia genes SLC2A1 and FBP1 in patients with osteosarcoma, and used the expression of these two genes to divide the patients with osteosarcoma into high-risk and low-risk groups. Then, we first constructed a prognostic model based on the patient's risk value and compared the survival difference between the high expression group and the low expression group. Second, in the high expression group and the low expression group, compare the differences in tumor invasion and inflammatory gene expression between the two groups of immune cells. Finally, the ferroptosis-related genes with differences between the high expression group and the low expression group were screened, and the correlation between these genes was analyzed. In the high-risk group, immune cells with higher tumor invasiveness, macrophages M0 and immune cells with lower invasiveness included: mast cell resting, regulatory T cells (Tregs) and monocytes. Finally, among genes related to ferroptosis, we found AKR1C2, AKR1C1 and ALOX15 that may be related to hypoxia. These ferroptosis-related genes were discovered for the first time in osteosarcoma. Among them, the hypoxia gene FBP1 is positively correlated with the ferroptosis genes AKR1C1 and ALOX15, and the hypoxia gene SLC2A1 is negatively correlated with the ferroptosis genes AKR1C2, AKR1C1 and ALOX15. This study constructed a prognostic model based on hypoxia-related genes SLC2A1 and FBP1 in patients with osteosarcoma, and explored their correlation with immune cells, inflammatory markers and ferroptosis-related genes. This indicates that SLC2A1 and FBP1 are promising targets for osteosarcoma research.
Efficacy and safety of apatinib in patients with recurrent or metastatic head and neck squamous cell carcinoma: a retrospective multi-center study
Authors: Liu Zijing , Zheng Zhuangzhuang , Dong Lihua , Guo Xiao , Jia Xiaojing , Wang Jianfeng , Meng Lingbin , Cui Xiangyan , Jiang Xin
Published: October 2022

Apatinib is a novel antiangiogenic agent that targets vascular endothelial growth factor 2. The aim of our study was to explore the efficacy and safety of apatinib in the treatment of patients with recurrence or metastasis (R/M) inoperable head and neck squamous cell carcinoma (HNSCC). This multi-center retrospective study analyzed 53 cases of recurrent or metastatic inoperable HNSCC who had progressed or recurred after undergoing standard radiotherapy, chemotherapy, and immunotherapy treated with apatinib from March 2017 to August 2021. Patients continued apatinib until the time of disease progression or onset of intolerable adverse events. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), objective response rate (ORR), and disease control rate (DCR) and incidence of adverse events. Univariable and multivariable analyses were performed to determine prognostic factors. The main adverse events were counted, and the severity of the adverse reactions was evaluated. Fifty-three patients with recurrent or metastatic inoperable R/M HNSCC who had progressed or recurred after standard radiotherapy, chemotherapy, and immunotherapy were included. The ORR was 15.1%, and the DCR was 86.8%. The median PFS was 4.4 months (95% confidence interval [CI] 3.7–5.0 months) and the median OS was 6.6 months (95% CI 5.3–7.9 months). The number of apatinib lines was an influencing factor for both PFS and OS, and the Eastern Cooperative Oncology Group (ECOG) score, tumor differentiation, and apatinib duration were only the influencing factors for OS. Of these, only the ECOG score was an independent predictor of OS. The most common adverse reactions were hypertension (39.6%), hand-foot syndrome (32.1%), fatigue (32.1%), oral ulcers (28.3%), and nausea and vomiting (20.8%). Most adverse reactions were grade 1 or 2. Apatinib mesylate has good efficacy for recurrent/metastatic inoperable HNSCC as second-line and above-line treatment. ECOG score was an independent prognostic factors of OS in patients who were treated with apatinib. In addition, the adverse effects of apatinib mesylate were relatively mild.
Drug transporters OAT1 and OAT3 have specific effects on multiple organs and gut microbiome as revealed by contextualized metabolic network reconstructions
Authors: Jamshidi Neema , Nigam Sanjay K.
Published: October 2022

In vitro and in vivo studies have established the organic anion transporters OAT1 (SLC22A6, NKT) and OAT3 (SLC22A8) among the main multi-specific “drug” transporters. They also transport numerous endogenous metabolites, raising the possibility of drug-metabolite interactions (DMI). To help understand the role of these drug transporters on metabolism across scales ranging from organ systems to organelles, a formal multi-scale analysis was performed. Metabolic network reconstructions of the omics-alterations resulting from Oat1 and Oat3 gene knockouts revealed links between the microbiome and human metabolism including reactions involving small organic molecules such as dihydroxyacetone, alanine, xanthine, and p-cresol—key metabolites in independent pathways. Interestingly, pairwise organ-organ interactions were also disrupted in the two Oat knockouts, with altered liver, intestine, microbiome, and skin-related metabolism. Compared to older models focused on the “one transporter-one organ” concept, these more sophisticated reconstructions, combined with integration of a multi-microbial model and more comprehensive metabolomics data for the two transporters, provide a considerably more complex picture of how renal “drug” transporters regulate metabolism across the organelle (e.g. endoplasmic reticulum, Golgi, peroxisome), cellular, organ, inter-organ, and inter-organismal scales. The results suggest that drugs interacting with OAT1 and OAT3 can have far reaching consequences on metabolism in organs (e.g. skin) beyond the kidney. Consistent with the Remote Sensing and Signaling Theory (RSST), the analysis demonstrates how transporter-dependent metabolic signals mediate organ crosstalk (e.g., gut-liver-kidney) and inter-organismal communication (e.g., gut microbiome-host).
New insight into the swimming kinematics of wild Green sea turtles (Chelonia mydas)
Authors: van der Geest Nick , Garcia Lorenzo , Nates Roy , Godoy Daniel A.
Published: October 2022

Biomechanically, sea turtles could be perceived as birds of the ocean as they glide and flap their forelimbs to produce the necessary forces required for locomotion, making sea turtles an interesting animal to study. However, being an endangered species makes studying the sea turtle's biomechanics a complex problem to solve, both technically and ethically, without causing disturbance. This work develops a novel, non-invasive procedure to develop full three-dimensional kinematics for wild sea turtles by filming the animals in Australia's Great Barrier Reef using underwater drones without disturbing them. We found that the wild animals had very different swimming patterns than previous studies on juveniles in captivity. Our findings show that the flipper goes through a closed-loop trajectory with extended sweeping of the flipper tip towards the centre of the carapace to create a clapping motion. We have named this the “sweep stroke” and in contrast to previously described four-stage models, it creates a five-stage cycle swimming locomotion model. The model presented here could lead to a better comprehension of the sea turtle propulsion methods and their fluid–structure interaction.
SILA: a system for scientific image analysis
Authors: Moreira Daniel , Cardenuto João Phillipe , Shao Ruiting , Baireddy Sriram , Cozzolino Davide , Gragnaniello Diego , Abd-Almageed Wael , Bestagini Paolo , Tubaro Stefano , Rocha Anderson , Scheirer Walter , Verdoliva Luisa , Delp Edward
Published: October 2022

A great deal of the images found in scientific publications are retouched, reused, or composed to enhance the quality of the presentation. In most instances, these edits are benign and help the reader better understand the material in a paper. However, some edits are instances of scientific misconduct and undermine the integrity of the presented research. Determining the legitimacy of edits made to scientific images is an open problem that no current technology can perform satisfactorily in a fully automated fashion. It thus remains up to human experts to inspect images as part of the peer-review process. Nonetheless, image analysis technologies promise to become helpful to experts to perform such an essential yet arduous task. Therefore, we introduce SILA, a system that makes image analysis tools available to reviewers and editors in a principled way. Further, SILA is the first human-in-the-loop end-to-end system that starts by processing article PDF files, performs image manipulation detection on the automatically extracted figures, and ends with image provenance graphs expressing the relationships between the images in question, to explain potential problems. To assess its efficacy, we introduce a dataset of scientific papers from around the globe containing annotated image manipulations and inadvertent reuse, which can serve as a benchmark for the problem at hand. Qualitative and quantitative results of the system are described using this dataset.
Hereditary spastic paraplegia SPG13 mutation increases structural stability and ATPase activity of human mitochondrial chaperonin
Authors: Chen Lingling , Syed Aiza , Balaji Adhitya
Published: October 2022

Human mitochondrial chaperonin mHsp60 is broadly associated with various human health conditions and the V72I mutation in mHsp60 causes a form of hereditary spastic paraplegia, a neurodegenerative disease. The main function of mHsp60 is to assist folding of mitochondrial proteins in an ATP-dependent manner. In this study, we unexpectedly found that mutant mHsp60V72I was more stable structurally and more active in the ATPase activity than the wildtype. Analysis of our recently solved cryo-EM structure of mHsp60 revealed allosteric roles of V72I in structural stability and ATPase activity, which were supported by studies including those using the V72A mutation. Despite with the increases in structural stability and ATPase activity, mHsp60V72I was less efficient in folding malate dehydrogenase, a putative mHsp60 substrate protein in mitochondria and also commonly used in chaperonin studies. In addition, although mHsp60V72I along with its cochaperonin mHsp10 was able to substitute the E. coli chaperonin system in supporting cell growth under normal temperature of 37 °C, it was unable under heat shock temperature of 42 °C. Our results support the importance of structural dynamics and an optimal ATP turnover that mHsp60 has evolved for its function and physiology. We propose that unproductive energy utilization, or hyperactive ATPase activity and compromised folding function, not mutually exclusive, are responsible for the V72I pathology in neurodegenerative disease.
Demonstration of 100 Gbps coherent free-space optical communications at LEO tracking rates
Authors: Walsh Shane M. , Karpathakis Skevos F. E. , McCann Ayden S. , Dix-Matthews Benjamin P. , Frost Alex M. , Gozzard David R. , Gravestock Charles T. , Schediwy Sascha W.
Published: October 2022

Free-space optical communications are poised to alleviate the data-flow bottleneck experienced by spacecraft as traditional radio frequencies reach their practical limit. While enabling orders-of-magnitude gains in data rates, optical signals impose much stricter pointing requirements and are strongly affected by atmospheric turbulence. Coherent detection methods, which capitalize fully on the available degrees of freedom to maximize data capacity, have the added complication of needing to couple the received signal into single-mode fiber. In this paper we present results from a coherent 1550 nm link across turbulent atmosphere between a deployable optical terminal and a drone-mounted retroreflector. Through 10 Hz machine vision optical tracking with nested 200 Hz tip/tilt adaptive optics stabilisation, we corrected for pointing errors and atmospheric turbulence to maintain robust single mode fiber coupling, resulting in an uninterrupted 100 Gbps optical data link while tracking at angular rates of up to 1.5 deg/s, equivalent to that of spacecraft in low earth orbit. With the greater data capacity of coherent communications and compatibility with extant fiber-based technologies being demonstrated across static links, ground-to-low earth orbit links of Terabits per second can ultimately be achieved with capable ground stations.
Efficacy and safety of dulaglutide compared with the first-line hypoglycemic drugs in Asian patients with type 2 diabetes: a systematic review and meta-analysis
Authors: Yu Bin , Lin Fei , Wang Maoru , Ning Hong , Ling Baodong , Rao Youyi
Published: October 2022

To assess the efficacy and safety of dulaglutide in the treatment of Asian type 2 diabetes mellitus (T2DM), along with first-line hypoglycemic drugs. Systematic review and meta-analysis. Cochrane Library, Pubmed, Embase, and www.clinicaltrials.gov databases were searched from inception to September 27, 2022. The studies evaluating adults (≥ 18 years) undergoing dulaglutide (0.75 mg and 1.5 mg) and first-line hypoglycemic drugs were considered. There were only English languages. We used Stata 12.0 software to detect the risk of bias. 4 randomized controlled trials (RCTs), and 1 observational study. Both dulaglutide 0.75 mg dose group and 1.5 mg dose group could significantly reduce HbA1c [Dulaglutide 0.75 mg: WMD = − 0.20, 95% CI (− 0.28, − 0.11), P < 0.0001; Dulaglutide 1.5 mg: WMD = − 0.49, 95% CI (− 0.67, − 0.30), P < 0.0001] in Asian T2DM patients. In reducing fasting blood glucose (FBG) level, there was no significant difference observed in 2 dose groups. The body weight of patients in both dulaglutide dose groups was significantly reduced. In safety, the incidence of adverse events in the dulaglutide 0.75 mg dose group was slightly higher than that in the first-line drug group, but there was no statistically significant difference in the incidence of adverse events between the 1.5 mg dose group and the first-line drug group. Furthermore, the incidences of hypoglycemic events in both groups were higher than that in the first-line drug group. Two doses of dulaglutide showed better efficacy for Asian T2DM patients, but patients should be vigilant about the occurrence of hypoglycemia and gastrointestinal discomfort. However, more number and better quality of RCTs are suggested to confirm long-term safety and efficacy.
Deoxygenation lowers the thermal threshold of coral bleaching
Authors: Alderdice Rachel , Perna Gabriela , Cárdenas Anny , Hume Benjamin C. C. , Wolf Martin , Kühl Michael , Pernice Mathieu , Suggett David J. , Voolstra Christian R.
Published: October 2022

Exposure to deoxygenation from climate warming and pollution is emerging as a contributing factor of coral bleaching and mortality. However, the combined effects of heating and deoxygenation on bleaching susceptibility remain unknown. Here, we employed short-term thermal stress assays to show that deoxygenated seawater can lower the thermal limit of an Acropora coral by as much as 1 °C or 0.4 °C based on bleaching index scores or dark-acclimated photosynthetic efficiencies, respectively. Using RNA-Seq, we show similar stress responses to heat with and without deoxygenated seawater, both activating putative key genes of the hypoxia-inducible factor response system indicative of cellular hypoxia. We also detect distinct deoxygenation responses, including a disruption of O2-dependent photo-reception/-protection, redox status, and activation of an immune response prior to the onset of bleaching. Thus, corals are even more vulnerable when faced with heat stress in deoxygenated waters. This highlights the need to integrate dissolved O2 measurements into global monitoring programs of coral reefs.
Innovative binary sorption of Cobalt(II) and methylene blue by Sargassum latifolium using Taguchi and hybrid artificial neural network paradigms
Authors: Moussa Zeiad , Ghoniem Abeer A. , Elsayed Ashraf , Alotaibi Amenah S. , Alenzi Asma Massad , Hamed Sahar E. , Elattar Khaled M. , Saber WesamEldin I. A.
Published: October 2022

The present investigation has been designed by Taguchi and hybrid artificial neural network (ANN) paradigms to improve and optimize the binary sorption of Cobalt(II) and methylene blue (MB) from an aqueous solution, depending on modifying physicochemical conditions to generate an appropriate constitution for a highly efficient biosorption by the alga; Sargassum latifolium. Concerning Taguchi's design, the predicted values of the two responses were comparable to actual ones. The biosorption of Cobalt(II) ions was more efficient than MB, the supreme biosorption of Cobalt(II) was verified in run L21 (93.28%), with the highest S/N ratio being 39.40. The highest biosorption of MB was reached in run L22 (74.04%), with a S/N ratio of 37.39. The R2 and adjusted R2 were in reasonable values, indicating the validity of the model. The hybrid ANN model has exclusively emerged herein to optimize the biosorption of both Cobalt(II) and MB simultaneously, therefore, the ANN model was better than the Taguchi design. The predicted values of Cobalt(II) and MB biosorption were more obedience to the ANN model. The SEM analysis of the surface of S. latifolium showed mosaic form with massive particles, as crosslinking of biomolecules of the algal surface in the presence of Cobalt(II) and MB. Viewing FTIR analysis showed active groups e.g., hydroxyl, α, β-unsaturated ester, α, β-unsaturated ketone, N–O, and aromatic amine. To the best of our knowledge, there are no reports deeming the binary sorption of Cobalt(II) and MB ions by S. latifolium during Taguchi orthogonal arrays and hybrid ANN.
Lithium deportment by size of a calcined spodumene ore
Authors: Nazir Muhammad Kashif , Dyer Laurence , Tadesse Bogale , Albijanic Boris , Kashif Nadia
Published: October 2022

Calcination of spodumene is used to convert α-spodumene to more reactive β-spodumene, has been shown to greatly impact the physical characteristics of some of the components in the ore. This work investigates the energy efficiency of different grinding circuits used for upgrading the lithium content in the finer fraction of the calcined spodumene ore. The results showed that closed-circuit grinding resulted in 89% lithium recovery of the finest size fractions (− 0.6 mm) while open-circuit grinding led to 65% lithium recovery for the same grinding time. Closed-circuit grinding consumed lower energy than open-circuit grinding. The grade of the finest size fraction in the case of the open-circuit grinding was 1.7 times more than that in the case of the closed-circuit grinding. This work shows the potential of using different grinding modes to maximize energy efficiency and lithium deportment by size. However, it is suggested that open circuit grinding should be used for beneficiations of spodumene ores.
Opto-mechanically generated resonant field enhancement
Authors: Fresno-Hernández Alicia , Marqués Manuel I.
Published: October 2022

A link between the resonant cumulative field enhancement experienced by a chain of plasmonic nanoparticles in a light field and the orientation of the chain with respect to the field is obtained. We calculate analytically the optical torque and the equilibrium configuration and we show how stable orientations are triggered by the geometric resonance conditions. Analytical predictions are checked using numerical calculations based on the coupled dipoles method (CDA) for the particular case of a chain of silver nanoparticles. The reported resonance driven optical torque allows for a tuning of the orientation of the chain depending on radiation’s wavelength.
Catalytic nanozyme Zn/Cl-doped carbon quantum dots as ratiometric fluorescent probe for sequential on-off-on detection of riboflavin, Cu2+ and thiamine
Authors: Dadkhah Sahar , Mehdinia Ali , Jabbari Ali , Manbohi Ahmad
Published: October 2022

A novel metal-doped Zn/Cl carbon quantum dots (Zn/Cl-CQDs) was developed successfully as ratiometric fluorescent probes for the sequential on-off-on detection of riboflavin, Cu2+ ion and thiamine. The excellent catalytic performance of the Zn/Cl-CQDs nanozyme serves as an ideal platform for sensitive detection of thiamine. Due to the addition of riboflavin to the Zn/Cl-CQDs, the blue emission peak of Zn/Cl-CQDs at 440 nm remains unaffected and used as an internal reference approach, while the green emission peak of riboflavin at 520 nm appeared and increased remarkably. Following the presence of Cu2+, a quenching blue fluorescence signal of Zn/Cl-CQDs was observed which resulted in consequent fluorescent ‘turn-off’ response toward Cu2+ ion. Finally, upon the addition of thiamine to the above solution under alkaline condition, the blue emission of Zn/Cl-CQDs was gradually recovered. The prepared Zn/Cl-CQDs could act as a nanozyme catalyst for directly catalyzing the oxidation of non-fluorescent substrate of thiamine to produce highly fluorescent substrate of thiochrome. As a result, the blue fluorescence emission peak at 440 nm was recovered. Eventually, the sequential detection properties of ratiometric probes for riboflavin, Cu2+ ion and thiamine were successfully applied in VB2 tablets, drinking water and VB1 tablet with good recoveries of 96.21%, 98.25% and 98.44%, respectively.
A novel method to monitor COVID-19 fatality rate in real-time, a key metric to guide public health policy
Authors: Qu Yuanke , Lee Chun Yin , Lam K. F.
Published: October 2022

An accurate estimator of the real-time fatality rate is warranted to monitor the progress of ongoing epidemics, hence facilitating the policy-making process. However, most of the existing estimators fail to capture the time-varying nature of the fatality rate and are often biased in practice. A simple real-time fatality rate estimator with adjustment for reporting delays is proposed in this paper using the fused lasso technique. This approach is easy to use and can be broadly applied to public health practice as only basic epidemiological data are required. A large-scale simulation study suggests that the proposed estimator is a reliable benchmark for formulating public health policies during an epidemic with high accuracy and sensitivity in capturing the changes in the fatality rate over time, while the other two commonly-used case fatality rate estimators may convey delayed or even misleading signals of the true situation. The application to the COVID-19 data in Germany between January 2020 and January 2022 demonstrates the importance of the social restrictions in the early phase of the pandemic when vaccines were not available, and the beneficial effects of vaccination in suppressing the fatality rate to a low level since August 2021 irrespective of the rebound in infections driven by the more infectious Delta and Omicron variants during the fourth wave.
Grassland coverage change and its humanity effect factors quantitative assessment in Zhejiang province, China, 1980–2018
Authors: Lü Linyou , Zhao Yan , Chu Lei , Wang Yongcui , Zhou Quanlai
Published: October 2022

This study aims to make clear of grassland coverage change and quantitative assessment its effect factors. We collected the data from the National Bureau of Statistics (http://www.stats.gov.cn) and "China 20th Century Land Use/Cover Change (LUCC) Spatio-temporal Platform". Grassland coverage area showed an upward trend from 1980 to 1990, and the grassland coverage area is gradually decreasing from 1990 to 2000, and the grassland coverage area has not changed much from 2000 to 2018. The medium-coverage grassland area has the highest correlation with the total population, and the high-coverage grassland area has the lowest correlation with the total population. Land use types and the composite of gross agricultural output have influence on grassland coverage area. It is hoped that relevant policies should consider land use types and ecological benefits while balancing economic development and urban development.
On the future zonal contrasts of equatorial Pacific climate: Perspectives from Observations, Simulations, and Theories
Authors: Lee Sukyoung , L’Heureux Michelle , Wittenberg Andrew T. , Seager Richard , O’Gorman Paul A. , Johnson Nathaniel C.
Published: October 2022

Changes in the zonal gradients of sea surface temperature (SST) across the equatorial Pacific have major consequences for global climate. Therefore, accurate future projections of these tropical Pacific gradients are of paramount importance for climate mitigation and adaptation. Yet there is evidence of a dichotomy between observed historical gradient trends and those simulated by climate models. Observational records appear to show a “La Niña-like” strengthening of the zonal SST gradient over the past century, whereas most climate model simulations project “El Niño-like” changes toward a weaker gradient. Here, studies of these equatorial Pacific climate trends are reviewed, focusing first on data analyses and climate model simulations, then on theories that favor either enhanced or weakened zonal SST gradients, and then on notable consequences of the SST gradient trends. We conclude that the present divergence between the historical model simulations and the observed trends likely either reflects an error in the model’s forced response, or an underestimate of the multi-decadal internal variability by the models. A better understanding of the fundamental mechanisms of both forced response and natural variability is needed to reduce the uncertainty. Finally, we offer recommendations for future research directions and decision-making for climate risk mitigation.
Rewiring glucose metabolism improves 5-FU efficacy in p53-deficient/KRASG12D glycolytic colorectal tumors
Authors: Ludikhuize Marlies C. , Gevers Sira , Nguyen Nguyen T. B. , Meerlo Maaike , Roudbari S. Khadijeh Shafiei , Gulersonmez M. Can , Stigter Edwin C. A. , Drost Jarno , Clevers Hans , Burgering Boudewijn M. T. , Rodríguez Colman Maria J.
Published: October 2022

Despite the fact that 5-fluorouracil (5-FU) is the backbone for chemotherapy in colorectal cancer (CRC), the response rates in patients is limited to 50%. The mechanisms underlying 5-FU toxicity are debated, limiting the development of strategies to improve its efficacy. How fundamental aspects of cancer, such as driver mutations and phenotypic heterogeneity, relate to the 5-FU response remains obscure. This largely relies on the limited number of studies performed in pre-clinical models able to recapitulate the key features of CRC. Here, we analyzed the 5-FU response in patient-derived organoids that reproduce the different stages of CRC. We find that 5-FU induces pyrimidine imbalance, which leads to DNA damage and cell death in the actively proliferating cancer cells deficient in p53. Importantly, p53-deficiency leads to cell death due to impaired cell cycle arrest. Moreover, we find that targeting the Warburg effect in KRASG12D glycolytic tumor organoids enhances 5-FU toxicity by further altering the nucleotide pool and, importantly, without affecting non-transformed WT cells. Thus, p53 emerges as an important factor in determining the 5-FU response, and targeting cancer metabolism in combination with replication stress-inducing chemotherapies emerges as a promising strategy for CRC treatment.
Ag NCs as a potent antibiofilm agent against pathogenic Pseudomonas aeruginosa and Acinetobacter baumannii and drug-resistant Bacillus subtilis by affecting chemotaxis and flagellar assembly pathway genes
Authors: Singh Anirudh , Rani Komal , Tandon Vibha , Sahoo Amaresh Kumar , Samanta Sintu Kumar
Published: October 2022

Ag NCs can mediate biofilm degradation through the regulation of bacterial chemotaxis and flagellar assembly pathway genes.
In situencapsulation of iron oxide nanoparticles into nitrogen-doped carbon nanotubes as anodic electrode materials of lithium ion batteries
Authors: Chen Ming , Liu Feng-Ming , Zhao Hui , Chen Shan-Shuai , Qian Xing , Yuan Zhong-Yong , Wan Rong
Published: October 2022

Fe-based oxides are considered as promising anode materials for lithium-ion batteries (LIBs) due to their high theoretical capacities, low cost, natural abundance and environmental friendliness.
Metallic WN plasmonic fabricated g-C3N4 significantly steered photocatalytic hydrogen evolution under visible and near-infrared light
Authors: Tahir Warisha , Ullah Sami , Ullah Ikram , Li Jing-Han , Ling Cong , Lu Xiao-Jie , Qian Xiao-Jun , Wang Gang , Pan Yueyin , Xu An-Wu
Published: October 2022

Energy level diagram and charge transfer mechanism of WN/CN-x plasmonic photocatalysts.
Red and near-infrared emitting phosphors based on Eu3+- or Nd3+-doped lanthanum niobates prepared by the sol–gel route
Authors: Grecco Manfré Mateus , Labaki Hayra do Prado , Souza Vítor dos Santos de , Gonçalves Rogéria R.
Published: October 2022

Structural and luminescence studies on Eu3+- and Nd3+-doped lanthanum niobates. High quenching concentration of Nd3+-doped samples and no quenching concentration for up to 20 mol% Eu3+samples with dopant concentration-dependent properties observed.