bluuebunny/crossref_metadata_2025 huggingface dataset:
ASP-2/Trans-sialidase chimeric protein induces robust protective immunity in experimental models of Chagas’ disease
Authors: Castro Julia T. , Brito Rory , Hojo-Souza Natalia S. , Azevedo Bárbara , Salazar Natalia , Ferreira Camila P. , Junqueira Caroline , Fernandes Ana Paula , Vasconcellos Ronnie , Cardoso Jamille M. , Aguiar-Soares Rodrigo D. O. , Vieira Paula M. A. , Carneiro Cláudia M. , Valiate Bruno , Toledo Cristiane , Salazar Andres M. , Caballero Otávia , Lannes-Vieira Joseli , Teixeira Santuza R. , Reis Alexandre B. , Gazzinelli Ricardo T.
Published: May 2023

Immunization with the Amastigote Surface Protein-2 (ASP-2) and Trans-sialidase (TS) antigens either in the form of recombinant protein, encoded in plasmids or human adenovirus 5 (hAd5) confers robust protection against various lineages of Trypanosoma cruzi. Herein we generated a chimeric protein containing the most immunogenic regions for T and B cells from TS and ASP-2 (TRASP) and evaluated its immunogenicity in comparison with our standard protocol of heterologous prime-boost using plasmids and hAd5. Mice immunized with TRASP protein associated to Poly-ICLC (Hiltonol) were highly resistant to challenge with T. cruzi, showing a large decrease in tissue parasitism, parasitemia and no lethality. This protection lasted for at least 3 months after the last boost of immunization, being equivalent to the protection induced by DNA/hAd5 protocol. TRASP induced high levels of T. cruzi-specific antibodies and IFNγ-producing T cells and protection was primarily mediated by CD8+ T cells and IFN-γ. We also evaluated the toxicity, immunogenicity, and efficacy of TRASP and DNA/hAd5 formulations in dogs. Mild collateral effects were detected at the site of vaccine inoculation. While the chimeric protein associated with Poly-ICLC induced high levels of antibodies and CD4+ T cell responses, the DNA/hAd5 induced no antibodies, but a strong CD8+ T cell response. Immunization with either vaccine protected dogs against challenge with T. cruzi. Despite the similar efficacy, we conclude that moving ahead with TRASP together with Hiltonol is advantageous over the DNA/hAd5 vaccine due to pre-existing immunity to the adenovirus vector, as well as the cost-benefit for development and large-scale production.
Establishment of isotype-switched, antigen-specific B cells in multiple mucosal tissues using non-mucosal immunization
Authors: Prior John T. , Limbert Vanessa M. , Horowitz Rebecca M. , D’Souza Shaina J. , Bachnak Louay , Godwin Matthew S. , Bauer David L. , Harrell Jaikin E. , Morici Lisa A. , Taylor Justin J. , McLachlan James B.
Published: May 2023

Although most pathogens infect the human body via mucosal surfaces, very few injectable vaccines can specifically target immune cells to these tissues where their effector functions would be most desirable. We have previously shown that certain adjuvants can program vaccine-specific helper T cells to migrate to the gut, even when the vaccine is delivered non-mucosally. It is not known whether this is true for antigen-specific B cell responses. Here we show that a single intradermal vaccination with the adjuvant double mutant heat-labile toxin (dmLT) induces a robust endogenous, vaccine-specific, isotype-switched B cell response. When the vaccine was intradermally boosted, we detected non-circulating vaccine-specific B cell responses in the lamina propria of the large intestines, Peyer’s patches, and lungs. When compared to the TLR9 ligand adjuvant CpG, only dmLT was able to drive the establishment of isotype-switched resident B cells in these mucosal tissues, even when the dmLT-adjuvanted vaccine was administered non-mucosally. Further, we found that the transcription factor Batf3 was important for the full germinal center reaction, isotype switching, and Peyer’s patch migration of these B cells. Collectively, these data indicate that specific adjuvants can promote mucosal homing and the establishment of activated, antigen-specific B cells in mucosal tissues, even when these adjuvants are delivered by a non-mucosal route. These findings could fundamentally change the way future vaccines are formulated and delivered.
Strong and ductile titanium–oxygen–iron alloys by additive manufacturing
Authors: Song Tingting , Chen Zibin , Cui Xiangyuan , Lu Shenglu , Chen Hansheng , Wang Hao , Dong Tony , Qin Bailiang , Chan Kang Cheung , Brandt Milan , Liao Xiaozhou , Ringer Simon P. , Qian Ma
Published: May 2023

Titanium alloys are advanced lightweight materials, indispensable for many critical applications1,2. The mainstay of the titanium industry is the α–β titanium alloys, which are formulated through alloying additions that stabilize the α and β phases3–5. Our work focuses on harnessing two of the most powerful stabilizing elements and strengtheners for α–β titanium alloys, oxygen and iron1–5, which are readily abundant. However, the embrittling effect of oxygen6,7, described colloquially as ‘the kryptonite to titanium’8, and the microsegregation of iron9 have hindered their combination for the development of strong and ductile α–β titanium–oxygen–iron alloys. Here we integrate alloy design with additive manufacturing (AM) process design to demonstrate a series of titanium–oxygen–iron compositions that exhibit outstanding tensile properties. We explain the atomic-scale origins of these properties using various characterization techniques. The abundance of oxygen and iron and the process simplicity for net-shape or near-net-shape manufacturing by AM make these α–β titanium–oxygen–iron alloys attractive for a diverse range of applications. Furthermore, they offer promise for industrial-scale use of off-grade sponge titanium or sponge titanium–oxygen–iron10,11, an industrial waste product at present. The economic and environmental potential to reduce the carbon footprint of the energy-intensive sponge titanium production12 is substantial.
Deterministic evolution and stringent selection during preneoplasia
Authors: Karlsson Kasper , Przybilla Moritz J. , Kotler Eran , Khan Aziz , Xu Hang , Karagyozova Kremena , Sockell Alexandra , Wong Wing H. , Liu Katherine , Mah Amanda , Lo Yuan-Hung , Lu Bingxin , Houlahan Kathleen E. , Ma Zhicheng , Suarez Carlos J. , Barnes Chris P. , Kuo Calvin J. , Curtis Christina
Published: May 2023

The earliest events during human tumour initiation, although poorly characterized, may hold clues to malignancy detection and prevention1. Here we model occult preneoplasia by biallelic inactivation of TP53, a common early event in gastric cancer, in human gastric organoids. Causal relationships between this initiating genetic lesion and resulting phenotypes were established using experimental evolution in multiple clonally derived cultures over 2 years. TP53 loss elicited progressive aneuploidy, including copy number alterations and structural variants prevalent in gastric cancers, with evident preferred orders. Longitudinal single-cell sequencing of TP53-deficient gastric organoids similarly indicates progression towards malignant transcriptional programmes. Moreover, high-throughput lineage tracing with expressed cellular barcodes demonstrates reproducible dynamics whereby initially rare subclones with shared transcriptional programmes repeatedly attain clonal dominance. This powerful platform for experimental evolution exposes stringent selection, clonal interference and a marked degree of phenotypic convergence in premalignant epithelial organoids. These data imply predictability in the earliest stages of tumorigenesis and show evolutionary constraints and barriers to malignant transformation, with implications for earlier detection and interception of aggressive, genome-instable tumours.
Engineered tRNAs suppress nonsense mutations in cells and in vivo
Authors: Albers Suki , Allen Elizabeth C. , Bharti Nikhil , Davyt Marcos , Joshi Disha , Perez-Garcia Carlos G. , Santos Leonardo , Mukthavaram Rajesh , Delgado-Toscano Miguel Angel , Molina Brandon , Kuakini Kristen , Alayyoubi Maher , Park Kyoung-Joo Jenny , Acharya Grishma , Gonzalez Jose A. , Sagi Amit , Birket Susan E. , Tearney Guillermo J. , Rowe Steven M. , Manfredi Candela , Hong Jeong S. , Tachikawa Kiyoshi , Karmali Priya , Matsuda Daiki , Sorscher Eric J. , Chivukula Pad , Ignatova Zoya
Published: May 2023

Nonsense mutations are the underlying cause of approximately 11% of all inherited genetic diseases1. Nonsense mutations convert a sense codon that is decoded by tRNA into a premature termination codon (PTC), resulting in an abrupt termination of translation. One strategy to suppress nonsense mutations is to use natural tRNAs with altered anticodons to base-pair to the newly emerged PTC and promote translation2–7. However, tRNA-based gene therapy has not yielded an optimal combination of clinical efficacy and safety and there is presently no treatment for individuals with nonsense mutations. Here we introduce a strategy based on altering native tRNAs into  efficient suppressor tRNAs (sup-tRNAs) by individually fine-tuning their sequence to the physico-chemical properties of the amino acid that they carry. Intravenous and intratracheal lipid nanoparticle (LNP) administration of sup-tRNA in mice restored the production of functional proteins with nonsense mutations. LNP–sup-tRNA formulations caused no discernible readthrough at endogenous native stop codons, as determined by ribosome profiling. At clinically important PTCs in the cystic fibrosis transmembrane conductance regulator gene (CFTR), the sup-tRNAs re-established expression and function in cell systems and patient-derived nasal epithelia and restored airway volume homeostasis. These results provide a framework for the development of tRNA-based therapies with a high molecular safety profile and high efficacy in targeted PTC suppression.
A pan-influenza antibody inhibiting neuraminidase via receptor mimicry
Authors: Momont Corey , Dang Ha V. , Zatta Fabrizia , Hauser Kevin , Wang Caihong , di Iulio Julia , Minola Andrea , Czudnochowski Nadine , De Marco Anna , Branch Kaitlin , Donermeyer David , Vyas Siddhant , Chen Alex , Ferri Elena , Guarino Barbara , Powell Abigail E. , Spreafico Roberto , Yim Samantha S. , Balce Dale R. , Bartha Istvan , Meury Marcel , Croll Tristan I. , Belnap David M. , Schmid Michael A. , Schaiff William Timothy , Miller Jessica L. , Cameroni Elisabetta , Telenti Amalio , Virgin Herbert W. , Rosen Laura E. , Purcell Lisa A. , Lanzavecchia Antonio , Snell Gyorgy , Corti Davide , Pizzuto Matteo Samuele
Published: May 2023

Rapidly evolving influenza A viruses (IAVs) and influenza B viruses (IBVs) are major causes of recurrent lower respiratory tract infections. Current influenza vaccines elicit antibodies predominantly to the highly variable head region of haemagglutinin and their effectiveness is limited by viral drift1 and suboptimal immune responses2. Here we describe a neuraminidase-targeting monoclonal antibody, FNI9, that potently inhibits the enzymatic activity of all group 1 and group 2 IAVs, as well as Victoria/2/87-like, Yamagata/16/88-like and ancestral IBVs. FNI9 broadly neutralizes seasonal IAVs and IBVs, including the immune-evading H3N2 strains bearing an N-glycan at position 245, and shows synergistic activity when combined with anti-haemagglutinin stem-directed antibodies. Structural analysis reveals that D107 in the FNI9 heavy chain complementarity-determinant region 3 mimics the interaction of the sialic acid carboxyl group with the three highly conserved arginine residues (R118, R292 and R371) of the neuraminidase catalytic site. FNI9 demonstrates potent prophylactic activity against lethal IAV and IBV infections in mice. The unprecedented breadth and potency of the FNI9 monoclonal antibody supports its development for the prevention of influenza illness by seasonal and pandemic viruses.
Chimera: An atlas of regular vines on up to 8 nodes
Authors: Morales-Nápoles Oswaldo , Rajabi-Bahaabadi Mojtaba , Torres-Alves Gina Alexandra , ’t Hart Cornelis Marcel Pieter
Published: May 2023

Vine copulas have become the standard tool for modelling complex probabilistic dependence. It has been shown that the number of regular vines grows extremely quickly with the number of nodes. Chimera is the first attempt to map the vast space of regular vines. Software for operating with regular vines is available for R, matlab and Python. However, no dataset containing all regular vines is available. Our atlas of regular vines, Chimera, comprises all 24 4 × 4 matrices representing regular vines on 4 nodes, 480 5 × 5 matrices representing regular vines on 5 nodes, 23,040 6 × 6 matrices representing regular vines on 6 nodes, 2,580,480 7 × 7 matrices representing regular vines on 7 nodes and 660,602,880 8 × 8 matrices representing regular vines on 8 nodes. Regular vines in Chimera are classified according to their tree-equivalence class. We fit all regular vines to synthetic data to demonstrate the potential of Chimera. Chimera provides thus a tool for researchers to navigate this vast space in an orderly fashion.
Mitochondrial DNA and local ecological knowledge reveal two lineages of leatherback turtle on the beaches of Oaxaca, Mexico
Authors: Castillo-Morales Carlos Abraham , Sáenz-Arroyo Andrea , Castellanos-Morales Gabriela , Ruíz-Montoya Lorena
Published: May 2023

Despite multiple conservation efforts of the Mexican government, the leatherback turtle is at serious risk of extinction. In this study, we investigated the possible presence of a genetic bottleneck that could prevent the recovery of this species and compared these findings with those of the olive ridley turtle, which is in true recovery. Our results confirmed that a demographic change occurred in the past and the presence of two different leatherback turtle lineages that diverged approximately 13.5 million years ago. Local ecological knowledge (LEK) also described the presence of these two lineages and warned that one is at higher risk of extinction than the other. Genetic analysis confirmed 124 mutations between the two lineages, and much lower genetic diversity in one lineage than the other. Our study highlights and substantiates the power of mixing LEK, environmental history, and genetics to better understand conservation challenges of highly threatened species such as the leatherback turtle. Moreover, we report a new lineage of the leatherback turtle which may represent a distinct species. Future studies should focus on morphological, ecological, biogeographical, evolutionary and conservation perspectives for the analysis of the new lineage.
Face masks influence emotion judgments of facial expressions: a drift–diffusion model
Authors: Williams W. Craig , Haque Eisha , Mai Becky , Venkatraman Vinod
Published: May 2023

Face masks slow the spread of SARS-CoV-2, but it has been unknown how masks might reshape social interaction. One important possibility is that masks may influence how individuals communicate emotion through facial expressions. Here, we clarify to what extent—and how—masks influence facial emotion communication, through drift–diffusion modeling (DDM). Over two independent pre-registered studies, conducted three and 6 months into the COVID-19 pandemic, online participants judged expressions of 6 emotions (anger, disgust, fear, happiness, sadness, surprise) with the lower or upper face “masked” or unmasked. Participants in Study 1 (N = 228) correctly identified expressions above chance with lower face masks. However, they were less likely—and slower—to correctly identify these expressions relative to without masks, and they accumulated evidence for emotion more slowly—via decreased drift rate in DDM. This pattern replicated and intensified 3 months later in Study 2 (N = 264). These findings highlight how effectively individuals still communicate with masks, but also explain why they can experience difficulties communicating when masked. By revealing evidence accumulation as the underlying mechanism, this work suggests that time-sensitive situations may risk miscommunication with masks. This research could inform critical interventions to promote continued mask wearing as needed.
Integrated analysis of how gender and body weight affect the intestinal microbial diversity of Gymnocypris chilianensis
Authors: Zhao Zhongmeng , Zhao Han , Zhang Lu , Huang Zhipeng , Ke Hongyu , Liu Ya , Duan Yuanliang , Li Huadong , Wang Xiongyan , Li Qiang
Published: May 2023

Intestinal microorganisms that living in the mucosa and contents of the gastrointestinal tract of animals, have close links with their hosts over a long evolutionary history. The community structure of the fish intestinal microbiota is associated with food, living environment, and the growth stage. To screen for potential probiotics that can be used for regulating breeding behaviors, this study focused on the diversity of fish intestinal microorganisms. This study aimed to investigate the effects of sex and body weight on the intestinal microbial diversity ofGymnocypris chilianensisin the wild. The results showed that the significant high diversity and richness of intestinal microbiota were fould in heavier individuals, and males. The dominant bacterial phyla ofG. chilianensiswere Proteobacteria, Firmicutes, and Bacteroidetes. In addition, the abundance of Firmicutes varied significantly among different body weights. The genus profile revealed that small individuals were dominated byWeissella, while females were dominated byAeromonas, and both large individuals and males were dominated by other genera. Phylogenetic relationships and UPGMA clustering analysis showed significant differences among the groups. In general, the two main factors that have an effect on the intestinal microbiota diversity of wildG. chilianensisare sex and body weight.
Modelling environmental DNA transport in rivers reveals highly resolved spatio-temporal biodiversity patterns
Authors: Carraro Luca , Blackman Rosetta C. , Altermatt Florian
Published: May 2023

The ever-increasing threats to riverine ecosystems call for novel approaches for highly resolved biodiversity assessments across taxonomic groups and spatio-temporal scales. Recent advances in the joint use of environmental DNA (eDNA) data and eDNA transport models in rivers (e.g., eDITH) allow uncovering the full structure of riverine biodiversity, hence elucidating ecosystem processes and supporting conservation measures. We applied eDITH to a metabarcoding dataset covering three taxonomic groups (fish, invertebrates, bacteria) and three seasons for a catchment sampled for eDNA at 73 sites. We upscaled eDNA-based biodiversity predictions to approximately 1900 reaches, and assessed α- and β-diversity patterns across seasons and taxonomic groups over the whole network. Genus richness predicted by eDITH was generally higher than values from direct eDNA analysis. Both predicted α- and β-diversity varied depending on season and taxonomic group. Predicted fish α-diversity increased downstream in all seasons, while invertebrate and bacteria α-diversity either decreased downstream or were unrelated to network position. Spatial β-diversity mostly decreased downstream, especially for bacteria. The eDITH model yielded a more refined assessment of freshwater biodiversity as compared to raw eDNA data, both in terms of spatial coverage, diversity patterns and effect of covariates, thus providing a more complete picture of freshwater biodiversity.
Improving the efficiency of RMSProp optimizer by utilizing Nestrove in deep learning
Authors: Elshamy Reham , Abu-Elnasr Osama , Elhoseny Mohamed , Elmougy Samir
Published: May 2023

There are several methods that have been discovered to improve the performance of Deep Learning (DL). Many of these methods reached the best performance of their models by tuning several parameters such as Transfer Learning, Data augmentation, Dropout, and Batch Normalization, while other selects the best optimizer and the best architecture for their model. This paper is mainly concerned with the optimization algorithms in DL. It proposes a modified version of Root Mean Squared Propagation (RMSProp) algorithm, called NRMSProp, to improve the speed of convergence, and to find the minimum of the loss function quicker than the original RMSProp optimizer. Moreover, NRMSProp takes the original algorithm, RMSProp, a step further by using the advantages of Nesterov Accelerated Gradient (NAG). It also takes in consideration the direction of the gradient at the next step, with respect to the history of the previous gradients, and adapts the value of the learning rate. As a result, this modification helps NRMSProp to convergence quicker than the original RMSProp, without any increase in the complexity of the RMSProp. In this work, many experiments had been conducted to evaluate the performance of NRMSProp with performing several tests with deep Convolution Neural Networks (CNNs) using different datasets on RMSProp, Adam, and NRMSProp optimizers. The experimental results showed that NRMSProp has achieved effective performance, and accuracy up to 0.97 in most cases, in comparison to RMSProp and Adam optimizers, without any increase in the complexity of the algorithm and with fine amount of memory and time.
Feasibility of spinal cord imaging at 7 T using rosette trajectory with magnetization transfer preparation and compressed sensing
Authors: Mahmud Sultan Z. , Denney Thomas S. , Bashir Adil
Published: May 2023

MRI is a valuable diagnostic tool to investigate spinal cord (SC) pathology. SC MRI can benefit from the increased signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) at ultra-high fields such as 7 T. However, SC MRI acquisitions with routine Cartesian readouts are prone to image artifacts caused by physiological motion. MRI acquisition techniques with non-Cartesian readouts such as rosette can help reduce motion artifacts. The purpose of this study was to demonstrate the feasibility of high-resolution SC imaging using rosette trajectory with magnetization transfer preparation (MT-prep) and compressed sensing (CS) at 7 T. Five healthy volunteers participated in the study. Images acquired with rosette readouts demonstrated reduced motion artifacts compared to the standard Cartesian readouts. The combination of multi-echo rosette-readout images improved the CNR by approximately 50% between the gray matter (GM) and white matter (WM) compared to single-echo images. MT-prep images showed excellent contrast between the GM and WM with magnetization transfer ratio (MTR) and cerebrospinal fluid normalized MT signal (MTCSF) = 0.12 ± 0.017 and 0.74 ± 0.013, respectively, for the GM; and 0.18 ± 0.011 and 0.58 ± 0.009, respectively, for the WM. Under-sampled acquisition using rosette readout with CS reconstruction demonstrated up to 6 times faster scans with comparable image quality as the fully-sampled acquisition.
Proteomics and secreted lipidomics of mouse-derived bone marrow cells exposed to a lethal level of ionizing radiation
Authors: Tatara Yota , Monzen Satoru
Published: May 2023

High doses of ionizing radiation (IR) exposure can lead to the development of severe acute radiation syndrome with bone marrow failure. Defining risk factors that predict adverse events is a critical mission to guide patient selection for personalized treatment protocols. Since non-hematopoietic stem cells act as feeder cells in the niche and their secreted lipids may regulate hematopoietic stem cells, we focused on non-hematopoietic stem cells and aimed to discover biomarkers that can assess radiation exposure from their secreted lipids. Bone marrow stromal cells (BMSCs) and osteoblast differentiation-inducing cells (ODICs) isolated from mouse femurs were exposed to lethal doses of IR and the proteomic differences between BMSC and ODIC cell layers were compared. We observed an increased Nrf2-mediated oxidative stress response and IL6 expression in ODICs and decreased expression of mitochondrial proteins in BMSCs. To elucidate secreted factors, lipidomics of the cultures were profiled; the relevant lipids distinguishing IR-exposed and control groups of BMSC were acyl-acyl phosphatidylcholine (PC aa C34:1 and PC aa C34:4), lysophosphatidylcholine (lyso-PC a C18:0 and lyso PC a C17:0) and sphingomyelin (SM C20:2). These analyses suggest that certain lipids are candidate markers for the toxic effects of IR.
Necrosulfonamide exerts neuroprotective effect by inhibiting necroptosis, neuroinflammation, and α-synuclein oligomerization in a subacute MPTP mouse model of Parkinson’s disease
Authors: Leem Yea-Hyun , Kim Do-Yeon , Park Jung-Eun , Kim Hee-Sun
Published: May 2023

Parkinson’s disease (PD) is an incurable movement disorder characterized by dopaminergic cell loss, neuroinflammation, and α-synuclein pathology. Herein, we investigated the therapeutic effects of necrosulfonamide (NSA), a specific inhibitor of mixed lineage kinase domain-like protein (MLKL), in a subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. MLKL is an executor of necroptosis, a programmed cell death pathway that causes inflammation. Repeated administration of NSA resulted in the recovery of impaired motor performance and dopaminergic degeneration. Furthermore, NSA inhibited the phosphorylation, ubiquitylation, and oligomerization of MLKL, all of which are associated with MLKL cell death-inducing activity in dopaminergic cells in the substantia nigra (SN). NSA also inhibited microglial activation and reactive astrogliosis as well as the MPTP-induced expression of proinflammatory molecules such as tumor necrosis factor-α, interleukin-1β, inducible nitric oxide synthase, and cystatin F. Furthermore, NSA inhibited α-synuclein oligomerization and phosphorylation in the SN of MPTP-treated mice by inhibiting the activity of glycogen synthase kinase 3β and matrix metalloproteinase-3. In conclusion, NSA has anti-necroptotic, anti-inflammatory, and anti-synucleinopathic effects on PD pathology. Therefore, NSA is a potential therapeutic candidate for PD.
GPX4 overexpressed non-small cell lung cancer cells are sensitive to RSL3-induced ferroptosis
Authors: Kim Joo-Won , Min Dong Wha , Kim Dasom , Kim Joohee , Kim Min Jung , Lim Hyangsoon , Lee Ji-Yun
Published: May 2023

Ferroptosis can be induced by inhibiting antioxidant enzymes GPX4 or system Xc−, increased intracellular iron concentrations, and lipid peroxidation. Recently, it has been suggested that ferroptosis can be an effective way to induce cancer cell death, although the specific relevance and mechanism of ferroptosis have not been fully elucidated. Here, we investigated the anticancer effects of ferroptosis inducers erastin and RSL3 on non-small cell lung cancer (NSCLC) cells. RSL3 induced cell death more effectively in NSCLC cells than erastin, with limited cytotoxicity in BEAS-2B normal bronchial epithelial cells. The sensitivity of NSCLC cells to RSL3 induced death was dependent on GPX4 expression levels; the effect of RSL3 was reversed by ferrostatin-1 (a ferroptosis inhibitor) but not by Z-VAD-FMK, chloroquine, bafilomycin A1, or necrostatin-1. RSL3 induced ferroptosis by promoting lipid peroxidation, elevating intracellular LIP concentration and ROS level, and blocking GSH-to-GSSH conversion through the inhibition of GPX4 and induction of Nrf2/HO1. Furthermore, RSL3 induced autophagosomes but disrupted the formation of autolysosomes with lysosomal membrane destabilization. GPX4 knockdown had a similar effect on ferroptosis phenotypes as RSL3. Taken together, RSL3-induced ferroptosis depends on the regulation of GPX4-Nrf2/HO1 in NSCLC cells. These results may be useful in predicting the ferroptosis response in NSCLC as well as drug resistant cancer cells.
Inferring pseudogene–MiRNA associations based on an ensemble learning framework with similarity kernel fusion
Authors: Fan Chunyan , Ding Mingchao
Published: May 2023

Accumulating evidence shows that pseudogenes can function as microRNAs (miRNAs) sponges and regulate gene expression. Mining potential interactions between pseudogenes and miRNAs will facilitate the clinical diagnosis and treatment of complex diseases. However, identifying their interactions through biological experiments is time-consuming and labor intensive. In this study, an ensemble learning framework with similarity kernel fusion is proposed to predict pseudogene–miRNA associations, named ELPMA. First, four pseudogene similarity profiles and five miRNA similarity profiles are measured based on the biological and topology properties. Subsequently, similarity kernel fusion method is used to integrate the similarity profiles. Then, the feature representation for pseudogenes and miRNAs is obtained by combining the pseudogene–pseudogene similarities, miRNA–miRNA similarities. Lastly, individual learners are performed on each training subset, and the soft voting is used to yield final decision based on the prediction results of individual learners. The k-fold cross validation is implemented to evaluate the prediction performance of ELPMA method. Besides, case studies are conducted on three investigated pseudogenes to validate the predict performance of ELPMA method for predicting pseudogene–miRNA interactions. Therefore, all experiment results show that ELPMA model is a feasible and effective tool to predict interactions between pseudogenes and miRNAs.
Selenoprotein P concentrations and risk of progression from mild cognitive impairment to dementia
Authors: Vinceti Marco , Urbano Teresa , Chiari Annalisa , Filippini Tommaso , Wise Lauren A. , Tondelli Manuela , Michalke Bernhard , Shimizu Misaki , Saito Yoshiro
Published: May 2023

There is a growing literature investigating the effects of selenium on the central nervous system and cognitive function. However, little is known about the role of selenoprotein P, the main selenium transporter, which can also have adverse biological effects. We conducted a prospective cohort study of individuals aged 42–81 years who received a clinical diagnosis of mild cognitive impairment. Using sandwich ELISA methods, we measured full-length selenoprotein P concentrations in serum and cerebrospinal fluid to assess the relation with dementia incidence during a median follow-up of 47.3 months. We used Cox proportional hazards regression and restricted cubic splines to model such relation. Of the 54 participants, 35 developed dementia during follow-up (including 26 cases of Alzheimer’s dementia). Selenoprotein P concentrations in serum and cerebrospinal fluid were highly correlated, and in spline regression analyses they each showed a positive non-linear association with dementia risk, particularly after excluding dementia cases diagnosed within 24 months of follow-up. We also observed differences in association according to the dementia subtypes considered. Risk ratios of dementia peaked at 2–6 at the highest levels of selenoprotein P, when compared to its median level, also depending on matrix, analytical methodology and dementia subtype. Findings of this study, the first to assess selenoprotein P levels in the central nervous system in vivo and the first to use a prospective study design to evaluate associations with dementia, suggest that higher circulating concentrations of selenoprotein P, both in serum and cerebrospinal fluid, predict progression of MCI to dementia. However, further confirmation of these findings is required, given the limited statistical precision of the associations and the potential for residual confounding.
High-throughput proteomics profiling-derived signature associated with chemotherapy response and survival for stage II/III colorectal cancer
Authors: Ye Shu-Biao , Cheng Yi-Kan , Li Pei-Si , Zhang Lin , Zhang Lian-Hai , Huang Yan , Chen Ping , Wang Yi , Wang Chao , Peng Jian-Hong , Shi Li-Shuo , Ling Li , Wu Xiao-Jian , Qin Jun , Yang Zi-Huan , Lan Ping
Published: May 2023

Adjuvant chemotherapy (ACT) is usually used to reduce the risk of disease relapse and improve survival for stage II/III colorectal cancer (CRC). However, only a subset of patients could benefit from ACT. Thus, there is an urgent need to identify improved biomarkers to predict survival and stratify patients to refine the selection of ACT. We used high-throughput proteomics to analyze tumor and adjacent normal tissues of stage II/III CRC patients with /without relapse to identify potential markers for predicting prognosis and benefit from ACT. The machine learning approach was applied to identify relapse-specific markers. Then the artificial intelligence (AI)-assisted multiplex IHC was performed to validate the prognostic value of the relapse-specific markers and construct a proteomic-derived classifier for stage II/III CRC using 3 markers, including FHL3, GGA1, TGFBI. The proteomics profiling-derived signature for stage II/III CRC (PS) not only shows good accuracy to classify patients into high and low risk of relapse and mortality in all three cohorts, but also works independently of clinicopathologic features. ACT was associated with improved disease-free survival (DFS) and overall survival (OS) in stage II (pN0) patients with high PS and pN2 patients with high PS. This study demonstrated the clinical significance of proteomic features, which serve as a valuable source for potential biomarkers. The PS classifier provides prognostic value for identifying patients at high risk of relapse and mortality and optimizes individualized treatment strategy by detecting patients who may benefit from ACT for survival.
HRD effects on first-line adjuvant chemotherapy and PARPi maintenance therapy in Chinese ovarian cancer patients
Authors: Li Lei , Gu Yu , Zhang Mengpei , Shi Xiaohua , Li Zhe , Xu Xinyun , Sun Tianqi , Dong Yu , Xue Chao , Zhu Xiaoru , Lv Ran , Jiao Kai , Ji Xuwo , Wang Li-juan , Zhang Yang , Liang Zhiyong , Jin Ying , Yin Rutie , Wu Ming , Liang Han
Published: May 2023

Homologous recombination deficiency (HRD) testing has been approved by FDA for selecting epithelial ovarian cancer (EOC) patients who may benefit from the first-line poly (ADP-ribose) polymerase inhibitor (PARPi) maintenance therapy. However, the effects of HRD on the clinical outcomes of first-line chemotherapy and first-line PARPi maintenance therapy have not been rigorously evaluated in Chinese EOC patients. Here, we developed an HRD assay and applied it to two large retrospectively collected Chinese EOC patient cohorts. In the first-line adjuvant chemotherapy cohort (FACT, N = 380), HRD status significantly improved PFS (median, 15.6 months vs. 9.4 months; HR, 0.688; 95% CI, 0.526–0.899; P = 0.003) and OS (median, 89.5 months vs. 60.9 months; HR, 0.636; 95% CI, 0.423–0.955; P = 0.008). In the first-line PARPi maintenance therapy cohort (FPMT, N = 83), HRD status significantly improved PFS (median, NA vs. 12 months; HR, 0.438; 95% CI, 0.201–0.957; P = 0.033) and OS (median, NA vs. NA months; HR, 0.12; 95% CI, 0.029–0.505; P = 0.001). Our results demonstrate that HRD status is a significant predictor for PFS and OS in both first-line chemotherapy and first-line PARPi maintenance therapy, providing strong real-world evidence for conducting genetic testing and improving clinical recommendations for Chinese EOC patients.
Label-free nanoscale mapping of intracellular organelle chemistry
Authors: Greaves George E. , Kiryushko Darya , Auner Holger W. , Porter Alexandra E. , Phillips Chris C.
Published: May 2023

The ability to image cell chemistry at the nanoscale is key for understanding cell biology, but many optical microscopies are restricted by the ~(200–250)nm diffraction limit. Electron microscopy and super-resolution fluorescence techniques beat this limit, but rely on staining and specialised labelling to generate image contrast. It is challenging, therefore, to obtain information about the functional chemistry of intracellular components. Here we demonstrate a technique for intracellular label-free chemical mapping with nanoscale (~30 nm) resolution. We use a probe-based optical microscope illuminated with a mid-infrared laser whose wavelengths excite vibrational modes of functional groups occurring within biological molecules. As a demonstration, we chemically map intracellular structures in human multiple myeloma cells and compare the morphologies with electron micrographs of the same cell line. We also demonstrate label-free mapping at wavelengths chosen to target the chemical signatures of proteins and nucleic acids, in a way that can be used to identify biochemical markers in the study of disease and pharmacology.
Rat hippocampal CA1 region represents learning-related action and reward events with shorter latency than the lateral entorhinal cortex
Authors: Soma Shogo , Ohara Shinya , Nonomura Satoshi , Suematsu Naofumi , Yoshida Junichi , Pastalkova Eva , Sakai Yutaka , Tsutsui Ken-Ichiro , Isomura Yoshikazu
Published: May 2023

The hippocampus and entorhinal cortex are deeply involved in learning and memory. However, little is known how ongoing events are processed in the hippocampal-entorhinal circuit. By recording from head-fixed rats during action-reward learning, here we show that the action and reward events are represented differently in the hippocampal CA1 region and lateral entorhinal cortex (LEC). Although diverse task-related activities developed after learning in both CA1 and LEC, phasic activities related to action and reward events differed in the timing of behavioral event representation. CA1 represented action and reward events almost instantaneously, whereas the superficial and deep layers of the LEC showed a delayed representation of the same events. Interestingly, we also found that ramping activity towards spontaneous action was correlated with waiting time in both regions and exceeded that in the motor cortex. Such functional activities observed in the entorhinal-hippocampal circuits may play a crucial role for animals in utilizing ongoing information to dynamically optimize their behaviors.
Impact of the metal core on the electrochemiluminescence of a pair of atomically precise Au20 nanocluster isomers
Authors: Chen Shuang , Liu Ying , Kuang Kaiyang , Yin Bing , Wang Xiaojian , Jiang Lirong , Wang Pu , Pei Yong , Zhu Manzhou
Published: May 2023

Although the electrochemiluminescence (ECL) of metal nanoclusters has been reported, revealing the correlation between structure and ECL at an atomic level is highly challenging. Here, we reported the impact of the metal core of Au20(SAdm)12(CHT)4 (Au20-AC for short; SAdm = 1-adamantanethiolate; CHT= cyclohexanethiol) and its isomer Au20(TBBT)16 (TBBT = 4-tert-butylthiophenol) on their solution-state and solid-state electrochemiluminescence. In self-annihilation ECL experiments, Au20-AC showed a strong cathodic ECL but a weak anodic ECL, while the ECL signal of Au20(TBBT)16 was weak and barely detectable. Density functional theory (DFT) calculations showed that the Au7 kernel of [Au20-AC]- is metastable, weakening its anodic ECL. Au20-AC in solution-state displayed an intense co-reactant ECL in the near-infrared region, which is 7 times higher than that of standard Ru(bpy)32+. The strongest solid-state ECL emissions of Au20-AC and Au20(TBBT)16 were at 860 and 770 nm, respectively — 15 nm red-shifted for Au20-AC and 20 nm blue-shifted for Au20(TBBT)16, compared to their corresponding solid-state photoluminescence (PL) emissions. This work shows that ECL is significantly affected by the subtle differences of the metal core, and offers a potential basis for sensing and immunoassay platforms based on atomically precise emissive metal nanoclusters.
Regioselective access to polycyclic N-heterocycles via homogeneous copper-catalyzed cascade cyclization of allenynes
Authors: Wei Kua-Fei , Liu Qing , Ma Guang , Jiang Xiao-Lei , Zhu Xiu-Hong , Ru Guang-Xin , Shen Wen-Bo
Published: May 2023

Polycyclic N-heterocycles are important structural motifs commonly found in bioactive compounds, however, their selective construction via the cyclization of allenynes remains challenging yet highly desirable. Here we show a homogeneous copper-catalyzed hetero Diels−Alder (HDA) reaction of allenynes with cis-diazenes (PTAD, 4-phenyl-1,2,4-triazoline-3,5-dione), allowing the practical and efficient synthesis of a diverse array of valuable polycyclic N-heterocycles. A temperature-controlled and stereocontrolled chemoselectivity of the reaction was observed, leading to the chemodivergent synthesis of tetracyclic pyrrolidines, pentacyclic triazepanes and tricyclic pyrrolidines. Compared with related Au-catalyzed cyclization of allenynes, this copper catalysis achieves cyclization of allenynes terminating in C–N bond formation via the HDA reaction.
Biomass-derived functional materials as carriers for enzymes: towards sustainable and robust biocatalysts
Authors: Bisht Meena , Thayallath Sarath Kumar , Bharadwaj Pranav , Franklin Gregory , Mondal Dibyendu
Published: May 2023

This review details the potential of BDFMs as promising carriers for enzymes for the design of sustainable and robust biocatalysts with improved activity, stability, and reusability.
Vascularized human brain organoid on-chip
Authors: Tan Sin Yen , Feng Xiaohan , Cheng Lily Kwan Wai , Wu Angela Ruohao
Published: May 2023

We review the existingin vitrohuman brain models and elaborate on various strategies that enable the curation of a vascularized human brain organoid using microfluidic devices.
Molecular dynamic simulation reveals the molecular interactions of epidermal growth factor receptor with musk xylene are involved in the carcinogenicity
Authors: Fei Huaxing , Li Wen , Lu Nan , Liu Qinghuo , Zhang Youyu
Published: May 2023

MD simulation results revealed that MXcan bind to the ECD of EGFR in four binding sites. The affinity of MX toward ECD was sIII > sI > sII > sIV. sIII was coincidentally located at the binding area of EGA, which is natural ligand of EGFR.
30% efficient triple-cation perovskite solar cells under indoor illumination enabled by rare earth EuCl3 doping
Authors: Xu Jie , Reddy Sathy Harshavardhan , Castriotta Luigi Angelo , Podapangi Suresh Kumar , Luce Marco , Cricenti Antonio , Di Carlo Aldo , Brown Thomas M.
Published: May 2023

EuCl3 doping in triple-cation perovskites boosts efficiency of photovoltaic cells from 27% to 30% at 1000 lx under indoor lighting. Furthermore, t50 lifetimes (times at which efficiencies half) more than doubled under thermal stress tests at 85 °C.
Advances in deoxyribonucleic acid extraction techniques and point-of-care molecular diagnosis of foodborne pathogens
Authors: Sivakumar Rajamanickam , Lee Nae Yoon
Published: May 2023

A conventional molecular assay-based point-of-care (POC) diagnostic test involves three major stages: deoxyribonucleic acid (DNA) extraction, amplification, and amplicon detection.
Controlling the size of GO in GO/nAg nanocomposite coatings on orthodontic nickel–titanium alloy toward excellent anti-corrosion, antibacterial, and tribological properties
Authors: Dai Danni , Li Dan , Zhang Chao
Published: May 2023

GO/nAg coatings constructed via pulse electrodeposition showed excellent surface properties.
Silk fibroin-based piezoelectric nanofibrous scaffolds for rapid wound healing
Authors: Yue Xiaoyang , Wang Zengkai , Shi Hui , Wu Rongrong , Feng Yonghai , Yuan Liang , Hou Shuai , Song Xiaolu , Liu Lei
Published: May 2023

LN/CNTs/SF piezoelectric nanofibrous scaffolds with improved piezoelectricity, biocompatibility and mechanical strength were used for rapid wound healing.
Steering on-surface polymerization through coordination with a bidentate ligand
Authors: Jiang Hao , Lu Jiayi , Zheng Fengru , Zhu Zhiwen , Yan Yuyi , Sun Qiang
Published: May 2023

We achieved a double-chain structure through sequential metal–ligand coordination and C–C coupling on Au(111).
A general scheme for generating NMR supersequences combining high- and low-sensitivity experiments
Authors: Yong Jonathan R. J. , Kupče Ēriks , Claridge Tim D. W.
Published: May 2023

The vertical interleaving of NOAH supersequences combines modules with very differing sensitivities.
A tetranuclear magnesium hydride cluster with a four-coordinate hydride in near square-planar geometry
Authors: Seifert Fabian , Görls Helmar , Kupfer Stephan , Kretschmer Robert
Published: May 2023

A dimeric magnesium hydride cluster has been synthesized. In the solid state it features a hydride ion that is coordinated to four magnesium ions at the same time in an unusual nearly square-planar fashion.
Pillar[5]arene based water-soluble [3]pseudorotaxane with enhanced fluorescence emission for cell imaging and both type I and II photodynamic cancer therapy
Authors: Zhang Yue , Wang Yang , Chen Tingting , Han Ying , Yan Chaoguo , Wang Jin , Lu Bing , Ma Longtao , Ding Yue , Yao Yong
Published: May 2023

Water-soluble [3]pseudorotaxane based on pillar[5]arene with enhanced fluorescence emission has been constructed successfully, and can be further applied in cell imaging and both type I & II photodynamic cancer therapy.
PIDA-mediated N–N bond formation to access pyrazolidine-3,5-diones: a novel process for uricosuric agents G-25671 and sulfinpyrazone
Authors: Halder Priyanka , Mhaske Santosh B.
Published: May 2023

An efficient PIDA-mediated intramolecular dehydrogenative N–N bond formation protocol has been established to access the pyrazolidine-3,5-dione core of sulfinpyrazone class of drugs by avoiding carcinogenic and expensive diphenylhydrazines.
Enzyme-immobilized spherical covalent organic frameworks as nanoreactors for heterogeneous biocatalysis
Authors: Yuan Rongrong , He Yujie , Tang Bo , He Hongming
Published: May 2023

Uniform spherical COFs were prepared to immobilize horseradish peroxidase with high loading capacity. The HRP@COF exhibited good reusability and enhanced tolerance to extreme circumstances.
Identification of linear scaling relationships in polysulfide conversion on α-In2Se3-supported single-atom catalysts
Authors: Wang Hui , Zou Lin , Li Min , Zhang Long
Published: May 2023

Engineering of 2D α-In2Se3via TM atom adsorption is capable of suppressing the shuttle effect and accelerating the kinetics of polysulfide conversion. Linear scaling relationships in polysulfide conversion on single-atom catalysts (SACs) are found.
A cage-specific hydrate equilibrium model for robust predictions of industrially-relevant mixtures
Authors: Zhu David J. , Norris Bruce W. E. , Aman Zachary M. , May Eric F.
Published: May 2023

Specific descriptions of guest–water interactions on the basis of the hydrate cage-type enables a 40% reduction in the number of parameters while maintaining hydrate equilibrium predictions.
Extending the optical temperature sensing range of Cr3+ by synchronously tuning 2E and 4T2 emission
Authors: Ou Jiaqi , Fang Shuangqiang , Zhu Qiangqiang , Zhai Yue , Zhang Hong , Wang Le
Published: May 2023

Al3+ induced synchronously tuning 2E and 4T2 emission greatly broaden the temperature sensing range of Cr3+.
Harnessing abiotic organic chemistry in living systems for biomedical applications
Authors: Wu Jiayingzi , Lin Jing , Huang Peng
Published: May 2023

Abiotic organic chemistry reactions typically occur outside of biological context. This review describes the mechanisms and examples for harnessing abiotic organic chemistry in living systems and highlights the relevant biomedical applications.
Theoretical assessments of Pd–PdO phase transformation and its impacts on H2O2 synthesis and decomposition pathways
Authors: Vyas Manasi , Fajardo-Rojas Fernando , Gómez-Gualdrón Diego A. , Kwon Stephanie
Published: May 2023

This work highlights how Pd–O arrangements and particle sizes impact primary H2O2 selectivities and yields in its direct synthesis.
Degradation of metribuzin in the UV/chlorine process: kinetic model, degradation by-products and transformation pathways
Authors: Hu Chen-Yan , Huang Dan-Dan , Lin Yi-Li , Wang Qiang-Bing , Xu Ling , Dong Zi-Yi , Wu Yi-Hui , Ji Sheng-Jie
Published: May 2023

Metribuzin degradation in UV/chlorine process followed pseudo-first-order kinetics.
Unified quantum theory of electrochemical kinetics by coupled ion–electron transfer
Authors: Bazant Martin Z.
Published: May 2023

A general theory of coupled ion–electron transfer (CIET) is presented, which unifies Marcus kinetics of electron transfer (ET) with Butler–Volmer kinetics of ion transfer (IT).
Maternal vitamin D deficiency and brain functions: a never-ending story
Authors: Saidi Lidia , Hammou Habib , Sicard Flavie , Landrier Jean-François , Mounien Lourdes
Published: May 2023

Maternal vitamin D deficiency affects brain development during foetal life and causes alterations that may persist into adulthood.