bluuebunny/crossref_metadata_2025 huggingface dataset:
Hexokinase HK3-mediated O-GlcNAcylation of EP300: a key regulator of PD-L1 expression and immune evasion in ccRCC
Authors: Zhang Wei , Zhao Enyang , Li Zhuolun , Liu Weiyang , Wang Jinpeng , Hou Wenbin , Zhang Nan , Yu Yang , Li Xuedong , You Bosen
Published: August 2024

Clear cell renal cell carcinoma (ccRCC) demonstrates enhanced glycolysis, critically contributing to tumor development. Programmed death-ligand 1 (PD-L1) aids tumor cells in evading T-cell-mediated immune surveillance. Yet, the specific mechanism by which glycolysis influences PD-L1 expression in ccRCC is not fully understood. Our research identified that the glycolysis-related gene (GRG) HK3 has a unique correlation with PD-L1 expression. HK3 has been identified as a key regulator of O-GlcNAcylation in ccRCC. O-GlcNAcylation exists on the serine 900 (Ser900) site of EP300 and can enhance its stability and oncogenic activity by preventing ubiquitination. Stably expressed EP300 works together with TFAP2A as a co-transcription factor to promote PD-L1 transcription and as an acetyltransferase to stabilize PD-L1 protein. Furthermore, ccRCC exhibits interactive dynamics with tumor-associated macrophages (TAMs). The uridine 5′-diphospho-N-acetylglucosamine (UDP-GlcNAc), which serves as a critical substrate for the O-GlcNAcylation process, facilitates TAMs polarization. In ccRCC cells, HK3 expression is influenced by IL-10 secreted by M2 TAMs. Our study elucidates that HK3-mediated O-GlcNAcylation of EP300 is involved in tumor immune evasion. This finding suggests potential strategies to enhance the efficacy of immune checkpoint blockade therapy.
Advancements in melanoma immunotherapy: the emergence of Extracellular Vesicle Vaccines
Authors: He Guijuan , Li Yichuan , Zeng Yuyang , Zhang Yong , Jiang Qiong , Zhang Qi , Zhu Jinjin , Gong Jun
Published: August 2024

Malignant melanoma represents a particularly aggressive type of skin cancer, originating from the pathological transformation of melanocytes. While conventional interventions such as surgical resection, chemotherapy, and radiation therapy are available, their non-specificity and collateral damage to normal cells has shifted the focus towards immunotherapy as a notable approach. Extracellular vesicles (EVs) are naturally occurring transporters, and are capable of delivering tumor-specific antigens and directly engaging in the immune response. Multiple types of EVs have emerged as promising platforms for melanoma vaccination. The effectiveness of EV-based melanoma vaccines manifests their ability to potentiate the immune response, particularly by activating dendritic cells (DCs) and CD8+ T lymphocytes, through engineering a synergy of antigen presentation and targeted delivery. Here, this review mainly focuses on the construction strategies for EV vaccines from various sources, their effects, and immunological mechanisms in treating melanoma, as well as the shortcomings and future perspectives in this field. These findings will provide novel insights into the innovative exploitation of EV-based vaccines for melanoma immune therapy.
Autosomal dominant stromal corneal dystrophy associated with a SPARCL1 missense variant
Authors: Braddock Freddie L. , Gardner Jessica C. , Bhattacharyya Nihar , Sanchez-Pintado Beatriz , Costa Marcos , Zarouchlioti Christina , Szabo Anita , Lišková Petra , Cheetham Michael E. , Young Robert D. , Thaung Caroline , Davidson Alice E. , Tuft Stephen J. , Hardcastle Alison J.
Published: August 2024

Corneal dystrophies are phenotypically and genetically heterogeneous, often resulting in visual impairment caused by corneal opacification. We investigated the genetic cause of an autosomal dominant corneal stromal dystrophy in a pedigree with eight affected individuals in three generations. Affected individuals had diffuse central stromal opacity, with reduced visual acuity in older family members. Histopathology of affected cornea tissue removed during surgery revealed mild stromal textural alterations with alcianophilic deposits. Whole genome sequence data were generated for four affected individuals. No rare variants (MAF < 0.001) were identified in established corneal dystrophy genes. However, a novel heterozygous missense variant in exon 4 of SPARCL1, NM_004684: c.334G > A; p.(Glu112Lys), which is predicted to be damaging, segregated with disease. SPARC-like protein 1 (SPARCL1) is a secreted matricellular protein involved in cell migration, cell adhesion, tissue repair, and remodelling. Interestingly, SPARCL1 has been shown to regulate decorin. Heterozygous variants in DCN, encoding decorin, cause autosomal dominant congenital stromal corneal dystrophy, suggesting a common pathogenic pathway. Therefore, we performed immunohistochemistry to compare SPARCL1 and decorin localisation in corneal tissue from an affected family member and an unaffected control. Strikingly, the level of decorin was significantly decreased in the corneal stroma of the affected tissue, and SPARCL1 appeared to be retained in the epithelium. In summary, we describe a novel autosomal dominant corneal stromal dystrophy associated with a missense variant in SPARCL1, extending the phenotypic and genetic heterogeneity of inherited corneal disease.
A gut microbiota rheostat forecasts responsiveness to PD-L1 and VEGF blockade in mesothelioma
Authors: Zhang Min , Bzura Aleksandra , Baitei Essa Y. , Zhou Zisen , Spicer Jake B. , Poile Charlotte , Rogel Jan , Branson Amy , King Amy , Barber Shaun , Kamata Tamihiro , Dzialo Joanna , Harber James , Greystoke Alastair , Nusrat Nada , Faulkner Daniel , Sun Qianqian , Nolan Luke , Hahne Jens C. , Scotland Molly , Walter Harriet , Darlison Liz , Morgan Bruno , Bajaj Amrita , Brookes Cassandra , Hollox Edward J. , Lubawska Dominika , Jama Maymun , Griffiths Gareth , Nakas Apostolos , Kutywayo Kudzayi , Luo Jin-Li , Klampatsa Astero , Cooper Andrea , Halder Koirobi , Wells-Jordan Peter , Zhou Huiyu , Dudbridge Frank , Thomas Anne , Richards Catherine Jane , Pritchard Catrin , Yang Hongji , Barer Michael , Fennell Dean A.
Published: August 2024

Malignant mesothelioma is a rare tumour caused by asbestos exposure that originates mainly from the pleural lining or the peritoneum. Treatment options are limited, and the prognosis is dismal. Although immune checkpoint blockade (ICB) can improve survival outcomes, the determinants of responsiveness remain elusive. Here, we report the outcomes of a multi-centre phase II clinical trial (MiST4, NCT03654833) evaluating atezolizumab and bevacizumab (AtzBev) in patients with relapsed mesothelioma. We also use tumour tissue and gut microbiome sequencing, as well as tumour spatial immunophenotyping to identify factors associated with treatment response. MIST4 met its primary endpoint with 50% 12-week disease control, and the treatment was tolerable. Aneuploidy, notably uniparental disomy (UPD), homologous recombination deficiency (HRD), epithelial-mesenchymal transition and inflammation with CD68+ monocytes were identified as tumour-intrinsic resistance factors. The log-ratio of gut-resident microbial genera positively correlated with radiological response to AtzBev and CD8+ T cell infiltration, but was inversely correlated with UPD, HRD and tumour infiltration by CD68+ monocytes. In summary, a model is proposed in which both intrinsic and extrinsic determinants in mesothelioma cooperate to modify the tumour microenvironment and confer clinical sensitivity to AtzBev. Gut microbiota represent a potentially modifiable factor with potential to improve immunotherapy outcomes for individuals with this cancer of unmet need.
Mechanism and regulation of cargo entry into the Commander endosomal recycling pathway
Authors: Butkovič Rebeka , Walker Alexander P. , Healy Michael D. , McNally Kerrie E. , Liu Meihan , Veenendaal Tineke , Kato Kohji , Liv Nalan , Klumperman Judith , Collins Brett M. , Cullen Peter J.
Published: August 2024

Commander is a multiprotein complex that orchestrates endosomal recycling of integral cargo proteins and is essential for normal development. While the structure of this complex has recently been described, how cargo proteins are selected for Commander-mediated recycling remains unclear. Here we identify the mechanism through which the unstructured carboxy-terminal tail of the cargo adaptor sorting nexin-17 (SNX17) directly binds to the Retriever sub-complex of Commander. SNX17 adopts an autoinhibited conformation where its carboxy-terminal tail occupies the cargo binding groove. Competitive cargo binding overcomes this autoinhibition, promoting SNX17 endosomal residency and the release of the tail for Retriever association. Furthermore, our study establishes the central importance of SNX17-Retriever association in the handover of integrin and lipoprotein receptor cargoes into pre-existing endosomal retrieval sub-domains. In describing the principal mechanism of cargo entry into the Commander recycling pathway we provide key insight into the function and regulation of this evolutionary conserved sorting pathway.
Rapid heating rates define the volatile emission and regolith composition of (3200) Phaethon
Authors: Suttle Martin D. , Olbrich Lorenz. F. , Bays Charlotte. L. , Riches Liza
Published: August 2024

Asteroid (3200) Phaethon experiences extreme solar radiant heating ( ~ 750 °C) during perihelion (0.14 au), leading to comet-like activity. The regolith composition and mechanism of volatile emission are unknown but key to understanding JAXA’s DESTINY+ mission data (fly-by in 2029) and the fate of near-Sun asteroids more generally. By subjecting CM chondrite fragments to fast, open system, cyclic heating (2-20 °C/min), simulating conditions on Phaethon we demonstrate that rapid heating rates combine with the low permeability, resulting in reactions between volatile gases and decomposing minerals. The retention of S-bearing gas limits the thermal decomposition of Fe-sulphides, allowing these minerals to survive repeated heating cycles. Slow escape of S-bearing gases provides a mechanism for repeated gas release from a thermally processed surface and, therefore the comet-like activity without requiring surface renewal to expose fresh material each perihelion cycle. We predict Phaethon regolith is composed of olivine, Fe-sulphides, Ca-sulphates and hematite.
Detecting single gravitons with quantum sensing
Authors: Tobar Germain , Manikandan Sreenath K. , Beitel Thomas , Pikovski Igor
Published: August 2024

The quantization of gravity is widely believed to result in gravitons – particles of discrete energy that form gravitational waves. But their detection has so far been considered impossible. Here we show that signatures of single graviton exchange can be observed in laboratory experiments. We show that stimulated and spontaneous single-graviton processes can become relevant for massive quantum acoustic resonators and that stimulated absorption can be resolved through continuous sensing of quantum jumps. We analyze the feasibility of observing the exchange of single energy quanta between matter and gravitational waves. Our results show that single graviton signatures are within reach of experiments. In analogy to the discovery of the photo-electric effect for photons, such signatures can provide the first experimental clue of the quantization of gravity.
Structural insights into Frizzled3 through nanobody modulators
Authors: Hillier James , Zhao Yuguang , Carrique Loic , Malinauskas Tomas , Ruza Reinis R. , Chang Tao-Hsin , Yi Gangshun , Duyvesteyn Helen M. E. , Yu Jing , Lu Weixian , Pardon Els , Steyaert Jan , Zhu Yanan , Ni Tao , Jones E. Yvonne
Published: August 2024

The Wnt receptor Frizzled3 (FZD3) is important for brain axonal development and cancer progression. We report structures of FZD3 in complex with extracellular and intracellular binding nanobodies (Nb). The crystal structure of Nb8 in complex with the FZD3 cysteine-rich domain (CRD) reveals that the nanobody binds at the base of the lipid-binding groove and can compete with Wnt5a. Nb8 fused with the Dickkopf-1 C-terminal domain behaves as a FZD3-specific Wnt surrogate, activating β-catenin signalling. The cryo-EM structure of FZD3 in complex with Nb9 reveals partially resolved density for the CRD, which exhibits positional flexibility, and a transmembrane conformation that resembles active GPCRs. Nb9 binds to the cytoplasmic region of FZD3 at the putative Dishevelled (DVL) or G protein-binding site, competes with DVL binding, and inhibits GαS coupling. In combination, our FZD3 structures with nanobody modulators map extracellular and intracellular interaction surfaces of functional, and potentially therapeutic, relevance.
Rapid intra-host diversification and evolution of SARS-CoV-2 in advanced HIV infection
Authors: Ko Sung Hee , Radecki Pierce , Belinky Frida , Bhiman Jinal N. , Meiring Susan , Kleynhans Jackie , Amoako Daniel , Guerra Canedo Vanessa , Lucas Margaret , Kekana Dikeledi , Martinson Neil , Lebina Limakatso , Everatt Josie , Tempia Stefano , Bylund Tatsiana , Rawi Reda , Kwong Peter D. , Wolter Nicole , von Gottberg Anne , Cohen Cheryl , Boritz Eli A.
Published: August 2024

Previous studies have linked the evolution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic variants to persistent infections in people with immunocompromising conditions, but the processes responsible for these observations are incompletely understood. Here we use high-throughput, single-genome amplification and sequencing (HT-SGS) to sequence SARS-CoV-2 spike genes from people with HIV (PWH, n = 22) and people without HIV (PWOH, n = 25). In PWOH and PWH with CD4 T cell counts (i.e., CD4 counts) ≥ 200 cells/μL, we find that most SARS-CoV-2 genomes sampled in each person share one spike sequence. By contrast, in people with advanced HIV infection (i.e., CD4 counts < 200 cells/μL), HT-SGS reveals a median of 46 distinct linked groupings of spike mutations per person. Elevated intra-host spike diversity in people with advanced HIV infection is detected immediately after COVID-19 symptom onset, and early intra-host spike diversity predicts SARS-CoV-2 shedding duration among PWH. Analysis of longitudinal timepoints reveals rapid fluctuations in spike sequence populations, replacement of founder sequences by groups of new haplotypes, and positive selection at functionally important residues. These findings demonstrate remarkable intra-host genetic diversity of SARS-CoV-2 in advanced HIV infection and suggest that adaptive intra-host SARS-CoV-2 evolution in this setting may contribute to the emergence of new variants of concern.
Predictions enable top-down pattern separation in the macaque face-processing hierarchy
Authors: Nigam Tarana , Schwiedrzik Caspar M.
Published: August 2024

Distinguishing faces requires well distinguishable neural activity patterns. Contextual information may separate neural representations, leading to enhanced identity recognition. Here, we use functional magnetic resonance imaging to investigate how predictions derived from contextual information affect the separability of neural activity patterns in the macaque face-processing system, a 3-level processing hierarchy in ventral visual cortex. We find that in the presence of predictions, early stages of this hierarchy exhibit well separable and high-dimensional neural geometries resembling those at the top of the hierarchy. This is accompanied by a systematic shift of tuning properties from higher to lower areas, endowing lower areas with higher-order, invariant representations instead of their feedforward tuning properties. Thus, top-down signals dynamically transform neural representations of faces into separable and high-dimensional neural geometries. Our results provide evidence how predictive context transforms flexible representational spaces to optimally use the computational resources provided by cortical processing hierarchies for better and faster distinction of facial identities.
Cooperative insulation of regulatory domains by CTCF-dependent physical insulation and promoter competition
Authors: Ealo Thais , Sanchez-Gaya Victor , Respuela Patricia , Muñoz-San Martín María , Martin-Batista Elva , Haro Endika , Rada-Iglesias Alvaro
Published: August 2024

The specificity of gene expression during development requires the insulation of regulatory domains to avoid inappropriate enhancer-gene interactions. In vertebrates, this insulator function is mostly attributed to clusters of CTCF sites located at topologically associating domain (TAD) boundaries. However, TAD boundaries allow some physical crosstalk across regulatory domains, which is at odds with the specific and precise expression of developmental genes. Here we show that developmental genes and nearby clusters of CTCF sites cooperatively foster the robust insulation of regulatory domains. By genetically dissecting a couple of representative loci in mouse embryonic stem cells, we show that CTCF sites prevent undesirable enhancer-gene contacts (i.e. physical insulation), while developmental genes preferentially contribute to regulatory insulation through non-structural mechanisms involving promoter competition rather than enhancer blocking. Overall, our work provides important insights into the insulation of regulatory domains, which in turn might help interpreting the pathological consequences of certain structural variants.
The translocation assembly module (TAM) catalyzes the assembly of bacterial outer membrane proteins in vitro
Authors: Wang Xu , Nyenhuis Sarah B. , Bernstein Harris D.
Published: August 2024

The translocation and assembly module (TAM) has been proposed to play a crucial role in the assembly of a small subset of outer membrane proteins (OMPs) in Proteobacteria based on experiments conducted in vivo using tamA and tamB mutant strains and in vitro using biophysical methods. TAM consists of an OMP (TamA) and a periplasmic protein that is anchored to the inner membrane by a single α helix (TamB). Here we examine the function of the purified E. coli complex in vitro after reconstituting it into proteoliposomes. We find that TAM catalyzes the assembly of four model OMPs nearly as well as the β-barrel assembly machine (BAM), a universal heterooligomer that contains a TamA homolog (BamA) and that catalyzes the assembly of almost all E. coli OMPs. Consistent with previous results, both TamA and TamB are required for significant TAM activity. Our study provides direct evidence that TAM can function as an independent OMP insertase and describes a new method to gain insights into TAM function.
Translation in Bacillus subtilis is spatially and temporally coordinated during sporulation
Authors: Iwańska Olga , Latoch Przemysław , Kopik Natalia , Kovalenko Mariia , Lichocka Małgorzata , Serwa Remigiusz , Starosta Agata L.
Published: August 2024

The transcriptional control of sporulation in Bacillus subtilis is reasonably well understood, but its translational control is underexplored. Here, we use RNA-seq, ribosome profiling and fluorescence microscopy to study the translational dynamics of B. subtilis sporulation. We identify two events of translation silencing and describe spatiotemporal changes in subcellular localization of ribosomes during sporulation. We investigate the potential regulatory role of ribosomes during sporulation using a strain lacking zinc-independent paralogs of three zinc-dependent ribosomal proteins (L31, L33 and S14). The mutant strain exhibits delayed sporulation, reduced germination efficiency, dysregulated translation of metabolic and sporulation-related genes, and disruptions in translation silencing, particularly in late sporulation.
A phase 3 study (PATHWAY) of palbociclib plus tamoxifen in patients with HR-positive/HER2-negative advanced breast cancer
Authors: Noguchi Emi , Yamanaka Takashi , Mukai Hirofumi , Yamamoto Naohito , Chung Chi-Feng , Lu Yen-Shen , Chang Dwan-Ying , Sohn Joohyuk , Kim Gun Min , Lee Kyung-Hun , Lee Soo-Chin , Iwasa Tsutomu , Iwata Hiroji , Watanabe Kenichi , Jung Kyung Hae , Tanabe Yuko , Kang Seok Yun , Yasojima Hiroyuki , Aogi Kenjiro , Tokunaga Eriko , Sim Sung Hoon , Yap Yoon Sim , Matsumoto Koji , Tseng Ling-Ming , Umeyama Yoshiko , Sudo Kazuki , Kojima Yuki , Hata Tomomi , Kuchiba Aya , Shibata Taro , Nakamura Kenichi , Fujiwara Yasuhiro , Tamura Kenji , Yonemori Kan
Published: August 2024

Palbociclib combined with endocrine therapy is approved for treating patients with hormone-receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2−) advanced breast cancer; however, data on palbociclib combined with tamoxifen are limited. We investigated the efficacy and safety of palbociclib–tamoxifen in patients with HR+/HER2− advanced breast cancer. This double-blind phase 3 study included 184 women who were randomly assigned 1:1 to receive palbociclib–tamoxifen or placebo–tamoxifen. Pre/perimenopausal women also received goserelin. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS) and safety. Median PFS was 24.4 months (95% confidence interval [CI], 13.1–32.4) with palbociclib–tamoxifen and 11.1 months (95% CI, 7.4–14.6) with placebo–tamoxifen (hazard ratio [HR], 0.60; 95% CI, 0.43–0.85; P = 0.002). Palbociclib–tamoxifen improved PFS in patients who were treated with first-line or second-line endocrine therapy and pre-, peri-, and postmenopausal patients. Though OS data are still immature (median not reached in both groups), an overall risk reduction of 27% (HR, 0.73; 95% CI, 0.44–1.21) with palbociclib–tamoxifen was observed at the time of PFS analysis. The most common grade 3/4 adverse event with palbociclib–tamoxifen was neutropenia (89.0% [none were febrile] versus 1.1% with placebo–tamoxifen). There were no deaths owing to adverse events in either group. Among patients with HR+/HER2− advanced breast cancer, palbociclib–tamoxifen resulted in significantly longer PFS than tamoxifen alone. Early OS data showed a trend favoring palbociclib–tamoxifen. Trial registration: ClinicalTrials.gov number, NCT03423199. Study registration date: February 06, 2018.
Beating one bit of communication with and without quantum pseudo-telepathy
Authors: Márton István , Bene Erika , Diviánszky Péter , Vértesi Tamás
Published: August 2024

According to Bell’s theorem, certain entangled states cannot be simulated classically using local hidden variables (LHV). Suppose that we can augment LHV by some amount of classical communication. The question then arises as to how many bits are needed to simulate entangled states? There is very strong evidence that a single bit of communication is powerful enough to simulate projective measurements on any two-qubit entangled state. However, the problem of simulating measurements on higher-dimensional systems remains largely unexplored. In this study, we present Bell-like scenarios, even with three inputs per party, in which bipartite correlations resulting from measurements on higher-dimensional states cannot be simulated with a single bit of communication. We consider the case where the communication direction is fixed and the case where it is bidirectional. To this end, we introduce constructions based on parallel repetition of pseudo-telepathy games and an original algorithm based on branch-and-bound technique to compute the one-bit classical bound. Two copies of emblematic Bell expressions, such as the Magic square pseudo-telepathy game, prove to be particularly powerful, requiring a 16 × 16 state to beat the bidirectional one-bit classical bound, and look a promising candidate for implementation on an optical platform.
Bolometric detection of Josephson radiation
Authors: Karimi Bayan , Steffensen Gorm Ole , Higginbotham Andrew P. , Marcus Charles M. , Levy Yeyati Alfredo , Pekola Jukka P.
Published: August 2024

One of the most promising approaches towards large-scale quantum computation uses devices based on many Josephson junctions. Yet, even today, open questions regarding the single junction remain unsolved, such as the detailed understanding of the quantum phase transitions, the coupling of the Josephson junction to the environment or how to improve the coherence of a superconducting qubit. Here we design and build an engineered on-chip reservoir connected to a Josephson junction that acts as an efficient bolometer for detecting the Josephson radiation under non-equilibrium, that is, biased conditions. The bolometer converts the a.c. Josephson current at microwave frequencies up to about 100 GHz into a temperature rise measured by d.c. thermometry. A circuit model based on realistic parameter values captures both the current–voltage characteristics and the measured power quantitatively. The present experiment demonstrates an efficient, wide-band, thermal detection scheme of microwave photons and provides a sensitive detector of Josephson dynamics beyond the standard conductance measurements.
High-resolution greenspace dynamic data cube from Sentinel-2 satellites over 1028 global major cities
Authors: Wu Shengbiao , Song Yimeng , An Jiafu , Lin Chen , Chen Bin
Published: August 2024

Greenspace, offering multifaceted ecological and socioeconomic benefits to the nature system and human society, is integral to the 11th Sustainable Development Goal pertaining to cities and communities. Spatially and temporally explicit information on greenspace is a premise to gauge the balance between its supply and demand. However, existing efforts on urban greenspace mapping primarily focus on specific time points or baseline years without well considering seasonal fluctuations, which obscures our knowledge of greenspace’s spatiotemporal dynamics in urban settings. Here, we combined spectral unmixing approach, time-series phenology modeling, and Sentinel-2 satellite images with a 10-m resolution and nearly 5-day revisit cycle to generate a four-year (2019–2022) 10-m and 10-day resolution greenspace dynamic data cube over 1028 global major cities (with an urbanized area >100 km2). This data cube can effectively capture greenspace seasonal dynamics across greenspace types, cities, and climate zones. It also can reflect the spatiotemporal dynamics of the cooling effect of greenspace with Landsat land surface temperature data. The developed data cube provides informative data support to investigate the spatiotemporal interactions between greenspace and human society.
Quantum mechanical electronic and geometric parameters for DNA k-mers as features for machine learning
Authors: Masuda Kairi , Abdullah Adib A. , Pflughaupt Patrick , Sahakyan Aleksandr B.
Published: August 2024

We are witnessing a steep increase in model development initiatives in genomics that employ high-end machine learning methodologies. Of particular interest are models that predict certain genomic characteristics based solely on DNA sequence. These models, however, treat the DNA as a mere collection of four, A, T, G and C, letters, dismissing the past advancements in science that can enable the use of more intricate information from nucleic acid sequences. Here, we provide a comprehensive database of quantum mechanical (QM) and geometric features for all the permutations of 7-meric DNA in their representative B, A and Z conformations. The database is generated by employing the applicable high-cost and time-consuming QM methodologies. This can thus make it seamless to associate a wealth of novel molecular features to any DNA sequence, by scanning it with a matching k-meric window and pulling the pre-computed values from our database for further use in modelling. We demonstrate the usefulness of our deposited features through their exclusive use in developing a model for A->C mutation rates.
Effects of mulberry leaf enrichment with Lepidium sativum L. seed powder suspension on the economic parameters of Bombyx mori L
Authors: Alfazairy Ahlam A. , Elsakhawy Deena A. , El-Meniawi Fatma A. , Hashem Mohamed , Rawash Ibrahem A.
Published: August 2024

The phytochemicals of high nutritional and functional properties in Lepidium sativum L. (garden cress) seeds have nominated their seed powder (regardless of the concentration used) for enrichment of mulberry leaves in order to enhance Bombyx mori L. larval feeding, and consequently to gain ground in sericulture industry. As expected, B. mori larval feeding on L. sativum-enriched mulberry leaves showed not only a remarkable increase in mean values of certain economic parameters of B. mori, such as cocoon weight, cocoon shell weight, pupal weight, and egg yield, compared with the control group, but also showed a phenomenal increase in egg counts (on average, ca. 958–1256 eggs laid per female moth) and a significant increase in egg size (measured as egg surface area and egg volume). Male or female moth larval diet has significantly influenced the reproductive performance or fitness of both sexes of B. mori in terms of large-sized moths (measured as forewing, hind femur, and hind tibia lengths) and highly fecund moths (i.e., increased fecundity and spermatophore counts per female moth, and large-sized eggs). On the basis of B. mori female moth reproductive index, the female moths from L. sativum-fed larvae proved to have a lower reproductive index compared to their corresponding value for females of the control group, indicating more efficient utilization of larval resources for B. mori reproduction. Quantification of the three main physiological resources viz., protein, lipid and carbohydrate in the internal reproductive tract of B. mori female moths at death has nominated the female moth abdomens, or simply their bodies, as being a reasonable natural source of protein, lipid, and carbohydrate, to be involved in certain manufactures (e.g., pet feed formulations) instead of discarding them as a source of environmental pollution. Evidently, the L. sativum seed powder is of considerable interest because it remarkably improves the performance of such an economically important insect, B. mori. This is the first study for evaluating the efficacy of L. sativum seed powder in sericulture field to enhance B. mori productivity parameters.
Radiation synthesis of sodium alginate/gelatin based ultra-absorbent hydrogel for efficient water and nitrogen management in wheat under drought stress
Authors: El-diehy Mahmoud A. , Farghal Ibrahim I. , Amin Mohamed A. , Ghobashy Mohamed mohamady , Nowwar Abdelatti I. , Gayed H. M.
Published: August 2024

The main focus of this study was on using radiation to make an ultra-absorbent hydrogel (UAH) from sodium alginate (SA) and gelatin (GL) biopolymers. This UAH can effectively handle water and nitrogen in wheat farming during drought stress. The hydrogel was synthesized by gamma irradiation-induced SA/GL/polyacrylamide crosslinking at 10–40 kGy. Varying SA/GL ratios affected swelling and the gel fraction of SA/GL/PAm hydrogels. The (SA/GL 17/83) hydrogel exhibited a 40.03 g/g swelling degree, while increasing SA content resulted in higher swelling, peaking at 75.5 g/g for (SA/GL 83/17). This indicated a synergistic interaction between SA and GL. The gel fraction also increased from 76.8 to 90.3%, with a higher GL content reflecting increased crosslinking. After multiple hydrolysis cycles, the hydrogel achieved 1293 (g/g) swelling and 36 days of water retention. When applied to wheat (Triticuma estivum) under drought stress, it significantly improved shoot length (18%), root length (43%), shoot fresh weight (49%), and shoot dry weight (51%) under extreme drought. The significant increases in protein and carbohydrate content in both shoots (up to 32% and 19%, respectively) and grains (up to 21% and 24%, respectively), along with the reduction in proline content (up to 38%), demonstrate that ultra-absorbent hydrogel (UAH) effectively enhances nitrogen content, photosynthesis, and overall plant health in wheat under varying drought stress levels. This novel SA/GL-based UAH holds promise for addressing water scarcity and agricultural challenges, offering a sustainable solution for water and nitrogen management under drought stress.
Using a novel bio-based cationic flocculant for food industry wastewater treatment
Authors: Ahmed Ghada E. , Hassan Gamal K. , Gomaa Elshimaa H. , Aly Samar A. , Salem Sanaa Y. , Badr Entsar E. , Aboelghait Karim M. , fify Ahmed A.
Published: August 2024

Wastewater from the food industry is considered harmful to human health and aquatic life, as well as polluting water and soil. This research is centered around finding an affordable and easy physicochemical method for dealing with waste generated by the food industry. To accomplish this goal, a new bio-based flocculant called 4-benzyl-4-(2-oleamidoethylamino-2-oxoethyl) morpholin-4-ium chloride was created using sustainable sources, specifically crude olive pomace oil. Its chemical structure was confirmed using various spectroscopic techniques such as FTIR, 1H-NMR, mass spectra, and 13C-NMR. This new bio-based cationic flocculant was combined with alum to act as a coagulant in the waste treatment process. Also, a study was conducted to determine the optimal conditions for the coagulation-flocculation process parameters, namely, pH and alum dosage, on COD and removal efficiency. The results showed that the optimal conditions for flocculation were achieved at pH 5.8, with 680 mg/L alum and 10 mg/L of commercial flocculant dose compared to only 5 mg/L of a new bio-based cationic flocculant. A comparison was made between the new bio-cationic flocculant and a commercial CTAB one for treating wastewater in the food industry. The study found that the new bio-based cationic flocculant was more effective in reducing the chemical oxygen demand, achieving a reduction of 61.3% compared to 54.6% for using a commercial cationic flocculant. Furthermore, using a new bio-based cationic flocculant costs only 0.49 $/g, which is less than the present cationic flocculant, which costs 0.93 $/g. The adoption of this new flocculant provides a sustainable alternative to existing industrial wastewater treatment processes
Vincamine exerts hepato-protective activity during colon ligation puncture-induced sepsis by modulating oxidative stress, apoptosis, and TNFα/Nrf-2/Keap-1 signaling pathways
Authors: Alaaeldin Rania , Mohyeldin Reham H. , Sharata Ehab E. , Attya Mina Ezzat , Fathy Moustafa
Published: August 2024

Sepsis is a pathological and biochemical disorder induced by numerous infections, leading to critical illness and a high mortality rate worldwide. Vincamine is an indole alkaloid compound obtained from the leaves of Vinca minor. The present study aims to investigate the hepato-protective activity of vincamine during colon ligation puncture (CLP)-induced sepsis at the molecular level. Sepsis was induced using the CLP model. Liver function enzymes such as ALT and AST were analyzed. The hepatic antioxidant status (SOD and GSH), lipid peroxidation (MDA), the pro-inflammatory cytokines (TNFα, IL-6, and IL-1β), bax, bcl2, and cleaved caspase 3 proteins were estimated. Nrf-2 and Keap-1 protein expression was evaluated using western blotting. Histopathological investigation of liver tissues was also performed. CLP-induced sepsis led to liver injury through the elevation of ALT and AST liver enzymes. Oxidative stress was initiated during CLP via the suppression of hepatic GSH content and SOD activity and the elevation of MDA. The inflammatory condition was activated by the upregulation of TNFα, IL-6, IL-1β, and Keap-1 and the downregulation of Nrf-2 proteins. The apoptosis was initiated through the activation of bax and cleaved caspase 3 protein expression and inhibition of bcl2 protein expression. However, vincamine significantly improved the hepatic histological abnormalities and decreased liver enzymes (ALT and AST). It ameliorated oxidative stress, as evidenced by reducing the hepatic MDA content and increasing the SOD activity and GSH content. Moreover, vincamine reduced the hepatic content of TNFα, IL-6, IL-1β, and Keap-1 and increased Nrf-2 protein expression. Additionally, it upregulated bcl2 protein expression and downregulated bax and cleaved caspase 3 protein expression. Vincamine exhibited hepato-protective potential during CLP-induced sepsis via the cross-connection of antioxidant, anti-inflammatory, and anti-apoptotic activities by modulating TNFα/IL-6/IL-1β/Nrf-2/Keap-1 and regulating bax/bcl2/cleaved caspase 3 signaling pathways.
On flow fluctuations in ruptured and unruptured intracranial aneurysms: resolved numerical study
Authors: Huang Feng , Janiga Gábor , Berg Philipp , Hosseini Seyed Ali
Published: August 2024

Flow fluctuations have emerged as a promising hemodynamic metric for understanding of hemodynamics in intracranial aneurysms. Several investigations have reported flow instabilities using numerical tools. In this study, the occurrence of flow fluctuations is investigated using either Newtonian or non-Newtonian fluid models in five patient-specific intracranial aneurysms using high-resolution lattice Boltzmann simulation methods. Flow instabilities are quantified by computing power spectral density, proper orthogonal decomposition, and fluctuating kinetic energy of velocity fluctuations. Our simulations reveal substantial flow instabilities in two of the ruptured aneurysms, where the pulsatile inflow through the neck leads to hydrodynamic instability, particularly around the rupture position, throughout the entire cardiac cycle. In other monitoring points, the flow instability is primarily observed during the deceleration phase; typically, the fluctuations begin just after peak systole, gradually decay, and the flow returns to its original, laminar pulsatile state during diastole. Additionally, we assess the rheological impact on flow dynamics. The disparity between Newtonian and non-Newtonian outcomes remains minimal in unruptured aneurysms, with less than a 5% difference in key metrics. However, in ruptured cases, adopting a non-Newtonian model yields a substantial increase in the fluctuations within the aneurysm sac, with up to a 30% higher fluctuating kinetic energy compared to the Newtonian model. The study highlights the importance of using appropriate high-resolution simulations and non-Newtonian models to capture flow fluctuation characteristics that may be critical for assessing aneurysm rupture risk.
All-2D CVD-grown semiconductor field-effect transistors with van der Waals graphene contacts
Authors: Hoque Md. Anamul , George Antony , Ramachandra Vasudev , Najafidehaghani Emad , Gan Ziyang , Mitra Richa , Zhao Bing , Sahoo Satyaprakash , Abrahamsson Maria , Liang Qiuhua , Wiktor Julia , Turchanin Andrey , Kubatkin Sergey , Lara-Avila Samuel , Dash Saroj P.
Published: August 2024

Two-dimensional (2D) semiconductors and van der Waals (vdW) heterostructures with graphene have generated enormous interest for future electronic, optoelectronic, and energy-harvesting applications. The electronic transport properties and correlations of such hybrid devices strongly depend on the quality of the materials via chemical vapor deposition (CVD) process, their interfaces and contact properties. However, detailed electronic transport and correlation properties of the 2D semiconductor field-effect transistor (FET) with vdW graphene contacts for understanding mobility limiting factors and metal-insulator transition properties are not explored. Here, we investigate electronic transport in scalable all-2D CVD-grown molybdenum disulfide (MoS2) FET with graphene contacts. The Fermi level of graphene can be readily tuned by a gate voltage to enable a nearly perfect band alignment and, hence, a reduced and tunable Schottky barrier at the contact with good field-effect channel mobility. Detailed temperature-dependent transport measurements show dominant phonon/impurity scattering as a mobility limiting mechanisms and a gate-and bias-induced metal-insulator transition in different temperature ranges, which is explained in light of the variable-range hopping transport. These studies in such scalable all-2D semiconductor heterostructure FETs will be useful for future electronic and optoelectronic devices for a broad range of applications.
Tissue-resident memory T cells in epicardial adipose tissue comprise transcriptionally distinct subsets that are modulated in atrial fibrillation
Authors: Vyas Vishal , Sandhar Balraj , Keane Jack M. , Wood Elizabeth G. , Blythe Hazel , Jones Aled , Shahaj Eriomina , Fanti Silvia , Williams Jack , Metic Nasrine , Efremova Mirjana , Ng Han Leng , Nageswaran Gayathri , Byrne Suzanne , Feldhahn Niklas , Marelli-Berg Federica , Chain Benny , Tinker Andrew , Finlay Malcolm C. , Longhi M. Paula
Published: August 2024

Atrial fibrillation (AF) is the most common sustained arrhythmia and carries an increased risk of stroke and heart failure. Here we investigated how the immune infiltrate of human epicardial adipose tissue (EAT), which directly overlies the myocardium, contributes to AF. Flow cytometry analysis revealed an enrichment of tissue-resident memory T (TRM) cells in patients with AF. Cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) and single-cell T cell receptor (TCR) sequencing identified two transcriptionally distinct CD8+ TRM cells that are modulated in AF. Spatial transcriptomic analysis of EAT and atrial tissue identified the border region between the tissues to be a region of intense inflammatory and fibrotic activity, and the addition of TRM populations to atrial cardiomyocytes demonstrated their ability to differentially alter calcium flux as well as activate inflammatory and apoptotic signaling pathways. This study identified EAT as a reservoir of TRM cells that can directly modulate vulnerability to cardiac arrhythmia.
Human breast tissue engineering in health and disease
Authors: Buchholz Maj-Britt , Scheerman Demi I , Levato Riccardo , Wehrens Ellen J , Rios Anne C
Published: August 2024

The human mammary gland represents a highly organized and dynamic tissue, uniquely characterized by postnatal developmental cycles. During pregnancy and lactation, it undergoes extensive hormone-stimulated architectural remodeling, culminating in the formation of specialized structures for milk production to nourish offspring. Moreover, it carries significant health implications, due to the high prevalence of breast cancer. Therefore, gaining insight into the unique biology of the mammary gland can have implications for managing breast cancer and promoting the well-being of both women and infants. Tissue engineering techniques hold promise to narrow the translational gap between existing breast models and clinical outcomes. Here, we provide an overview of the current landscape of breast tissue engineering, outline key requirements, and the challenges to overcome for achieving more predictive human breast models. We propose methods to validate breast function and highlight preclinical applications for improved understanding and targeting of breast cancer. Beyond mammary gland physiology, representative human breast models can offer new insight into stem cell biology and developmental processes that could extend to other organs and clinical contexts.
A ligand-modulated photostable Mn(i)–carbonyl complex for preferential conversion of CO2 to CO in water
Authors: Das Chandan , Ghosh Suchismita , Biswas Rathindranath , Lahiri Goutam K. , Dutta Arnab
Published: August 2024

A strategically designed redox-active ligand ensures proper electronic balance in an Mn(i)–carbonyl template to induce photostability and water solubility.
Neutral and ionic N-methyl phenylazo-3,5-(di-2-pyridyl)pyrazole photoswitches: probes for reversible pH modulation by light
Authors: Singh Sapna , Velloth Archana , Rajani  , Goyal Manu , Kaur Navneet , Singh Sanjay , Venkataramani Sugumar
Published: August 2024

Design, synthesis, photoswitching and computational studies of N-methyl arylazo-3,5-(di-2-pyridyl)pyrazoles and their N-alkyl pyridinium derivatives as probes for pH modulation.
Precision synthesis of diblock copolymers via free radical photopolymerization
Authors: Li Jingfang , Deng Qilu , Xing Zhihao , Yu Jiaxin , Li Wenjie , Zhou Xianju , Zhu Xiaoqun , Nie Jun
Published: August 2024

Diblock copolymers of phenyl methacrylate and butyl methacrylate were synthesized using dual-wavelength photopolymerization with a bifunctional photoinitiator PAA-2959.
Time-resolved photoelectron diffraction imaging of methanol photodissociation involving molecular hydrogen ejection
Authors: Yoshikawa Kazuki , Kanno Manabu , Xue Hao , Kishimoto Naoki , Goto Soki , Ota Fukiko , Tamura Yoshiaki , Trinter Florian , Fehre Kilian , Kaiser Leon , Stindl Jonathan , Tsitsonis Dimitrios , Schöffler Markus , Dörner Reinhard , Boll Rebecca , Erk Benjamin , Mazza Tommaso , Mullins Terence , Rivas Daniel E. , Schmidt Philipp , Usenko Sergey , Meyer Michael , Wang Enliang , Rolles Daniel , Rudenko Artem , Kukk Edwin , Jahnke Till , Díaz-Tendero Sergio , Martín Fernando , Hatada Keisuke , Ueda Kiyoshi
Published: August 2024

We explore time- and momentum-resolved photoelectron diffraction imaging (TMR-PED) to visualize hydrogen dynamics during methanol dication dissociation. Our approach allows real-time tracking of hydrogen migration and molecular fragmentation.
Enhanced deep potential model for fast and accurate molecular dynamics: application to the hydrated electron
Authors: Gao Ruiqi , Li Yifan , Car Roberto
Published: August 2024

Enhancements to the Deep Potential network integrate message-passing, achieving high accuracy with significant speed advantages. Applied to solvated electron in bulk water, confirming the cavity model and determining structural properties.
Calcite–aragonite transformation in an eggshell: a crucial role of organics and assessment of the impact of milling conditions on its extent using Taguchi design
Authors: Kenges Kairat , Karafiludis Stephanos , Džunda Róbert , Tampubolon Imelda Octa , Satybaldiyev Bagdat , Emmerling Franziska , Baláž Matej
Published: August 2024

The occurrence of calcite–aragonite phase transformation when a mechanically activated eggshell is triggered by the presence of the organic material (eggshell membrane).
Closed-loop recyclable polymers: from monomer and polymer design to the polymerization–depolymerization cycle
Authors: Yang Shuaiqi , Du Shuai , Zhu Jin , Ma Songqi
Published: August 2024

We present the state-of-the-art of circular polymers based on monomer and polymer design and reversible ring-opening and addition polymerization reactions without the involvement of other reactants.
An advanced furoxan-bridged heat-resistant explosive
Authors: Li Chengchuang , Zhu Teng , Tang Jie , Lei Caijin , Yu Guoyang , Yang Yanqiang , Yang Hongwei , Xiao Chuan , Cheng Guangbin
Published: August 2024

OTF simultaneously meets the high requirements of high density, high detonation velocity, excellent decomposition temperature, and low impact sensitivity, which is rarely reported in the field of energetic materials.
Preparation of Zn2GeO4:Mn,In persistent luminescence nanoparticle composites for the detection of copper ions
Authors: Han Yao-Xing , Abdurahman Renagul , Zhang Yue , Liu Shi-Ji , Yang Xiu-Zhen , Guo Xuan-He , Zhang Rui , Pan Xing-Hong , Yin Xue-Bo
Published: August 2024

Preparation of persistent luminescent nanoparticle composites for the detection of copper ions using the aggregation-induced quenching principle.
Feasibility of nitride-based nanocages for the targeted delivery of ifosfamide: a DFT exploration
Authors: Rahman Aoly Ur , Saaduzzaman D. M. , Hasan Syed Mahedi , Sikder Md. Kabir Uddin
Published: August 2024

Schematic diagram of prospective targeted drug delivery approach for ifosfamide using nitride-based nanocage.
Constructing poly(ethylene oxide)-based composite solid electrolytes: starting from the internal mechanism in batteries
Authors: Wang Jian-Cang , Liu Xin-Yu , Zhang Nan , Wang Peng-Fei , Zhu Yan-Rong , Shu Jie , Li Chun-Sheng , Yi Ting-Feng
Published: August 2024

Solid polymer electrolytes (SPEs) represented by poly(ethylene oxide) (PEO) stand out in the realms of environmental sustainability and processability.
Concise asymmetric total synthesis of (+)-arbornamine
Authors: Zheng Ming , Wang Cheng , Jiang Huanfeng , Ma Zhiqiang
Published: August 2024

(+)-Arbornamine was synthesized in 11 steps from Bn-protected tryptamine. The strategy features an enantioselective monobenzoylation reaction and a cascade intramolecular Heck–hemiamination reaction.