bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing a genomic-based strategy to confirm microbial identity in bio-inputs containing multiple strains: an easy, fast, and low-cost multiplex PCR applied to inoculants carrying soybean Bradyrhizobium
Authors: de Paiva Rolla-Santos Amanda Alves , Terra Leonardo Araujo , Ribeiro Renan Augusto , Nogueira Marco Antonio , Hungria Mariangela
Published: July 2024

Brazil stands out in research, industrial development, and farmers' use of microbial inoculants, with an emphasis on getting benefits from the biological nitrogen fixation process with the soybean crop. Nowadays, about 140 million doses of inoculants are commercialized annually for the soybean in the country, and strain identification is achieved by rep-PCR, an effective but time-consuming method. Aiming to develop an easy, low-cost, and low-time-consuming method, we used a complete genome-based approach based on the unequivocal identification of unique genes present in the genomes of each of the four Bradyrhizobium strains used in commercial inoculants: Bradyrhizobium elkanii strains SEMIA 587 and SEMIA 5019, Bradyrhizobium japonicum SEMIA 5079, and Bradyrhizobium diazoefficiens SEMIA 5080. The unique pairs of primers able to amplify genomic regions of different sizes allowed the identification of the four strains in a simple multiplex polymerase chain reaction (PCR). Validation was confirmed by using single colonies, multiple cultures, and commercial inoculants. The number of labor hours of a technician was 3.08 times higher, and the final cost was 3.25 times higher in the rep-PCR than in the multiplex PCR. Most importantly, the results for multiplex PCR were obtained on the same day, in contrast with 15 days in the traditional methodology. The genomic approach developed can be easily applied to a variety of microbial inoculants worldwide, in addition to studies of ecology and evaluation of the competitiveness of the strains.

Graphical Abstract
Fat Mass and Obesity-Associated Protein Regulates Granulosa Cell Aging by Targeting Matrix Metalloproteinase-2 Gene Via an N6-Methyladenosine-YT521-B Homology Domain Family Member 2-Dependent Pathway in Aged Mice
Authors: Li Linshuang , Yang Le , Shen Lin , Zhao Yiqing , Wang Lan , Zhang Hanwang
Published: July 2024

In this study, we aimed to investigate the molecular mechanisms of RNA N6-methyladenosine (m6A) modification and how its associated proteins affect granulosa cell aging. A granulosa cell senescence model was constructed to detect the differences in total RNA m6A modification levels and the expression of related enzymes. Changes in downstream molecular expression and the effects on the cellular senescence phenotype were explored by repeatedly knocking down and overexpressing the key genes fat mass and obesity-associated protein (FTO), YT521-B homology domain family member 2 (YTHDF2), and matrix metalloproteinase-2 (MMP2). There was an increased total RNA m6A modification and decreased expression of the demethylase FTO and target gene MMP2 in senescent granulosa cells. FTO and MMP2 knockdown promoted granulosa cell senescence, whereas FTO and MMP2 overexpression retarded it. YTHDF2 and FTO can bind to the messenger RNA of MMP2. The extracellular signal-regulated kinase (ERK) pathway, which is downstream of MMP2, retarded the process of granulosa cell senescence through ERK activators. In granulosa cells, FTO can regulate the expression of MMP2 in an m6A-YTHDF2-dependent manner, influencing the activation status of the ERK pathway and contributing to the aging process of granulosa cells.
Evolution of the Italian pasta ripiena: the first steps toward a scientific classification
Authors: Nazari Vazrick , Pasqualone Antonella , Pieroni Andrea , Todisco Valentina , Belardinelli Sofia , Pievani Telmo
Published: July 2024

In this study, phylogenetic and biogeographic methods are used to investigate the evolutionary relationships between various types of Italian pasta ripiena (filled pasta) and related representatives from across Eurasia, using information from their geography, shape, content and cooking methods. Our results showed that, with the exception of the Sardinian Culurgiones, all the other pasta ripiena from Italy likely had a single origin in the northern parts of the country. Based on the proposed evolutionary hypothesis, the Italian pasta are divided into two main clades: a ravioli clade mainly characterized by a more or less flat shape, and a tortellini clade mainly characterized by a three-dimensional shape. The implications of these findings are further discussed.
Measurement of regional green finance development and its coordination with economic development: a study on the Yangtze River Delta region of China
Authors: Song Yazhi , Xu Hantian , Li Yin , Jiang Jing Jing , Ye Bin
Published: July 2024

The green transformation of industry and sustainable economic development both require considerable investment. In this regard, green finance that is compatible with economic development can help cope with the massive demand for capital. Taken China’s Yangtze River Delta (YRD) as an example, this study is to measure the coordination degree between green finance and economic development. First, the concept, content and scope of green finance is defined based on the new financial regulation mechanism. Second, a green finance measurement index is built to calculate the green finance index for 30 Chinese provinces by the CFA test. Third, based on the economic structure index, an economic development index is built. Testing the rationality of green financial index and the economic development index, this paper finally measures the degree of coordination between green finance and economic development in the YRD. The results reveal that, first, green finance is a financial instrument that integrates financial industry development, environmental improvement, and economic growth. The measurement of the green financial development index includes the sum of regional green credit, green investment, green securities, and green insurance. Second, after years' development, the comprehensive score of YRD’s coupling coordination degree exceeds 0.8 in 2020, which shows a high level of coordinated development between green finance and economic construction. However, there is a 2-year timing effect between the economic development and green finance index increase, which reveals that green finance development in the YRD requires further policy guidance and support. This study’s findings can provide a theoretical reference and case support for the further development of green finance and related policies in China.
Drug repurposing: a retrospective revolution in breast cancer medicine
Authors: Shivani Dave , Misari Patel , Anand Nanavaty , Nandita Chawla , Jignesh Shah
Published: July 2024

Breast cancer is a complex disease involving numerous pathways, making effective treatment quite challenging. Among the current scenario, drug repurposing serves as one of the best alternatives for drug discovery as a time-efficient and cost-effective strategy to determine new therapeutic indications for previously approved drug molecules. This is the reason behind the increased popularity of drug repurposing not only in the pharma industry but also in the civil sector and academics as a faster and less expensive way to increase the repertoire of licensed cancer therapies. In the current review, we have tried to perform an in-depth review of the current state of repurposed medications available for the treatment of breast cancer. Studies conducted on various noncancer medications showing possible anticancer effects were also included. Furthermore, the various repurposed drugs available for breast cancer treatment have been further segregated according to their indicative class and possible mechanism of action.
Phylogenetic analysis of virulent strains of the Newcastle disease virus isolated from deceased chickens in Tanzania's Morogoro and Iringa regions
Authors: Amoia Charlie F. , Hakizimana Jean N. , Chengula Augustino A. , Makange Mariam R. , Weger-Lucarelli James , Misinzo Gerald
Published: July 2024

Background

Newcastle disease (ND) is a viral disease affecting a wide range of bird species and has a considerable financial impact on the world's poultry market. The ND virus (NDV) strains currently circulating in poultry throughout Africa, and especially in East Africa, exhibit significant genetic variation.

Objectives

The primary objective of the present investigation was to investigate the NDV genotypes in chickens raised in backyards in Tanzania's Morogoro and Iringa districts, which were associated with ND outbreaks.

Methods

Two tissue samples from chickens taken during a suspected ND outbreak in Tanzania's Morogoro (Eastern zone) and Iringa (Southern highlands zone) were subjected to reverse transcription polymerase chain reaction targeting the fusion (F) and hemagglutinin-neuraminidase (HN) genes, followed by sequencing.

Results

Based on comprehensive analysis of the entire F and HN gene sequences, the viruses were categorized as genotype VII and displayed significant genetic similarity with NDV strains previously identified in Mozambique, South Africa, Zambia, Zimbabwe, Botswana, Southeast Asia, and China. The uniformity in the amino acid cleavage site motif of the F protein across the examined NDV isolates, characterized by 112R–R–Q/K–K–R–F117, indicates their classification as virulent strains.

Conclusion

Regularly characterizing circulating strains and expanding the study to other parts of Tanzania may help to enhance disease control by giving a more precise picture of the situation regarding ND, especially in light of the issues posed by NDV genotype VII elsewhere.
Building Successful Partnerships Between State Health Departments and Attorney General Offices: The Minnesota Example
Authors: Farley Dana , Leone Carman , Palmer Caroline
Published: July 2024

In recent years, the Minnesota Attorney General’s Office and the Minnesota Department of Health have cultivated a productive partnership to strengthen the state’s multidisciplinary response to overlapping health equity and social justice issues. This article describes shared efforts in three areas: post-conviction justice, drug overdose, and human trafficking/exploitation.
State Driving Under the Influence of Drugs Laws
Authors: Origenes Alexandra N. , White Sarah A. , McGinty Emma E. , Vernick Jon S.
Published: July 2024

Drug-impaired driving is a growing problem in the U.S. States regulate drug-impaired driving in different ways. Some do not name specific drugs or amounts. Others do identify specific drugs and may regulate cannabis separately. We provide up-to-date information about these state laws.
Unlocking Public Health Data: Navigating New Legal Guardrails and Emerging AI Challenges
Authors: Cochlin Fallon J. , Curran Charles D. , Schmit Cason D.
Published: July 2024

Here, we analyze the public health implications of recent legal developments — including privacy legislation, intergovernmental data exchange, and artificial intelligence governance — with a view toward the future of public health informatics and the potential of diverse data to inform public health actions and drive population health outcomes.
Local Public Health Departments at the Intersection of Climate Change, Health Equity, and Public Health Laws and Policies
Authors: Agahi Massoud , Bartlett Erika , Lawton Betsy , McAdams Jennie , Roy Rachel , Salehi Cameron
Published: July 2024

Public health laws and policies are uniquely able to mitigate the adverse and inequitable health impacts of climate change. This article summarizes some key considerations in developing such laws and policies and a variety of approaches local public health departments are using to increase climate resilience and health equity.
Upholding Tribal Sovereignty in Federal, State, and Local Emergency Vaccine Distribution Plans
Authors: Erb Heather , Peterson Kristin , Sunshine Brittany , Sunshine Gregory ,   the CDC COVID-19 Vaccine Task Force Federal Entities Team
Published: July 2024

Cross jurisdictional collaboration efforts and emergency vaccine plans that are consistent with Tribal sovereignty are essential to public health emergency preparedness. The widespread adoption of clearly written federal, state, and local vaccine plans that address fundamental assumptions in vaccine distribution to Tribal nations is imperative for future pandemic response.
On the Move: 2023 Observations on Real Time Graben Formation, Grindavík, Iceland
Authors: De Pascale Gregory P. , Fischer Tomáš J. , Moreland William Michael , Geirsson Halldór , Hrubcová Pavla , Drouin Vincent , Forester Danielle , Payet‐‐Clerc Méline , da Silveira Diana Brum , Vlček Josef , Ófeigsson Benedikt G. , Höskuldsson Ármann , Torfadóttir Helga Kristín , Valdimarsdóttir Iðunn Kara , Blöndal Birta Dís Jónsdóttir , Jónsdóttir Ingibjörg , Jónsson Sigurjón , Thordarson Thor
Published: July 2024

Grabens, or valleys formed during extensional tectonic events, are common but rarely observed during formation. In November 2023, inelastic surface deformation formed abruptly along Iceland's plate boundary in Grindavík. We documented graben formation in real‐time through satellite mapping (InSAR), seismicity, GNSS data, repeated lidar surveys, and field mapping. Five normal faults and ∼12 fissures ruptured the surface delineating two grabens separated by a horst, a context not present in other contemporary case studies. The graben normal faults slipped rapidly (over hours) and maximum surface motions coincided with the occurrence of turbulent seismic swarms in both space and time. Although 3 eruptions took place ∼15 km northeast of Grindavík from 2021 to 2023, attributed to magma intrusions (i.e., dikes), none of these also formed grabens. Thus, the Grindavík grabens shows evidence for tectonic origins. Real‐time monitoring of these phenomena provide insight into graben formation on Earth and potentially on other planets.
Extended Energy Conversion and Electron Acceleration Behind Dipolarization Front
Authors: Xing X. N. , Liu C. M. , Liu Y. Y. , Zhao B. N.
Published: July 2024

Energy transfer and transport in the terrestrial magnetotails are primarily driven by dipolarization fronts (DFs) embedded inside plasma jets. The DF‐driven energy transfer has hitherto been believed to occur locally at the fronts. Different from the traditional knowledge, here we present the first observation of persistent energy conversion extended far behind a DF. The persistent energy conversion, which was dominated by energy loads and mainly contributed by electron currents, developed inside a turbulent, decaying flux pileup region (FPR), nearly 10 dDF (DF’s thickness) behind the DF. The energy transfer chain may be initiated by interaction between the ion flow and ambient plasmas and closed by electron dynamics, leading to electron acceleration perpendicular to magnetic field. These results highlight that electron physics in turbulent FPRs plays a crucial role in the energy transport in the planetary magnetospheres.
Wearable cuffless blood pressure tracking: when will they be good enough?
Authors: Schutte Aletta E.
Published: July 2024

Wearable health monitoring is a multibillion-dollar industry. But the holy grail is probably getting it right for blood pressure monitoring without a cuff, because raised blood pressure is very common and the leading cause of death in the world. Many have tried and failed, but industry is persisting: numerous cuffless wearable blood pressure devices are on the market, several technologies have been developed, hundreds of patents are registered every year, and some devices already have regulatory approval. However, to convince the die-hard blood pressure critic is a different ball game. To understand the challenges of currently accepted methods and cuffless devices, I performed a 24-h blood pressure monitoring self-test, including measurements when awake, asleep and watching an intense match of the Rugby World Cup final, with the purpose to demonstrate the challenges and opportunities we face. Blood pressure was monitored using five different devices simultaneously: validated left and right arm cuff blood pressure, and three cuffless wearable devices (wrist-band, chest patch and a ring). Whilst none of these devices proved to be perfect in capturing a physiologically challenging measure, namely blood pressure, it emphasised that our current practice of a single blood pressure measurement in clinical practice should be revisited. It further begs the question of when cuffless measurements will be good enough to incorporate in clinical decision-making.
An 18-gene signature of recurrence-associated endothelial cells predicts tumor progression and castration resistance in prostate cancer
Authors: Lin Bing-Biao , Huang Qingqing , Yan Binyuan , Liu Mingcheng , Zhang Zhiqian , Lei Hanqi , Huang Ronghua , Dong Jin-Tang , Pang Jun
Published: July 2024

Background

The prognostic and therapeutic implications of endothelial cells (ECs) heterogeneity in prostate cancer (PCa) are poorly understood.

Methods

We investigated associations of EC heterogeneity with PCa recurrence and castration resistance in 8 bulk transcriptomic and 4 single-cell RNA-seq cohorts. A recurrence-associated EC (RAEC) signature was constructed by comparing 11 machine learning algorithms through nested cross-validation. Functional relevances of RAEC-specific genes were also tested.

Results

A subset of ECs was significantly associated with recurrence in primary PCa and named RAECs. RAECs were characteristic of tip and immature cells and were enriched in migration, angiogenesis, and collagen-related pathways. We then developed an 18-gene RAEC signature (RAECsig) representative of RAECs. Higher RAECsig scores independently predicted tumor recurrence and performed better or comparably compared to clinicopathological factors and commercial gene signatures in multiple PCa cohorts. Of the 18 RAECsig genes, FSCN1 was upregulated in ECs from PCa with higher Gleason scores; and the silencing of FSCN1, TMEME255B, or GABRD in ECs either attenuated tube formation or inhibited PCa cell proliferation. Finally, higher RAECsig scores predicted castration resistance in both primary and castration-resistant PCa.

Conclusion

This study establishes an endothelial signature that links a subset of ECs to prostate cancer recurrence and castration resistance.
Structural basis of tethered agonism and G protein coupling of protease-activated receptors
Authors: Guo Jia , Zhou Yun-Li , Yang Yixin , Guo Shimeng , You Erli , Xie Xin , Jiang Yi , Mao Chunyou , Xu H. Eric , Zhang Yan
Published: July 2024

Protease-activated receptors (PARs) are a unique group within the G protein-coupled receptor superfamily, orchestrating cellular responses to extracellular proteases via enzymatic cleavage, which triggers intracellular signaling pathways. Protease-activated receptor 1 (PAR1) is a key member of this family and is recognized as a critical pharmacological target for managing thrombotic disorders. In this study, we present cryo-electron microscopy structures of PAR1 in its activated state, induced by its natural tethered agonist (TA), in complex with two distinct downstream proteins, the Gq and Gi heterotrimers, respectively. The TA peptide is positioned within a surface pocket, prompting PAR1 activation through notable conformational shifts. Contrary to the typical receptor activation that involves the outward movement of transmembrane helix 6 (TM6), PAR1 activation is characterized by the simultaneous downward shift of TM6 and TM7, coupled with the rotation of a group of aromatic residues. This results in the displacement of an intracellular anion, creating space for downstream G protein binding. Our findings delineate the TA recognition pattern and highlight a distinct role of the second extracellular loop in forming β-sheets with TA within the PAR family, a feature not observed in other TA-activated receptors. Moreover, the nuanced differences in the interactions between intracellular loops 2/3 and the Gα subunit of different G proteins are crucial for determining the specificity of G protein coupling. These insights contribute to our understanding of the ligand binding and activation mechanisms of PARs, illuminating the basis for PAR1’s versatility in G protein coupling.
Orchestration of antiviral responses within the infected central nervous system
Authors: Pavlou Andreas , Mulenge Felix , Gern Olivia Luise , Busker Lena Mareike , Greimel Elisabeth , Waltl Inken , Kalinke Ulrich
Published: July 2024

Many newly emerging and re-emerging viruses have neuroinvasive potential, underscoring viral encephalitis as a global research priority. Upon entry of the virus into the CNS, severe neurological life-threatening conditions may manifest that are associated with high morbidity and mortality. The currently available therapeutic arsenal against viral encephalitis is rather limited, emphasizing the need to better understand the conditions of local antiviral immunity within the infected CNS. In this review, we discuss new insights into the pathophysiology of viral encephalitis, with a focus on myeloid cells and CD8+ T cells, which critically contribute to protection against viral CNS infection. By illuminating the prerequisites of myeloid and T cell activation, discussing new discoveries regarding their transcriptional signatures, and dissecting the mechanisms of their recruitment to sites of viral replication within the CNS, we aim to further delineate the complexity of antiviral responses within the infected CNS. Moreover, we summarize the current knowledge in the field of virus infection and neurodegeneration and discuss the potential links of some neurotropic viruses with certain pathological hallmarks observed in neurodegeneration.
Twist angle-dependent transport properties of twisted bilayer graphene
Authors: Kim Jin Hong , Kang Seoung-Hun , Yoon Duhee , Kim Hakseong , Kim Jin-Soo , Haidari Mohd Musaib , Jang Dong Jin , Ko Jin-Yong , Son Young-Woo , Park Bae Ho , Choi Jin Sik
Published: July 2024

Twisted bilayer graphene (tBLG) with small twist angles has attracted significant attention because of its unique electronic properties arising from the formation of a moiré superlattice. In this study, we systematically characterized the twist-angle-dependent electronic and transport properties of tBLG grown via chemical vapor deposition. This characterization included parameters such as the charge-neutral point voltage, carrier concentration, resistance, and mobility, covering a wide range of twist angles from 0° to 30°. We experimentally demonstrated that these parameters exhibited twist-angle-dependent moiré period trends, with high twist angles exceeding 9°, revealing more practically useful features, including improved mobilities compared to those of single-layer graphene. In addition, we demonstrated that the doping states and work functions were weakly dependent on the twist angles, as confirmed by additional first-principles calculations. This study provides valuable insights into the transport properties of tBLG and its potential for practical applications in the emerging field of twistronics.
Amplified warming of North American cold extremes linked to human-induced changes in temperature variability
Authors: Blackport Russell , Fyfe John C.
Published: July 2024

How global warming is impacting winter cold extremes is uncertain. Previous work has found decreasing winter temperature variability over North America which suggests a reduction in frequency and intensity of cold extremes relative to mean changes. However, others argue that cold air outbreaks are becoming more likely because of Arctic-induced changes in atmospheric circulation. Here we show that cold extremes over North America have warmed substantially faster than the winter mean temperature since 1980. This amplified warming is linked to both decreasing variance and changes in higher moments of the temperature distributions. Climate model simulations with historical forcings robustly capture the observed trends in extremes and variability. A pattern-based detection and attribution analysis shows that the changes in variability are detectable in observations and can be attributed to human influence. Our results highlight that human emissions are warming North American extreme cold temperatures beyond only shifting the winter mean temperature.
KAP1 negatively regulates RNA polymerase II elongation kinetics to activate signal-induced transcription
Authors: Hyder Usman , Challa Ashwini , Thornton Micah , Nandu Tulip , Kraus W. Lee , D’Orso Iván
Published: July 2024

Signal-induced transcriptional programs regulate critical biological processes through the precise spatiotemporal activation of Immediate Early Genes (IEGs); however, the mechanisms of transcription induction remain poorly understood. By combining an acute depletion system with several genomics approaches to interrogate synchronized, temporal transcription, we reveal that KAP1/TRIM28 is a first responder that fulfills the temporal and heightened transcriptional demand of IEGs. Acute KAP1 loss triggers an increase in RNA polymerase II elongation kinetics during early stimulation time points. This elongation defect derails the normal progression through the transcriptional cycle during late stimulation time points, ultimately leading to decreased recruitment of the transcription apparatus for re-initiation thereby dampening IEGs transcriptional output. Collectively, KAP1 plays a counterintuitive role by negatively regulating transcription elongation to support full activation across multiple transcription cycles of genes critical for cell physiology and organismal functions.
CoPheScan: phenome-wide association studies accounting for linkage disequilibrium
Authors: Manipur Ichcha , Reales Guillermo , Sul Jae Hoon , Shin Myung Kyun , Longerich Simonne , Cortes Adrian , Wallace Chris
Published: July 2024

Phenome-wide association studies (PheWAS) facilitate the discovery of associations between a single genetic variant with multiple phenotypes. For variants which impact a specific protein, this can help identify additional therapeutic indications or on-target side effects of intervening on that protein. However, PheWAS is restricted by an inability to distinguish confounding due to linkage disequilibrium (LD) from true pleiotropy. Here we describe CoPheScan (Coloc adapted Phenome-wide Scan), a Bayesian approach that enables an intuitive and systematic exploration of causal associations while simultaneously addressing LD confounding. We demonstrate its performance through simulation, showing considerably better control of false positive rates than a conventional approach not accounting for LD. We used CoPheScan to perform PheWAS of protein-truncating variants and fine-mapped variants from disease and pQTL studies, in 2275 disease phenotypes from the UK Biobank. Our results identify the complexity of known pleiotropic genes such as APOE, and suggest a new causal role for TGM3 in skin cancer.
Advanced parametrization for the production of high-energy solid-state lithium pouch cells containing polymer electrolytes
Authors: Lee Wonmi , Lee Juho , Yu Taegyun , Kim Hyeong-Jong , Kim Min Kyung , Jang Sungbin , Kim Juhee , Han Yu-Jin , Choi Sunghun , Choi Sinho , Kim Tae-Hee , Park Sang-Hoon , Jin Wooyoung , Song Gyujin , Seo Dong-Hwa , Jung Sung-Kyun , Kim Jinsoo
Published: July 2024

Lithium batteries with solid-state electrolytes are an appealing alternative to state-of-the-art non-aqueous lithium-ion batteries with liquid electrolytes because of safety and energy aspects. However, engineering development at the cell level for lithium batteries with solid-state electrolytes is limited. Here, to advance this aspect and produce high-energy lithium cells, we introduce a cell design based on advanced parametrization of microstructural and architectural parameters of electrode and electrolyte components. To validate the cell design proposed, we assemble and test (applying a stack pressure of 3.74 MPa at 45 °C) 10-layer and 4-layer solid-state lithium pouch cells with a solid polymer electrolyte, resulting in an initial specific energy of 280 Wh kg−1 (corresponding to an energy density of 600 Wh L−1) and 310 Wh kg−1 (corresponding to an energy density of 650 Wh L−1) respectively.
Inhibition of DUSP18 impairs cholesterol biosynthesis and promotes anti-tumor immunity in colorectal cancer
Authors: Zhou Xiaojun , Wang Genxin , Tian Chenhui , Du Lin , Prochownik Edward V. , Li Youjun
Published: July 2024

Tumor cells reprogram their metabolism to produce specialized metabolites that both fuel their own growth and license tumor immune evasion. However, the relationships between these functions remain poorly understood. Here, we report CRISPR screens in a mouse model of colo-rectal cancer (CRC) that implicates the dual specificity phosphatase 18 (DUSP18) in the establishment of tumor-directed immune evasion. Dusp18 inhibition reduces CRC growth rates, which correlate with high levels of CD8+ T cell activation. Mechanistically, DUSP18 dephosphorylates and stabilizes the USF1 bHLH-ZIP transcription factor. In turn, USF1 induces the SREBF2 gene, which allows cells to accumulate the cholesterol biosynthesis intermediate lanosterol and release it into the tumor microenvironment (TME). There, lanosterol uptake by CD8+ T cells suppresses the mevalonate pathway and reduces KRAS protein prenylation and function, which in turn inhibits their activation and establishes a molecular basis for tumor cell immune escape. Finally, the combination of an anti-PD-1 antibody and Lumacaftor, an FDA-approved small molecule inhibitor of DUSP18, inhibits CRC growth in mice and synergistically enhances anti-tumor immunity. Collectively, our findings support the idea that a combination of immune checkpoint and metabolic blockade represents a rationally-designed, mechanistically-based and potential therapy for CRC.
Germline β−1,3-glucan deposits are required for female gametogenesis in Arabidopsis thaliana
Authors: Pinto Sara C. , Leong Weng Herng , Tan Hweiting , McKee Lauren , Prevost Amelie , Ma Chao , Shirley Neil. J. , Petrella Rosanna , Yang Xiujuan , Koltunow Anna M. , Bulone Vincent , Kanaoka Masahiro M. , Higashyiama Tetsuya , Coimbra Sílvia , Tucker Matthew R.
Published: July 2024

Correct regulation of intercellular communication is a fundamental requirement for cell differentiation. In Arabidopsis thaliana, the female germline differentiates from a single somatic ovule cell that becomes encased in β−1,3-glucan, a water insoluble polysaccharide implicated in limiting pathogen invasion, regulating intercellular trafficking in roots, and promoting pollen development. Whether β−1,3-glucan facilitates germline isolation and development has remained contentious, since limited evidence is available to support a functional role. Here, transcriptional profiling of adjoining germline and somatic cells revealed differences in gene expression related to β−1,3-glucan metabolism and signalling through intercellular channels (plasmodesmata). Dominant expression of a β−1,3-glucanase in the female germline transiently perturbed β−1,3-glucan deposits, allowed intercellular movement of tracer molecules, and led to changes in germline gene expression and histone marks, eventually leading to termination of germline development. Our findings indicate that germline β−1,3-glucan fulfils a functional role in the ovule by insulating the primary germline cell, and thereby determines the success of downstream female gametogenesis.
Nucleation phenomena and extreme vulnerability of spatial k-core systems
Authors: Xue Leyang , Gao Shengling , Gallos Lazaros K. , Levy Orr , Gross Bnaya , Di Zengru , Havlin Shlomo
Published: July 2024

K-core percolation is a fundamental dynamical process in complex networks with applications that span numerous real-world systems. Earlier studies focus primarily on random networks without spatial constraints and reveal intriguing mixed-order transitions. However, real-world systems, ranging from transportation and communication networks to complex brain networks, are not random but are spatially embedded. Here, we study k-core percolation on two-dimensional spatially embedded networks and show that, in contrast to regular percolation, the length of connections can control the transition type, leading to four different types of phase transitions associated with interesting phenomena and a rich phase diagram. A key finding is the existence of a metastable phase where microscopic localized damage, independent of system size, can cause a macroscopic phase transition, a result which cannot be achieved in traditional percolation. In this case, local failures spontaneously propagate the damage radially until the system collapses, a phenomenon analogous to the nucleation process.
Plasmonic trimers designed as SERS-active chemical traps for subtyping of lung tumors
Authors: Zhao Xing , Liu Xiaojing , Chen Dexiang , Shi Guodong , Li Guoqun , Tang Xiao , Zhu Xiangnan , Li Mingze , Yao Lei , Wei Yunjia , Song Wenzhe , Sun Zixuan , Fan Xingce , Zhou Zhixin , Qiu Teng , Hao Qi
Published: July 2024

Plasmonic materials can generate strong electromagnetic fields to boost the Raman scattering of surrounding molecules, known as surface-enhanced Raman scattering. However, these electromagnetic fields are heterogeneous, with only molecules located at the ‘hotspots’, which account for ≈ 1% of the surface area, experiencing efficient enhancement. Herein, we propose patterned plasmonic trimers, consisting of a pair of plasmonic dimers at the bilateral sides and a trap particle positioned in between, to address this challenge. The trimer configuration selectively directs probe molecules to the central traps where ‘hotspots’ are located through chemical affinity, ensuring a precise spatial overlap between the probes and the location of maximum field enhancement. We investigate the Raman enhancement of the Au@Al2O3-Au-Au@Al2O3 trimers, achieving a detection limit of 10−14 M of 4-methylbenzenethiol, 4-mercaptopyridine, and 4-aminothiophenol. Moreover, single-molecule SERS sensitivity is demonstrated by a bi-analyte method. Benefiting from this sensitivity, our approach is employed for the early detection of lung tumors using fresh tissues. Our findings suggest that this approach is sensitive to adenocarcinoma but not to squamous carcinoma or benign cases, offering insights into the differentiation between lung tumor subtypes.
Molecular modeling applied to corrosion inhibition: a critical review
Authors: Castillo-Robles José María , de Freitas Martins Ernane , Ordejón Pablo , Cole Ivan
Published: July 2024

In the last few years, organic corrosion inhibitors have been used as a green alternative to toxic inorganic compounds to prevent corrosion in materials. Nonetheless, the fundamental mechanisms determining their inhibition performance are still far from understood. Molecular modeling can provide important insights into those mechanisms, allowing for a detailed analysis of the corrosion inhibition (CI) process. However, CI modeling is frequently underexplored and commonly used in a standardized way following a pre-determined recipe to support experimental data. We highlight six fundamental aspects (A) that one should consider when modeling CI: (A1) the electronic properties of isolated inhibitors, (A2) the interaction of the inhibitor with the surface, (A3) the surface model, (A4) the effect of the anodic and cathodic zones on the surface, (A5) the solvent effects, and (A6) the electrodes’ potential effects. While A1-A3 are more frequently investigated, A4-A6 and some more complex surface models from A3 are usually not considered and represent gaps in the CI modeling literature. In this review, we discuss the main features of molecular modeling applied to CI, considering the aforementioned key aspects and focusing on the gaps that the emerging approaches aim to fill. Filling these gaps will allow performing more detailed simulations of the CI process, which, coupled with artificial intelligence (AI) methods and multiscale approaches, might construct the bridge between the nanoscale CI modeling and the continuum scale of the CI processes.
Benchmarking and integrating human B-cell receptor genomic and antibody proteomic profiling
Authors: Lê Quý Khang , Chernigovskaya Maria , Stensland Maria , Singh Sachin , Leem Jinwoo , Revale Santiago , Yadin David A. , Nice Francesca L. , Povall Chelsea , Minns Danielle H. , Galson Jacob D. , Nyman Tuula A. , Snapkow Igor , Greiff Victor
Published: July 2024

Immunoglobulins (Ig), which exist either as B-cell receptors (BCR) on the surface of B cells or as antibodies when secreted, play a key role in the recognition and response to antigenic threats. The capability to jointly characterize the BCR and antibody repertoire is crucial for understanding human adaptive immunity. From peripheral blood, bulk BCR sequencing (bulkBCR-seq) currently provides the highest sampling depth, single-cell BCR sequencing (scBCR-seq) allows for paired chain characterization, and antibody peptide sequencing by tandem mass spectrometry (Ab-seq) provides information on the composition of secreted antibodies in the serum. Yet, it has not been benchmarked to what extent the datasets generated by these three technologies overlap and complement each other. To address this question, we isolated peripheral blood B cells from healthy human donors and sequenced BCRs at bulk and single-cell levels, in addition to utilizing publicly available sequencing data. Integrated analysis was performed on these datasets, resolved by replicates and across individuals. Simultaneously, serum antibodies were isolated, digested with multiple proteases, and analyzed with Ab-seq. Systems immunology analysis showed high concordance in repertoire features between bulk and scBCR-seq within individuals, especially when replicates were utilized. In addition, Ab-seq identified clonotype-specific peptides using both bulk and scBCR-seq library references, demonstrating the feasibility of combining scBCR-seq and Ab-seq for reconstructing paired-chain Ig sequences from the serum antibody repertoire. Collectively, our work serves as a proof-of-principle for combining bulk sequencing, single-cell sequencing, and mass spectrometry as complementary methods towards capturing humoral immunity in its entirety.
Data driven multiple objective optimization of AAO process towards wastewater effluent biological toxicity reduction
Authors: Hu Jie , Yin Ran , Wang Jinfeng , Ren Hongqiang
Published: July 2024

While the anaerobic-anoxic-oxic (AAO) process is the most widely applied biological wastewater treatment process in municipal wastewater treatment plants (WWTPs), it struggles to meet the increasing demands on biological toxicity control of the treated effluent. To tackle this challenge, this study develops machine learning (ML)-based models for optimizing the AAO treatment process towards improving its toxicity reduction efficacy for the effluent. The water quality parameters, treatment process parameters, and biological toxicity information (based on the nematode bioassay) of the effluent collected from 122 WWTPs in China are used to train the models. The validated models accurately predict the effluent’s quality parameters (average R2 = 0.81) and the biological toxicity reduction ratio of treatment process (R2 = 0.86). To further improve the toxicity reduction, we developed a multiple objective optimization framework to optimize the AAO process via unit process recombination. In the short-range unit combination, the toxicity reduction ratio of the four-unit combined processes (up to 79.8% of anaerobic-aerobic-anaerobic-aerobic) is significantly higher than others. After optimization, it helps to improve the average toxicity reduction efficacy of 122 WWTPs from 48.6% to 70.7%, with a maximum of 87.5%. The methodologies and findings derived from this work are expected to provide the foundation for the optimization, expansion, and technical transformation of biological wastewater treatment in WWTPs.
The nature of the last universal common ancestor and its impact on the early Earth system
Authors: Moody Edmund R. R. , Álvarez-Carretero Sandra , Mahendrarajah Tara A. , Clark James W. , Betts Holly C. , Dombrowski Nina , Szánthó Lénárd L. , Boyle Richard A. , Daines Stuart , Chen Xi , Lane Nick , Yang Ziheng , Shields Graham A. , Szöllősi Gergely J. , Spang Anja , Pisani Davide , Williams Tom A. , Lenton Timothy M. , Donoghue Philip C. J.
Published: July 2024

The nature of the last universal common ancestor (LUCA), its age and its impact on the Earth system have been the subject of vigorous debate across diverse disciplines, often based on disparate data and methods. Age estimates for LUCA are usually based on the fossil record, varying with every reinterpretation. The nature of LUCA’s metabolism has proven equally contentious, with some attributing all core metabolisms to LUCA, whereas others reconstruct a simpler life form dependent on geochemistry. Here we infer that LUCA lived ~4.2 Ga (4.09–4.33 Ga) through divergence time analysis of pre-LUCA gene duplicates, calibrated using microbial fossils and isotope records under a new cross-bracing implementation. Phylogenetic reconciliation suggests that LUCA had a genome of at least 2.5 Mb (2.49–2.99 Mb), encoding around 2,600 proteins, comparable to modern prokaryotes. Our results suggest LUCA was a prokaryote-grade anaerobic acetogen that possessed an early immune system. Although LUCA is sometimes perceived as living in isolation, we infer LUCA to have been part of an established ecological system. The metabolism of LUCA would have provided a niche for other microbial community members and hydrogen recycling by atmospheric photochemistry could have supported a modestly productive early ecosystem.
Specific CD4+ T cell phenotypes associate with bacterial control in people who ‘resist’ infection with Mycobacterium tuberculosis
Authors: Sun Meng , Phan Jolie M. , Kieswetter Nathan S. , Huang Huang , Yu Krystle K. Q. , Smith Malisa T. , Liu Yiran E. , Wang Chuangqi , Gupta Sanjana , Obermoser Gerlinde , Maecker Holden Terry , Krishnan Akshaya , Suresh Sundari , Gupta Neha , Rieck Mary , Acs Peter , Ghanizada Mustafa , Chiou Shin-Heng , Khatri Purvesh , Boom W. Henry , Hawn Thomas R. , Stein Catherine M. , Mayanja-Kizza Harriet , Davis Mark M. , Seshadri Chetan
Published: July 2024

A subset of individuals exposed to Mycobacterium tuberculosis (Mtb) that we refer to as ‘resisters’ (RSTR) show evidence of IFN-γ− T cell responses to Mtb-specific antigens despite serially negative results on clinical testing. Here we found that Mtb-specific T cells in RSTR were clonally expanded, confirming the priming of adaptive immune responses following Mtb exposure. RSTR CD4+ T cells showed enrichment of TH17 and regulatory T cell-like functional programs compared to Mtb-specific T cells from individuals with latent Mtb infection. Using public datasets, we showed that these TH17 cell-like functional programs were associated with lack of progression to active tuberculosis among South African adolescents with latent Mtb infection and with bacterial control in nonhuman primates. Our findings suggested that RSTR may successfully control Mtb following exposure and immune priming and established a set of T cell biomarkers to facilitate further study of this clinical phenotype.
AgCNER, the First Large-Scale Chinese Named Entity Recognition Dataset for Agricultural Diseases and Pests
Authors: Yao Xiaochuang , Hao Xia , Liu Ruilin , Li Lin , Guo Xuchao
Published: July 2024

Named entity recognition is a fundamental subtask for knowledge graph construction and question-answering in the agricultural diseases and pests field. Although several works have been done, the scarcity of the Chinese annotated dataset has restricted the development of agricultural diseases and pests named entity recognition(ADP-NER). To address the issues, a large-scale corpus for the Chinese ADP-NER task named AgCNER was first annotated. It mainly contains 13 categories, 206,992 entities, and 66,553 samples with 3,909,293 characters. Compared with other datasets, AgCNER maintains the best performance in terms of the number of categories, entities, samples, and characters. Moreover, this is the first publicly available corpus for the agricultural field. In addition, the agricultural language model AgBERT is also fine-tuned and released. Finally, the comprehensive experimental results showed that BiLSTM-CRF achieved F1-score of 93.58%, which would be further improved to 94.14% using BERT. The analysis from multiple aspects has verified the rationality of AgCNER and the effectiveness of AgBERT. The annotated corpus and fine-tuned language model are publicly available at https://doi.org/XXX and https://github.com/guojson/AgCNER.git.
An UltraMNIST classification benchmark to train CNNs for very large images
Authors: Gupta Deepak K. , Bamba Udbhav , Thakur Abhishek , Gupta Akash , Agarwal Rohit , Sharan Suraj , Demir Ertugul , Agarwal Krishna , Prasad Dilip K.
Published: July 2024

Current convolutional neural networks (CNNs) are not designed for large scientific images with rich multi-scale features, such as in satellite and microscopy domain. A new phase of development of CNNs especially designed for large images is awaited. However, application-independent high-quality and challenging datasets needed for such development are still missing. We present the ‘UltraMNIST dataset’ and associated benchmarks for this new research problem of ‘training CNNs for large images’. The dataset is simple, representative of wide-ranging challenges in scientific data, and easily customizable for different levels of complexity, smallest and largest features, and sizes of images. Two variants of the problem are discussed: standard version that facilitates the development of novel CNN methods for effective use of the best available GPU resources and the budget-aware version to promote the development of methods that work under constrained GPU memory. Several baselines are presented and the effect of reduced resolution is studied. The presented benchmark dataset and baselines will hopefully trigger the development of new CNN methods for large scientific images.
Effect of Flammulina velutipes polysaccharide on mitochondrial apoptosis in lung adenocarcinoma A549 cells
Authors: Zhao Fei , Chen Dan-yang , Jing Bo , Jiang Yu , Liu Lan-yue , Song Hui
Published: July 2024

FVP is a polysaccharide extracted from Flammulina velutipes with immunomodulatory, anti-tumor, and anti-oxidation activities. In this study, we obtained the crude polysaccharide FVP-C from the water extract of Flammulina velutipes, and its main component FVP-S1 was obtained after further purification. Upon structural identification, we found that FVP-C is a neutral polysaccharide, and FVP-S1 was an acidic golden mushroom polysaccharide, consisting of glucuronic acid, xylose, and glucose. Lung adenocarcinoma (A549) was treated with FVP-S1 and FVP-C, respectively, and we found that FVP-S1 and FVP-C inhibited the proliferation and migration ability of tumor cells, as well as changed the morphology of the tumor cells and caused chromosome sheteropythosis, among which FVP-S1 had the best inhibition effect. The results of flow cytometry experiments and mitochondrial membrane potential, RT-qPCR, and Western blot showed that FVP-S1 and FVP-C were able to decrease the mitochondrial membrane potential, increase the expression level of apoptotic proteins Casepase-3 and Casepase-9 proteins, and at the same time, increase the ratio of Bax and Bcl-2, which promoted apoptosis of tumor cells. In conclusion, these data indicated that FVP-S1 and FVP-C were able to induce apoptosis in A549 cells through the mitochondrial pathway, which played an important role in inhibiting tumor cells.