bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthetic anti-RNA antibody derivatives for RNA visualization in mammalian cells
Authors: Banna Hasan Al , Berg Kimberley , Sadat Tasnia , Das Naba Krishna , Paudel Roshan , D'Souza Victoria , Koirala Deepak
Published: December 2024

Although antibody derivatives, such as Fabs and scFvs, have revolutionized the cellular imaging, quantification and tracking of proteins, analogous tools and strategies are unavailable for cellular RNA visualization. Here, we developed four synthetic anti-RNA scFv (sarabody) probes and their green fluorescent protein (GFP) fusions and demonstrated their potential to visualize RNA in live mammalian cells. We expressed these sarabodies and sarabody–GFP modules, purified them as soluble proteins, characterized their binding interactions with their corresponding epitopes and finally employed two of the four modules, sara1-GFP and sara1c-GFP, to visualize a target messenger RNA in live U2OS cells. Our current RNA imaging strategy is analogous to the existing MCP-MS2 system for RNA visualization, but additionally, our approach provides robust flexibility for developing target RNA-specific imaging modules, as epitope-specific probes can be selected from a library generated by diversifying the sarabody complementarity determining regions. While we continue to optimize these probes, develop new probes for various target RNAs and incorporate other fluorescence proteins like mCherry and HaloTag, our groundwork results demonstrated that these first-of-a-kind immunofluorescent probes will have tremendous potential for tracking mature RNAs and may aid in visualizing and quantifying many cellular processes as well as examining the spatiotemporal dynamics of various RNAs.
The target of rapamycin kinase is a positive regulator of plant fatty acid and lipid synthesis
Authors: Liu Hui , Blanford Jantana , Shi Hai , Schwender Jorg , Shanklin John , Zhai Zhiyang
Published: December 2024

In eukaryotes, target of rapamycin (TOR), a conserved protein sensor kinase, integrates diverse environmental cues, including growth factor signals, energy availability, and nutritional status, to direct cell growth. In plants, TOR is activated by light and sugars and regulates a wide range of cellular processes, including protein synthesis and metabolism. Fatty acid (FA) synthesis is a key to membrane biogenesis that is required for cell growth. To elucidate the primary regulatory role(s) of TOR in lipid metabolism, we followed FA and lipid changes in plants with altered TOR protein levels or activity for short durations, using Nicotiana benthamiana leaves, Arabidopsis seedlings, and Brassica napus cell suspension cultures. Transient expression of TOR significantly elevated the levels of total FA (TFA) in N. benthamiana leaves. Conversely, treatment of Arabidopsis seedlings with the TOR-specific inhibitor Torin 2 for 1 d caused significant reductions in FA and membrane lipids. Similarly, incubating oil–producing B. napus suspension culture cells with Torin 2 for 8 h led to significant decreases in the levels of TFA and triacylglycerol. The results from 3 independent systems presented here establish that TOR positively regulates lipid synthesis in plants, consistent with its role in animals. Furthermore, RNA-seq analysis of Torin 2-treated Arabidopsis seedlings showed that TOR promotes the upregulation of several genes involved in de novo FA synthesis while downregulating several genes involved in lipid turnover, which we propose as a mechanistic explanation for its promotion of lipid synthesis and accumulation.
Rare Cutaneous Primary Presentation of Extracavitary Primary Effusion Lymphoma
Authors: Mehta Apoorva , Luyten Sophia , Vencato da Silva Tiago , Bacchi Carlos , Gru Alejandro
Published: December 2024

Primary effusion lymphoma (PEL) is a rare and aggressive B-cell lymphoma typically associated with human herpesvirus 8 (HHV-8) and Epstein–Barr virus infections. It classically presents as a malignant effusion in body cavities, but rarely presents with an extracavitary variant characterized by solid tumors in lymph nodes or extranodal sites such as the gastrointestinal tract, skin, lungs, and nervous system. This case report describes an unusual presentation of primary cutaneous extracavitary PEL in an HIV-positive patient that has only been reported in 8 cases previously. The patient presented with a skin nodule in the right supraclavicular area. Histopathologic examination showed a malignant infiltrate in the dermis composed of sheets of plasmablasts. The immunophenotype of the cells shows the characteristic coinfection with HHV-8 and Epstein–Barr virus. The case presented herein contributes to expand the reported literature on primary cutaneous extracavitary PEL and performs a comprehensive review of this entity, which most dermatopathologists are unfamiliar with.
“Pathway Leap”: A New Molecular Phenomenon to Consider in the Pathogenesis of Melanocytic Tumors
Authors: Fernandez-Flores Angel
Published: December 2024

Introduction:

The current WHO classification of melanocytic tumors distinguishes 9 pathogenic routes. This classification is based on the conceptual interpretation that melanocytic tumors evolve from benign counterparts, accumulating mutations, eventually developing into melanomas with metastatic and potentially lethal capacity. In this article, we present a molecular study of 2 melanocytic tumors that suggest a “leap” from pathogenic routes IV to I.

Materials and Methods:

Two recent melanocytic tumors were selected, each exhibiting 2 contiguous melanocytic populations of distinct morphology, without separation between them. One population corresponded to a common melanocytic nevus (with morphology consistent with route I), while the other population displayed epithelioid morphology, consistent with route IV. Immunohistochemical studies were performed in both cases, as well as molecular studies using PCR to search for mutations in the NRAS and BRAF genes. For the molecular study, both populations were manually separated by microdissection.

Results:

In both cases, the melanocytic population consistent with route I showed a BRAF mutation. In both cases, the epithelioid population did not present a BRAF mutation. No NRAS mutations were observed in any of the populations.

Conclusions:

These findings suggest the existence of a molecular phenomenon of “leap” between pathways, which we have termed “pathway leap.” This could explain the enigmatic group of tumors that the WHO classifies under the heading of “combined nevi.” This group could be more frequent than suspected, because microdissection is not a technique commonly used in the daily diagnosis of melanocytic tumors.
Vegetative Pyoderma Gangrenosum Mimicking Squamous Cell Carcinoma: A Poorly Recognized Diagnostic Challenge
Authors: Hoang Megan , Maymone Mayra B. C. , Telang Gladys H. , Seo Su-Jean , Robinson-Bostom Leslie
Published: December 2024

Pyoderma gangrenosum (PG) is a rare inflammatory neutrophilic dermatosis that is difficult to diagnose due to non-specific clinical, laboratory, and histopathologic features. Distinguishing pseudoepitheliomatous hyperplasia (PEH) from squamous cell carcinoma (SCC) is also histopathologically challenging. The connection between PEH and PG is not well recognized, and instances of PG mimicking SCC are rare. We report a case of vegetative PG accompanied by PEH, originally mistaken for SCC. A 78-year-old woman presented with a 3-month history of an ulcerated, exophytic, and painful mass on her right lower leg. An incisional biopsy revealed PEH and neutrophilic microabscesses, initially raising concerns for SCC keratoacanthoma type with PEH or well-differentiated, infiltrative SCC. However, following additional review of clinical and histopathologic findings at the cutaneous oncology tumor board, the diagnosis of vegetative PG with associated PEH was favored. This case highlights the significance of recognizing PEH as a histopathology feature that can be seen in PG and lead to difficulty distinguishing PG with PEH from SCC. We stress the importance of promptly diagnosing PG through clinical and histopathologic correlation to prevent diagnostic delays and unnecessary surgeries or treatments.
Applying a two-stage generalized synthetic control approach to quantify the heterogeneous health effects of extreme weather events: A 2018 large wildfire in California event as a case study
Authors: Letellier Noemie , Hale Maren , Salim Kasem U. , Ma Yiqun , Rerolle Francois , Schwarz Lara , Benmarhnia Tarik
Published: December 2024

Extreme weather events, including wildfires, are becoming more intense, frequent, and expansive due to climate change, thus increasing negative health outcomes. However, such effects can vary across space, time, and population subgroups, requiring methods that can handle multiple exposed units, account for time-varying confounding, and capture heterogeneous treatment effects. In this article, we proposed an approach based on staggered generalized synthetic control methods to study heterogeneous health effects, using the 2018 California wildfire season as a case study. This study aimed to estimate the effects of the November 2018 California wildfires, one of the state’s deadliest and most destructive wildfire seasons, on respiratory and circulatory health, document heterogeneity in health impacts, and investigate drivers of this heterogeneity. We applied a two-stage generalized synthetic control method to compare health outcomes in exposed (from 8 November to 5 December 2018) versus unexposed counties and used random-effects meta-regression to evaluate the effect modification of county-level socioeconomic variables on the observed health effects of the November 2018 wildfires. We observed an increase in respiratory hospitalizations for most exposed counties when compared with unexposed counties, with significant increases in Fresno, San Francisco, San Joaquin, San Mateo, and Santa Clara counties. No effect on circulatory hospitalizations was observed. County-level sociodemographic characteristics seem to not modulate the effects of wildfire smoke on respiratory hospitalizations. This novel two-stage framework can be applied in broader settings to understand spatially and temporally compounded health impacts of climate hazards. We provide codes in R for reproducibility and replication purposes.
Drug Delivery in PROSE Device as Alternative to Frequent Drop Administration in Severe Ocular Surface Disease
Authors: Bian Yandong , Jacobs Deborah S.
Published: December 2024

The design of the prosthetic replacement of the ocular surface ecosystem (PROSE) device allows it to serve as a novel drug delivery system. In this article, we describe the off-label administration of amphotericin B and cenegermin by instillation in the PROSE device reservoir for the treatment of Candida keratitis in the setting of a persistent epithelial defect.
Comparison of Alternative Approaches to Using Race-and-Ethnicity Data in Estimating Differences in Health Care and Social Determinants of Health
Authors: Martino Steven C. , Dembosky Jacob W. , Hambarsoomian Katrin , Haviland Amelia M. , Weech-Maldonado Robert , Beckett Megan K. , Hill Torrey , Elliott Marc N.
Published: December 2024

Objective:

The objective of this study was to compare 2 approaches for representing self-reported race-and-ethnicity, additive modeling (AM), in which every race or ethnicity a person endorses counts toward measurement of that category, and a commonly used mutually exclusive categorization (MEC) approach. The benchmark was a gold-standard, but often impractical approach that analyzes all combinations of race-and-ethnicity as distinct groups.

Methods:

Data came from 313,739 respondents to the 2021 Medicare Consumer Assessment of Healthcare Providers and Systems (CAHPS) surveys who self-reported race-and-ethnicity. We used regression to estimate how accurately AM and MEC approaches predicted racial-and-ethnic differences in 5 CAHPS patient experience measures and 4 patient characteristics that we considered proxies for social determinants of health (SDOH): age, educational attainment, and self-reported general and mental health. We calculated average residual error proportions for AM and MEC estimates relative to all-combination estimates.

Results:

In predicting CAHPS scores by race-and-ethnicity, on average 0.9% of the variance across groups in the AM and MEC approaches represented a departure from the gold standard. In predicting proxy SDOH variables, on average 4.7% of the AM variance across groups and 7.1% of the MEC variance across groups represented departures from the gold standard.

Conclusion:

Researchers may want to consider AM over MEC when modeling outcomes by race-and-ethnicity given that AM outperforms MEC in predicting racial-and-ethnic differences in proxy SDOH characteristics and is comparably accurate in predicting differences in patient experience. Unlike MEC, AM does not assume that every multiracial person has similar outcomes and that Hispanic persons have similar outcomes irrespective of race.
Sociodemographic characteristics of SARS-CoV-2 serosurveillance studies with diverse recruitment strategies, Canada, 2020 to 2023
Authors: Knight Matthew J. , Yu Yuan , Chen Jiacheng , O’Brien Sheila F. , Buckeridge David L. , Charlton Carmen , Russell W. Alton
Published: December 2024

Background

Serological testing was a key component of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) surveillance. Social distancing interventions, resource limitations, and the need for timely data led to serosurveillance studies using a range of recruitment strategies, which likely influenced study representativeness. Characterizing representativeness in surveillance is crucial to identify gaps in sampling coverage and to assess health inequities.

Methods

We retrospectively analyzed three pre-existing longitudinal cohorts, two convenience samples using residual blood, and one de novo probabilistic survey conducted in Canada between April 2020 – November 2023. We calculated study specimen counts by age, sex, urbanicity, race/ethnicity, and neighborhood deprivation quintiles. We derived a ‘representation ratio’ as a simple metric to assess generalizability to a target population and various sociodemographic strata.

Results

The six studies included 1,321,675 specimens. When stratifying by age group and sex, 65% of racialized minority subgroups were moderately underrepresented (representation ratio < 0.75). Representation was generally higher for older Canadians, urban neighborhoods, and neighborhoods with low material deprivation. Rural representation was highest in a study that used outpatient laboratory blood specimens. Racialized minority representation was highest in a de novo probabilistic survey cohort.

Conclusion

While no study had adequate representation of all subgroups, less traditional recruitment strategies were more representative of some population dimensions. Understanding demographic representativeness and barriers to recruitment are important considerations when designing population health surveillance studies.
Slow spatial migration can help eradicate cooperative antimicrobial resistance in time-varying environments
Authors: Hernández-Navarro Lluís , Distefano Kenneth , Täuber Uwe C. , Mobilia Mauro
Published: December 2024

Antimicrobial resistance (AMR) is a global threat and combating its spread is of paramount importance. AMR often results from a cooperative behaviour with shared drug protection. Micro-bial communities generally evolve in volatile, spatially structured settings. Migration, fluctuations, and environmental variability significantly impact AMR. While AMR is enhanced by migration in static conditions, this changes in time-fluctuating spatially structured environments. We consider a two-dimensional metapopulation consisting of demes in which drug-resistant and sensitive cells evolve in a time-changing environment containing a toxin against which protection can be shared. Cells migrate between demes and connect them. When the environment varies neither too quickly nor too slowly, population bottlenecks cause fluctuation-driven extinctions, countered by migration. We investigate the influence of migration and environmental variability on AMR, determining the near-optimal conditions for resistance eradication. We show how slow migration speeds up and enhances AMR clearance. We discuss our study’s impact on laboratory-controlled experiments.

Author summary

As the number of microbes resisting antimicrobial drugs grows alarmingly, it is of paramount importance to tackle this major societal issue. Resistant microbes often inhibit antibiotics in the environment around them, and hence offer protection to drug-sensitive bacteria in a form of cooperative behaviour. Moreover, microbes typically are distributed in space and live in time-changing environments, where they are subject to random fluctuations. Environmental variability, fluctuations, and spatial dispersal all have a strong influence on the drug resistance of microbial organisms. Here we investigate the evolution of antimicrobial resistance in time-varying spatial environments by combining computational and mathematical means. We study the dynamics of drug-resistant and sensitive cells in the presence of an antimicrobial drug, when microbes are spatially distributed across a two-dimensional grid of well-mixed sub-populations (demes). Cells migrate between neighbouring demes, connecting these sub-populations, and are subject to sudden changes of environment. We show that when environmental variations occur neither too rarely nor too often, the joint effect of slow migration and fluctuations can help eradicate drug resistance by speeding up and enhancing the extinction probability of resistant bacteria. We also discuss how our findings can be probed in laboratory experiments.
CEBPA repression by MECOM blocks differentiation to drive aggressive leukemias
Authors: Fleming Travis J. , Antoszewski Mateusz , Lambo Sander , Gundry Michael C. , Piussi Riccardo , Wahlster Lara , Shah Sanjana , Reed Fiona E. , Dong Kevin D. , Paulo Joao A. , Gygi Steven P. , Mimoso Claudia , Goldman Seth R. , Adelman Karen , Perry Jennifer A. , Pikman Yana , Stegmaier Kimberly , Barrachina Maria N. , Machlus Kellie R. , Hovestadt Volker , Arruda Andrea , Minden Mark D. , Voit Richard A. , Sankaran Vijay G.
Published: December 2024

Acute myeloid leukemias (AMLs) have an overall poor prognosis with many high-risk cases co-opting stem cell gene regulatory programs, yet the mechanisms through which this occurs remain poorly understood. Increased expression of the stem cell transcription factor, MECOM, underlies one key driver mechanism in largely incurable AMLs. How MECOM results in such aggressive AML phenotypes remains unknown. To address existing experimental limitations, we engineered and applied targeted protein degradation with functional genomic readouts to demonstrate that MECOM promotes malignant stem cell-like states by directly repressing pro-differentiation gene regulatory programs. Remarkably and unexpectedly, a single node in this network, a MECOM-boundcis-regulatory element located 42 kb downstream of the myeloid differentiation regulatorCEBPA, is both necessary and sufficient for maintaining MECOM-driven leukemias. Importantly, targeted activation of this regulatory element promotes differentiation of these aggressive AMLs and reduces leukemia burdenin vivo, suggesting a broadly applicable differentiation-based approach for improving therapy.
The RAB27A effector SYTL5 regulates mitophagy and mitochondrial metabolism
Authors: Lapao Ana , Johnson Lauren Sophie , Trachsel-Moncho Laura , Singh Sakshi , Wui Ng Matthew Yoke , Nakken Sigve , Eskelinen Eeva-Liisa , Simonsen Anne
Published: December 2024

SYTL5 is a member of the Synaptotagmin-Like (SYTL) protein family that differs from the Synaptotagmin family by having a unique N-terminal Synaptotagmin homology domain that directly interacts with the small GTPase RAB27A. Several SYTL protein family members have been implicated in plasma membrane transport and exocytosis, but the specific function of SYTL5 remains unknown. We here show that SYTL5 is a RAB27A effector and that both proteins localise to mitochondria and vesicles containing mitochondrial material. Mitochondrial recruitment of SYTL5 depends on its interaction with functional RAB27A. We demonstrate that SYTL5-RAB27A positive vesicles containing mitochondrial material and LAMP1 form during hypoxia and that SYTL5 and RAB27A promote mitophagy under hypoxia mimicking conditions, indicating a role for these proteins in mitophagy. Indeed, we find that SYTL5 interacts with proteins involved in vesicle-mediated transport and cellular response to stress and that its depletion compromises mitochondrial respiration and increases glucose uptake. Intriguingly, SYTL5 expression is significantly reduced in tumours of the adrenal gland, and correlates positively with survival for patients with adrenocortical carcinoma.
Caspofungin binding to iron compromises its antifungal efficacy againstCandida albicans
Authors: Pedras Andreia , Malta Luís Cláudia , Lima Luís M. P. , Mil-Homens Dalila , Amaral Catarina , Duarte Américo G. , Antunes Wilson , Gaspar-Cordeiro Ana , Louro Ricardo O. , Lamosa Pedro , Soares Cláudio M. , Lousa Diana , Pimentel Catarina
Published: December 2024

Echinocandin drugs, such as caspofungin, inhibit the synthesis of β-1,3-D-glucans, which are essential components of the fungal cell wall. These drugs are often the preferred option for treating invasive fungal infections (IFIs) caused byCandidaspp. due to their superior efficacy compared to other antifungal agents. Iron overload conditions, which exacerbate fungal burden, are well-documented as significant risk factors for the progression of IFIs. Recent in vitro studies have suggested that iron overload may also reduce the efficacy of cell wall-perturbing agents, such as echinocandins, againstCandida albicans, by altering the composition of the fungal cell wall. Here, we show that iron loading conditions which do not interfere with the cell wall composition are still capable of recapitulating the caspofungin-resistant phenotype induced by iron inC. albicans. Spectroscopic analyses provided evidence that caspofungin binds to iron through its ethylenediamine moiety and two amide groups. Consistent with the in vitro activity of β-1,3-D-glucan synthase, molecular dynamics simulations revealed that, when bound to iron, caspofungin undergoes conformational changes that may reduce its ability to inhibit the enzyme. Importantly, the in vivo antifungal efficacy of caspofungin is compromised in aGalleria mellonellamodel of IFI caused byC. albicanssimulating a context of iron overload. This effect may extend beyondC. albicansinfections, as the antagonism between iron and caspofungin was also observed in other medically important fungi causing IFIs.
Effective Markovian dynamics method of solving non-Markovian dynamics of stochastic gene expression
Authors: Li Youming , Jia Chen
Published: December 2024

Experiments have shown that over 10% of proteins are degraded non-exponentially. Gene expression models for non-exponentially degraded proteins are notoriously difficult to solve since the underlying stochastic dynamics is non-Markovian. Here we develop an effective Markovian dynamics (EMD) method which converts a large class of non-Markovian models into effective Markovian ones so that they have the same mRNA and protein distributions at any fixed time. Using the EMD approach, we analytically solve some classical gene expression models with non-exponential or delayed protein decay, whose exact distributions are previously unknown and fail to be obtained using conventional queueing theory. Our theory successfully explains why non-exponentially degraded proteins on average have smaller mRNA-protein correlation than exponentially degraded proteins, and it predicts that bimodality is significantly enhanced in the presence of delayed protein degradation.
Behavior and survival of earthworm (Eisenia andrei) to exposure to glyphosate-contaminated weed compost
Authors: Vazquez Maria Luisa Velazquez , Ortiz-Ceballos Gustavo C. , Yáñez-Rivera Beatriz , Ortiz-Ceballos Angel I.
Published: December 2024

Weeds growing in crops contribute to the maintenance of soil biodiversity; for example, they are a source of organic matter and nutrients for soil invertebrates. However, little is known about the impact of glyphosate-contaminated weeds on the behavior and survival of earthworms. The objective of this study was to evaluate the behavior and survival of the earthwormEisenia andreiupon exposure to a glyphosate-contaminated weed compost. The study employed standardized avoidance and acute tests to assess the repellency and mortality ofE. andreiearthworms at four doses of the commercial herbicide (l/ha): Control = 0, Low = 2, Medium = 4, and High = 6. The avoidance essay results indicated that earthworms with similar biomass did not avoid glyphosate-contaminated weed composts, with avoidance rates < 80%. However, the acute test revealed that increasing the herbicide dose led to a reduction in earthworm growth and mortality. Consequently, it was concluded that weed composts with glyphosate exerted a toxic effect on the survival ofE. andrei. It is recommended that future studies focus on the microbiota associated withE. andreiin the decomposition of the weed and the degradation of the herbicide.
Donor Strand Complementation and Calcium Ion Coordination Drive the Chaperone-free Polymerization of Archaeal Cannulae
Authors: Sleutel Mike , Sonani Ravi R. , Miller Jessalyn G. , Wang Fengbin , Socorro Andres Gonzalez , Chen Yang , Martin Reece , Demeler Borries , Rudolph Michael J. , Alva Vikram , Remaut Han , Egelman Edward H. , Conticello Vincent P.
Published: December 2024

Cannulae are tubular protein filaments that accumulate on the extracellular surface of the hyperthermophilic archaeonPyrodictium abyssiduring cell division. Cannulae have been postulated to act as a primitive extracellular matrix through which cells could communicate or exchange material, although their native biological function remains obscure. Here, we report cryoEM structural analyses ofex vivocannulae and ofin vitroprotein assemblies derived from recombinant cannula-like proteins. Three-dimensional reconstructions ofP. abyssicannulae revealed that the structural interactions between protomers in the native and recombinant filaments were based on donor strand complementation, a form of non-covalent polymerization in which a donor β-strand from one subunit is inserted into an acceptor groove in a β-sheet of a neighboring subunit. Donor strand complementation in cannulae is reinforced through calcium ion coordination at the interfaces between structural subunits in the respective assemblies. While donor strand complementation occurs during the assembly of chaperone-usher pili, this process requires the participation of accessory proteins that are localized in the outer membrane. In contrast, we demonstrate that calcium ions can induce assembly of cannulae in the absence of other co-factors. Crystallographic analysis of a recombinant cannula-like protein monomer provided evidence that calcium ion binding primes the precursor for donor strand invasion through unblocking of the acceptor groove. Bioinformatic analysis suggested that structurally homologous cannula-like proteins occurred within the genomes of other hyperthermophilic archaea and were encompassed within the TasA superfamily of biomatrix proteins. CryoEM structural analyses of tubular filaments derived fromin vitroassembly of a recombinant cannula-like protein from an unculturedHyperthermusspecies revealed a common mode of assembly to thePyrodictiumcannulae, in which donor strand complementation and calcium ion binding stabilized longitudinal and lateral assembly in tubular 2D sheets.
Osthole Suppresses Prostate Cancer Progression by Modulating PRLR and the JAK2/STAT3 Signaling Axis
Authors: Yan Linjun , He Yuanqiao , Cui Qi , Wang Xiaohong , Lv Feng , Cao Keyue , Shao Yuanjian
Published: December 2024

Prostate cancer is a common malignancy in men with limited effective treatment options, highlighting the urgent need for novel therapeutic approaches. Osthole, a natural coumarin compound with antitumor properties, has demonstrated potential in targeting various cancers. This study investigates the therapeutic effects of Osthole in prostate cancer by focusing on its ability to target the Prolactin Receptor (PRLR) and modulate the JAK2/STAT3 signaling pathway. Using a combination of network pharmacology, in vitro assays, and in vivo experiments, we first employed network pharmacology to predict Osthole’s potential targets, identifying 68 targets shared with prostate cancer, including AKT1, TNF, IL6, STAT3, and CTNNB1. We then confirmed these targets and assessed the effects of Osthole on cell proliferation, migration, and apoptosis using the Cell Counting Kit-8 (CCK-8) and transwell invasion assays. To further elucidate the molecular interactions and protein expression levels, we employed molecular docking and western blot analysis. Our findings revealed that Osthole significantly inhibited prostate cancer cell proliferation and migration in a dose-dependent manner and reduced tumor volume in in vivo assays. Western blot analysis also indicated that Osthole downregulated PRLR expression and decreased the phosphorylation of JAK2 and STAT3, suggesting the inhibition of the JAK2/STAT3 pathway. These results collectively highlight the therapeutic potential of Osthole in targeting prostate cancer cells through PRLR and modulating the JAK2/STAT3 pathway, warranting further clinical exploration.
Mapping of Shore Area Wetlands in Lake Tana Biosphere Reserve, Ethiopia Using Sentinel-1A SAR and Multi-Source Data
Authors: Wondim Yirga Kebede , Melese Ayalew Wondie , Assefa Workiyie Worie
Published: December 2024

Shore area wetlands (lacustrine fringe) play a critical role as ecotones that support biodiversity, provide habitats for spawning and refuge, and exhibit high levels of primary productivity. They facilitate significant exchanges of materials between aquatic and terrestrial ecosystems. To effectively manage and preserve these important resources, it is essential to understand their distribution, size, and dynamic changes. This study aimed to create an accurate map of shoreline wetlands using multi-temporal and multi-source data, wetland indicators (hydrology, vegetation, hydric soils), and radar imagery from Sentinel-1A, employing Geomatica software. Additionally, ArcGIS software was used to map the topographic position, Lake Bathymetry, and hydric soil indicators for wetlands. The analytical hierarchy process and weighted overlay methods were also applied in the mapping process for integrating all the indicators to obtain the final extent of shoreline wetlands. The topography position wetland indicator map covered about 55,364ha, while hydric soils covered around 55,151 ha within a 3 km buffer from Lake Tana. The map of hydrology indicator for wetlands revealed that permanently inundated areas accounted for roughly 591,312 ha, and when temporarily inundated areas were included, the total coverage increased to 607,053 ha. Hydrophytic vegetation, including invasive water hyacinth, covered over 74,772 ha. Overall, shoreline wetlands were predominantly located within three kilometers of the terrestrial area from Lake Tana, totaling 26,664 ha. The overall accuracy of land use and cover classification was recorded at 79%, with a Kappa statistic of 0.70, indicating that the resulting map is of acceptable quality. The integration of multi-temporal and multi-source data, along with wetland indicators and radar imagery from Sentinel-1A using Geomatica software, has provided valuable insights into the spatial distribution of shoreline wetlands in Lake Tana. The findings from this study will serve as an important reference for future research aimed at effectively managing and conserving these vital resources.
The genetic diversity and populational specificity of the human gut virome at single nucleotide resolution
Authors: Wang Xiuchao , Dong Quanbin , Huang Pan , Yang Shuai , Gao Mengke , Zhang Chengcheng , Zhang Chuan , Deng Youpeng , Huang Zijing , Ma Beining , Jiao Yuwen , Zhou Yan , Wu Tingting , Zou Huayiyang , Shi Jing , Sheng Yanhui , Wang Yifeng ,   CGVR Consortium, Tang Liming , Hu Shixian , Duan Yi , Sun Wei , Chen Wei , Zhai Qixiao , Kong Xiangqing , Chen Lianmin
Published: December 2024

Large-scale characterization of gut viral genomes provides strain-resolved insights into host-microbe interactions. However, existing viral genomes are mainly derived from Western populations, limiting our understanding of global gut viral diversity and functional variations necessary for personalized medicine and addressing regional health disparities.

Here, we introduce the Chinese Gut Viral Reference (CGVR) set, consisting of 120,568 viral genomes from 3,234 deeply sequenced fecal samples collected nationwide, covering 72,751 viral species-level clusters (VSCs), nearly 90% of which are absent from current databases. Analysis of single nucleotide variations (SNVs) in 233 globally prevalent VSCs revealed that 18.9% showed significant genetic stratification between Chinese and non-Chinese populations, potentially linked to bacterial infection susceptibility. The predicted bacterial hosts of population-stratified viruses exhibit distinct genetic components associated with health-related functions, including multidrug resistance. Additionally, viral strain diversity at the SNV level correlated with human phenotypic traits, such as age and gastrointestinal issues like constipation. Our analysis also indicates that the human gut bacteriome is specifically shaped by the virome, which mediates associations with human phenotypic traits.

This foundational resource underscores the unique genetic makeup of the gut virome across populations and emphasizes the importance of recognizing gut viral genetic heterogeneity for deeper insights into regional health implications.
Search for singly charmed dibaryons in baryon-baryon scattering
Authors: Cui Yao , Wu Yuheng , Huang Hongxia , Ping Jialun , Zhu Xinmei
Published: December 2024

We perform a systematical investigation of the singly charmed dibaryon system with strangeness numbers S=−1, −3, and −5 in the framework of the chiral quark model. Two resonance states with strangeness numbers S=−1 are obtained in the baryon-baryon scattering process. In the ΛΛc and NΞc* scattering phase shifts, the

Σ

Σ

c

appears as a resonance state with the mass and width 3591–3614 MeV and 11.75 MeV, respectively. In the NΞc and NΞc′ scattering phase shifts, the ΣΣc* exhibits as a resonance state with the mass and width 3621–3624 MeV and 14.9 MeV, respectively. All these heavy-flavor dibaryons are worth searching for in experiments. Besides, we would like to emphasize that the coupling calculation between the bound channels and open channels is indispensable. The study of the scattering process maybe an effective way to look for the genuine resonances.

Published by the American Physical Society
2024
95 GeV Higgs boson and spontaneous
CP
-violation at the finite temperature
Authors: Gao Jing , Han Xiao-Fang , Ma Jinghong , Wang Lei , Xu Haotian
Published: December 2024

The ATLAS and CMS collaborations reported a diphoton excess in the invariant mass distribution around the 95.4 GeV with a local significance of 3.1σ. Moreover, there is another 2.3σ local excess in the bb¯ final state at large electron-positron collider in the same mass region. A plausible solution is that the Higgs sector is extended to include an additional Higgs boson with a mass of 95.4 GeV. We study a complex singlet scalar extension of the two-Higgs-doublet model in which the 95.4 GeV Higgs is from the mixing of three CP-even Higgs fields. In addition, the extended Higgs potential can achieve spontaneous CP-violation at the finite temperature and restore CP symmetry at the present temperature of the Universe. We find that the model can simultaneously explain the baryon asymmetry of the Universe, the diphoton and bb¯ excesses around the 95.4 GeV while satisfying various relevant constraints including the experiments of collider and electric dipole moment.

Published by the American Physical Society
2024
Maximal flavor violating
U(1)Lμ−Lτ
model with a singly charged scalar
Authors: Huang Fei , Sun Jin
Published: December 2024

The U(1)Lμ−Lτ Z′ model has emerged as a promising candidate to address the longstanding muon (g−2)μ anomaly. Flavor-conserving Z′ interactions are subject to stringent constraints from the neutrino trident process and NA64μ experiments, which limit the Z′ mass to mZ′<40  MeV. To circumvent these constraints, flavor-conserving Z′ interactions can be converted into maximal flavor-violating interactions through a discrete exchange symmetry. Maximal flavor-violating Z′ interactions contribute to τ→μνν¯ via the neutral current, yet the parameter space for this process conflicts with the (g−2)μ allowed regions. To resolve this conflict, we propose introducing a singly charged scalar that mediates via charged current interactions. This scalar is anticipated to produce a negative contribution to the lepton (g−2)l while concurrently inducing the tau decay τ→μνν¯. Three distinct scenarios arise from the introduction of singly charged scalars: the OLL operator, driven by weak singlet and triplet, and the OLR operator, driven by weak doublet. Our analysis of the phenomenology in these three cases reveals that the tension between the muon (g−2)μ anomaly and τ→μνν¯ for large Z′ masses can be effectively alleviated only by the singly charged scalars from the weak triplet, whereas the singlet and doublet scenarios fall short. Furthermore, the singly charged scalars from the weak triplet offer an additional explanation for the electron (g−2)e anomaly. Our findings indicate that weak triplets could play a crucial role in Z′ models, potentially providing valuable insights for future research into U(1) frameworks.

Published by the American Physical Society
2024
Finite Feynman integrals
Authors: Gambuti Giulio , Kosower David A. , Novichkov Pavel P. , Tancredi Lorenzo
Published: December 2024

We describe an algorithm to organize Feynman integrals in terms of their infrared properties. Our approach builds upon the theory of Landau singularities, which we use to classify all configurations of loop momenta that can give rise to infrared divergences. We then construct bases of numerators for arbitrary Feynman integrals, which cancel all singularities and render the integrals finite. Through the same analysis, one can also classify so-called evanescent and evanescently finite Feynman integrals. These are integrals whose vanishing or finiteness relies on properties of dimensional regularization. To illustrate the use of these integrals, we display how to obtain a simpler form for the leading-color two-loop four-gluon scattering amplitude through the choice of a suitable basis of finite integrals. In particular, when all gluon helicities are equal, we show that with our basis the most complicated double-box integrals do not contribute to the finite remainder of the scattering amplitude.

Published by the American Physical Society
2024
Theory of spin and orbital charge conversion at the surface states of
Bi1−xSbx
topological insulator
Authors: Pezo Armando , George Jean-Marie , Jaffrès Henri
Published: December 2024

Topological insulators are quantum materials involving time-reversal protected surface states making them appealing candidates for the design of the next generation of highly efficient spintronic devices. The very recent observation of large transient spin-charge conversion and subsequent powerful THz emission from Co/Bi1−xSbx bilayers clearly demonstrates such potentiality and feasibility for the near future. Among the exotic properties appearing in and at the surface of such quantum materials, spin-momentum locking and Rashba-Edelstein effects remain as key ingredients to effectively convert the spin degree of freedom into a charge or a voltage signal. In this work, we extend our analyses to the quantification of orbital momentum-locking and related orbital charge conversion effects in Bi.85Sb.15 via orbital Rashba-Edelstein effects. In that sense, we will provide some clear theoretical and numerical insights implemented by multiorbital and slab tight-binding methods to clarify our recent experimental results obtained by THz spectroscopy in the time domain.

Published by the American Physical Society
2024
New audiences’ theater attendance in China: the impacts of transmedia storytelling, fan economy and social media marketing
Authors: Chen Xi , Zhao Mingda
Published: December 2024

Purpose

With the rise of new generations of audiences, the marketing environment of theaters has undergone significant changes. The study investigates how transmedia storytelling, fan economy and social media marketing influence new audiences’ curiosity and drive their attendance intention at theater performances.

Design/methodology/approach

This study utilized an online questionnaire, collecting 1,032 valid responses from participants predominantly aged 18–30 (62.02%). Respondents from mainland China completed measures on five main variables.

Findings

The study reveals that curiosity played a mediating role in the influence of transmedia adaptation and social media marketing on attendance. Specifically, transmedia adaptation and social media marketing both positively impact attendance through curiosity. However, idol starring does not significantly affect either curiosity or attendance.

Research limitations/implications

Limitations include potential recall bias due to a high proportion of respondents with prior theater experience and preliminary measurement scales for idol starring. Future research could explore the interactions between transmedia adaptation and social media marketing and consider cross-cultural studies.

Practical implications

The study suggests that transmedia adaptation and social media marketing can effectively attract and engage new theatergoers.

Social implications

By targeting new audiences, this research highlights how modern marketing strategies can enhance audience engagement and accessibility of performing arts in China.

Originality/value

This research provides novel insights into new audiences’ decision-making process of their first visit to the theater. It offers a unique perspective on attendance behavior, addressing gaps in understanding audience engagement in performing arts.
Cartography of controversy as an approach to inquiry into care and the city: a case study with architecture students
Authors: España-Naveira Paloma , Morales Soler Eva , Blanco-López Ángel
Published: December 2024

Purpose

The purpose of this study is to design, implement and evaluate an instructional module aimed at architecture students, using the cartography of controversy approach to inquire into the issue of spaces of care in the city. This research addresses the critical need for students to engage with the complexities of care in domestic and public spaces.

Design/methodology/approach

This research employs a case study approach, complemented by elements of action research, to investigate the impact of an instructional module on architecture students. The module is implemented with 18 architecture students. Results are obtained through the analysis of students' works: initial controversy maps, collaborative cartography and final design proposals.

Findings

The results obtained suggest that the instructional module helped students to reflect on spaces of care in the city from a multidimensional, systemic and critical perspective. A significant shift in students' perspectives on it, with a notable increase in a more critical position by the end of the module. The initial controversy maps made it possible to visualize the level of complexity of the controversy perceived by the students. The projects carried out by the students relate and develop aspects of care that appeared in the initial controversy maps and collaborative mapping.

Originality/value

This study contributes to the field of architectural education by highlighting the value of cartography of controversy as a novel approach for fostering a critical view of spaces of care in the city. This could help students in designing their projects to address the complexities of care spaces in the city.
Unravelling the impact: supervisor incivility on employee health and the role of affective rumination
Authors: Kyei-Poku Ivy , Orozco Quijano Elsa Patricia
Published: December 2024

Purpose

This study investigates the influence of supervisor incivility on two important employee health-related outcomes–somatic complaints and emotional exhaustion. Similarly, the study examines the role of affective rumination as a mediator between the supervisor incivility–somatic complaints and emotional exhaustion relationship.

Design/methodology/approach

We collected data in three phases, separated by an interval of four weeks. The final sample comprised 154 employees from diverse occupations and professions. Partial least squares–structural equation modelling was used to examine the research model.

Findings

Employees’ perceptions of supervisor incivility increased somatic complaints and emotional exhaustion experiences. Moreover, drawing on the conservation of resources and the effort-recovery theories, we found support for the mediating role of affective rumination for somatic complaints but not for emotional exhaustion.

Practical implications

To help protect organizations from financial and productivity losses related to supervisor incivility, we encouraged organizations to be aware of supervisors’ uncivil behaviours and provide training on how to deal with such behaviours. We further advise organizations to coach supervisors on uncivil prevention and the importance of modelling proper behaviours.

Originality/value

This study expands the limited knowledge of supervisor incivility and health outcomes. Specifically, using a time-lagged design, the findings show that affective rumination is an essential mechanism for understanding the impact of supervisor incivility on health outcomes. Moreover, understanding how supervisor incivility impacts employee health outcomes is vital for advancing theory and designing interventions to mitigate adverse effects.
Include, care, reward and enhance to build a well-being HRM system based on perceived effectiveness and fairness of HRM practices
Authors: Boulet Maude
Published: December 2024

Purpose

One of the criticisms that can be addressed to the existing HRM literature is that performance is often the primary target, leaving well-being as a secondary consideration. This study aims to put employee well-being at the center of HRM concerns. By focusing on needs-supply fit and social exchange theories, our approach focuses on employees’ perceptions of the effectiveness and fairness of HRM practices.

Design/methodology/approach

Based on a sample of 740 workers collected via an electronic survey, HRM practices were grouped into bundles using factor analysis to form an HRM system. The impact of the HRM system and its bundles on employee well-being and job performance was analyzed using structural equation modeling (SEM). The mediating role of well-being was tested with Stata’s medsem package.

Findings

The HRM system and its bundles (Include, Care, Reward and Enhance) derived from the perceived effectiveness and fairness of HRM practices have a positive direct effect on employee well-being and a positive indirect effect on job performance through the mediating role of well-being. However, the bundles have no direct effect on job performance, highlighting the importance of integrating employee well-being into HRM concerns.

Originality/value

These findings reveal that when employees consider HRM practices to be fair and effective, it promotes their well-being, which has a positive impact on their job performance.