bluuebunny/crossref_metadata_2025 huggingface dataset:
Nomogram model for predicting invasive placenta in patients with placenta previa: integrating MRI findings and clinical characteristics
Authors: Huang Fang , Lyu Guo-Rong , Lai Qing-Quan , Li Yuan-Zhe
Published: January 2024

This study aims to validate a nomogram model that predicts invasive placenta in patients with placenta previa, utilizing MRI findings and clinical characteristics. A retrospective analysis was conducted on a training cohort of 269 patients from the Second Affiliated Hospital of Fujian Medical University and a validation cohort of 41 patients from Quanzhou Children’s Hospital. Patients were classified into noninvasive and invasive placenta groups based on pathological reports and intraoperative findings. Three clinical characteristics and eight MRI signs were collected and analyzed to identify risk factors and develop the nomogram model. The mode’s performance was evaluated in terms of its discrimination, calibration, and clinical utility. Independent risk factors incorporated into the nomogram included the number of previous cesarean sections ≥ 2 (odds ratio [OR] 3.32; 95% confidence interval [CI] 1.28–8.59), type-II placental bulge (OR 17.54; 95% CI 3.53–87.17), placenta covering the scar (OR 2.92; CI 1.23–6.96), and placental protrusion sign (OR 4.01; CI 1.06–15.18). The area under the curve (AUC) was 0.908 for the training cohort and 0.803 for external validation. The study successfully developed a highly accurate nomogram model for predicting invasive placenta in placenta previa cases, based on MRI signs and clinical characteristics.
The local variation of the Gaussian modulus enables different pathways for fluid lipid vesicle fusion
Authors: Bottacchiari Matteo , Gallo Mirko , Bussoletti Marco , Casciola Carlo Massimo
Published: January 2024

Viral infections, fertilization, neurotransmission, and many other fundamental biological processes rely on membrane fusion. Straightforward calculations based on the celebrated Canham–Helfrich elastic model predict a large topological energy barrier that prevents the fusion process from being thermally activated. While such high energy is in accordance with the physical barrier function of lipid membranes, it is difficult to reconcile with the biological mechanisms involved in fusion processes. In this work, we use a Ginzburg–Landau type of free energy that recovers the Canham–Helfrich model in the limit of small width-to-vesicle-extension ratio, with the additional ability to handle topological transitions. We show that a local modification of the Gaussian modulus in the merging region both dramatically lowers the elastic energy barrier and substantially changes the minimal energy pathway for fusion, in accordance with experimental evidence. Therefore, we discuss biological examples in which such a modification might play a crucial role.
The long-term effects of heated tobacco product exposure on the central nervous system in a mouse model of prodromal Alzheimer's disease
Authors: Yamada Hidetada , Yamazaki Yu , Takebayashi Yoshiko , Yazawa Kyosuke , Sasanishi Miwako , Motoda Atsuko , Nakamori Masahiro , Morino Hiroyuki , Takahashi Tetsuya , Maruyama Hirofumi
Published: January 2024

Heated tobacco products (HTPs) have emerged as novel alternatives to conventional cigarettes (CCs), marketed by the tobacco industry as having a reduced potential for harm. Nevertheless, a significant dearth of information remains regarding the long-term effects of HTPs on the central nervous system (CNS). Here, we sought to shed light on the repercussions of prolonged exposure to HTPs on the CNS, employing a mouse model mimicking prodromal Alzheimer's disease (AD). Our study entailed subjecting App knock-in mice to 16 weeks of HTP exposure, administered 5 days per week, with serum cotinine concentration serving as confirmation of HTP exposure within this model. Histological analysis, aimed at assessing amyloid pathology, unveiled a minimal impact attributable to HTPs. However, exploration of differentially expressed genes in the cerebral cortex, using unadjusted p values, indicated an association between HTP exposure and non-inflammatory pathways, specifically linked to neurohypophyseal and neuropeptide hormone activity within the CNS. Of note, similar results have already been observed after exposure to CCs in vivo. Our study not only contributes insights into the potential non-inflammatory effects of HTPs within the context of AD pathogenesis but also underscores the significance of continued research to comprehend the full scope of their impact on the CNS.
Arylsulfatases and neuraminidases modulate engagement of CCR5 by chemokines by removing key electrostatic interactions
Authors: Pinheiro Inês , Calo Nicolas , Paolini-Bertrand Marianne , Hartley Oliver
Published: January 2024

The chemokine receptor CCR5 is known to exist in cell surface subpopulations that differ in their capacity to engage ligands. One proposed explanation for this phenomenon is the presence of CCR5 species with different levels of post-translational modifications (PTMs). Tyrosine sulfation and O-glycan sialylation are PTMs that add negative charges to the extracellular domain of CCR5 and make strong contributions to chemokine binding but it is not known whether cellular mechanisms to control their levels exist. In this study we used a combination of sulfation-sensitive and sulfation-insensitive CCR5 ligands to show that the rate of turnover of CCR5 tyrosine sulfation is more rapid than the rate of turnover of the receptor itself. This suggests that the steady state level of CCR5 sulfation is maintained through the combination of tyrosine protein sulfotransferase (TPST), the trans-Golgi network (TGN)-resident ‘source enzyme, and a ‘sink’ activity that removes tyrosine sulfation from CCR5. By measuring the effects on ligand binding of knockdown and overexpression experiments, we provided evidence that non-lysosomal cellular arylsulfatases, particularly ARSG, ARSI and ARSJ, are CCR5 sulfation ‘sink’ enzymes. We also used targeted knockdown and sialylation-sensitive and insensitive chemokines to identify the sialidase NEU3 as a candidate ‘sink’ enzyme for CCR5 O-glycan sialylation. This study provides the first experimental evidence of activity of sulfatase and sialidase ‘sink’ enzymes on CCR5, providing a potential mechanism for cells to control steady-state levels of these PTMs and thereby exert dynamic control over receptor-ligand interactions at the cell surface and during receptor desensitization.
Exploring shared therapeutic targets in diabetic cardiomyopathy and diabetic foot ulcers through bioinformatics analysis
Authors: Wu Hanlin , Yang Zheming , Wang Jing , Bu Yuxin , Wang Yani , Xu Kai , Li Jing , Yan Chenghui , Liu Dan , Han Yaling
Published: January 2024

Advanced diabetic cardiomyopathy (DCM) patients are often accompanied by severe peripheral artery disease. For patients with DCM combined with diabetic foot ulcer (DFU), there are currently no good therapeutic targets and drugs. Here, we investigated the underlying network of molecular actions associated with the occurrence of these two complications. The datasets were downloaded from the Gene Expression Omnibus (GEO) database. We performed enrichment and protein–protein interaction analyses, and screened for hub genes. Construct transcription factors (TFs) and microRNAs regulatory networks for validated hub genes. Finally, drug prediction and molecular docking verification were performed. We identified 299 common differentially expressed genes (DEGs), many of which were involved in inflammation and lipid metabolism. 6 DEGs were identified as hub genes (PPARG, JUN, SLC2A1, CD4, SCARB1 and SERPINE1). These 6 hub genes were associated with inflammation and immune response. We identified 31 common TFs and 2 key miRNAs closely related to hub genes. Interestingly, our study suggested that fenofibrate, a lipid-lowering medication, holds promise as a potential treatment for DCM combined with DFU due to its stable binding to the identified hub genes. Here, we revealed a network involves a common target for DCM and DFU. Understanding these networks and hub genes is pivotal for advancing our comprehension of the multifaceted complications of diabetes and facilitating the development of future therapeutic interventions.
Targeting HDACs for diffuse large B-cell lymphoma therapy
Authors: Wu Chunyan , Song Qiao , Gao Sophie , Wu Shaoling
Published: January 2024

Histone deacetylases (HDACs) are involved in tumorigenesis and progression, however, their role in diffuse large B-cell lymphoma (DLBCL) is not well understood. In this study, we examined the expression levels, mutations, and clinical significance of HDACs in DLBCL. Additionally, we investigated the therapeutic potential of Chidamide, a novel HDAC inhibitor, to provide scientific evidence for targeting HDACs in DLBCL patients. We extracted transcriptome data of DLBCLs––including 47 lymph node samples and 337 whole-blood-cell controls––from The Cancer Genome Atlas. Bioinformatic analyses of HDAC expression, mutation, and correlation with the clinical significance of DLBCL patients were performed with the Gene Expression Profiling Interactive Analysis, GENEMANIA, and web-based software including cBioPortal and WebGestalt. To examine the therapeutic effect of Chidamide, DLBCL cell lines (WSU-DLCL-2 and DB cells) were employed. Cell proliferation and apoptosis were analyzed with Cell Counting Kit-8 and flow cytometry assays. The impact of Chidamide treatment was also analyzed by RNA sequencing of treated DB cells. Western blot was used to explore the molecular mechanism of the cytotoxicity of Chidamide on DLBCL cell lines. The expression of some HDACs (HDAC1, 2, 3, 4, 6, 7, 8, and 9) were significantly higher in the lymph node samples of DLBCL than that in whole-blood-cell controls. Moreover, we found that the mutation rate of HDACs was also higher in DLBCL tissues, although the overall survival of DLBCL patients was not associated with HDAC expression. Chidamide was found to have a cytotoxic effect on DLBCL cells in a dose-dependent manner, while transcriptome analysis and western blot revealed that using it for treatment impacted several biological processes, including PI3K/AKT signaling, mTOR signaling, the cell cycle, and apoptosis pathways. Alterations of HDAC genes, including enhanced expression and mutations, are positively related to DLBCL. Targeting HDACs with specific inhibitors such as Chidamide may represent a potential therapeutic approach for DLBCL patients.
Community-based prevalence and associated factors of sarcopenia in the Vietnamese elderly
Authors: Pham Lan-Anh Thi , Nguyen Binh Thanh , Huynh Dao Tieu , Nguyen Binh-Minh Le Thi , Tran Phuong-Anh Nhat , Van Vo Tam , Bui Hy-Han Thi , Thai Truc Thanh
Published: January 2024

Sarcopenia, a condition characterized by muscle mass decline, is one of the leading health problems in the elderly. This study determined the rate of sarcopenia according to criteria by Asian Working Group for Sarcopenia (AWGS) and related factors in elderly people. A community-based cross-sectional study was conducted in 632 people aged 60 years or over in Ho Chi Minh City. Data were collected through a predefined questionnaire and direct measurement. Sarcopenia was identified based on the Inbody 770 machine and AWGS criteria. The prevalence of sarcopenia was 32.0%. Participants with advanced age, low education, unemployment, low level of family economics and frailty were more likely to have sarcopenia. Among these, frailty had the highest impact on sarcopenia, with significantly higher odds of having sarcopenia found in participants with pre-frailty (OR = 4.80, 95% CI 2.75–8.38, p < 0.001) and frailty (OR = 21.16, 95% CI 8.96–49.97, p < 0.001). In contrast, BMI was inversely associated with sarcopenia. Sarcopenia is prevalent in the Vietnamese elderly. Apart from social demographic characteristics including age, education, employment and family economic status, frailty appeared to be an important risk factor. Early screening, referral, and treatment of sarcopenia among the elderly having a high risk of sarcopenia are recommended.
Geodetic imaging of magma ascent through a bent and twisted dike during the Tajogaite eruption of 2021 (La Palma, Canary Islands)
Authors: Przeor Monika , Castaldo Raffaele , D’Auria Luca , Pepe Antonio , Pepe Susi , Sagiya Takeshi , Solaro Giuseppe , Tizzani Pietro , Barrancos Martínez José , Pérez Nemesio
Published: January 2024

On Sept. 19th, 2021, the largest historical eruption on the island of La Palma began, which had a significant scientific, social, and economic impact. The 2021 Tajogaite eruption was characterised by short precursors, lasting only 8 days. The seismicity started on Sept. 11th with a westward and upward migration of hypocenters. Permanent GNSS stations started recording deformation on Sept. 12th on the island's western side, which reached more than 15 cm just before the eruption. After the eruption onset, the ground deformation increased, reaching a maximum on Sept. 22nd and showing a nearly steady deflation trend in the following months. To better understand the dynamics of the eruption, we exploited a joint dataset of GNSS and Sentinel-1 SBAS time series along both ascending and descending orbits. To obtain the geometry of the causative source of the ground deformation, we combined the result of a preliminary non-linear inversion and the precise location of the seismicity. The resulting geometry of the source is that of a twisted dike bending eastward. We performed inverse modelling to obtain the spatiotemporal kinematics of the opening function of the dike. The forward modelling has been realised using a 3D finite-element approach considering the island's topography. Our findings reveal a close correspondence between the magmatic intrusion and pre-eruptive seismicity. The ascent of the magma occurred along two branches, and the rheology of a previously identified ductile layer strongly affected the magma propagation process. Finally, we found evidence of an early shallow deformation, which we interpret as the effect of ascending hydrothermal fluids. Our findings highlight the need for advanced modelling to understand pre-eruptive processes in basaltic volcanoes.
Association between metabolites in tryptophan-kynurenine pathway and inflammatory bowel disease: a two-sample Mendelian randomization
Authors: Yu Fangqian , Du Yutong , Li Cong , Zhang Haiyan , Lai Weiming , Li Sheng , Ye Zhenhao , Fu Wenbin , Li Shumin , Li Xiang-Guang , Luo Ding
Published: January 2024

Previous observational studies have suggested an association between tryptophan (TRP)–kynurenine (KYN) pathway and inflammatory bowel disease (IBD). However, whether there is a causal relationship among them remains unclear. Therefore, a two-sample Mendelian randomization (MR) study was conducted to explore the potential causal effects of crucial metabolites in TRP–KYN pathway on IBD and its subtypes. Using summary data from genome-wide association studies, a two-sample MR was employed to evaluate the genetic associations between TRP and KYN as exposures and IBD as an outcome. The inverse variance weighted method was used as the primary MR analysis, with MR-Egger, weighted mode, simple mode, and weighted median methods as complementary analyses. The odds ratios (OR) and 95% confidence intervals (CI) were determined for TRP–IBD (OR 0.739, 95% CI [0.697; 0.783]), TRP–UC (OR 0.875, 95% CI [0.814; 0.942]), TRP–CD (OR 0.685, 95% CI [0.613; 0.765]), KYN–IBD (OR 4.406, 95% CI [2.247; 8.641]), KYN–UC (OR 2.578, 95% CI [1.368; 4.858], and KYN–CD (OR 13.516, 95% CI [4.919; 37.134]). Collectively, the MR analysis demonstrated a significant protective association between TRP and IBD, whereas KYN was identified as a risk factor for IBD.
Pinpointing top inhibitors for GSK3β from pool of indirubin derivatives using rigorous computational workflow and their validation using molecular dynamics (MD) simulations
Authors: Pandya Vamangi , Rao Priyashi , Prajapati Jignesh , Rawal Rakesh M. , Goswami Dweipayan
Published: January 2024

Glycogen synthase kinase-3β (GSK3β) is a pivotal protein kinase implicated in a spectrum of debilitating diseases, encompassing cancer, diabetes, and neurodegenerative disorders. While the therapeutic potential of GSK3β inhibition is widely recognized, there remains an unmet need for a rigorous, systematic analysis probing the theoretical inhibition dynamics of a comprehensive library of indirubin derivatives against GSK3β using advanced computational methodologies. Addressing this gap, this study embarked on an ambitious endeavor, leveraging indirubin—a renowned scaffold—as a template to curate a vast library of 1000 indirubin derivatives from PubChem. These were enriched with varied substitutions and modifications, identified via a structure similarity search with a Tanimoto similarity threshold of 85%. Harnessing a robust virtual screening workflow, we meticulously identified the top 10 contenders based on XP docking scores. Delving deeper, we gauged the binding free energy differentials (ΔGBind) of these hits, spotlighting the top three compounds that showcased unparalleled binding prowess. A comparative pharmacophore feature mapping with the reference inhibitor OH8, co-crystallized with GSK3β (PDB ID: 6Y9R), was undertaken. The binding dynamics of these elite compounds were further corroborated with 100 ns molecular dynamics simulations, underlining their stable and potent interactions with GSK3β. Remarkably, our findings unveil that these indirubin derivatives not only match but, in certain scenarios, surpass the binding affinity and specificity of OH8. By bridging this research chasm, our study amplifies the therapeutic promise of indirubin derivatives, positioning them as frontrunners in the quest for groundbreaking GSK3β inhibitors, potentially revolutionizing treatments for a myriad of ailments.
Alterations in mitochondria isolated from peripheral blood mononuclear cells and tumors of patients with epithelial ovarian cancers
Authors: Charoenkwan Kittipat , Apaijai Nattayaporn , Sriwichaiin Sirawit , Chattipakorn Nipon , Chattipakorn Siriporn C.
Published: January 2024

Metabolic alterations play an essential role in ovarian carcinogenesis. The flexibility of mitochondrial functions facilitates cellular adaptation to the tough environment associated with carcinogenesis. An understanding of the differences in mitochondrial functions in normal ovaries and cancers could provide a basis for further exploration of future mitochondria-based screening, diagnosis, prognostic prediction, and targeted therapy for epithelial ovarian cancers. The main objective of this study was to assess mitochondrial function profiles measured from PBMCs and ovarian tissues of epithelial ovarian cancers in comparison with normal ovaries. A total of 36 patients were recruited for the study, all of whom underwent primary surgical treatment for malignant epithelial ovarian neoplasm. Of these, 20 patients were in the early stage and 16 patients were in the advanced stage. Additionally, 21 patients who had pelvic surgery for benign gynecologic conditions, with normal ovaries incidentally removed, were recruited as controls. At the time of surgery, a blood sample was collected from each participant for PBMC isolation, and ovarian tissue was retained for molecular studies. These studies included the examination of oxidative stress, mitochondrial mass, mitochondrial respiration, mitochondrial reactive oxygen species (ROS), mitochondrial membrane potential (MMP) changes, and mitochondrial swelling. Clinical and histopathological data were also collected and compared between different stages of epithelial ovarian cancers: early-stage (group 1), advanced-stage (group 2), and normal ovaries (group 3). The levels of cellular oxidative stress, mitochondrial mass, and mitochondrial biogenesis in the peripheral blood mononuclear cells (PBMCs) of participants with ovarian cancer were significantly lower than those of the control group. However, the mitochondrial respiratory parameters measured from the PBMCs were similar across all three groups. Furthermore, mitochondrial membrane depolarization and mitochondrial swelling were observed in ovarian tissues of both early-stage and advanced-stage cancer groups. We demonstrated the dynamic nature of mitochondrial ROS production, biogenesis, and respiratory function in response to epithelial ovarian carcinogenesis. The flexibility of mitochondrial functions under diverse conditions may make it a challenging therapeutic target for ovarian cancer.
Short- and long-term effects of essential oils on swine spermatozoa during liquid phase refrigeration
Authors: Troisio Ilaria , Bertocchi Martina , Ventrella Domenico , Scozzoli Maurizio , Di Vito Maura , Truzzi Eleonora , Benvenuti Stefania , Mattarelli Paola , Bacci Maria Laura , Elmi Alberto
Published: January 2024

The application of essential oils as potential alternatives to antibiotics in swine semen storage is promising, due to their antioxidant and antibacterial properties. However, detrimental effects on spermatozoa should be clarified first. The aim of this study was to evaluate 9 essential oils (EOs; Satureja montana, Pelargonium graveolens, Cymbopogon nardus, Melaleuca leucadendron, Eucaliptus globulus, Citrus limon, Lavandula angustifolia, Lavandula hybrida, Mentha piperita) and a blend (GL mix) on key morpho-functional parameters of swine spermatozoa. Test compounds were firstly chemo-characterized and experimental doses were prepared by suspending a fixed number of spermatozoa with 3 different concentrations (0.1, 0.5, 1 mg/mL) of EOs. Experimental doses were stored at 16 °C and sampled after 3 and 120 h for analysis. Overall, S. montana, P. graveolens and L. angustifolia EOs induced the strongest alterations, with C. nardus and E. globulus EOs being the best tolerated. Swine spermatozoa represent a good preliminary testing platform to screen toxicity and its different patterns. The comprehensive overview on the potential mechanisms of action of some of the most common EOs, despite of the direct aim of the study being swine reproduction, may be exploited in other fields of research within both veterinary and human medicine.
Stepwise reduction of graphene oxide and studies on defect-controlled physical properties
Authors: Das Poulomi , Ibrahim Sk , Chakraborty Koushik , Ghosh Surajit , Pal Tanusri
Published: January 2024

Graphene oxide (GO) is a monolayer of oxidized graphene which is a convenient and potential candidate in a wide range of fields of applications like electronics, photonics, optoelectronics, energy storage, catalysis, chemical sensors, and many others. GO is often composed of various oxygen-containing groups such as hydroxyl, carboxyl, and epoxy. One appealing method for achieving graphene-like behavior with sp2 hybridized carbon is the reduction of GO i.e. formation of reduced graphene oxide (RGO). A stepwise reduction GO to form a family of RGO, containing various quantities of oxygen-related defects was carried out. Herein, the defects related chemical and physical properties of GO and the RGO family were studied and reported in an effort to understand how the properties of RGO vary with the reduction rate. Although there are several reports on various features and applications of GO and RGO but a systematic investigation of the variation of the physical and chemical properties in RGO with the varying quantities of oxygeneous defects is imperative for the engineered physical properties in achieving the desired field of applications. We have attempted to look at the role of sp2 and sp3 carbon fractions, which are present in RGO-based systems, and how they affect the electrical, optoelectronic, and adsorption characteristics.
Validation of a method to assess night myopia in a clinical setting
Authors: Gené-Sampedro Andrés , Basulto Marset Mercedes , Monsálvez Romin Daniel , Montecelo Salvado Susana , Bueno-Gimeno Inmaculada
Published: January 2024

A study was conducted with 115 subjects who regularly drove at night to validate a refraction protocol for detecting refractive visual changes from daytime to nighttime conditions. Objective and subjective refractions were performed in both photopic and mesopic conditions, with a dark adaptation period before the mesopic subjective refraction. The results showed that in mesopic conditions, visual acuity decreased by 0.2 logMAR units on average (p < 0.01), and there was a myopic refractive shift of − 0.36 ± 0.20 D (p < 0.01). Most subjects (92.2%) exhibited a myopic refractive shift of at least 0.12 D. Compensation of refractive shift improved mesopic visual acuity by 0.06 logMAR on average (p < 0.01) and higher refractive shifts showed higher improvement. Night Rx was preferred by 82.1% of subjects with myopic refractive shift. Gender and age did not significantly affect the refractive shift, although myopes showed a higher shift compared to emmetropes (p < 0.01). The refractive shift remained stable over time when the time slot of the day did not change (p < 0.01). Night Rx protocol proved to be a robust and accurate method for identifying drivers with refractive changes when transitioning from photopic to mesopic conditions. The high prevalence and inter-individual variability of Rx shift highlight the need of customized refraction.
Inter-model robustness of the forced change of the ENSO-Indian Summer Monsoon Teleconnection
Authors: Aneesh Sundaresan , Bódai Tamás
Published: January 2024

Concerning the robustness of predicting the forced response of the El Niño—Southern Oscillation-Indian summer monsoon (ENSO-ISM) teleconnection based on 9 CMIP-class models, we come to distinguish three time periods. (1) In the late 20th century, the trend was insignificant in most models, which does not permit a statement on robustness in this period. Thus the weakening of the teleconnection reported from the observational data might not be truly forced. (2) Furthermore, we find it typical that under global warming in the first part of the 21st century, the teleconnection is strengthening or non-decreasing. This considerable inter-model robustness is owed to an increasing ENSO variability as well as coupling strength. (3) At the end of the 21st century, however, under strong forcing, the teleconnection change is not robustly modeled: the ENSO variability change is not projected robustly across models, either with respect to the start or the rate of the ENSO variance decline, competing this time with an increase of the coupling strength. The difference in the projected coupling coefficient between models is mainly attributed to the disagreement in the projected ENSO-induced changes in the regional Hadley cell and SST patterns over the ISM domain, despite the agreement on the projected eastward shift of the Walker cell over the Pacific Ocean.
El Niño phase transition by deforestation in the Maritime Continent
Authors: Wei Shengbiao , Wang Xin , Wang Chunzai , Xie Qiang
Published: January 2024

El Niño-Southern Oscillation (ENSO), an irregular alternation between warm El Niño and cold La Niña phases, is the most prominent air-sea interaction phenomenon on Earth and greatly affects global weather and climate. Nevertheless, it remains unclear whether human activity can alter the characteristics of ENSO. We demonstrate, using reanalysis data and coupled general circulation models, that deforestation over the Maritime Continent (MC) favors a rapid transition of El Niño to La Niña. Deforestation over the MC can induce a regional enhancement in precipitation, which in turn leads to the strengthening of the easterly trade winds over the western equatorial Pacific owing to the Gill-response. These stronger trade winds, by inducing a shoaled thermocline in the eastern Pacific, are favorable for the development of cold sea surface temperature anomalies in the eastern equatorial Pacific during El Niño decaying years. Our results suggest that El Niño is more likely to be followed by La Niña if MC deforestation continues in the future.
Delayed coastal inundations caused by ocean dynamics post-Hurricane Matthew
Authors: Park Kyungmin , Di Lorenzo Emanuele , Zhang Yinglong J. , Wang Harry , Ezer Tal , Ye Fei
Published: January 2024

Post Hurricane Abnormal Water Level (PHAWL) poses a persistent inundation threat to coastal communities, yet unresolved knowledge gaps exist regarding its spatiotemporal impacts and causal mechanisms. Using a high-resolution coastal model with a set of observations, we find that the PHAWLs are up to 50 cm higher than the normal water levels for several weeks and cause delayed inundations around residential areas of the U.S. Southeast Coast (USSC). Numerical experiments reveal that while atmospheric forcing modulates the coastal PHAWLs, ocean dynamics primarily driven by the Gulf Stream control the mean component and duration of the shelf-scale PHAWLs. Because of the large spatial impact of the post-hurricane oceanic forcing, the coastal hazards are not limited to a direct hit from a hurricane but can be detected throughout the USSC where the oceanic processes reach.
Historical footprints and future projections of global dust burden from bias-corrected CMIP6 models
Authors: Liu Jun , Wang Xiaofan , Wu Dongyou , Wei Hailun , Li Yu , Ji Mingxia
Published: January 2024

Dust aerosols significantly affect the Earth’s climate, not only as a source of radiation, but also as ice nuclei, cloud condensation nuclei and thus affect CO2 exchange between the atmosphere and the ocean. However, there are large deviations in dust model simulations due to limited observations on a global scale. Based on ten initial Climate Models Intercomparison Project Phase Six (CMIP6) models, the multi-model ensemble (MME) approximately underestimates future changes in global dust mass loading (DML) by 7–21%, under four scenarios of shared socioeconomic pathways (SSPs). Therefore, this study primarily constrains the CMIP6 simulations under various emission scenarios by applying an equidistant cumulative distribution function (EDCDF) method combined with the Modern-Era Retrospective Analysis for Research and Applications version 2 (MERRA2) datasets based on observation assimilation. We find that the results (19.0–26.1 Tg) for 2000–2014 are closer to MERRA2 (20.0–24.8 Tg) than the initial simulations (4.4–37.5 Tg), with model deviation reduced by up to 75.6%. We emphasize that the DML during 2081–2100 is expected to increase significantly by 0.023 g m–2 in North Africa and the Atlantic region, while decreasing by 0.006 g m–2 in the Middle East and East Asia. In comparison with internal variability and scenario uncertainty, model uncertainty accounts for more than 70% of total uncertainty. When bias correction is applied, model uncertainty significantly decreases by 65% to 90%, resulting in a similar variance contribution to internal variability.
Cholesterol modulates type I/II TGF-β receptor complexes and alters the balance between Smad and Akt signaling in hepatocytes
Authors: Chaudhary Roohi , Goodman Laureen S. , Wang Sai , Asimakopoulos Anastasia , Weiskirchen Ralf , Dooley Steven , Ehrlich Marcelo , Henis Yoav I.
Published: January 2024

Cholesterol mediates membrane compartmentalization, affecting signaling via differential distribution of receptors and signaling mediators. While excessive cholesterol and aberrant transforming growth factor-β (TGF-β) signaling characterize multiple liver diseases, their linkage to canonical vs. non-canonical TGF-β signaling remained unclear. Here, we subjected murine hepatocytes to cholesterol depletion (CD) or enrichment (CE), followed by biophysical studies on TGF-β receptor heterocomplex formation, and output to Smad2/3 vs. Akt pathways. Prior to ligand addition, raft-dependent preformed heteromeric receptor complexes were observed. Smad2/3 phosphorylation persisted following CD or CE. CD enhanced phospho-Akt (pAkt) formation by TGF-β or epidermal growth factor (EGF) at 5 min, while reducing it at later time points. Conversely, pAkt formation by TGF-β or EGF was inhibited by CE, suggesting a direct effect on the Akt pathway. The modulation of the balance between TGF-β signaling to Smad2/3 vs. pAkt (by TGF-β or EGF) has potential implications for hepatic diseases and malignancies.
Multiple reaction monitoring assays for large-scale quantitation of proteins from 20 mouse organs and tissues
Authors: Michaud Sarah A. , Pětrošová Helena , Sinclair Nicholas J. , Kinnear Andrea L. , Jackson Angela M. , McGuire Jamie C. , Hardie Darryl B. , Bhowmick Pallab , Ganguly Milan , Flenniken Ann M. , Nutter Lauryl M. J. , McKerlie Colin , Smith Derek , Mohammed Yassene , Schibli David , Sickmann Albert , Borchers Christoph H.
Published: January 2024

Mouse is the mammalian model of choice to study human health and disease due to its size, ease of breeding and the natural occurrence of conditions mimicking human pathology. Here we design and validate multiple reaction monitoring mass spectrometry (MRM-MS) assays for quantitation of 2118 unique proteins in 20 murine tissues and organs. We provide open access to technical aspects of these assays to enable their implementation in other laboratories, and demonstrate their suitability for proteomic profiling in mice by measuring normal protein abundances in tissues from three mouse strains: C57BL/6NCrl, NOD/SCID, and BALB/cAnNCrl. Sex- and strain-specific differences in protein abundances are identified and described, and the measured values are freely accessible via our MouseQuaPro database: http://mousequapro.proteincentre.com. Together, this large library of quantitative MRM-MS assays established in mice and the measured baseline protein abundances represent an important resource for research involving mouse models.
scMD facilitates cell type deconvolution using single-cell DNA methylation references
Authors: Cai Manqi , Zhou Jingtian , McKennan Chris , Wang Jiebiao
Published: January 2024

The proliferation of single-cell RNA-sequencing data has led to the widespread use of cellular deconvolution, aiding the extraction of cell-type-specific information from extensive bulk data. However, those advances have been mostly limited to transcriptomic data. With recent developments in single-cell DNA methylation (scDNAm), there are emerging opportunities for deconvolving bulk DNAm data, particularly for solid tissues like brain that lack cell-type references. Due to technical limitations, current scDNAm sequences represent a small proportion of the whole genome for each single cell, and those detected regions differ across cells. This makes scDNAm data ultra-high dimensional and ultra-sparse. To deal with these challenges, we introduce scMD (single cell Methylation Deconvolution), a cellular deconvolution framework to reliably estimate cell type fractions from tissue-level DNAm data. To analyze large-scale complex scDNAm data, scMD employs a statistical approach to aggregate scDNAm data at the cell cluster level, identify cell-type marker DNAm sites, and create precise cell-type signature matrixes that surpass state-of-the-art sorted-cell or RNA-derived references. Through thorough benchmarking in several datasets, we demonstrate scMD’s superior performance in estimating cellular fractions from bulk DNAm data. With scMD-estimated cellular fractions, we identify cell type fractions and cell type-specific differentially methylated cytosines associated with Alzheimer’s disease.
Discovery from Hypericum elatoides and synthesis of hyperelanitriles as α-aminopropionitrile-containing polycyclic polyprenylated acylphloroglucinols
Authors: Xie Jin-Yan , Li Pengfei , Yan Xi-Tao , Gao Jin-Ming
Published: January 2024

The search for lead compounds with anti-neuroinflammatory activity from structurally ‘optimized’ natural products is a crucial and promising strategy in the quest to discover safe and efficacious agents for treating neurodegenerative diseases. A phytochemical investigation on the aerial portions of Hypericum elatoides led to the isolation of five nitrogenous polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperelanitriles A–D (1–4) and hyperelamine A (5). Their structures were determined by spectroscopic analysis, ECD and NMR calculations, and X-ray crystallography. To the best of our knowledge, compounds 1–4 represent the first examples of acylphloroglucinols featuring an α-aminonitrile moiety, while 5 is a rare enamine-containing PPAP. Further, the synthesis of these naturally occurring PPAP-based nitriles or amines was accomplished. Compound 5 exhibited inhibitory activity against LPS-activated NO production in BV-2 cells, potentially through the suppression of TLR-4/NF-κB signaling. Here we show the isolation, structural elucidation, synthesis, and bioactive evaluation of compounds 1–5.
Collective variable model for the dynamics of liquid crystal skyrmions
Authors: Alvim Tomás , Gama Margarida M. Telo da , Tasinkevych Mykola
Published: January 2024

Liquid crystal skyrmions are topologically protected spatially-localized distortions of the director field which exhibit particle-like properties including translational motion in oscillating electric fields. Here, we develop a collective variable model of the skyrmion dynamics, extending the approach of Long and Selinger proposed earlier for one dimensional systems. The model relates the skyrmion motion to a complex dynamics of the width of the twist wall around the skyrmion core. The width evolves in a non-reciprocal way, quantifying squirming deformations of the high twist region within on and off states of the field. We analyze in details the average skyrmion velocity as a function of the frequency and strength of the field as well as its duty cycle. The model predictions agrees qualitatively with experiments and results of numerical minimization of the Frank-Oseen model. Our results provide insights into the conditions necessary to observe velocity reversal as a function of the field parameters.
Rebuilding the vibrational wavepacket in TRAS using attosecond X-ray pulses
Authors: Wang Chao , Gong Maomao , Zhao Xi , Nan Quan Wei , Yu Xin Yue , Cheng Yongjun , Kimberg Victor , Liu Xiao-Jing , Vendrell Oriol , Ueda Kiyoshi , Zhang Song Bin
Published: January 2024

Time-resolved X-ray photoelectron spectroscopy (TXPS) is a well-established technique to probe coherent nuclear wavepacket dynamics using both table-top and free-electron-based ultrafast X-ray lasers. Energy resolution, however, becomes compromised for a very short pulse duration in the sub-femtosecond range. By resonantly tuning the X-ray pulse to core-excited states undergoing Auger decay, this drawback of TXPS can be mitigated. While resonant Auger-electron spectroscopy (RAS) can recover the vibrational structures not hidden by broadband excitation, the full reconstruction of the wavepacket is a standing challenge. Here, we theoretically demonstrate how the complete information of a nuclear wavepacket, i.e., the populations and relative phases of the vibrational states constituting the wavepacket, can be retrieved from time-resolved RAS (TRAS) measurements. Thus, TRAS offers key insights into coupled nuclear and electronic dynamics in complex systems on ultrashort timescales, providing an alternative to leverage femtosecond and attosecond X-ray probe pulses.
Stakeholder-driven transformative adaptation is needed for climate-smart nutrition security in sub-Saharan Africa
Authors: Jennings Stewart , Challinor Andrew , Smith Pete , Macdiarmid Jennie I. , Pope Edward , Chapman Sarah , Bradshaw Catherine , Clark Heather , Vetter Sylvia , Fitton Nuala , King Richard , Mwamakamba Sithembile , Madzivhandila Tshilidzi , Mashingaidze Ian , Chomba Christian , Nawiko Masiye , Nyhodo Bonani , Mazibuko Ndumiso , Yeki Precious , Kuwali Pamela , Kambwiri Alfred , Kazi Vivian , Kiama Agatha , Songole Abel , Coskeran Helen , Quinn Claire , Sallu Susannah , Dougill Andrew , Whitfield Stephen , Kunin Bill , Meebelo Nalishebo , Jamali Andrew , Kantande Dhaquirs , Makundi Prosper , Mbungu Winfred , Kayula Frank , Walker Sue , Zimba Sibongile , Galani Yamdeu Joseph Hubert , Kapulu Ndashe , Galdos Marcelo Valadares , Eze Samuel , Tripathi Hemant , Sait Steven , Kepinski Stefan , Likoya Emmanuel , Greathead Henry , Smith Harriet Elizabeth , Mahop Marcelin Tonye , Harwatt Helen , Muzammil Maliha , Horgan Graham , Benton Tim
Published: January 2024

Improving nutrition security in sub-Saharan Africa under increasing climate risks and population growth requires a strong and contextualized evidence base. Yet, to date, few studies have assessed climate-smart agriculture and nutrition security simultaneously. Here we use an integrated assessment framework (iFEED) to explore stakeholder-driven scenarios of food system transformation towards climate-smart nutrition security in Malawi, South Africa, Tanzania and Zambia. iFEED translates climate–food–emissions modelling into policy-relevant information using model output implication statements. Results show that diversifying agricultural production towards more micronutrient-rich foods is necessary to achieve an adequate population-level nutrient supply by mid-century. Agricultural areas must expand unless unprecedented rapid yield improvements are achieved. While these transformations are challenging to accomplish and often associated with increased greenhouse gas emissions, the alternative for a nutrition-secure future is to rely increasingly on imports, which would outsource emissions and be economically and politically challenging given the large import increases required.
Eruption plumes extended more than 30 km in altitude in both phases of the Millennium eruption of Paektu (Changbaishan) volcano
Authors: Costa Antonio , Mingari Leonardo , Smith Victoria C. , Macedonio Giovanni , McLean Danielle , Folch Arnau , Lee Jeonghyun , Yun Sung-Hyo
Published: January 2024

The Millennium Eruption of Paektu volcano, on the border of China and North Korea, generated tephra deposits that extend >1000 km from the vent, making it one of the largest eruptions in historical times. Based on observed thicknesses and compositions of the deposits, the widespread tephra dispersal is attributed to two eruption phases fuelled by chemically distinct magmas that produced both pyroclastic flows and fallout deposits. We used an ensemble-based method with a dual step inversion, in combination with the FALL3D atmospheric tephra transport model, to constrain these two different phases. The volume of the two distinct phases has been calculated. The results indicate that about 3-16 km3 (with a best estimate of 7.2 km3) and 4-20 km3 (with a best estimate of 9.3 km3) of magma were erupted during the comendite and trachyte phases of the eruption, respectively. Eruption rates of up to 4 × 108 kg/s generated plumes that extended 30-40 km up into the stratosphere during each phase.
High urban flood risk and no shelter access disproportionally impacts vulnerable communities in the USA
Authors: Ermagun Alireza , Smith Virginia , Janatabadi Fatemeh
Published: January 2024

Vulnerable communities are disproportionately placed in low-lying, flood-prone neighborhoods, with deficient infrastructure and limited access to shelter. Here we present a methodology to study the risk of urban floods in tandem with access to shelter to reduce the risk of flooding to communities and prevent a natural hazard from turning into a human disaster. We integrate access to national emergency shelters into a national risk index for riverine floods in eight U.S. cities at the block group level using clustering techniques. The results show shelters are more accessible for inner-city residents regardless of the risk level, and communities with high risk of flood and low access to shelter are disproportionately home to the underserved populations of Asians and the elderly. The outcomes delineate the disparity in equity related to urban floods and support plans and policy needs by identifying and prioritizing areas to improve emergency responses and resource allocations.
Agricultural fertilisers contribute substantially to microplastic concentrations in UK soils
Authors: Cusworth Samuel J. , Davies William J. , McAinsh Martin R. , Gregory Andrew S. , Storkey Jonathan , Stevens Carly J.
Published: January 2024

Since their invention, plastics have driven a revolution in behavior in all aspects of our lives, including agriculture. In-use and as a waste material, plastics degrade and accumulate in agricultural systems. Accumulation of plastic pollution in agricultural systems has negative impacts on human health and agricultural productivity but little is known about concentrations of microplastics in soils. Here we used a historical time series to examine changes to microplastic concentrations in agricultural soils over time. Microplastics were stained with Nile Red and quantified using fluorescence microscopy. We demonstrate that microplastic concentrations increased at higher rates in soils that are amended with either organic or inorganic fertiliser between 1966 and 2022, suggesting that agricultural fertilisers are an important contributor to microplastic concentrations in agricultural soils over time. This study provides evidence that agricultural soils are receptors and reservoirs of microplastic pollution, a legacy which is growing over time.
Outgassing behaviour during highly explosive basaltic eruptions
Authors: Bamber Emily C. , La Spina Giuseppe , Arzilli Fabio , Polacci Margherita , Mancini Lucia , de’ Michieli Vitturi Mattia , Andronico Daniele , Corsaro Rosa Anna , Burton Mike R.
Published: January 2024

Explosivity of basaltic eruptions is related to the efficiency in which exsolved gas can separate from the melt during ascent, which is controlled by magma permeability. However, basaltic pyroclasts from eruptions of varying explosivity can show similar permeability, indicating a possible complex relationship between permeability, outgassing and eruptive style. Here, we provide 3D measurements of basaltic pyroclasts using X-ray microtomography. We investigate the role of permeability and outgassing on magma ascent dynamics by using a numerical conduit model. Among the permeable parameters, bubble number density and friction coefficient largely affect explosivity. However, for fast ascending basaltic magmas, gas-melt coupling is maintained independent of magma permeability. In this case, magma storage conditions may determine eruptive style, driving rapid magma ascent, crystallisation and bubble nucleation, producing a highly explosive eruption. Monitoring parameters which reveal pre-eruptive conditions may assist hazard mitigation, particularly for basaltic systems which exhibit a wide range in eruptive style.
A beneficial adaptive role for CHOP in driving cell fate selection during ER stress
Authors: Liu Kaihua , Zhao Chaoxian , Adajar Reed C , DeZwaan-McCabe Diane , Rutkowski D Thomas
Published: January 2024

Cellular stresses elicit signaling cascades that are capable of either mitigating the inciting dysfunction or initiating cell death. During endoplasmic reticulum (ER) stress, the transcription factor CHOP is widely recognized to promote cell death. However, it is not clear whether CHOP also has a beneficial role during adaptation. Here, we combine a new, versatile, genetically modified Chop allele with single cell analysis and with stresses of physiological intensity, to rigorously examine the contribution of CHOP to cell fate. Paradoxically, we find that CHOP promotes death in some cells, but proliferation—and hence recovery—in others. Strikingly, this function of CHOP confers to cells a stress-specific competitive growth advantage. The dynamics of CHOP expression and UPR activation at the single cell level suggest that CHOP maximizes UPR activation, which in turn favors stress resolution, subsequent UPR deactivation, and proliferation. Taken together, these findings suggest that CHOP’s function can be better described as a “stress test” that drives cells into either of two mutually exclusive fates—adaptation or death—during stresses of physiological intensity.