Huoxue Jiedu Huayu recipe inhibits macrophage-secreted vascular endothelial growth factor-a on angiogenesis and alleviates renal fibrosis in the contralateral kidneys of unilateral ureteral obstruction rats.

OBJECTIVE：To elucidate the mechanism by which Huoxue Jiedu Huayu recipe (, HJHR) regulates angiogenesis in the contralateral kidney of unilateral ureteral obstruction (UUO) rats and the mechanism by which it reduces of renal fibrosis. METHODS: Male Wistar rats were randomly divided into 4 groups: the sham group, UUO group (180 d of left ureter ligation), UUO plus eplerenone (EPL) group, and UUO plus HJHR group. After 180 d of oral drug administration, blood and contralateral kidneys were collected for analysis. Angiogenesis- and fibrosis-related indexes were detected. RESULTS: HJHR and EPL improved structural damage and renal interstitial fibrosis in the contralateral kidney and reduced the protein expression levels of α-smooth muscle actin (α-SMA), vimentin and collagen I. Moreover, these treatments could reduce the expression of vascular endothelial growth factor-A (VEGFA) by inhibiting the infiltration of macrophages. Furthermore, HJHR and EPL significantly reduced the expression of CD34 and CD105 by downregulating VEGFA production, which inhibited angiogenesis. Finally, the coexpressions of CD34, CD105 and α-SMA were decreased in the HJHR and EPL groups, indicating that endothelial-to-mesenchymal transition was inhibited. CONCLUSIONS: These findings confirm that HJHR alleviates contralateral renal fibrosis by inhibiting VEGFA-induced angiogenesis, encourage the use of HJHR against renal interstitial fibrosis and provide a theoretical basis for the clinical management of patients with CKD.

Taxa-dependent temporal trends in the abundance and size of sea urchins in subtropical eastern Australia.

Subtropical reefs host a dynamic mix of tropical, subtropical, and temperate species that is changing due to shifts in the abundance and distribution of species in response to ocean warming. In these transitional communities, biogeographic affinity is expected to predict changes in species composition, with projected increases of tropical species and declines in cool-affinity temperate species. Understanding population dynamics of species along biogeographic transition zones is critical, especially for habitat engineers such as sea urchins that can facilitate ecosystem shifts through grazing. We investigated the population dynamics of sea urchins on coral-associated subtropical reefs at 7 sites in eastern Australia (28.196° S to 30.95° S) over 9 years (2010-2019), a period impacted by warming and heatwaves. Specifically, we investigated the density and population size structure of taxa with temperate (Centrostephanus rodgersii, Phyllacanthus parvispinus), subtropical (Tripneustes australiae) and tropical (Diadema spp.) affinities. Counter to expectation, biogeographic affinity did not explain shifts in species abundances in this region. Although we expected the abundance of tropical species to increase at their cold range boundaries, tropical Diadema species declined across all sites. The subtropical T. australiae also showed declines, while populations of the temperate C. rodgersii were remarkably stable throughout our study period. Our results show that temporal patterns of sea urchin populations in this region cannot be predicted by bio-geographic affinity alone and contribute critical information about the population dynamics of these important herbivores along this biogeographic transition zone.

2D Vanadium Sulfides: Synthesis, Atomic Structure Engineering, and Charge Density Waves.

Two ultimately thin vanadium-rich 2D materials based on VS2 are created via molecular beam epitaxy and investigated using scanning tunneling microscopy, X-ray photoemission spectroscopy, and density functional theory (DFT) calculations. The controlled synthesis of stoichiometric single-layer VS2 or either of the two vanadium-rich materials is achieved by varying the sample coverage and sulfur pressure during annealing. Through annealing of small stoichiometric single-layer VS2 islands without S pressure, S-vacancies spontaneously order in 1D arrays, giving rise to patterned adsorption. Via the comparison of DFT calculations with scanning tunneling microscopy data, the atomic structure of the S-depleted phase, with a stoichiometry of V4S7, is determined. By depositing larger amounts of vanadium and sulfur, which are subsequently annealed in a S-rich atmosphere, self-intercalated ultimately thin V5S8-derived layers are obtained, which host 2 × 2 V-layers between sheets of VS2. We provide atomic models for the thinnest V5S8-derived structures. Finally, we use scanning tunneling spectroscopy to investigate the charge density wave observed in the 2D V5S8-derived islands.

Analyzing the effectiveness of energy aid for driving the transition towards energy decarbonization; Evidence from Asian developing countries.

Environmental degradation poses a significant challenge in many developing countries, as they heavily rely on fossil fuels to drive economic activities. The transition towards renewable energy is crucial to mitigate ecological depletion, yet numerous Asian developing countries may struggle to achieve the desired levels of renewable energy adoption due to financial constraints. Foreign aid in the energy sector can expedite this transition process. This study aims to examine the impact of foreign aid on the energy decarbonization transition in 22 Asian developing countries from 2003 to 2022 to analyze its contributions and challenges to promote renewable energy adoption. This paper incorporates the two types of foreign aid in the energy sector (nonrenewable and renewable energy aid) provided by the OECD to developing economies. Utilizing the System-Generalized Method of Moments (Sys-GMM), the findings reveal that energy aid significantly contributes to the transition towards energy decarbonization by providing financial support for embracing renewable energy technologies. Specifically, the analysis indicates that a 1% increase in energy aid leads to approximately 3% enhancement in the decarbonization transition process. Moreover, this study adds to the existing body of knowledge by examining the mediating impact of human capital and financial development as well as the moderating effect of institutional quality and demand for clean fuel. These factors play a pivotal role in energy decarbonization transition by fostering financial development and enhancing human capital through capacity-building initiatives and facilitating the adoption of renewable energy technologies.

Protective Potential of Methanol Extract of Drymaria cordata Willd. ex Schult (MEDC) on Letrozole-Induced Polycystic Ovary Syndrome Via Modulation of Apoptotic Markers, Sex Hormones and Antioxidant Status in Rat Model.

Polycystic ovary syndrome (PCOS) is a gynecological disorder among reproductive-aged women and a major cause of infertility. Different treatment options are being employed but with side effects. This has mandated alternative treatment options, especially complementary therapy. This study therefore investigated the possible protective effects of methanol extract of Drymaria cordata in Letrozole-induced PCOS. The plant is folklorically used in the treatment of diverse ailments including PCOS, fibroids, uterine/ovarian/breast tumors, and cancers. Forty-eight female Wistar rats were acclimatized and initially divided into two groups: group I(control group) and group II(PCOS group). PCOS was induced by the oral administration of letrozole/high-fat diet for 21 days. After the induction, the PCOS group was sub-divided into four groups (n = 4): group II (positive control with PCOS), group III (MET 2mg/kg), group IV (MEDC 200mg/kg), and group V (MEDC 400mg/kg). Rats were orally treated with MET and MEDC for six weeks after the PCOS induction. At the end of the experimental period, blood samples were collected, sera were separated, mitochondria were isolated, and the mPT, some apoptotic biomarkers, hormonal and lipid profiles, and oxidative stress markers were determined. Ovarian histological evaluation and GC-MS analysis of MEDC were carried out. There was no significant mPT pore opening in the PCOS (untreated) group. However, treatments with MEDC caused significant mPT pore opening, upraised caspase 9, caspase 3, and Bax, and decreased anti-apoptotic Bcl-2 levels. The MEDC treatments restored the hormonal and lipid profiles, increased the levels of GSH-Px and SOD and decreased TBARS. Histological examination revealed resolved ovarian cysts and improved follicular growth with MEDC treatments. Comparable results were observed for both MEDC and metformin. The GC-MS analysis revealed the presence of some major pharmacologically relevant compounds. These findings suggest that MEDC contains phytochemicals that can protect against letrozole-induced PCOS possibly by normalizing the impaired hormonal balance, restoring the lipid profile, and improving the antioxidant milieu of the system.

Barriers to Providing Transitional Supports for Autistic Students: Insights of School Professionals.

Following high school exit, many autistic young adults are not enrolled in post-secondary education or employed, and few are engaged in community activities. This disengagement among autistic young adults may be a result of the limited or inadequate supports provided to autistic transition-age youth in schools. Therefore, the purpose of the current study is to explore how school professionals report preparing transition-age autistic youth for adulthood and the barriers that make it difficult for school professionals to provide quality transition services. We surveyed 21 school professionals who work with transition-age autistic students. The survey solicited descriptions of transition supports provided to youth, and barriers that make it difficult for school professionals to provide high quality transition supports. Qualitative content analysis was used to identify themes from the data. Participants described barriers related to the autistic youth they taught or supported, their families, the classroom environment, and the community. Barriers were either framed as deficits inherent to autistic students and their families, or larger systemic issues that make it challenging to implement high quality transition supports. We recommend implementation of autism-specific trainings within teacher preparation programs and school districts, professional development opportunities that create spaces for educators to challenge and resist deficit views of autism, and development of strengths-based transition programs that are implemented by school-based professionals who work with autistic students.

7-amino carboxycoumarin 2 inhibits lactate induced epithelial-to-mesenchymal transition via MPC1 in oral and breast cancer cells.

Lactate is an oncometabolite that play important role in tumor aggressiveness. Lactate from the tumor microenvironment (TME) is taken up by cancer cells as an energy resource via mitochondrial oxidative phosphorylation (or OXPHOS). In the present study, by using an online meta-analysis tool we demonstrated that in oral squamous cancer cells (OSCCs) glycolytic and OXPHOS governing genes are overexpressed, like in breast cancer. For experimental demonstration, we treated the OSCC cell line (SCC4) and breast cancer cells (MDA-MB-231) with sodium L-lactate and analyzed its effects on changes in EMT and migration. For the therapeutic intervention of lactate metabolism, we used AZD3965 (an MCT1 inhibitor), and 7ACC2 (an MPC inhibitor). Like breast cancer, oral cancer tissues showed increased transcripts of 12 genes that were previously shown to be associated with glycolysis and OXPHOS. We experimentally demonstrated that L-lactate treatment induced mesenchymal markers and migration of cancer cells, which was significantly neutralized by MPC inhibitor that is, 7ACC2. Such an effect on EMT status was not observed with AZD3965. Furthermore, we showed that lactate treatment increases the MPC1 expression in both cancer cells, and this might be the reason why cancer cells in the high lactate environment are more sensitive to 7ACC2. Overall, our present findings demonstrate that extracellular lactate positively regulates the MPC1 protein expression in cancer cells, thereby putting forward the notion of using 7ACC2 as a potential therapeutic alternative to inhibit malignant oxidative cancers. Future preclinical studies are warranted to validate the present findings.

Unveiling the role of KSHV-infected human mesenchymal stem cells in Kaposi's sarcoma initiation.

Kaposi's sarcoma (KS) may derive from Kaposi's sarcoma herpesvirus (KSHV)-infected human mesenchymal stem cells (hMSCs) that migrate to sites characterized by inflammation and angiogenesis, promoting the initiation of KS. By analyzing the RNA sequences of KSHV-infected primary hMSCs, we have identified specific cell subpopulations, mechanisms, and conditions involved in the initial stages of KSHV-induced transformation and reprogramming of hMSCs into KS progenitor cells. Under proangiogenic environmental conditions, KSHV can reprogram hMSCs to exhibit gene expression profiles more similar to KS tumors, activating cell cycle progression, cytokine signaling pathways, endothelial differentiation, and upregulating KSHV oncogenes indicating the involvement of KSHV infection in inducing the mesenchymal-to-endothelial (MEndT) transition of hMSCs. This finding underscores the significance of this condition in facilitating KSHV-induced proliferation and reprogramming of hMSCs towards MEndT and closer to KS gene expression profiles, providing further evidence of these cell subpopulations as precursors of KS cells that thrive in a proangiogenic environment.

Intercalation-Induced Localized Conversion Reaction in h-CuSe for Ultrafast-Rechargeable and Long-Cycling Sodium Metal Battery.

Cathode materials of sodium-based batteries with high specific capacity and fast charge/discharge mode, as well as ultralong reversible cycles at wide applied temperatures, are essential for future development of advanced energy storage system. Developing transition metal selenides with intercalation features provides a new strategy for realizing the above cathode materials. Herein, we report a storage mechanism of sodium ion in hexagonal CuSe (h-CuSe) based on the DFT guidance. We reveal that the two-dimensional ion intercalation triggers localized redox reaction in the h-CuSe bulk phase, termed intercalation-induced localized conversion (ILC) mechanism, to stabilize the sodium storage structure by forming localized Cu7Se4 transition phase and adjusting the near-edge coordination state of the Cu sites to achieve high reversible capacity and ultra-long cycling life, while allowing rapid charge/discharge cycling over a wide temperature range. This article is protected by copyright. All rights reserved.

Nanoscale-Confined Synthesis of 2D Metal Compounds for Electrochemical Applications.

2D metal compounds, such as transition metal dichalcogenides (TMDs), layered double hydroxides (LDHs), and MXenes, are emerging as important electrocatalyst materials in the transition to a sustainable energy future. Aided by their high surface area, electrical conductivity, and tunable electronic properties, these materials have provided a crucial research thrust in enhancing the efficiency of green hydrogen production, fuel cells, and carbon reduction processes. Most importantly, the synthesis of nanostructured 2D compounds, while challenging, is the key to optimizing their catalytic performance. Recent advancements in this field have highlighted the potential of 2D metal compounds in revolutionizing energy conversion technologies, which entails the discovery of new material compositions, the development of novel synthetic routes, and the integration of these materials into practical energy conversion systems. This review presents an overview of the distinctive characteristics of nanoscale-confined 2D metal compounds, the challenges encountered in their synthesis, and electrochemical applications.

Antiferroelectric Ceramics for Energy-Efficient Capacitors by Theory-Guided Discovery.

Antiferroelectric ceramics, via the electric-field-induced antiferroelectric (AFE) - ferroelectric (FE) phase transitions, show great promise for high-energy-density capacitors. Yet, currently, only 70∼80% energy release is found during a charge-discharge cycle. Here, for PbZrO3-based oxides, we apply geometric nonlinear theory of martensitic phase transitions (first used to guide supercompatible shape-memory alloys) to predict the reversibility of the AFE-FE transition by using density-functional theory to assess AFE/FE interfacial lattice-mismatch strain that assures ultralow electric hysteresis and extended fatigue lifetime. We observe a good correlation of mismatch strain with electric hysteresis, hence, with energy efficiency of AFE capacitors. Guided by theory, we conduct high-throughput materials search and discover AFE compositions with a near-perfect charge-discharge energy efficiency (98.2%), i.e., near-zero hysteresis. And the fatigue life of the capacitor reaches 79.5 million charge-discharge cycles, a factor of 80 enhancement over AFE ceramics with large electric hysteresis. This article is protected by copyright. All rights reserved.

Generation and characterisation of scalable and stable human pluripotent stem cell-derived microvascular-like endothelial cells for cardiac applications.

Coronary microvascular disease (CMD) and its progression towards major adverse coronary events pose a significant health challenge. Accurate in vitro investigation of CMD requires a robust cell model that faithfully represents the cells within the cardiac microvasculature. Human pluripotent stem cell-derived endothelial cells (hPSC-ECs) offer great potential; however, they are traditionally derived via differentiation protocols that are not readily scalable and are not specified towards the microvasculature. Here, we report the development and comprehensive characterisation of a scalable 3D protocol enabling the generation of phenotypically stable cardiac hPSC-microvascular-like ECs (hPSC-CMVECs) and cardiac pericyte-like cells. These were derived by growing vascular organoids within 3D stirred tank bioreactors and subjecting the emerging 3D hPSC-ECs to high-concentration VEGF-A treatment (3DV). Not only did this promote phenotypic stability of the 3DV hPSC-ECs; single cell-RNA sequencing (scRNA-seq) revealed the pronounced expression of cardiac endothelial- and microvascular-associated genes. Further, the generated mural cells attained from the vascular organoid exhibited markers characteristic of cardiac pericytes. Thus, we present a suitable cell model for investigating the cardiac microvasculature as well as the endothelial-dependent and -independent mechanisms of CMD. Moreover, owing to their phenotypic stability, cardiac specificity, and high angiogenic potential, the cells described within would also be well suited for cardiac tissue engineering applications.

Impact of COVID-19 on celebration of death, mortuary, and funerary customs in Bangladesh: A qualitative study.

Introduction: During the COVID-19 pandemic, restrictions significantly impacted religious activities related to death celebrations, mortuary practices, and funerary rituals in Bangladesh. Bereaved families faced a harsh reality, unable to perform the full rituals for their loved ones due to the pandemic outbreak. This study explores the adjustments and modifications made in cultural rituals and how they affected bereaved families and close relatives. Objective: This study aims to explore how the COVID-19 pandemic impacted the observance of death rituals in Bangladesh and the effects on bereaved families and close relatives. Methods: This study employed a qualitative approach and gathered data through 3 key informant interviews (KIIs) and 58 in-depth interviews (IDIs) conducted between December 2020 and January 2021. Purposive sampling was employed to recruit participants from three distinct groups: (1) individuals who had experienced the death of a relative during the pandemic, (2) caregivers who provided support to those experiencing loss, and (3) volunteers actively involved with funeral and burial services. This selection strategy ensured a diverse range of perspectives on the impact of the pandemic on death rituals. Results: The pandemic forced people to observe funerals or make significant sacrifices to traditional practices reluctantly. Disruptions to long-standing traditions and widespread emotional toll were as various segments of society struggled to find closure in saying goodbye to loved ones. Due to the severity of the pandemic, people became heavily reliant on priests, crematorium workers, and funeral volunteers for mortuary services. Both Hindu and Muslim religions discouraged family gatherings during post-burial rituals. The fear of contracting the virus further limited bereaved families' ability to bid farewell to their deceased loved ones properly. Conclusion: This research highlights the profound impact of the pandemic on death rituals and the resulting emotional distress for bereaved families in Bangladesh. The findings are pivotal in guiding the development of concrete policies for future pandemic preparedness and response. Such policies might encompass guidelines for safe and culturally sensitive mortuary practices, psychosocial support and grief counseling initiatives for affected communities, and strategies to mitigate religious anxieties during public health emergencies.

Unraveling the dynamic transcriptomic changes during the dimorphic transition of Talaromyces marneffei through time-course analysis.

Introduction: Systemic dimorphic fungi pose a significant public health challenge, causing over one million new infections annually. The dimorphic transition between saprophytic mycelia and pathogenic yeasts is strongly associated with the pathogenesis of dimorphic fungi. However, despite the dynamic nature of dimorphic transition, the current omics studies focused on dimorphic transition primarily employ static strategies, partly due to the lack of suitable dynamic analytical methods. Methods: We conducted time-course transcriptional profiling during the dimorphic transition of Talaromyces marneffei, a model organism for thermally dimorphic fungi. To capture non-uniform and nonlinear transcriptional changes, we developed DyGAM-NS (dynamic optimized generalized additive model with natural cubic smoothing). The performance of DyGAM-NS was evaluated by comparison with seven other commonly used time-course analysis methods. Based on dimorphic transition induced genes (DTIGs) identified by DyGAM-NS, cluster analysis was utilized to discern distinct gene expression patterns throughout dimorphic transitions of T. marneffei. Simultaneously, a gene expression regulatory network was constructed to probe pivotal regulatory elements governing the dimorphic transitions. Results: By using DyGAM-NS, model, we identified 5,223 DTIGs of T. marneffei. Notably, the DyGAM-NS model showcases performance on par with or superior to other commonly used models, achieving the highest F1 score in our assessment. Moreover, the DyGAM-NS model also demonstrates potential in predicting gene expression levels throughout temporal processes. The cluster analysis of DTIGs suggests divergent gene expression patterns between mycelium-to-yeast and yeast-to-mycelium transitions, indicating the asymmetrical nature of two transition directions. Additionally, leveraging the identified DTIGs, we constructed a regulatory network for the dimorphic transition and identified two zinc finger-containing transcription factors that potentially regulate dimorphic transition in T. marneffei. Discussion: Our study elucidates the dynamic transcriptional profile changes during the dimorphic transition of T. marneffei. Furthermore, it offers a novel perspective for unraveling the underlying mechanisms of fungal dimorphism, emphasizing the importance of dynamic analytical methods in understanding complex biological processes.

Challenges Nurses Face in Providing Care for Patients with Juvenile Idiopathic Arthritis.

OBJECTIVES: This study aimed at identifying challenges nurses face in caring for patients with juvenile idiopathic arthritis (JIA) in Japan. METHODS: Nurses certified by the Japan Rheumatism Foundation were asked to describe their challenges with caring for JIA patients. Data was analyzed using qualitative content analysis. RESULTS: Responses were collected from 89 participants. 58 issues were identified from 40 participants with experience caring for JIA patients. Sixteen categories emerged, grouped into five challenges: communication, understanding, expertise, system, and collaboration. Care for JIA patients included different challenges from adult patients with rheumatoid arthritis, such as complicated patient-parent relationships, inadequate patient independence and insufficient patient information. Moreover, 76 issues from 49 participants with no experience were identified. Seven categories emerged, grouped into two challenges: expertise and opportunity. Issues included in expertise between both groups were similar. Even with no experience caring for JIA patients, nurses recognized the importance of acquiring knowledge. CONCLUSION: This is the first study in Japan regarding the difficulties nurses face in caring for JIA patients. Multidisciplinary team care and a comprehensive understanding of the patient journey, including relationships with guardians, acquaintances, and healthcare providers, is crucial to improve treatment outcome and overall patient quality of life.

Collective dynamics of liquid sulphur across the polymerisation transition temperature probed by inelastic x-ray scattering.

Inelastic x-ray scattering (IXS) experiments on liquid sulphur were carried out below (140◦C) and above (180◦C) the polymerisation temperature Tλ of about 159◦C to investigate changes in the collective dynamics of this unique liquid, that exhibits a liquid‒liquid transition. As reported earlier, broad longitudinal acoustic excitation signals were observed at both temperatures, and only the width of the quasielastic peaks slightly decreased when the temperature crossed the transition temperature. A model analysis was performed using a generalised Langevin formalism with a memory function having one thermal and two viscoelastic decay channels with the help of simple sparse modelling, and large positive deviations from the hydrodynamic sound velocity by 51‒54% were observed. The fast viscoelastic relaxation time τµis close to the correlation times of intermolecular stretching and bending motions of local sulphur connections in both ring and chain structures, and is similar to those of other molecular liquids. The small contrasts in the IXS spectra across the λ transition result in large changes in only the slow viscoelastic decay time τα of the memory function. The τα value at 140◦C matches the mixed internal/external torsional modes of S8 molecules well, whereas that at 180◦C has no corresponding molecular motion mode. The kinematic viscosity values at thesmaller than the minimum values of macroscopic shear viscosity, in⃗dicating that largeQ 0 limit are much changes in relaxation dynamics are expected with Q in the GHz and MHz excitation regimes. .

What does the literature say about preceptorship and mentorship in radiography: A scoping review of the current research and identified knowledge gaps.

OBJECTIVES: Effective transition into radiography practice for newly qualified radiographers (NQR's), radiographers returning to practice after career breaks, and internationally trained radiographers requires support inclusive of preceptorship and mentorship. The purpose of this scoping review is to evaluate the literature pertaining to preceptorship and mentorship support in radiography to identify knowledge gaps. This is timely in view of the health and care professions council (HCPC) recently published preceptorship guidance. KEY FINDINGS: A scoping review methodology underpinned by Arksey and O'Malley framework was undertaken, which employed a systematic search using combined keywords and Medical Subject Heading terms (MeSH) related to preceptorship and mentorship, of electronic databases: CINAHL, Pubmed, Embase, Scopus and Google scholar. A predetermined inclusion and exclusion criteria were used to screen by three independent reviewers, the titles, abstract and full text of articles using Covidence software (www.covidence.org). 10 articles in the English language were selected for the final review. 1574 articles were retrieved and assessed for eligibility, and 10 articles published between 2006 and 2022 met the inclusion criteria. Most of the research was conducted in the United Kingdom and only one study was published in Australia. The studies mainly focused on experiences of NQR, and experienced radiographers' perspectives on preceptorship and mentorship in diagnostic and radiotherapy radiography. It was established from the studies that there is variation in approaches to the transition process in terms of types of programmes, duration, and quality. Self-reported increase in confidence and competence was noted as a central objective, and barriers to implementation were identified to include lack of awareness and accessibility to available programmes, lack of clarity on aims and intended benefits, and lack of employer support pertaining to protected time. CONCLUSION: The paucity of research renders current preceptorship and mentorship practices in radiography inadequate for effective transition of different radiography groups into their role. Further research is required to evaluate the models of preceptorship and mentorship, their impact and intended outcomes on radiography practice. IMPLICATIONS FOR PRACTICE: The identification of knowledge gaps in this area can support employers and researchers in the development of effective models of preceptorships and mentorship which can be evaluated for implementation for specific radiography groups.

Characterizing the antigenic evolution of pandemic influenza A (H1N1) pdm09 from 2009 to 2023.

The H1N1pdm09 virus has been a persistent threat to public health since the 2009 pandemic. Particularly, since the relaxation of COVID-19 pandemic mitigation measures, the influenza virus and SARS-CoV-2 have been concurrently prevalent worldwide. To determine the antigenic evolution pattern of H1N1pdm09 and develop preventive countermeasures, we collected influenza sequence data and immunological data to establish a new antigenic evolution analysis framework. A machine learning model (XGBoost, accuracy = 0.86, area under the receiver operating characteristic curve = 0.89) was constructed using epitopes, physicochemical properties, receptor binding sites, and glycosylation sites as features to predict the antigenic similarity relationships between influenza strains. An antigenic correlation network was constructed, and the Markov clustering algorithm was used to identify antigenic clusters. Subsequently, the antigenic evolution pattern of H1N1pdm09 was analyzed at the global and regional scales across three continents. We found that H1N1pdm09 evolved into around five antigenic clusters between 2009 and 2023 and that their antigenic evolution trajectories were characterized by cocirculation of multiple clusters, low-level persistence of former dominant clusters, and local heterogeneity of cluster circulations. Furthermore, compared with the seasonal H1N1 virus, the potential cluster-transition determining sites of H1N1pdm09 were restricted to epitopes Sa and Sb. This study demonstrated the effectiveness of machine learning methods for characterizing antigenic evolution of viruses, developed a specific model to rapidly identify H1N1pdm09 antigenic variants, and elucidated their evolutionary patterns. Our findings may provide valuable support for the implementation of effective surveillance strategies and targeted prevention efforts to mitigate the impact of H1N1pdm09.

Wake effects and temperature plumes: Coping with non-knowledge in the expansion of wind and geothermal energy.

Energy transitions are knowledge-intensive processes where a multitude of actors are trying to cope with inevitable knowledge gaps, surprises, and uncertainties. In this context, we focus on two techno-physical phenomena that are gaining practical relevance with the expansion of wind and geothermal energy extraction, and are surrounded by significant unknowns: wake effects and temperature plumes. Both phenomena can potentially affect the efficiency of energy production, but the extent of their impact is not yet known. Based on 28 semi-structured interviews with experts in the fields of wind and geothermal energy, we explore how different central actors perceive and interpret non-knowledge of wake effects and temperature plumes, and how they deal with it. We show that there are strategies for either using non-knowledge as a basis for action or simply ignoring it and sweeping knowledge gaps under the rug. Both strategies serve the function of protecting agency and keeping things going.

Modeling and Simulation of the NMDA Receptor at Coarse-Grained and Atomistic Levels.

N-Methyl-D-aspartate (NMDA) receptors are glutamate-gated excitatory channels that play essential roles in brain functions. While high-resolution structures were solved for an allosterically inhibited form of functional NMDA receptor, other key functional states (particularly the active open-channel state) have not yet been resolved at atomic resolutions. To decrypt the molecular mechanism of the NMDA receptor activation, structural modeling and simulation are instrumental in providing detailed information about the dynamics and energetics of the receptor in various functional states. In this chapter, we describe coarse-grained modeling of the NMDA receptor using an elastic network model and related modeling/analysis tools (e.g., normal mode analysis, flexibility and hotspot analysis, cryo-EM flexible fitting, and transition pathway modeling) based on available structures. Additionally, we show how to build an atomistic model of the active-state receptor with targeted molecular dynamics (MD) simulation and explore its energetics and dynamics with conventional MD simulation. Taken together, these modeling and simulation can offer rich structural and dynamic information which will guide experimental studies of the activation of this key receptor.