bluuebunny/crossref_metadata_2025 huggingface dataset:
Protective effects of polydatin against bone and joint disorders: thein vitroandin vivoevidence so far
Authors: Zhang Zhen , Sun Zhicheng , Jia Runze , Jiang Dingyu , Xu Zhenchao , Zhang Yilu , Wu Yun-Qi , Wang Xiyang
Published: April 2023

Polydatin is an active polyphenol displaying multifaceted benefits. Recently, growing studies have noticed its potential therapeutic effects on bone and joint disorders (BJDs). Therefore, this article reviews recentin vivoandin vitroprogress on the protective role of polydatin against BJDs. An insight into the underlying mechanisms is also presented. It was found that polydatin could promote osteogenesisin vitro, and symptom improvements have been disclosed with animal models of osteoporosis, osteosarcoma, osteoarthritis and rheumatic arthritis. These beneficial effects obtained in laboratory could be mainly attributed to the bone metabolism-regulating, anti-inflammatory, antioxidative, apoptosis-regulating and autophagy-regulating functions of polydatin. However, studies on human subjects with BJDs that can lead to early identification of the clinical efficacy and adverse effects of polydatin have not been reported yet. Accordingly, this review serves as a starting point for pursuing clinical trials. Additionally, future emphasis should also be devoted to the low bioavailability and prompt metabolism nature of polydatin. In summary, well-designed clinical trials of polydatin in patients with BJD are in demand, and its pharmacokinetic nature must be taken into account.
Using acoustic recording units to investigate the effects of logging of indigenous trees in the Amathole forests, South Africa on Cape Parrot Poicephalus robustus breeding and the presence of three primary cavity-excavating bird species
Authors: Rea Matthew , Elliot Julia , Carstens Johann C. , Leaver Jessica , Carstens Kate , Wimberger Kirsten , Cherry Michael I.
Published: April 2023

The Amathole forest complex is the breeding stronghold of the endemic and vulnerable Cape Parrot Poicephalus robustus, and is also one of only two forest complexes in South Africa formally harvested for timber. The aim of this study was to determine if formal harvesting of indigenous trees, primarily the two yellowwood species Afrocarpus falcatus and Podocarpus latifolius, in 9 of 16 Amathole forests has had any effect on the presence of Cape Parrots and three primary nest-excavating species, as well as on parrot breeding. The study used logging data from the past 25 years (1997–2021) as well as data collected by acoustic recording units over two breeding seasons from 2019 to 2021. Cape Parrots were present in 15 of 16 forests, but breeding calls were identified in only seven forests: five in logged and two in unlogged forests. Fourteen of the forests harboured all three primary excavators: Knysna Woodpecker Campethera notata, Olive Woodpecker Dendropicos griseocephalus, and Red-fronted Tinkerbird Pogoniulus pusillus. The last two species were absent from the adjacent Mount Thomas and Kologha forests, respectively, in which parrots were present, but no breeding calls were recorded. Logging of yellowwoods was not found to affect parrot breeding. However, due to the overlap between preferred parrot breeding sites and preferred trees for harvesting, we recommend that harvesting in the five harvested forest blocks where parrot breeding occurs be limited to tree falls, with no standing dead, dying, or damaged trees harvested, to ensure that potential nesting trees are not harvested.
Food self-provisioning: a review of health and climate implications
Authors: Suomalainen Milla , Hohenthal Johanna , Pyysiäinen Jarkko , Ruuska Toni , Rinkinen Jenny , Heikkurinen Pasi
Published: April 2023

Non-technical summary

The industrial food system is widely considered to be unsustainable due to its undesired climate and health effects. One proposed alternative to these problems is a more local system of food provisioning. This means involving individuals, households, and communities in growing and acquiring edibles, like vegetables and other food stuff. This study based on a literature review found that food self-provisioning practitioners are mainly driven by health concerns and less by reasoning linked to the environment, like climate change adaptation and mitigation. We propose that the potential of food self-provisioning is underutilised in developing the sustainability of food systems.

Technical summary

In this article, we review and analyse the literature and concept of ‘food self-provisioning’ in order to understand its potential as a response to contemporary challenges. The focus of the study is on investigating the meanings related to environmental problems, particularly climate change, and issues of health. Firstly, we show how food self-provisioning is conceptualised vis-à-vis health and the environment; and secondly, what the (potential) implications of food self-provisioning to interlinked human and non-human health and beyond are. Based on the conducted literature review (n = 44), meanings of food self-provisioning are found to connect primarily to issues of human health and only secondarily to environmental questions, and even more marginally to climate change mitigation and adaptation. Our analysis cuts across the scales of households, communities, cities, and regions, including their diverse geographies, and hereby also comments on the questions of multilevel organising of self-provisioning, and what the notion of ‘self’ implies in this context.

Social media summary

The potential of food self-provisioning is underutilised in developing the sustainability of food systems.
Towards a global sustainable development agenda built on social–ecological resilience
Authors: Scown Murray W. , Craig Robin K. , Allen Craig R. , Gunderson Lance , Angeler David G. , Garcia Jorge H. , Garmestani Ahjond
Published: April 2023

Non-technical summary

The United Nations' sustainable development goals (SDGs) articulate societal aspirations for people and our planet. Many scientists have criticised the SDGs and some have suggested that a better understanding of the complex interactions between society and the environment should underpin the next global development agenda. We further this discussion through the theory of social–ecological resilience, which emphasises the ability of systems to absorb, adapt, and transform in the face of change. We determine the strengths of the current SDGs, which should form a basis for the next agenda, and identify key gaps that should be filled.

Technical summary

The United Nations' sustainable development goals (SDGs) are past their halfway point and the next global development agenda will soon need to be developed. While laudable, the SDGs have received strong criticism from many, and scholars have proposed that adopting complex adaptive or social–ecological system approaches would increase the effectiveness of the agenda. Here we dive deeper into these discussions to explore how the theory of social–ecological resilience could serve as a strong foundation for the next global sustainable development agenda. We identify the strengths and weaknesses of the current SDGs by determining which of the 169 targets address each of 43 factors affecting social–ecological resilience that we have compiled from the literature. The SDGs with the strongest connections to social–ecological resilience are the environment-focus goals (SDGs 2, 6, 13, 14, 15), which are also the goals consistently under-prioritised in the implementation of the current agenda. In terms of the 43 factors affecting social–ecological resilience, the SDG strengths lie in their communication, inclusive decision making, financial support, regulatory incentives, economic diversity, and transparency in governance and law. On the contrary, ecological factors of resilience are seriously lacking in the SDGs, particularly with regards to scale, cross-scale interactions, and non-stationarity.

Social media summary

The post-2030 agenda should build on strengths of SDGs 2, 6, 13, 14, 15, and fill gaps in scale, variability, and feedbacks.
Seasonal Biotic Processes Vary the Carbon Turnover by Up To One Order of Magnitude in Wetlands
Authors: Pasut Chiara , Tang Fiona H. M. , Minasny Budiman , Warren Charles R. , Dijkstra Feike A. , Riley William J. , Maggi Federico
Published: April 2023

Soil Organic Carbon (SOC) turnover τ in wetlands and the corresponding governing processes are still poorly represented in numerical models. τ is a proxy to the carbon storage potential in each SOC pool and C fluxes within the whole ecosystem; however, it has not been comprehensively quantified in wetlands globally. Here, we quantify the turnover time τ of various SOC pools and the governing biotic and abiotic processes in global wetlands using a comprehensively tested process‐based biogeochemical model. Globally, we found that τ ranges between 1 and 1,000 years and is controlled by anaerobic (in 78% of global wetlands area) and aerobic (15%) respiration, and by abiotic destabilization from soil minerals (5%). τ in the remaining 2% of wetlands is controlled by denitrification, sulfur reduction, and leaching below the subsoil. τ can vary by up to one order of magnitude in temperate, continental, and polar regions due to seasonal temperature and can shift from being aerobically controlled to anaerobically controlled. Our findings of seasonal variability in SOC turnover suggest that wetlands are susceptible to climate‐induced shifts in seasonality, thus requiring better accounting of seasonal fluctuations at geographic scales to estimate C exchanges between land and atmosphere.
Classification of Interannual Surface Layer Salinity Variability
Authors: Katsura S. , Sprintall J. , Kido S. , Tanimoto Y. , Nonaka M.
Published: April 2023

Since surface layer salinity (SLS) mainly reflects sea surface freshwater flux and affects ocean circulation and upper ocean stratification by modifying seawater density, knowledge of SLS variability is important to better understand the global hydrological cycle and ocean and climate variability. The global pattern of SLS interannual variability has not received as much attention compared to the seasonal variability. The SLS interannual variability in the global ocean based on Argo profiling float data over 2003–2020 was classified into seven individual clusters. SLS interannual variability was found to be regionally different even within each ocean basin and primarily corresponded to large‐scale climate mode variability. The spatial distribution of the classified SLS clusters provides the first map of SLS interannual variability in the global ocean that largely reflects the variability of the global hydrological cycle.
Adapting to a Foggy Future Along Trans‐Arctic Shipping Routes
Authors: Song Shutong , Chen Yue , Chen Xianyao , Chen Changshuo , Li King‐Fai , Tung Ka‐Kit , Shao Qiuli , Liu Yilin , Wang Xiaoyu , Yi Li , Zhao Jinping
Published: April 2023

Rapid retreat of Arctic sea ice extends the area of open ocean for new trans‐Arctic shipping routes. However, the projected routes may be too optimistic in terms of savings in shipping costs from shortened trans‐Arctic distances as they do not consider the increased sea fog frequency (SFF) over areas of the retreating sea ice. We show that delays due to sea fog can be 1–4 days, about 23%–27% along the Northwest Passage and 4%–11% along the Northern Sea Route than previous estimated. We design a route based on the projected sea‐ice extent and SFF. The new route can reduce the sailing time by 0.3–1 day by detouring the routes with lighter impacts of sea fog. More importantly the new route will lower the risk of catastrophic accidents compared to the shortest route and saves the additional costs due to unscheduled port calls.
Effects of Energetic Particle Precipitation on Stratospheric Temperature During Disturbed Stratospheric Polar Vortex Conditions
Authors: Edvartsen J. Ø. , Maliniemi V. , Nesse H.
Published: April 2023

Recently, observational and re‐analysis studies have outlined potentially enhanced influence of Energetic Particle Precipitation (EPP) either at times preceding Sudden Stratospheric Warmings (SSW) or when the distribution of planetary wave activity is suitable. In addition, significant correlations have been found between EPP and the occurrence rate of SSWs when the phases of the Quasi‐Biennial Oscillation (QBO) are taken into account. Here we study the influence of EPP during disturbed stratospheric polar vortex conditions using chemistry‐climate model SOCOL‐MPIOM3 over the 20th century. When classifying disturbed conditions, the definition of minor SSWs are utilized along with a temperature gradient (day‐to‐day variations) criteria at 90°N and 10 hPa acting as a measure of the strength of the events. We find no influence of EPP on the occurrence rate of disturbed conditions over the last 100 year period. However, conditions preceding and during the disturbances are significantly different when EPP forcing is included into the model. This is especially true for stratospheric disturbances occurring in February. Furthermore, there is a clear tendency that the EPP effect becomes more notable after the 1950s. Our results imply that EPP forcing could be important for the stratospheric conditions during winter and that pre‐conditioning forced by atmospheric disturbances are an important factor when considering how the mechanism operates.
Concentration Field Estimation on Effluent Mixing and Transport With a Parameter‐Based Field Reconstruction Convolutional Neural Network and Random Forests
Authors: Yan Xiaohui , Cao Huade , Yin Penghai , Liu Jianwei , Zhu Zuhao
Published: April 2023

Estimating the concentration field of effluent mixing and transport is a challenging task because of the complex mechanisms and three‐dimensional (3D) variability, but it is of great importance for water quality assessment and water resources management. Sophisticated numerical models based on the 3D computational fluid dynamics (CFD) technique can provide accurate predictions, but they are computationally expensive and require high‐level 3D CFD expertise, impeding their widespread usage. This work primarily develops a Parameter‐based Field Reconstruction convolutional neural network (PFR‐CNN) that can predict the complete concentration field of a target variable using the main influencing parameters, and explores the possibility of employing the proposed network to model the process of effluent mixing and transport. A validated numerical solver, TwoLiquidMixingFoam, was utilized to provide extensive data for multiple vertical buoyant effluents. A PFR‐CNN was developed to estimate the concentration fields based on the densimetric Froude number (F) and normalized port spacing (S/D). The network was developed using the training‐validating dataset from the numerical dataset, and further assessed using additional testing data. A random forest model was also developed, and the results showed that both methods can provide good performance, but the PFR‐CNN method was more robust and required less disk storage space. The results of our study demonstrated that the proposed PFR‐CNN approach is a promising tool for estimating effluent mixing and transport, and can be potentially leveraged to estimate other variables in the field of water resources with the governing parameters.
The DACH1 gene is frequently deleted in prostate cancer, restrains prostatic intraepithelial neoplasia, decreases DNA damage repair, and predicts therapy responses
Authors: Li Zhiping , Jiao Xuanmao , Robertson A. Gordon , Di Sante Gabriele , Ashton Anthony W. , DiRocco Agnese , Wang Min , Zhao Jun , Addya Sankar , Wang Chenguang , McCue Peter A. , South Andrew P. , Cordon-Cardo Carlos , Liu Runzhi , Patel Kishan , Hamid Rasha , Parmar Jorim , DuHadaway James B. , Jones Steven J. M. , Casimiro Mathew C. , Schultz Nikolaus , Kossenkov Andrew , Phoon Lai Yee , Chen Hao , Lan Li , Sun Yunguang , Iczkowski Kenneth A. , Rui Hallgeir , Pestell Richard G.
Published: April 2023

Prostate cancer (PCa), the second leading cause of death in American men, includes distinct genetic subtypes with distinct therapeutic vulnerabilities. The DACH1 gene encodes a winged helix/Forkhead DNA-binding protein that competes for binding to FOXM1 sites. Herein, DACH1 gene deletion within the 13q21.31-q21.33 region occurs in up to 18% of human PCa and was associated with increased AR activity and poor prognosis. In prostate OncoMice, prostate-specific deletion of the Dach1 gene enhanced prostatic intraepithelial neoplasia (PIN), and was associated with increased TGFβ activity and DNA damage. Reduced Dach1 increased DNA damage in response to genotoxic stresses. DACH1 was recruited to sites of DNA damage, augmenting recruitment of Ku70/Ku80. Reduced Dach1 expression was associated with increased homology directed repair and resistance to PARP inhibitors and TGFβ kinase inhibitors. Reduced Dach1 expression may define a subclass of PCa that warrants specific therapies.
Management of chronic myeloid leukemia in 2023 – common ground and common sense
Authors: Senapati Jayastu , Sasaki Koji , Issa Ghayas C. , Lipton Jeffrey H. , Radich Jerald P. , Jabbour Elias , Kantarjian Hagop M.
Published: April 2023

With the improving knowledge of CML and its management, the goals of therapy need to be revisited to ensure an optimal use of the BCR::ABL1 TKIs in the frontline and later-line therapy of CML. In the frontline therapy of CML in the chronic phase (CML-CP), imatinib and the three second-generation TKIs (bosutinib, dasatinib and nilotinib) are associated with comparable survival results. The second-generation TKIs may produce earlier deep molecular responses, hence reducing the time to reaching a treatment-free remission (TFR). The choice of the second-generation TKI versus imatinib in frontline therapy is based on the treatment aims (survival, TFR), the CML risk, the drug cost, and the toxicity profile with respect to the patient’s comorbidities. The TKI dosing is more flexible than has been described in the registration trials, and dose adjustments can be considered both in the frontline and later-line settings (e.g., dasatinib 50 mg frontline therapy; dose adjusted schedules of bosutinib and ponatinib), as well as during an ongoing TKI therapy to manage toxicities, before considering changing the TKI. In patients who are not candidates for TFR, BCR::ABL1 (International Scale) transcripts levels <1% are acceptable, result in virtually similar survival as with deeper molecular remissions, and need not warrant a change of TKI. For patients with true resistance to second-generation TKIs or with the T315I gatekeeper mutation, the third-generation TKIs are preferred. Ponatinib should be considered first because of the cumulative experience and results in the CML subsets, including in T315I-mutated CML. A response-based dosing of ponatinib is safe and leads to high TKI compliance. Asciminib is a third-generation TKI with possibly a better toxicity profile, but lesser activity in T315I-mutated CML. Olverembatinib is another potent third-generation TKI with early promising results.
Treatment expectations in glaucoma: what matters most to patients?
Authors: Safitri Atika , Konstantakopoulou Evgenia , Hu Kuang , Gazzard Gus
Published: April 2023

Background/Objectives

Recent clinical trials in glaucoma have used patient-reported outcome measures (PROMs) of health-related quality of life to evaluate interventions. However, existing PROMs may not be sufficiently sensitive to capture changes in health status. This study aims to determine what really matters to patients by directly exploring their treatment expectations and preferences.

Subjects/Methods

We conducted a qualitative study using one-to-one semi-structured interviews to elicit patients’ preferences. Participants were recruited from two NHS clinics serving urban, suburban and rural populations in the UK. To be relevant across glaucoma patients under NHS care, participants were sampled to include a full range of demographic profiles, disease severities and treatment histories. Interview transcripts were evaluated using thematic analysis until no new themes emerged (saturation). Saturation was established when 25 participants with ocular hypertension, mild, moderate and advanced glaucoma had been interviewed.

Results

Themes identified were: Patients’ experiences of living with glaucoma, patients’ experiences of having glaucoma treatment, most important outcomes to patients, and COVID-related concerns. Participants specifically expressed their most important concerns, which were (i) disease-related outcomes (intraocular pressure control, maintaining vision, and being independent); and (ii) treatment-related outcomes (treatment that does not change, drop-freedom, and one-time treatment). Both disease-related and treatment-related experiences were covered prominently in interviews with patients across the spectrum of glaucoma severity.

Conclusions

Outcomes related both to the disease and its treatment are important to patients with different severities of glaucoma. To accurately evaluate quality of life in glaucoma, PROMs may need to assess both disease-related and treatment-related outcomes.
Dueling dynamics of low-angle normal fault rupture with splay faulting and off-fault damage
Authors: Biemiller J. , Gabriel A.-A. , Ulrich T.
Published: April 2023

Despite a lack of modern large earthquakes on shallowly dipping normal faults, Holocene Mw > 7 low-angle normal fault (LANF; dip<30°) ruptures are preserved paleoseismically and inferred from historical earthquake and tsunami accounts. Even in well-recorded megathrust earthquakes, the effects of non-linear off-fault plasticity and dynamically reactivated splay faults on shallow deformation and surface displacements, and thus hazard, remain elusive. We develop data-constrained 3D dynamic rupture models of the active Mai’iu LANF that highlight how multiple dynamic shallow deformation mechanisms compete during large LANF earthquakes. We show that shallowly-dipping synthetic splays host more coseismic slip and limit shallow LANF rupture more than steeper antithetic splays. Inelastic hanging-wall yielding localizes into subplanar shear bands indicative of newly initiated splay faults, most prominently above LANFs with thick sedimentary basins. Dynamic splay faulting and sediment failure limit shallow LANF rupture, modulating coseismic subsidence patterns, near-shore slip velocities, and the seismic and tsunami hazards posed by LANF earthquakes.
Machine learning prediction of the degree of food processing
Authors: Menichetti Giulia , Ravandi Babak , Mozaffarian Dariush , Barabási Albert-László
Published: April 2023

Despite the accumulating evidence that increased consumption of ultra-processed food has adverse health implications, it remains difficult to decide what constitutes processed food. Indeed, the current processing-based classification of food has limited coverage and does not differentiate between degrees of processing, hindering consumer choices and slowing research on the health implications of processed food. Here we introduce a machine learning algorithm that accurately predicts the degree of processing for any food, indicating that over 73% of the US food supply is ultra-processed. We show that the increased reliance of an individual’s diet on ultra-processed food correlates with higher risk of metabolic syndrome, diabetes, angina, elevated blood pressure and biological age, and reduces the bio-availability of vitamins. Finally, we find that replacing foods with less processed alternatives can significantly reduce the health implications of ultra-processed food, suggesting that access to information on the degree of processing, currently unavailable to consumers, could improve population health.
Inadequacy of fluvial energetics for describing gravity current autosuspension
Authors: Fukuda Sojiro , de Vet Marijke G. W. , Skevington Edward W. G. , Bastianon Elena , Fernández Roberto , Wu Xuxu , McCaffrey William D. , Naruse Hajime , Parsons Daniel R. , Dorrell Robert M.
Published: April 2023

Gravity currents, such as sediment-laden turbidity currents, are ubiquitous natural flows that are driven by a density difference. Turbidity currents have provided vital motivation to advance understanding of this class of flows because their enigmatic long run-out and driving mechanisms are not properly understood. Extant models assume that material transport by gravity currents is dynamically similar to fluvial flows. Here, empirical research from different types of particle-driven gravity currents is integrated with our experimental data, to show that material transport is fundamentally different from fluvial systems. Contrary to current theory, buoyancy production is shown to have a non-linear dependence on available flow power, indicating an underestimation of the total kinetic energy lost from the mean flow. A revised energy budget directly implies that the mixing efficiency of gravity currents is enhanced.
The effect of sustainable mobility transition policies on cumulative urban transport emissions and energy demand
Authors: Winkler Lisa , Pearce Drew , Nelson Jenny , Babacan Oytun
Published: April 2023

The growing urban transport sector presents towns and cities with an escalating challenge in the reduction of their greenhouse gas emissions. Here we assess the effectiveness of several widely considered policy options (electrification, light-weighting, retrofitting, scrapping, regulated manufacturing standards and modal shift) in achieving the transition to sustainable urban mobility in terms of their emissions and energy impact until 2050. Our analysis investigates the severity of actions needed to comply with Paris compliant regional sub-sectoral carbon budgets. We introduce the Urban Transport Policy Model (UTPM) for passenger car fleets and use London as an urban case study to show that current policies are insufficient to meet climate targets. We conclude that, as well as implementation of emission-reducing changes in vehicle design, a rapid and large-scale reduction in car use is necessary to meet stringent carbon budgets and avoid high energy demand. Yet, without increased consensus in sub-national and sectoral carbon budgets, the scale of reduction necessary stays uncertain. Nevertheless, it is certain we need to act urgently and intensively across all policy mechanisms available as well as developing new policy options.
Electronic signatures of Lorentzian dynamics and charge fluctuations in lithiated graphite structures
Authors: Jamnuch Sasawat , Pascal Tod A.
Published: April 2023

Lithium graphite intercalation compounds (Li-GICs) are essential materials for modern day portable electronics and obtaining insights into their atomic structure and thermodynamics is of fundamental interest. Here we explore the electronic and atomic states of Li-GICs at varying degrees of Lithium loading (i.e., “staging”) by means of ab-initio molecular dynamics simulations and simulated X-ray adsorption spectroscopy (XAS). We analyze the atomic correlation functions and shows that the enhancements of the Li-ion entropy with increased staging result from Lorentzian lithium-ion dynamics and charge fluctuations, which activate low-energy phonon modes. The associated electronic signatures are modulations of the unoccupied π*/σ* orbital energy levels and unambiguous fingerprints in Carbon K-edge XAS spectra. Thus, we extend the canonical view of XAS, establishing that these “static” measurements in fact encode the signature of the thermodynamic response and relaxation dynamics of the system. This causal link between atomic structure, spectroscopy, thermodynamics, and information theory can be generally exploited to better understand stability in solid-state electrochemical systems.
Integrated opposite charge grafting induced ionic-junction fiber
Authors: Xing Yi , Zhou Mingjie , Si Yueguang , Yang Chi-Yuan , Feng Liang-Wen , Wu Qilin , Wang Fei , Wang Xiaomin , Huang Wei , Cheng Yuhua , Zhang Ruilin , Duan Xiaozheng , Liu Jun , Song Ping , Sun Hengda , Wang Hongzhi , Zhang Jiayi , Jiang Su , Zhu Meifang , Wang Gang
Published: April 2023

The emergence of ionic-junction devices has attracted growing interests due to the potential of serving as signal transmission and translation media between electronic devices and biological systems using ions. Among them, fiber-shaped iontronics possesses a great advantage in implantable applications owing to the unique one-dimensional geometry. However, fabricating stable ionic-junction on curved surfaces remains a challenge. Here, we developed a polyelectrolyte based ionic-junction fiber via an integrated opposite charge grafting method capable of large-scale continuous fabrication. The ionic-junction fibers can be integrated into functions such as ionic diodes and ionic bipolar junction transistors, where rectification and switching of input signals are implemented. Moreover, synaptic functionality has also been demonstrated by utilizing the fiber memory capacitance. The connection between the ionic-junction fiber and sciatic nerves of the mouse simulating end-to-side anastomosis is further performed to realize effective nerve signal conduction, verifying the capability for next-generation artificial neural pathways in implantable bioelectronics.
HAPLN1 potentiates peritoneal metastasis in pancreatic cancer
Authors: Wiedmann Lena , De Angelis Rigotti Francesca , Vaquero-Siguero Nuria , Donato Elisa , Espinet Elisa , Moll Iris , Alsina-Sanchis Elisenda , Bohnenberger Hanibal , Fernandez-Florido Elena , Mülfarth Ronja , Vacca Margherita , Gerwing Jennifer , Conradi Lena-Christin , Ströbel Philipp , Trumpp Andreas , Mogler Carolin , Fischer Andreas , Rodriguez-Vita Juan
Published: April 2023

Pancreatic ductal adenocarcinoma (PDAC) frequently metastasizes into the peritoneum, which contributes to poor prognosis. Metastatic spreading is promoted by cancer cell plasticity, yet its regulation by the microenvironment is incompletely understood. Here, we show that the presence of hyaluronan and proteoglycan link protein-1 (HAPLN1) in the extracellular matrix enhances tumor cell plasticity and PDAC metastasis. Bioinformatic analysis showed that HAPLN1 expression is enriched in the basal PDAC subtype and associated with worse overall patient survival. In a mouse model for peritoneal carcinomatosis, HAPLN1-induced immunomodulation favors a more permissive microenvironment, which accelerates the peritoneal spread of tumor cells. Mechanistically, HAPLN1, via upregulation of tumor necrosis factor receptor 2 (TNFR2), promotes TNF-mediated upregulation of Hyaluronan (HA) production, facilitating EMT, stemness, invasion and immunomodulation. Extracellular HAPLN1 modifies cancer cells and fibroblasts, rendering them more immunomodulatory. As such, we identify HAPLN1 as a prognostic marker and as a driver for peritoneal metastasis in PDAC.
Carbon mitigation potential afforded by rooftop photovoltaic in China
Authors: Zhang Zhixin , Chen Min , Zhong Teng , Zhu Rui , Qian Zhen , Zhang Fan , Yang Yue , Zhang Kai , Santi Paolo , Wang Kaicun , Pu Yingxia , Tian Lixin , Lü Guonian , Yan Jinyue
Published: April 2023

Rooftop photovoltaics (RPVs) are crucial in achieving energy transition and climate goals, especially in cities with high building density and substantial energy consumption. Estimating RPV carbon mitigation potential at the city level of an entire large country is challenging given difficulties in assessing rooftop area. Here, using multi-source heterogeneous geospatial data and machine learning regression, we identify a total of 65,962 km2 rooftop area in 2020 for 354 Chinese cities, which represents 4 billion tons of carbon mitigation under ideal assumptions. Considering urban land expansion and power mix transformation, the potential remains at 3-4 billion tons in 2030, when China plans to reach its carbon peak. However, most cities have exploited less than 1% of their potential. We provide analysis of geographical endowment to better support future practice. Our study provides critical insights for targeted RPV development in China and can serve as a foundation for similar work in other countries.
UDP-glucosyltransferase OsUGT75A promotes submergence tolerance during rice seed germination
Authors: He Yongqi , Sun Shan , Zhao Jia , Huang Zhibo , Peng Liling , Huang Chengwei , Tang Zhengbin , Huang Qianqian , Wang Zhoufei
Published: April 2023

Submergence stress represents a major obstacle limiting the application of direct seeding in rice cultivation. Under flooding conditions, coleoptile elongation can function as an escape strategy that contributes to submergence tolerance during seed germination in rice; however, the underlying molecular bases have yet to be fully determined. Herein, we report that natural variation of rice coleoptile length subjected to submergence is determined by the glucosyltransferase encoding gene OsUGT75A. OsUGT75A regulates coleoptile length via decreasing free abscisic acid (ABA) and jasmonic acid (JA) levels by promoting glycosylation of these two phytohormones under submergence. Moreover, we find that OsUGT75A accelerates coleoptile length through mediating the interactions between JASMONATE ZIMDOMAIN (OsJAZ) and ABSCISIC ACID-INSENSITIVE (OsABI) proteins. Last, we reveal the origin of the haplotype that contributes to coleoptile length in response to submergence and transferring this haplotype to indica rice can enhance coleoptile length in submergence conditions. Thus, we propose that OsUGT75A is a useful target in breeding of rice varieties suitable for direct seeding cultivation.
Creasing in microscale, soft static friction
Authors: Glover Justin D. , Yang Xingwei , Long Rong , Pham Jonathan T.
Published: April 2023

Utilizing colloidal probe, lateral force microscopy and simultaneous confocal microscopy, combined with finite element analysis, we investigate how a microparticle starts moving laterally on a soft, adhesive surface. We find that the surface can form a self-contacting crease at the leading front, which results from a buildup of compressive stress. Experimentally, creases are observed on substrates that exhibit either high or low adhesion when measured in the normal direction, motivating the use of simulations to consider the role of adhesion energy and interfacial strength. Our simulations illustrate that the interfacial strength plays a dominating role in the nucleation of a crease. After the crease forms, it progresses through the contact zone in a Schallamach wave-like fashion. Interestingly, our results suggest that this Schallamach wave-like motion is facilitated by free slip at the adhesive, self-contacting interface within the crease.
TMEM25 inhibits monomeric EGFR-mediated STAT3 activation in basal state to suppress triple-negative breast cancer progression
Authors: Bi Jing , Wu Zhihui , Zhang Xin , Zeng Taoling , Dai Wanjun , Qiu Ningyuan , Xu Mingfeng , Qiao Yikai , Ke Lang , Zhao Jiayi , Cao Xinyu , Lin Qi , Chen Xiao Lei , Xie Liping , Ouyang Zhong , Guo Jujiang , Zheng Liangkai , Ma Chao , Guo Shiying , Chen Kangmei , Mo Wei , Fu Guo , Zhao Tong-Jin , Wang Hong-Rui
Published: April 2023

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor outcome and lacks of approved targeted therapy. Overexpression of epidermal growth factor receptor (EGFR) is found in more than 50% TNBC and is suggested as a driving force in progression of TNBC; however, targeting EGFR using antibodies to prevent its dimerization and activation shows no significant benefits for TNBC patients. Here we report that EGFR monomer may activate signal transducer activator of transcription-3 (STAT3) in the absence of transmembrane protein TMEM25, whose expression is frequently decreased in human TNBC. Deficiency of TMEM25 allows EGFR monomer to phosphorylate STAT3 independent of ligand binding, and thus enhances basal STAT3 activation to promote TNBC progression in female mice. Moreover, supplying TMEM25 by adeno-associated virus strongly suppresses STAT3 activation and TNBC progression. Hence, our study reveals a role of monomeric-EGFR/STAT3 signaling pathway in TNBC progression and points out a potential targeted therapy for TNBC.
Femtosecond-precision electronic clock distribution in CMOS chips by injecting frequency comb-extracted photocurrent pulses
Authors: Hyun Minji , Chung Hayun , Na Woongdae , Kim Jungwon
Published: April 2023

A clock distribution network (CDN) is a ubiquitous on-chip element that provides synchronized clock signals to all different circuit blocks in the chip. To maximize the chip performance, today’s CDN demands lower jitter, skew, and heat dissipation. Conventionally, on-chip clock signals have been distributed in the electric voltage domain, resulting in increased jitter, skew, and heat dissipation due to clock drivers. While low-jitter optical pulses have been locally injected in the chip, research on effective distribution of such high-quality clock signals has been relatively sparse. Here, we demonstrate femtosecond-precision distribution of electronic clocks using driver-less CDNs injected by photocurrent pulses extracted from an optical frequency comb source. Femtosecond-level on-chip jitter and skew can be achieved for gigahertz-rate clocking of CMOS chips by combining ultralow comb-jitter, multiple driver-less metal-meshes, and active skew control. This work shows the potential of optical frequency combs for distributing high-quality clock signals inside high-performance integrated circuits, including 3D integrated circuits.
Dissecting the conformational complexity and mechanism of a bacterial heme transporter
Authors: Wu Di , Mehdipour Ahmad R. , Finke Franziska , Goojani Hojjat G. , Groh Roan R. , Grund Tamara N. , Reichhart Thomas M. B. , Zimmermann Rita , Welsch Sonja , Bald Dirk , Shepherd Mark , Hummer Gerhard , Safarian Schara
Published: April 2023

Iron-bound cyclic tetrapyrroles (hemes) are redox-active cofactors in bioenergetic enzymes. However, the mechanisms of heme transport and insertion into respiratory chain complexes remain unclear. Here, we used cellular, biochemical, structural and computational methods to characterize the structure and function of the heterodimeric bacterial ABC transporter CydDC. We provide multi-level evidence that CydDC is a heme transporter required for functional maturation of cytochrome bd, a pharmaceutically relevant drug target. Our systematic single-particle cryogenic-electron microscopy approach combined with atomistic molecular dynamics simulations provides detailed insight into the conformational landscape of CydDC during substrate binding and occlusion. Our simulations reveal that heme binds laterally from the membrane space to the transmembrane region of CydDC, enabled by a highly asymmetrical inward-facing CydDC conformation. During the binding process, heme propionates interact with positively charged residues on the surface and later in the substrate-binding pocket of the transporter, causing the heme orientation to rotate 180°.
Dynamic mitochondrial transcription and translation in B cells control germinal center entry and lymphomagenesis
Authors: Yazicioglu Yavuz F. , Marin Eros , Sandhu Ciaran , Galiani Silvia , Raza Iwan G. A. , Ali Mohammad , Kronsteiner Barbara , Compeer Ewoud B. , Attar Moustafa , Dunachie Susanna J. , Dustin Michael L. , Clarke Alexander J.
Published: April 2023

Germinal center (GC) B cells undergo proliferation at very high rates in a hypoxic microenvironment but the cellular processes driving this are incompletely understood. Here we show that the mitochondria of GC B cells are highly dynamic, with significantly upregulated transcription and translation rates associated with the activity of transcription factor A, mitochondrial (TFAM). TFAM, while also necessary for normal B cell development, is required for entry of activated GC precursor B cells into the germinal center reaction; deletion of Tfam significantly impairs GC formation, function and output. Loss of TFAM in B cells compromises the actin cytoskeleton and impairs cellular motility of GC B cells in response to chemokine signaling, leading to their spatial disorganization. We show that B cell lymphoma substantially increases mitochondrial translation and that deletion of Tfam in B cells is protective against the development of lymphoma in a c-Myc transgenic mouse model. Finally, we show that pharmacological inhibition of mitochondrial transcription and translation inhibits growth of GC-derived human lymphoma cells and induces similar defects in the actin cytoskeleton.
Structural insights into thrombolytic activity of destabilase from medicinal leech
Authors: Marin Egor , Kornilov Daniil A. , Bukhdruker Sergey S. , Aleksenko Vladimir A. , Manuvera Valentin A. , Zinovev Egor V. , Kovalev Kirill V. , Shevtsov Mikhail B. , Talyzina Anna A. , Bobrovsky Pavel A. , Kuzmichev Pavel K. , Mishin Alexey V. , Gushchin Ivan Y. , Lazarev Vassili N. , Borshchevskiy Valentin I.
Published: April 2023

Destabilase from the medical leech Hirudo medicinalis belongs to the family of i-type lysozymes. It has two different enzymatic activities: microbial cell walls destruction (muramidase activity), and dissolution of the stabilized fibrin (isopeptidase activity). Both activities are known to be inhibited by sodium chloride at near physiological concentrations, but the structural basis remains unknown. Here we present two crystal structures of destabilase, including a 1.1 Å-resolution structure in complex with sodium ion. Our structures reveal the location of sodium ion between Glu34/Asp46 residues, which were previously recognized as a glycosidase active site. While sodium coordination with these amino acids may explain inhibition of the muramidase activity, its influence on previously suggested Ser49/Lys58 isopeptidase activity dyad is unclear. We revise the Ser49/Lys58 hypothesis and compare sequences of i-type lysozymes with confirmed destabilase activity. We suggest that the general base for the isopeptidase activity is His112 rather than Lys58. pKa calculations of these amino acids, assessed through the 1 μs molecular dynamics simulation, confirm the hypothesis. Our findings highlight the ambiguity of destabilase catalytic residues identification and build foundations for further research of structure–activity relationship of isopeptidase activity as well as structure-based protein design for potential anticoagulant drug development.
Early central cardiovagal dysfunction after high fat diet in a murine model
Authors: Strain Misty M. , Espinoza Liliana , Fedorchak Stephanie , Littlejohn Erica L. , Andrade Mary Ann , Toney Glenn M. , Boychuk Carie R.
Published: April 2023

High fat diet (HFD) promotes cardiovascular disease and blunted cardiac vagal regulation. Temporal onset of loss of cardiac vagal control and its underlying mechanism are presently unclear. We tested our hypothesis that reduced central vagal regulation occurs early after HFD and contributes to poor cardiac regulation using cardiovascular testing paired with pharmacology in mice, molecular biology, and a novel bi-transgenic mouse line. Results show HFD, compared to normal fat diet (NFD), significantly blunted cardio/pulmonary chemoreflex bradycardic responses after 15 days, extending as far as tested (> 30 days). HFD produced resting tachycardia by day 3, reflected significant loss of parasympathetic tone. No differences in bradycardic responses to graded electrical stimulation of the distal cut end of the cervical vagus indicated diet-induced differences in vagal activity were centrally mediated. In nucleus ambiguus (NA), surface expression of δ-subunit containing type A gamma-aminobutyric acid receptors (GABAA(δ)R) increased at day 15 of HFD. Novel mice lacking δ-subunit expression in vagal motor neurons (ChAT-δnull) failed to exhibit blunted reflex bradycardia or resting tachycardia after two weeks of HFD. Thus, reduced parasympathetic output contributes to early HFD-induced HR dysregulation, likely through increased GABAA(δ)Rs. Results underscore need for research on mechanisms of early onset increases in GABAA(δ)R expression and parasympathetic dysfunction after HFD.
LPS induces microglial activation and GABAergic synaptic deficits in the hippocampus accompanied by prolonged cognitive impairment
Authors: Jung Hyeji , Lee Dongsu , You Heejung , Lee Myungha , Kim Hyeonho , Cheong Eunji , Um Ji Won
Published: April 2023

Neuroinflammation impacts the brain and cognitive behavior through microglial activation. In this study, we determined the temporal sequence from microglial activation to synaptic dysfunction and cognitive behavior induced by neuroinflammation in mice. We found that LPS injection activated microglia within a short period, followed by impairments in GABAergic synapses, and that these events led to long-term cognitive impairment. We demonstrated that, 3 days after LPS injection, microglia in the hippocampus were significantly activated due to the LPS-induced inflammation in association with alterations in cellular morphology, microglial density, and expression of phagocytic markers. GABAergic synaptic impairments were detected at 4–6 days after LPS treatment, a time when microglia activity had returned to normal. Consequently, memory impairment persisted for 6 days after injection of LPS. Our results suggest that neuroinflammation induces microglia activation, GABAergic synaptic deficits and prolonged memory impairment over a defined temporal sequence. Our observations provide insight into the temporal sequence of neuroinflammation-associated brain pathologies. Moreover, the specific loss of inhibitory synapses accompanying the impaired inhibitory synaptic transmission provides mechanistic insight that may explain the prolonged cognitive deficit observed in patients with neuroinflammation. Thus, this study provides essential clues regarding early intervention strategies against brain pathologies accompanying neuroinflammation.
Influence of rootstock on endogenous hormones and color change in Cabernet Sauvignon grapes
Authors: Liu Zhiyu , Zhu Chunmei , Sun Junli , Zhang Zhijun , Zhao Shucheng , Shi Wenchao , Wang Wei , Zhao Baolong
Published: April 2023

Different rootstocks for grapes can significantly affect fruit color and quality, possibly by affecting hormone contents, related genetic pathways, and fruit coloring mechanisms in skin. ‘Cabernet Sauvignon’ was grafted to ‘5BB’, ‘SO4’, ‘140R’, ‘CS’, ‘3309M’ and ‘Vitis riparia’ rootstocks, with self-rooting seedlings as the control (CS/CS), and sampled from the early stage of veraison to the ripening stage. The effects of rootstock on the contents of gibberellin (GA3), auxin (IAA), and abscisic acid (ABA) in grape skin were determined alongside the expression levels of eight anthocyanin synthesis related genes using real-time fluorescence quantitative PCR methods. The rootstock cultivars exhibited accelerated fruit color change, and the CS/140R combination resulted in grapes with more color than the control group in the same period. With the development of fruit, the IAA and GA3 contents in the skin of different rootstock combinations showed trends of increasing initially, then decreasing, while the ABA content decreased initially and then increased. During the verasion (28 July), the various ‘Cabernet Sauvignon’ rootstock combinations exhibited varying degrees of increases in GA3, ABA, and IAA contents; correlation analysis showed that, at the start of veraison, the expression levels of the anthocyanin synthesis-related genes VvCHS, VvDFR, and VvUFGT had strong positive correlations with hormone contents, which indicated they are key genes involved in the endogenous hormone responsive anthocyanin biosynthesis pathway. The results of this study showed that rootstock regulates the fruit coloring process by influencing the metabolism level of peel hormones in the ‘Cabernet Sauvignon’ grape.