bluuebunny/crossref_metadata_2025_split huggingface dataset:
Manipulating the diffusion energy barrier at the lithium metal electrolyte interface for dendrite-free long-life batteries
Authors: Pokharel Jyotshna , Cresce Arthur , Pant Bharat , Yang Moon Young , Gurung Ashim , He Wei , Baniya Abiral , Lamsal Buddhi Sagar , Yang Zhongjiu , Gent Stephen , Xian Xiaojun , Cao Ye , Goddard William A. , Xu Kang , Zhou Yue 
Published: April 2024

AbstractConstructing an artificial solid electrolyte interphase (SEI) on lithium metal electrodes is a promising approach to address the rampant growth of dangerous lithium morphologies (dendritic and dead Li0) and low Coulombic efficiency that plague development of lithium metal batteries, but how Li+ transport behavior in the SEI is coupled with mechanical properties remains unknown. We demonstrate here a facile and scalable solution-processed approach to form a Li3N-rich SEI with a phase-pure crystalline structure that minimizes the diffusion energy barrier of Li+ across the SEI. Compared with a polycrystalline Li3N SEI obtained from conventional practice, the phase-pure/single crystalline Li3N-rich SEI constitutes an interphase of high mechanical strength and low Li+ diffusion barrier. We elucidate the correlation among Li+ transference number, diffusion behavior, concentration gradient, and the stability of the lithium metal electrode by integrating phase field simulations with experiments. We demonstrate improved reversibility and charge/discharge cycling behaviors for both symmetric cells and full lithium-metal batteries constructed with this Li3N-rich SEI. These studies may cast new insight into the design and engineering of an ideal artificial SEI for stable and high-performance lithium metal batteries.
Strain-insensitive viscoelastic perovskite film for intrinsically stretchable neuromorphic vision-adaptive transistors
Authors: Wang Chengyu , Bian Yangshuang , Liu Kai , Qin Mingcong , Zhang Fan , Zhu Mingliang , Shi Wenkang , Shao Mingchao , Shang Shengcong , Hong Jiaxin , Zhu Zhiheng , Zhao Zhiyuan , Liu Yunqi , Guo Yunlong 
Published: April 2024

AbstractStretchable neuromorphic optoelectronics present tantalizing opportunities for intelligent vision applications that necessitate high spatial resolution and multimodal interaction. Existing neuromorphic devices are either stretchable but not reconcilable with multifunctionality, or discrete but with low-end neurological function and limited flexibility. Herein, we propose a defect-tunable viscoelastic perovskite film that is assembled into strain-insensitive quasi-continuous microsphere morphologies for intrinsically stretchable neuromorphic vision-adaptive transistors. The resulting device achieves trichromatic photoadaptation and a rapid adaptive speed (<150 s) beyond human eyes (3 ~ 30 min) even under 100% mechanical strain. When acted as an artificial synapse, the device can operate at an ultra-low energy consumption (15 aJ) (far below the human brain of 1 ~ 10 fJ) with a high paired-pulse facilitation index of 270% (one of the best figures of merit in stretchable synaptic phototransistors). Furthermore, adaptive optical imaging is achieved by the strain-insensitive perovskite films, accelerating the implementation of next-generation neuromorphic vision systems.
Insights into vaccines for elderly individuals: from the impacts of immunosenescence to delivery strategies
Authors: Hou Yingying , Chen Min , Bian Yuan , Hu Yuan , Chuan Junlan , Zhong Lei , Zhu Yuxuan , Tong Rongsheng 
Published: April 2024

AbstractImmunosenescence increases the risk and severity of diseases in elderly individuals and leads to impaired vaccine-induced immunity. With aging of the global population and the emerging risk of epidemics, developing adjuvants and vaccines for elderly individuals to improve their immune protection is pivotal for healthy aging worldwide. Deepening our understanding of the role of immunosenescence in vaccine efficacy could accelerate research focused on optimizing vaccine delivery for elderly individuals. In this review, we analyzed the characteristics of immunosenescence at the cellular and molecular levels. Strategies to improve vaccination potency in elderly individuals are summarized, including increasing the antigen dose, preparing multivalent antigen vaccines, adding appropriate adjuvants, inhibiting chronic inflammation, and inhibiting immunosenescence. We hope that this review can provide a review of new findings with regards to the impacts of immunosenescence on vaccine-mediated protection and inspire the development of individualized vaccines for elderly individuals.
CDK4/6 inhibition sensitizes MEK inhibition by inhibiting cell cycle and proliferation in pancreatic ductal adenocarcinoma
Authors: Cheng Ke , Zhou Zijian , Chen Qiangxing , Chen Zixin , Cai Yu , Cai He , Wu Shangdi , Gao Pan , Cai Yunqiang , Zhou Jin , Wang Xin , Wu Zhong , Peng Bing 
Published: April 2024

AbstractPancreatic ductal adenocarcinoma (PDAC) is not sensitive to most chemotherapy drugs, leading to poor chemotherapy efficacy. Recently, Trametinib and Palbociclib have promising prospects in the treatment of pancreatic cancer. This article aims to explore the effects of Trametinib on pancreatic cancer and address the underlying mechanism of resistance as well as its reversal strategies. The GDSC (Genomics of Drug Sensitivity in Cancer) and CTD2 (Cancer Target Discovery and Development) were utilized to screen the potential drug candidate in PDAC cell lines. The dose-increase method combined with the high-dose shock method was applied to induce the Trametinib-resistant PANC-1 and MIA PaCa-2 cell lines. The CCK8 proliferation assay, colony formation assay, flow cytometry, and western blot were conducted to verify the inhibitory effect of Trametinib and Palbociclib. RNA-seq was performed in resistant PDAC cell lines to find the differential expression genes related to drug resistance and predict pathways leading to the reversal of Trametinib resistance. The GDSC and CTD2 database screening revealed that Trametinib demonstrates a significant inhibitory effect on PDAC. We found that Trametinib has a lower IC50 than Gemcitabine in PDAC cell lines. Both Trametinib and Gemcitabine can decrease the proliferation capacity of pancreatic cells, induce cell cycle arrest, and increase apoptosis. Simultaneously, the phosphorylation of the AKT and ERK pathways were inhibited by the treatment of Trametinib. In addition, the RNA-seq of Trametinib-induced resistance PDAC cell lines reveals that the cyclin-dependent kinase (CDK)-RB-E2F regulatory axis and G2/M DNA damage checkpoint might lead the drug resistance. Besides, the combination of Trametinib with Palbociclib could inhibit the proliferation and cell cycle of both resistant cells lines and also restore the sensitivity of drug-resistant cells to Trametinib. Last but not least, the interferon-α and interferon-γ expression were upregulated in resistance cell lines, which might lead to the reversal of drug resistance. The study shows Trametinib has a critical inhibitory effect on PDAC. Besides, the combination of Trametinib with Palbociclib can inhibit the proliferation of PDAC-resistant cells.
The impact of environmental regulation on green investment efficiency of thermal power enterprises in China-based on a three-stage exogenous variable model
Authors: Ren Fang-rong , Wu Tao-feng , Ren Yang-jun , Liu Xiao-yan , Yuan Xiaomei 
Published: April 2024

AbstractDue to the increased frequency of extreme weather events and the implementation of the China’s dual-carbon target, thermal power companies have been under pressure to construct green infrastructure and to actively pursue low-carbon transformation in response to stricter environmental regulations. This research thus selects 30 listed thermal power enterprises in China as study objects and assesses their green investment efficiency in the low-carbon transition process using three-stage DEA evaluation model with environmental regulation as an exogenous variable. Based on this, a benchmark regression model is used to corroborate the relationship between environmental regulation and green investment. Simultaneously, we carry out analysis to compare the correlation between thermal power firms’ green investment efficiency and their focus on green investments. The results show in terms of total efficiency that environmental regulation significantly improves the total efficiency of 80% of thermal power enterprises compared to the absence of this exogenous variable. With the addition of environmental regulation, firms’ total efficiency declines gradually in general from 2018 to 2022, with the mean value of efficiency falling by 0.068. In terms of stage-specific efficiency, the efficiency of the green investment stage of the majority of firms is between 0.3 and 0.6, which is much lower than that of the operational stage and the market performance stage. In terms of sub-indicator efficiency, both green investment efficiency and social donation efficiency among thermal power enterprises show obvious polarization, with 30% of them having an efficiency of 1 and 30% less than 0.1. In terms of green investment focus, thermal power unit renovation has a more obvious role in boosting the green investment efficiency of thermal power enterprises than do wind power and photovoltaic projects. Therefore, both governmental departments and thermal power enterprises need to take active measures in order to achieve green transformation from the perspective of green investment efficiency. Through the segmentation of important projects of green investment, this paper provides a reasonable investment direction reference for the sustainable transformation of China’s thermal power industry. It also provides a rich and novel theoretical basis for the Chinese government to further improve the relevant environmental protection laws and regulations of thermal power industry.
Blood groups and Rhesus status as potential predictors of outcomes in patients with cardiac resynchronisation therapy
Authors: Papageorgiou Nikolaos , Sohrabi Catrin , Bakogiannis Constantinos , Tsarouchas Anastasios , Kukendrarajah Kishore , Matiti Luso , Srinivasan Neil T. , Ahsan Syed , Sporton Simon , Schilling Richard J. , Hunter Ross J. , Muthumala Amal , Creta Antonio , Chow Anthony W. , Providencia Rui 
Published: April 2024

AbstractCardiac resynchronisation therapy (CRT) improves prognosis in patients with heart failure (HF) however the role of ABO blood groups and Rhesus factor are poorly understood. We hypothesise that blood groups may influence clinical and survival outcomes in HF patients undergoing CRT. A total of 499 patients with HF who fulfilled the criteria for CRT implantation were included. Primary outcome of all-cause mortality and/or heart transplant/left ventricular assist device was assessed over a median follow-up of 4.6 years (IQR 2.3–7.5). Online repositories were searched to provide biological context to the identified associations. Patients were divided into blood (O, A, B, and AB) and Rhesus factor (Rh-positive and Rh-negative) groups. Mean patient age was 66.4 ± 12.8 years with a left ventricular ejection fraction of 29 ± 11%. There were no baseline differences in age, gender, and cardioprotective medication. In a Cox proportional hazard multivariate model, only Rh-negative blood group was associated with a significant survival benefit (HR 0.68 [0.47–0.98], p = 0.040). No association was observed for the ABO blood group (HR 0.97 [0.76–1.23], p = 0.778). No significant interaction was observed with prevention, disease aetiology, and presence of defibrillator. Rhesus-related genes were associated with erythrocyte and platelet function, and cholesterol and glycated haemoglobin levels. Four drugs under development targeting RHD were identified (Rozrolimupab, Roledumab, Atorolimumab, and Morolimumab). Rhesus blood type was associated with better survival in HF patients with CRT. Further research into Rhesus-associated pathways and related drugs, namely whether there is a cardiac signal, is required.
Cytokine production by bovine adipose tissue stromal vascular fraction cells upon Neospora caninum stimulation
Authors: Oliveira Bárbara M. , Sidónio Beatriz , Correia Alexandra , Pinto Ana , Azevedo Maria M. , Sampaio Paula , Ferreira Paula G. , Vilanova Manuel , Teixeira Luzia 
Published: April 2024

AbstractIn bovines few studies addressed the contribution of adipose tissue to the host immune response to infection. Here we evaluated the in vitro response of bovine adipose tissue stromal vascular fraction (SVF) cells to the protozoan parasite Neospora caninum, using live and freeze-killed tachyzoites. Live N. caninum induced the production of IL-6, IL-1β and IL-10 by SVF cells isolated from subcutaneous adipose tissue (SAT), while in mesenteric adipose tissue (MAT) SVF cell cultures only IL-1β and IL-10 production was increased, showing slight distinct responses between adipose tissue depots. Whereas a clear IL-8 increase was detected in peripheral blood leucocytes (PBL) culture supernatants in response to live N. caninum, no such increase was observed in SAT or MAT SVF cell cultures. Nevertheless, in response to LPS, increased IL-8 levels were detected in all cell cultures. IL-10 levels were always increased in response to stimulation (live, freeze-killed N. caninum and LPS). Overall, our results show that bovine adipose tissue SVF cells produce cytokines in response to N. caninum and can therefore be putative contributors to the host immune response against this parasite.
Mechanism of antagonist ligand binding to REV-ERBα
Authors: Rahman Mohammad Homaidur , Hegazy Lamees 
Published: April 2024

AbstractREV-ERBα, a therapeutically promising nuclear hormone receptor, plays a crucial role in regulating various physiological processes such as the circadian clock, inflammation, and metabolism. However, the availability of chemical probes to investigate the pharmacology of this receptor is limited, with SR8278 being the only identified synthetic antagonist. Moreover, no X-ray crystal structures are currently available that demonstrate the binding of REV-ERBα to antagonist ligands. This lack of structural information impedes the development of targeted therapeutics. To address this issue, we employed Gaussian accelerated molecular dynamics (GaMD) simulations to investigate the binding pathway of SR8278 to REV-ERBα. For comparison, we also used GaMD to observe the ligand binding process of STL1267, for which an X-ray structure is available. GaMD simulations successfully captured the binding of both ligands to the receptor’s orthosteric site and predicted the ligand binding pathway and important amino acid residues involved in the antagonist SR8278 binding. This study highlights the effectiveness of GaMD in investigating protein–ligand interactions, particularly in the context of drug recognition for nuclear hormone receptors.
Expression and processing of mature human frataxin after gene therapy in mice
Authors: Rojsajjakul Teerapat , Selvan Nithya , De Bishnu , Rosenberg Jonathan B. , Kaminsky Stephen M. , Sondhi Dolan , Janki Peter , Crystal Ronald G. , Mesaros Clementina , Khanna Richie , Blair Ian A. 
Published: April 2024

AbstractFriedreich’s ataxia is a degenerative and progressive multisystem disorder caused by mutations in the highly conserved frataxin (FXN) gene that results in FXN protein deficiency and mitochondrial dysfunction. While gene therapy approaches are promising, consistent induction of therapeutic FXN protein expression that is sub-toxic has proven challenging, and numerous therapeutic approaches are being tested in animal models. FXN (hFXN in humans, mFXN in mice) is proteolytically modified in mitochondria to produce mature FXN. However, unlike endogenous hFXN, endogenous mFXN is further processed into N-terminally truncated, extra-mitochondrial mFXN forms of unknown function. This study assessed mature exogenous hFXN expression levels in the heart and liver of C57Bl/6 mice 7–10 months after intravenous administration of a recombinant adeno-associated virus encoding hFXN (AAVrh.10hFXN) and examined the potential for hFXN truncation in mice. AAVrh.10hFXN induced dose-dependent expression of hFXN in the heart and liver. Interestingly, hFXN was processed into truncated forms, but found at lower levels than mature hFXN. However, the truncations were at different positions than mFXN. AAVrh.10hFXN induced mature hFXN expression in mouse heart and liver at levels that approximated endogenous mFXN levels. These results suggest that AAVrh.10hFXN can likely induce expression of therapeutic levels of mature hFXN in mice.
Radiographic outcomes and non-union factor analysis in fragmentary segmental femoral shaft fractures (AO/OTA 32C3) treated with reamed antegrade nailing
Authors: Cho Won-Tae , Jang Jae Hoon , Park Seung Ryeol , Sohn Hoon-Sang 
Published: April 2024

AbstractThis study retrospectively assessed radiographic outcomes and risk factors associated with non-union in femoral shaft fragmentary segmental fractures (AO/OTA 32C3) treated with reamed antegrade intra-medullary nailing. Radiological outcomes, including union and alignment, were evaluated. The risk factors for non-union were investigated, including demographics and treatment-related characteristics, such as the number of interlocking screws, segmentation length, main third fragment length, distance of the main third fragment, width ratio and exposed nail length in one cortex from immediate post-operative radiographs. Multivariate logistic regression was used for statistical analysis. Among 2295 femoral shaft fracture patients from three level-1 trauma centers, 51 met the inclusion criteria. The radiological union was achieved in 37 patients (73%) with a mean union time of 10.7 ± 4.8 months. The acceptable axial alignment was observed in 30 patients (59%). Multiple logistic regression analysis identified only exposed nail length as a significant risk factor for non-union (odds ratio: 1.599, p = 0.003) and the cut-off value was 19.1 mm (sensitivity, 0.786; specificity, 0.811). The study revealed high rates of non-union (27%) and malalignment (41%). Therefore, patients who underwent intramedullary nailing with an exposed nail length greater than 19.1 mm or about twice the nail diameter should be cautioned of the potential non-union.
Acceptability of COVID-19 booster vaccine in malaysia: a cross-sectional study
Authors: Khoo Cheryl Minn Jee , Dea Eve Zhi Qing , Law Li Yeow , Wong Sharon Siew Tong , Ng Khuen Yen , Bakhtiar Athirah 
Published: April 2024

AbstractDespite the high efficacy and safety demonstrated in clinical trials, COVID-19 booster vaccination rates in Malaysia remain below 50% among the general public. This study explores the factors influencing public acceptance of the COVID-19 booster vaccine among the Malaysian population. The questionnaire included variables on sociodemographics, knowledge, and the Health Belief Model (HBM) constructs. Based on the Chi-squared test of contingencies, a t-test and multivariate logistic regression analysis on 411 collected responses, the findings revealed that older participants, individuals of Chinese ethnicity, and those with higher education levels and incomes were more willing to accept booster vaccinations. The analysis further identified perceived susceptibility, perceived severity and perceived barriers as significant predictors influencing booster vaccination acceptance rates. Healthcare policymakers may consider targeting interventions to diminish the obstacles associated with booster vaccinations. These intervention strategies include implementing health intervention programmes, such as public health awareness initiatives, to raise awareness of the risks and severity of COVID-19, ultimately encouraging higher uptake of booster vaccines.
Bioluminescence imaging of Cyp1a1-luciferase reporter mice demonstrates prolonged activation of the aryl hydrocarbon receptor in the lung
Authors: Veland Nicolas , Gleneadie Hannah J. , Brown Karen E. , Sardini Alessandro , Pombo Joaquim , Dimond Andrew , Burns Vanessa , Sarkisyan Karen , Schiering Chris , Webster Zoe , Merkenschlager Matthias , Fisher Amanda G. 
Published: April 2024

AbstractAryl hydrocarbon receptor (AHR) signalling integrates biological processes that sense and respond to environmental, dietary, and metabolic challenges to ensure tissue homeostasis. AHR is a transcription factor that is inactive in the cytosol but upon encounter with ligand translocates to the nucleus and drives the expression of AHR targets, including genes of the cytochrome P4501 family of enzymes such as Cyp1a1. To dynamically visualise AHR activity in vivo, we generated reporter mice in which firefly luciferase (Fluc) was non-disruptively targeted into the endogenous Cyp1a1 locus. Exposure of these animals to FICZ, 3-MC or to dietary I3C induced strong bioluminescence signal and Cyp1a1 expression in many organs including liver, lung and intestine. Longitudinal studies revealed that AHR activity was surprisingly long-lived in the lung, with sustained Cyp1a1 expression evident in discrete populations of cells including columnar epithelia around bronchioles. Our data link diet to lung physiology and also reveal the power of bespoke Cyp1a1-Fluc reporters to longitudinally monitor AHR activity in vivo.
State-dependent binding of cholesterol and an anionic lipid to the muscle-type Torpedo nicotinic acetylcholine receptor
Authors: Ananchenko Anna , Gao Rui Yan , Dehez François , Baenziger John E. 
Published: April 2024

AbstractThe ability of the Torpedo nicotinic acetylcholine receptor (nAChR) to undergo agonist-induced conformational transitions requires the presence of cholesterol and/or anionic lipids. Here we use recently solved structures along with multiscale molecular dynamics simulations to examine lipid binding to the nAChR in bilayers that have defined effects on nAChR function. We examine how phosphatidic acid and cholesterol, lipids that support conformational transitions, individually compete for binding with phosphatidylcholine, a lipid that does not. We also examine how the two lipids work synergistically to stabilize an agonist-responsive nAChR. We identify rapidly exchanging lipid binding sites, including both phospholipid sites with a high affinity for phosphatidic acid and promiscuous cholesterol binding sites in the grooves between adjacent transmembrane α-helices. A high affinity cholesterol site is confirmed in the inner leaflet framed by a key tryptophan residue on the MX α-helix. Our data provide insight into the dynamic nature of lipid-nAChR interactions and set the stage for a detailed understanding of the mechanisms by which lipids facilitate nAChR function at the neuromuscular junction.
China Southern Power Grid’s decarbonization likely to impact cropland and transboundary rivers
Authors: Jin Xiaoyu , Chowdhury A.F.M. Kamal , Liu Benxi , Cheng Chuntian , Galelli Stefano 
Published: April 2024

AbstractDecarbonizing the electricity sector requires massive investments in generation and transmission infrastructures that may impact both water and land resources. Characterizing these effects is key to ensure a sustainable energy transition. Here, we identify and quantify the unintended consequences of decarbonizing the China Southern Power Grid, China’s second-largest grid. We show that reaching carbon neutrality by 2060 is feasible; yet, doing so requires converting 40,000 square kilometers of land to support solar and wind as well as tapping on rivers to build ~32 gigawatts of hydropower. The impact of wind and solar development would span across multiple sectors, since crop and grassland constitute 90% of the identified sites. The construction of new dams may carry major externalities and trickle down to nearby countries, as most dams are located in transboundary rivers. Curbing the international footprint of this decarbonization effort would require additional investments (~12 billion United States dollars) in carbon capture technologies.