Browse Articles

Retraction: AI-assisted design of lightweight and strong 3D-printed wheels for electric vehicles

Author Correction: Fibrin Glue-aided, Instant Epicardial Placement Enhances the Efficacy of Mesenchymal Stromal Cell-Based Therapy for Heart Failure

Obesity drives depot-specific vascular remodeling in male white adipose tissue

Abstract Obesity-driven pathological expansion of white adipose tissue (WAT) is a key driver of endothelial dysfunction. However, early vascular alterations associated with over-nutrition also serve to exacerbate WAT dysfunction. Here, we conduct a single-cell transcriptomic analysis of WAT endothelium to delineate endothelial heterogeneity and elucidate vascular alterations and its consequence in a male murine model of obesity. We demarcate depot-specific differences in subcutaneous (sWAT) and visceral WAT (vWAT) endothelium through in sillico analysis and further corroboration of our findings. Moreover, we identify a sWAT-specific fenestrated endothelial cell (EC) subtype, which declines in obese conditions. Utilizing systemic anti-VEGFA blockade and genetic Vegfa manipulation, we demonstrate that VEGFA is necessary for maintaining fenestration in sWAT. Additionally, we detect this fenestrated EC subtype in male human WAT, which undergoes reduction in individuals with obesity. Collectively, this atlas serves as a valuable tool for future studies to decipher the functional significance of different WAT EC subtypes.

Fully automated workflow for designing patient-specific orthopaedic implants: Application to total knee arthroplasty

Background Osteoarthritis affects about 528 million people worldwide, causing pain and stiffness in the joints. Arthroplasty is commonly performed to treat joint osteoarthritis, reducing pain and improving mobility. Nevertheless, a significant share of patients remain unsatisfied with their surgery. Personalised arthroplasty was introduced to improve surgical outcomes however current solutions require delays, making it difficult to integrate in clinical routine. We propose a fully automated workflow to design patient-specific implants for total knee arthroplasty. Methods The proposed pipeline first uses artificial neural networks to segment the femur and tibia proximal and distal extremities. Then the full bones are reconstructed using augmented statistical shape models, combining shape and landmarks information. Finally, 77 morphological parameters are computed to design patient-specific implants. The developed workflow has been trained on 91 CT scans and evaluated on 41 CT scans, in terms of accuracy and execution time. Results The workflow accuracy was 0.4±0.2mm for segmentation, 1.0±0.3mm for full bone reconstruction, and 2.2±1.5mm for anatomical landmarks determination. The custom implants fitted the patients’ anatomy with 0.9±0.5mm accuracy. The whole process from segmentation to implants’ design lasted about 15 minutes. Conclusion The proposed workflow allows the establishment of a patient-specific pre-operative planning in a very short time, making it easily available for all patients. It performs a fast and reliable personalisation of knee implants, including CT segmentation, bone modelling, morphological analysis and implant design, without requiring any manual intervention. Combined with efficient implant manufacturing techniques, this solution could help answer the growing number of arthroplasties while reducing complications and improving patients’ satisfaction.

Author Correction: Host-derived protein profiles of human neonatal meconium across gestational ages

Wind resource assessment Offshore Fujian using 30-year wind estimates

China has set ambitious goals for the development of offshore wind energy to meet the increasing energy needs of coastal provinces. The initial phase of offshore wind energy development involves evaluating the wind resource and identifying the most promising locations for wind farms. It is crucial to assess the characteristics and potential of wind energy beforehand. This study conducts a comprehensive assessment of offshore wind resource near Fujian China. Wind measurement devices were deployed at XiaPu and PingTan to collect wind profile data and meteorological conditions for one year. Various wind characteristics, including average wind speed, frequency of wind direction, wind shears and turbulence intensity were analyzed. An adaptive Measure‑Correlate‑Predict methodology was utilized to estimate wind conditions over 30‑years span. Measured Wind energy density values range from 3082.63 and 11753.52 kWh/m2/year. The peak daily average wind speeds are prevailing between 12 a.m. and 11 p.m with lower turbulence intensity and higher wind shear exponent, such condition is suitable for development of wind power. The variation in the wind shear exponent, and wind speed changes with the seasons. The 90th percentile of turbulence intensity was found to be below the standard set for IEC Class A + The extreme wind speed associated with a 50-year return period was 38.0m/s at a height of 100m, leading to the recommendation of wind turbine class II. However, taking into account the ambient turbulence intensity, it might be advisable to upgrade the turbine class to IEC Class A+.

Purity of lithium metal electrode and its impact on lithium stripping in solid-state batteries

Abstract Recent studies emphasize that incorporating lithium metal electrodes can increase the energy density of next generation batteries. However, the production of lithium metal with high purity requires multi-stage purification steps due to its high reactivity. Furthermore, subsequent handling under inert conditions is required to prevent degradation. To circumvent handling of lithium metal and further improve energy density, researchers are exploring reservoir-free cells often referred to as “anode-free” cells. Reservoir-free cells are assembled without using lithium metal. Instead, lithium is electrodeposited at the interface between a current collector and a solid electrolyte from positive electrode materials during the first charge. Despite the potential of reservoir-free cells, there is limited understanding of the purity of electrodeposited lithium metal and how impurities might affect the electrochemical kinetics. This study examines first the purity of electrodeposited lithium at the steel|Li6PS5Cl interface. Then, it shows how impurities in lithium electrodes affect stripping capacity when using commercial lithium metal foils with both Li6PS5Cl and Li6.25Al0.25La3Zr2O12 as solid electrolytes. By using time-of-flight secondary mass spectrometry and X-ray photoelectron spectrometry, we reveal that a lithium layer with high purity is electrodeposited at the negative electrode in reservoir-free cells and that common impurities in lithium metal (reservoir-type) electrodes like e.g. sodium negatively influence the accessible lithium capacity during discharge.

Emotional impact of AI-generated vs. human-composed music in audiovisual media: A biometric and self-report study

Generative artificial intelligence (AI) has evolved rapidly, sparking debates about its impact on the visual and sonic arts. Despite its growing integration into creative industries, public opinion remains sceptical, viewing creativity as uniquely human. In music production, AI tools are advancing, yet emotional expression remains largely overlooked in development and research. This study examined whether AI-powered music creation can evoke the same emotional impact as human-created music in audiovisual contexts. Participants (N = 88) watched videos accompanied by different audio tracks across three conditions: human-created music (HCM), AI-generated music using more sophisticated and detailed keyword prompts (AI-KP) and AI-generated music using simpler and less detailed prompts based on discrete and dimensional emotional values (AI-DP). Biometric data and personal affective responses were registered during this process. The results show that both AI soundtracks led to wider pupil dilation compared with human-created music but did not differ significantly from each other. AI-generated music with sophisticated prompts (AI-KP) resulted in a higher blink rate and skin impedance level as markers of attention and cognitive load, while emotional valence remained consistent across conditions. Participants found AI-generated music more arousing that HCM, while HCM was perceived as more familiar than both AI conditions.

Family recipe

Abstract rule learning promotes cognitive flexibility in complex environments across species

Abstract Rapid learning in complex and changing environments is a hallmark of intelligent behavior. Humans achieve this in part through abstract concepts applicable to multiple, related situations. It is unclear, however, whether the computational mechanisms underlying rapid learning are unique to humans or also exist in other species. We combined behavioral, computational and electrophysiological analyses of a multidimensional rule-learning paradigm in male rats and in humans. We report that both species infer task rules by sequentially testing different hypotheses, rather than learning the correct action for all possible cue combinations. Neural substrates of hypothetical rules were detected in prefrontal network activity of both species. This species-conserved mechanism reduces task dimensionality and explains key experimental observations: sudden behavioral transitions and facilitated learning after prior experience. Our findings help to narrow the explanatory gap between human macroscopic and rodent microcircuit levels and provide a foundation for the translational investigation of impaired cognitive flexibility.

In-silico study of approved drugs as potential inhibitors against 3CLpro and other viral proteins of CoVID-19

The global pandemic, due to the emergence of COVID-19, has created a public health crisis. It has a huge morbidity rate that was never comprehended in the recent decades. Despite numerous efforts, potent antiviral drugs are lacking. Repurposing of drugs presents a low-cost and rapid solution for finding new drugs by exploiting known drugs. In this study, we employed an integrated In-Silico approach using molecular docking and machine learning regression models to explore the potential inhibitors against key proteins of SARS-CoV-2. A library of 5903 drugs from the ZINC database was retrieved and screened against three crucial viral targets: Spike glycoprotein (7LM9), main protease 3CLpro (7JSU), and Nucleocapsid protein (7DE1). Binding affinities were predicted by using molecular docking, and subsequent predictive regression models, Decision Tree Regression (DTR), Gradient Boosting, XGBoost, Extra Trees, KNNR, and MLP, were constructed employing MACCS molecular fingerprints. Among them, the DTR model had better predictive performance, as indicated by the highest R² and lowest RMSE. The highest ranked compounds possessed good binding affinities (−12.6 to −19.7 kcal/mol) and favorable pharmacokinetics. Importantly, five novel candidate compounds, namely ZINC003873365, ZINC085432544, ZINC008214470, ZINC085536956, and ZINC261494640, had multi-target potential and optimal binding interaction. This computational analysis yields useful information for lead prioritization and sets the stage for additional in vitro and in vivo confirmation of these drug candidates to combat COVID-19.

Structure of lymphostatin, a large multi-functional virulence factor of pathogenic Escherichia coli

Abstract Lymphostatin is a key virulence factor of enteropathogenic and enterohaemorrhagic Escherichia coli , playing roles in bacterial colonisation of the gut and in the inhibition of lymphocyte proliferation and proinflammatory responses. The protein’s glycosyltransferase and cysteine protease motifs are required for activity against lymphocytes, but high-resolution structural information has proven elusive. Here, we describe the structure of lymphostatin from enteropathogenic E. coli O127:H6 , determined by electron cryo-microscopy at different pH values. We observe three conformations of a highly complex molecule with two glycosyltransferase domains, one PaToxP-like protease domain, an ADP-ribosyltransferase domain, a vertex domain and a delivery domain. Long linkers hold these domains together and occlude the catalytic sites of the N-terminal glycosyltransferase and protease domains. Lymphostatin binds to bovine T-lymphocytes and HEK-293T cells, forming clusters at the plasma membrane that are internalized. With six distinct domains, lymphostatin can be regarded as a multitool of pathogenic Escherichia coli , enabling complex interactions with host cells.

Domestication as the driver of lower chronic stress levels in fish in catch-and-release recreational fisheries and aquaculture versus wild conspecifics

The manipulation of species’ attributes through selective breeding can produce domesticated traits including decreased stress responses (i.e., selecting for high stress resilience). Common carp Cyprinus carpio (“carp”) have been domesticated for centuries, with domesticated forms frequently used to enhance recreational catch-and-release fisheries around the world. In Atlantic salmon Salmo salar (“salmon”), two primary strains are evident, a wild strain and domesticated aquaculture strain. Here, we compared scale cortisol concentrations (a biomarker of fish chronic stress levels) between domesticated carp in catch-and-release pond fisheries and wild carp in waters with no angling. Carp of low scale cortisol concentration were apparent in all sampled populations, suggesting individuals of low stress sensitivity are encountered in both wild and domesticated strains, and in natural and captive environments. Carp with relatively high levels of scale cortisol were, however, only present in wild carp, suggesting high phenotypic variability in their chronic stress responses, with some individuals being highly sensitive to stress. In some wild carp, elevated scale cortisol concentrations could also have been indicative of adaptive responses to their heterogenous environments. We then compared wild versus farmed salmon scale cortisol levels, and found a similar pattern, with relatively high scale cortisol levels only detected in wild fish. These results indicate that while domesticated carp and salmon are exposed to potentially stressful environments, they appear to have some resilience against the adverse effects of chronic stress.

Can a pill replace exercise? Swigging this molecule gives mice benefits of working out

Coordinated early immune response in the lungs is required for effective control of SARS-CoV-2 replication

Abstract Despite waning of virus-neutralizing antibodies, protection against severe SARS-CoV-2 in the majority of immune individuals remains high, but the underlying immune mechanisms are incompletely understood. Here, rhesus macaques with pre-existing immunity from Novavax WA-1 and/or P.1 vaccines and WA-1 or P.1 infection are immunized with a bivalent WA-1/Omicron BA.5 Novavax vaccine ten months after the last exposure. The boost vaccination primarily increases the frequency of cross-reactive spike (S)-specific antibodies and B cells instead of inducing de novo BA.5-specific responses. Reinfection with heterologous Omicron XBB.1.5 six months after the boost vaccination results in low levels of virus replication in the respiratory tract compared with virus-naïve results from other studies. Whereas systemic S-specific immunity remains largely unchanged in all animals, the animals with complete protection from infection exhibit a stronger influx of S-specific IgG, monocytes, B cells and T cells into the bronchioalveolar space combined with expansion of CD69+CD103+ lung tissue-resident, S-specific CD8 T cells compared to actively infected animals. Our results underscore the importance of localized respiratory immune responses in mediating protection from Omicron reinfection and provide guidance for future vaccine development.

Population attributable fraction of risk factors for anemia among children aged 6–59 months: A multilevel complex data analysis using modified poisson regression model in Sub-Saharan Africa

Background Anemia among children under five remains a significant public health concern in sub-Saharan Africa (SSA). While numerous studies have examined its associated factors, limited evidence exists on the public health impact of modifiable risk factors. This study assessed the population-attributable fraction (PAF) of risk factors for anemia among children aged 6–59 months across 27 SSA countries. Methods A secondary data analysis was conducted using Demographic and Health Survey (DHS) data from 27 SSA countries, including a weighted sample of 124,285 children. Data management and analysis were done using STATA-14 software. The presence of clustering was assessed using the Intra-cluster Correlation Coefficient (ICC), Median Odds Ratio (MOR), and Likelihood Ratio Test (LRT). A multilevel modified Poisson regression model was employed to estimate adjusted Prevalence Odds Ratios (aPOR) and the corresponding PAF with 95% Confidence Intervals (CI), and the Population Attributable Fraction (PAF) with the 95% CI was estimated using the aPOR and the prevalence of exposure. Results The overall prevalence of anemia among children in SSA was 61.99% (95% CI: 61.73, 62.27). Significant risk factors included maternal anemia (PAF = 7.37%), low maternal education (PAF = 5.86% for no formal education), poor household wealth status (PAF = 3.52% for the poorest), lack of media exposure (PAF = 0.76%), child undernutrition (stunting PAF = 1.31%, underweight PAF = 0.84%), diarrheal (PAF = 1.19%) and febrile illness (PAF = 2.26%), and unimproved toilet facilities (PAF = 1.02%). Conclusion Maternal anemia, low maternal educational status, poverty, poor sanitation, inadequate media access, unimproved toilet facilities, and childhood illness significantly contribute to anemia in SSA. Targeted interventions to improve maternal and child health, enhance education, and ensure better nutrition and sanitation could help reduce childhood anemia in the region.

Predictive goal coding by dentate gyrus somatostatin-expressing interneurons in male mice

Abstract To select appropriate behaviour, individuals must rely on encoding of relevant features within their environment in the context of current and past experiences. This function has been linked to goal-associated activity patterns of hippocampal principal cells. Using single-unit recordings from optogenetically identified somatostatin-expressing interneurons (SOMIs) in the dentate gyrus of head-fixed mice trained in a spatial goal-oriented reward-learning task in virtual realities, we show that SOMI activity temporally precedes reward-locations in expert mice characterized by goal-anticipatory behaviour. Predictive goal-encoding by SOMIs is lost after translocation of learned goals to novel previously unrewarded sites leading to rapid reductions in anticipatory behaviour and fast reconfiguration of SOMI activity to times after reward onset in association with reward consumption at novel goal-sites. Chemogenetic silencing of SOMIs caused a loss of memory that trained goal-sites were no longer available. Thus, our data reveal the ability of SOMIs to flexibly encode goal-locations depending on current and past experiences to bias behavioral outcomes.

Differential interactions of ToLCNDV with different betasatellites reveal complex viral dynamics in N. benthamiana

Tomato leaf curl New Delhi virus (ToLCNDV), a bipartite begomovirus prevalent in Old World and major cotton-growing regions of Pakistan, has increasingly been found associated with diverse betasatellites. Although betasatellites, small circular DNA satellites, are typically associated with monopartite begomoviruses, they are known to enhance disease severity (pathogenicity), increase viral DNA accumulation, and expand virus host ranges. This study investigated the interaction between ToLCNDV and three widely distributed betasatellites – cotton leaf curl Multan betasatellite strain Multan (Mβ), cotton leaf curl Multan betasatellite strain Burewala (Bβ) and tobacco leaf curl betasatellite (Tbβ) – in Nicotiana benthamiana plants, focusing on the potential emergence of novel viral combinations in cotton-growing regions. Infectious clones of ToLCNDV (either DNA-A [TA] alone or with DNA-B [TB]) were co-inoculated with each betasatellite clone. Results revealed intriguing complexity and variability in interactions: betasatellite with TA/TB affected TB accumulation, suggesting a competition between them, while TA levels increased only in the presence of TB, not apparently with Bβ. Interestingly, Tβ accumulated to the higher levels in plants, followed by Bβ and Mβ, highlighting betasatellite-specific interactions. These findings suggest that ToLCNDV-betasatellite interactions are more intricate than simple antagonism. The co-occurence of ToLCNDV with diverse betasatellites in cotton-growing regions of Pakistan increases the likelihood of the emergence of novel and potentially more pathogenic viral combinations. These intricate interactions have significant implications for understanding the dynamics of CLCuD disease.

Constitutive expression of the transcriptional co-activator IκBζ promotes melanoma growth and immunotherapy resistance

Abstract IκBζ, a rather unknown co-regulator of NF-κB, can either activate or repress a subset of NF-κB target genes. While its role as an inducibly expressed, transcriptional regulator of cytokines and chemokines in immune cells is established, IκBζ’s function in solid cancer remains unclear. Here we show that IκBζ protein is constitutively expressed in a subfraction of melanoma cell lines, and around 30% of all melanoma cases, independently of its mRNA levels or known mutations. Deleting IκBζ in melanoma abrogates the activity and chromatin association of STAT3 and NF-κB, thereby reducing the expression of the pro-proliferative cytokines IL-1β and IL-6, thus impairing melanoma cell growth. Additionally, IκBζ suppresses Cxcl9, Cxcl10, and Ccl5 expression via HDAC3 and EZH2, which impairs the recruitment of NK and CD8+ T cells into the tumor, causing resistance to α-PD-1 immunotherapy in mice. Thus, tumor-derived IκBζ may serve as a therapeutic target and prognostic marker for melanoma with high tumor cell proliferation, cytotoxic T- and NK-cell exclusion, and unfavorable immunotherapy responses.

The impact of 8-week re-training following a 14-week period of training cessation on Greco-Roman Wrestlers

Background This study aimed to examine the changes in physical and physiological conditions in elite wrestlers from the Turkish National Wrestling Team, who experienced 14 weeks of restricted physical activity during the COVID-19 lockdown, followed by an 8-week period of retraining and competition. Methods Twenty male elite wrestlers from the National Greco-Roman Wrestling Team participated in the research. Heart Rate Variability values were measured during the training cessation period and for 8 weeks of subsequent training and then interpreted for training periods with different workloads. Body fat percentage values, initially measured during training cessation, were recorded at 2-week intervals during the training period. To determine the fitness status of wrestlers, the Specific Wrestling Fitness Test was used before and following the 8 weeks of training period. Results A gradual decrease in both body fat percentage and weight was observed throughout the course of the training period. The SWFT scores showed significant improvements (31.40 ± 2.91 vs. 37.40 ± 3.22) following the training period. Heart rate variability decreased during the detraining period, progressively improved throughout the 8-week retraining, and subsequently declined during the competition phase, reaching levels similar to those observed during training cessation. Conclusions Our results suggest that athletes undergo identical reactions in their autonomous nervous system during both competition and training cessation period. Obtaining a comprehensive understanding of these changes can enable coaches and athletes to make accurate decisions in order to optimize training adaptations and attain overall athletic success. Furthermore, over a period of eight weeks following a long non-training period, significant improvements in athletes’ body fat, muscle mass and wrestling performance can be achieved along with training. Moreover, HRV monitoring revealed that autonomic nervous system balance was compromised during both the 14-week detraining and the subsequent competition phases, underlining the need for careful training load management to optimize recovery and performance readiness.