Sirtuin 2 is a member of the sirtuin family nicotinamide adenine dinucleotide(NAD~+)-dependent deacetylases, known for its regulatory role in different processes, including inflammation. In this context, sirtuin 2 has...Sirtuin 2 is a member of the sirtuin family nicotinamide adenine dinucleotide(NAD~+)-dependent deacetylases, known for its regulatory role in different processes, including inflammation. In this context, sirtuin 2 has been involved in the modulation of key inflammatory signaling pathways and transcription factors by deacetylating specific targets, such as nuclear factor κB and nucleotide-binding oligomerization domain-leucine-rich-repeat and pyrin domain-containing protein 3(NLRP3). However, whether sirtuin 2-mediated pathways induce a pro-or an anti-inflammatory response remains controversial. Sirtuin 2 has been implicated in promoting inflammation in conditions such as asthma and neurodegenerative diseases, suggesting that its inhibition in these conditions could be a potential therapeutic strategy. Conversely, arthritis and type 2 diabetes mellitus studies suggest that sirtuin 2 is essential at the peripheral level and, thus, its inhibition in these pathologies would not be recommended. Overall, the precise role of sirtuin 2 in inflammation appears to be context-dependent, and further investigation is needed to determine the specific molecular mechanisms and downstream targets through which sirtuin 2 influences inflammatory processes in various tissues and pathological conditions. The present review explores the involvement of sirtuin 2 in the inflammation associated with different pathologies to elucidate whether its pharmacological modulation could serve as an effective strategy for treating this prevalent symptom across various diseases.展开更多
High-resolution transmission electron microscopy(HRTEM)promises rapid atomic-scale dynamic structure imaging.Yet,the precision limitations of aberration parameters and the challenge of eliminating aberrations in Cs-co...High-resolution transmission electron microscopy(HRTEM)promises rapid atomic-scale dynamic structure imaging.Yet,the precision limitations of aberration parameters and the challenge of eliminating aberrations in Cs-corrected transmission electron microscopy constrain resolution.A machine learning algorithm is developed to determine the aberration parameters with higher precision from small,lattice-periodic crystal images.The proposed algorithm is then validated with simulated HRTEM images of graphene and applied to the experimental images of a molybdenum disulfide(MoS_(2))monolayer with 25 variables(14 aberrations)resolved in wide ranges.Using these measured parameters,the phases of the exit-wave functions are reconstructed for each image in a focal series of MoS_(2)monolayers.The images were acquired due to the unexpected movement of the specimen holder.Four-dimensional data extraction reveals time-varying atomic structures and ripple.In particular,the atomic evolution of the sulfur-vacancy point and line defects,as well as the edge structure near the amorphous,is visualized as the resolution has been improved from about 1.75?to 0.9 A.This method can help salvage important transmission electron microscope images and is beneficial for the images obtained from electron microscopes with average stability.展开更多
Nickel-rich(Ni≥90%)layered oxides materials have emerged as a promising candidate for nextgeneration high-energy-density lithium-ion batteries(LIBs).However,their widespread application is hindered by structural fati...Nickel-rich(Ni≥90%)layered oxides materials have emerged as a promising candidate for nextgeneration high-energy-density lithium-ion batteries(LIBs).However,their widespread application is hindered by structural fatigue and lattice oxygen loss.In this work,an epitaxial surface rock-salt nanolayer is successfully developed on the LiNi_(0.9)Co_(0.1)O_(2)sub-surface via heteroatom anchoring utilizing high-valence element molybdenum modification.This in-situ formed conformal buffer phase with a thickness of 1.2 nm effectively suppresses the continuous interphase side-reactions,and thus maintains the excellent structure integrity at high voltage.Furthermore,theoretical calculations indicate that the lattice oxygen reversibility in the anion framework of the optimized sample is obviously enhanced due to the higher content of O 2p states near the Fermi level than that of the pristine one.Meanwhile,the stronger Mo-O bond further reduces cell volume alteration,which improves the bulk structure stability of modified materials.Besides,the detailed charge compensation mechanism suggests that the average oxidation state of Ni is reduced,which induces more active Li+participating in the redox reactions,boosting the cell energy density.As a result,the uniquely designed cathode materials exhibit an extraordinary discharge capacity of 245.4 mAh g^(-1)at 0.1 C,remarkable rate performance of 169.3 mAh g^(-1)at 10 C at 4.5 V,and a high capacity retention of 70.5% after 1000 cycles in full cells at a high cut-off voltage of 4.4 V.This strategy provides an valuable insight into constructing distinctive heterostructure on highperformance Ni-rich layered cathodes for LIBs.展开更多
Male infertility can result from impaired sperm motility caused by multiple morphological abnormalities of the flagella(MMAF).Distinct projections encircling the central microtubules of the spermatozoal axoneme play p...Male infertility can result from impaired sperm motility caused by multiple morphological abnormalities of the flagella(MMAF).Distinct projections encircling the central microtubules of the spermatozoal axoneme play pivotal roles in flagellar bending and spermatozoal movement.Mammalian sperm-associated antigen 17(SPAG17)encodes a conserved axonemal protein of cilia and flagella,forming part of the C1a projection of the central apparatus,with functions related to ciliary/flagellar motility,skeletal growth,and male fertility.This study investigated two novel homozygous SPAG17 mutations(M1:NM_206996.2,c.829+1G>T,p.Asp212_Glu276del;and M2:c.2120del,p.Leu707*)identified in four infertile patients from two consanguineous Pakistani families.These patients displayed the MMAF phenotype confirmed by Papanicolaou staining and scanning electron microscopy assays of spermatozoa.Quantitative real-time polymerase chain reaction(PCR)of patients’spermatozoa also revealed a significant decrease in SPAG17 mRNA expression,and immunofluorescence staining showed the absence of SPAG17 protein signals along the flagella.However,no apparent ciliary-related symptoms or skeletal malformations were observed in the chest X-rays of any of the patients.Transmission electron microscopy of axoneme cross-sections from the patients showed incomplete C1a projection and a higher frequency of missing microtubule doublets 1 and 9 compared with those from fertile controls.Immunofluorescence staining and Western blot analyses of spermatogenesis-associated protein 17(SPATA17),a component of the C1a projection,and sperm-associated antigen 6(SPAG6),a marker of the spring layer,revealed disrupted expression of both proteins in the patients’spermatozoa.Altogether,these findings demonstrated that SPAG17 maintains the integrity of spermatozoal flagellar axoneme,expanding the phenotypic spectrum of SPAG17 mutations in humans.展开更多
Acridid populations have increased significantly in recent years, causing damage to crops. Having biocontrol tools is important as it will help reduce the use of insecticides. This study reports the presence of Parago...Acridid populations have increased significantly in recent years, causing damage to crops. Having biocontrol tools is important as it will help reduce the use of insecticides. This study reports the presence of Paragordius varius in grasshoppers for the first time in Irapuato, Guanajuato, Mexico. Samples were taken from the grass around a water pond. A total of 1,225 grasshoppers were dissected to observe the presence of the worm. Seven species of grasshoppers were identified, with the most abundant species being Melanoplus differentialis. The parasitoid Paragordius varius, a nematomorph, parasitized male M. differentialis in greater numbers. This work is the first record of this parasitoid in Mexico and contributes to the knowledge of the biological control of acridids in Mexico.展开更多
MgATP is a stable complex formed by the chelation of Mg^(2+)with deprotonated adenosine-5'-triphosphate(ATP).In the cellular environment,MgATP plays a critical role in ATP hydrolysis,releasing substantial energy t...MgATP is a stable complex formed by the chelation of Mg^(2+)with deprotonated adenosine-5'-triphosphate(ATP).In the cellular environment,MgATP plays a critical role in ATP hydrolysis,releasing substantial energy to support essential biological functions.To understand the structure and stabilization mechanism of MgATP,we conducted a joint negative ion photoelectron spectroscopic and computational study of the[ATP^(4-)·Mg^(2+)]^(2-)complex dianion,using[ATP^(4-)·2H^(+)]^(2-)as a reference.The experimentally determined adiabatic and vertical detachment energies(ADE and VDE)of[ATP^(4-)·Mg^(2+)]^(2-)at 20 K are 3.51±0.05 eV and 3.82±0.05 eV,respectively.The major spectral features of[ATP^(4-)·Mg^(2+)]^(2-)are attributed to two theoretically identified isomers with unfolded geometries,which are stabilized primarily by electrostatic interactions between Mg^(2+)and the triphosphate and ribose groups,with four deprotonated oxygens forming a pseudo-tetrahedral coordination.In contrast,[ATP^(4-)·2H^(+)]^(2-)exhibits a fundamentally different stabilization mechanism.Although most of the fifteen identified[ATP^(4-)·2H^(+)]^(2-)isomers also adopt unfolded geometries,they are primarily stabilized by intramolecular hydrogen bonds within the triphosphate group and between triphosphate and ribose groups.The interaction between ATP^(4-)and two protons is found to be much weaker than that with Mg^(2+),and[ATP^(4-)·2H^(+)]^(2-)exhibits substantial structural flexibility compared to[ATP^(4-)·Mg^(2+)]^(2-)due to the conformational constraint of the triphosphate chain by Mg^(2+).Thirteen[ATP^(4-)·2H^(+)]^(2-)isomers with unfolded geometries likely account for the major high-EBE(electron-binding-energy)spectral features.Notably,for the first time,a low EBE and temperature-dependent spectral feature is observed and attributed to two folded isomers of[ATP^(4-)·2H^(+)]^(2-),which exist at 20 K but disappear at room temperature.This study provides valuable molecular-level insights into cellular MgATP that resides within the hydrophobic pockets of proteins.展开更多
Coal is a versatile energy resource and was a driver of the industrial revolution that transformed the economies of Europe and North America and the trajectory of civilization.In this work,a technoeconomic analysis wa...Coal is a versatile energy resource and was a driver of the industrial revolution that transformed the economies of Europe and North America and the trajectory of civilization.In this work,a technoeconomic analysis was performed for a coal-to-carbonfiber manufacture process developed at the University of Kentucky’s Center for Applied Energy Research.According to this process,coal,with decant oil as the solvent,was converted to mesophase pitch via solvent extraction,and the mesophase pitch was subsequently converted to carbon fiber.The total cost to produce carbon fibers from coal and decant oil via the solvent extraction process was estimated to be$11.50/kg for 50,000-tow pitch carbon fiber with a production volume of 3750 MT/year.The estimated carbon fiber cost was significantly lower than the current commercially available PAN-based carbon fiber price($20–$30/kg).With decant oil recycling rates of 50%and 70%in the solvent extraction process,the manufacturing cost of carbon fiber was estimated to be$9.90/kg and$9.50/kg of carbon fiber,respectively.A cradle-to-gate energy assessment revealed that carbon fiber derived from coal exhibited an embodied energy of 510 MJ/kg,significantly lower than that of conventionally produced carbon fiber from PAN.This notable difference is primarily attributed to the substantially higher conversion rate of coal-based mesophase pitch fibers into carbon fiber,surpassing PAN fibers by 1.6 times.These findings indicate that using coal for carbon fiber production through solvent extraction methods could offer a more energy-efficient and cost-competitive alternative to the traditional PAN based approach.展开更多
This paper presents our endeavors in developing the large-scale, ultra-high-resolution E3SM Land Model (uELM), specifically designed for exascale computers furnished with accelerators such as Nvidia GPUs. The uELM is ...This paper presents our endeavors in developing the large-scale, ultra-high-resolution E3SM Land Model (uELM), specifically designed for exascale computers furnished with accelerators such as Nvidia GPUs. The uELM is a sophisticated code that substantially relies on High-Performance Computing (HPC) environments, necessitating particular machine and software configurations. To facilitate community-based uELM developments employing GPUs, we have created a portable, standalone software environment preconfigured with uELM input datasets, simulation cases, and source code. This environment, utilizing Docker, encompasses all essential code, libraries, and system software for uELM development on GPUs. It also features a functional unit test framework and an offline model testbed for comprehensive numerical experiments. From a technical perspective, the paper discusses GPU-ready container generations, uELM code management, and input data distribution across computational platforms. Lastly, the paper demonstrates the use of environment for functional unit testing, end-to-end simulation on CPUs and GPUs, and collaborative code development.展开更多
Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and memory.Kinesin-4 KIF21A helps organize the microtubule-actin network at th...Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and memory.Kinesin-4 KIF21A helps organize the microtubule-actin network at the cell cortex by interacting with KANK1;however,whether KIF21A modulates dendritic structure and function in neurons remains unknown.In this study,we found that KIF21A was distributed in a subset of dendritic spines,and that these KIF21A-positive spines were larger and more structurally plastic than KIF21A-negative spines.Furthermore,the interaction between KIF21A and KANK1 was found to be critical for dendritic spine morphogenesis and synaptic plasticity.Knockdown of either KIF21A or KANK1 inhibited dendritic spine morphogenesis and dendritic branching,and these deficits were fully rescued by coexpressing full-length KIF21A or KANK1,but not by proteins with mutations disrupting direct binding between KIF21A and KANK1 or binding between KANK1 and talin1.Knocking down KIF21A in the hippocampus of rats inhibited the amplitudes of long-term potentiation induced by high-frequency stimulation and negatively impacted the animals’cognitive abilities.Taken together,our findings demonstrate the function of KIF21A in modulating spine morphology and provide insight into its role in synaptic function.展开更多
High-pressure β-Sn germanium may transform into diverse metastable allotropes with distinctive nanostructures and unique physical properties via multiple pathways under decompression.However,the mechanism and transit...High-pressure β-Sn germanium may transform into diverse metastable allotropes with distinctive nanostructures and unique physical properties via multiple pathways under decompression.However,the mechanism and transition kinetics remain poorly understood.Here,we investigate the formation of metastable phases and nanostructures in germanium via controllable transition pathways of β-Sn Ge under rapid decompression at different rates.High-resolution transmission electron microscopy reveals three distinct metastable phases with the distinctive nanostructures:an almost perfect st12 Ge crystal,nanosized bc8/r8 structures with amorphous boundaries,and amorphous Ge with nanosized clusters (0.8–2.5 nm).Fast in situ x-ray diffraction and x-ray absorption measurements indicate that these nanostructured products form in certain pressure regions via distinct kinetic pathways and are strongly correlated with nucleation rates and electronic transitions mediated by compression rate,temperature,and stress.This work provides deep insight into the controllable synthesis of metastable materials with unique crystal symmetries and nanostructures for potential applications.展开更多
Intensive dairying has diminished infectious disease resistance in dairy cattle and increased the risk of disorders affecting milk quality and productive life.Development of novel health monitoring technologies,optimi...Intensive dairying has diminished infectious disease resistance in dairy cattle and increased the risk of disorders affecting milk quality and productive life.Development of novel health monitoring technologies,optimization of disease treatment protocols using novel biomarkers,and development of antibiotic substitutes are necessary to further enhance the productivity of dairy cattle.Extracellular vesicles(EVs)are key mediators of cellular communication and are essential for maintaining intracellular homeostasis and regulating various physiological and pathological processes.Establishing a network of mechanisms by which EVs regulate physiological processes in dairy cattle will contribute to the development of new technologies for early disease diagnosis and disease treatment.This review summarizes the molecular characterization and advances in the study of EVs in dairy cattle and focuses on the reported mechanisms of action.Prospects and limitations for the application of EVs in monitoring health status,disease treatment and assisted reproduction are discussed.展开更多
In this paper, we propose a novel method using artificial neural networks(ANNs) to reconstruct the global 21 cm signal from measurements of the 21 cm power spectrum. The 21 cm global signal provides crucial informatio...In this paper, we propose a novel method using artificial neural networks(ANNs) to reconstruct the global 21 cm signal from measurements of the 21 cm power spectrum. The 21 cm global signal provides crucial information on cosmic evolution from the Dark Ages through cosmic dawn and the Epoch of Reionization. Single-dish telescopes directly measure the global signal, whereas interferometric experiments primarily measure spatial fluctuations,represented by the 21 cm power spectrum. While no direct mathematical relationship exists between these two observables-since they probe fundamentally independent Fourier modes-they are indirectly linked through their common dependence on underlying astrophysical and cosmological parameters. The ANN effectively learns this implicit, model-dependent relationship, enabling it to predict the global signal from the power spectrum. We demonstrate that the ANN accurately recovers the global 21 cm signal across a broad redshift range(z = 7.5–35)even under realistic observational noise scenarios corresponding to SKA-1 observations. The reconstruction accuracy depends significantly on the spatial scales(wavenumber k) included, with larger-scale modes yielding better results due to their stronger sensitivity to global astrophysical processes. Although the ANN method does not provide a model-independent verification of anomalous observations(e.g., the Experiment to Detect the Global Epoch of Reionization Signature absorption trough), it offers a computationally efficient and robust tool to infer the global signal within the context of standard astrophysical and cosmological models.展开更多
Background:Targeted T-cell therapy has emerged as a promising strategy for the treatment of hematological malignancies.However,its application to solid tumors presents significant challenges due to the limited accessi...Background:Targeted T-cell therapy has emerged as a promising strategy for the treatment of hematological malignancies.However,its application to solid tumors presents significant challenges due to the limited accessibility and heterogeneity.Localized delivery of tumor-specific T-cells using biomaterials has shown promise,however,procedures required for genetic modification and generation of a sufficient number of tumor-specific T-cells ex vivo remain major obstacles due to cost and time constraints.Methods:Polyethylene glycol(PEG)-based three-dimensional(3D)scaffolds were developed and conjugated with positively charged poly-L-lysine(PLL)using carbamide chemistry for efficient loading of lentiviruses(LVs)carrying tumor antigen-specific T-cell receptors(TCRs).The physical and biological properties of the scaffold were extensively characterized.Further,the scaffold loaded with OVA-TCR LVs was implanted in B16F10 cells expressing ovalbumin(B16-OVA)tumor model to evaluate the anti-tumor response and the presence of transduced T-cells.Results:Our findings demonstrate that the scaffolds do not induce any systemic inflammation upon subcutaneous implantation and effectively recruit T-cells to the site.In B16-OVA melanoma tumor-bearing mice,the scaffolds efficiently transduce host T-cells with OVA-specific TCRs.These genetically modified T-cells exhibit homing capability towards the tumor and secondary lymphoid organs,resulting in a significant reduction of tumor size and systemic increase in anti-tumor cytokines.Immune cell profiling revealed a significantly high percentage of transduced T-cells and a notable reduction in suppressor immune cells within the tumors of mice implanted with these scaffolds.Conclusions:Our scaffold-based T-cell therapy presents an innovative in situ localized approach for programming T-cells to target solid tumors.This approach offers a viable alternative to in vitro manipulation of T-cells,circumventing the need for large-scale in vitro generation and culture of tumor-specific T-cells.It offers an off-the-shelf alternative that facilitates the use of host cells instead of allogeneic cells,thereby,overcoming a major hurdle.展开更多
Sustainable aviation fuel(SAF)production from biomass and biowaste streams is an attractive option for decarbonizing the aviation sector,one of the most-difficult-to-electrify transportation sectors.Despite ongoing co...Sustainable aviation fuel(SAF)production from biomass and biowaste streams is an attractive option for decarbonizing the aviation sector,one of the most-difficult-to-electrify transportation sectors.Despite ongoing commercialization efforts using ASTM-certified pathways(e.g.,lipid conversion,Fischer-Tropsch synthesis),production capacities are still inadequate due to limited feedstock supply and high production costs.New conversion technologies that utilize lignocellulosic feedstocks are needed to meet these challenges and satisfy the rapidly growing market.Combining bio-and chemo-catalytic approaches can leverage advantages from both methods,i.e.,high product selectivity via biological conversion,and the capability to build C-C chains more efficiently via chemical catalysis.Herein,conversion routes,catalysis,and processes for such pathways are discussed,while key challenges and meaningful R&D opportunities are identified to guide future research activities in the space.Bio-and chemo-catalytic conversion primarily utilize the carbohydrate fraction of lignocellulose,leaving lignin as a waste product.This makes lignin conversion to SAF critical in order to utilize whole biomass,thereby lowering overall production costs while maximizing carbon efficiencies.Thus,lignin valorization strategies are also reviewed herein with vital research areas identified,such as facile lignin depolymerization approaches,highly integrated conversion systems,novel process configurations,and catalysts for the selective cleavage of aryl C-O bonds.The potential efficiency improvements available via integrated conversion steps,such as combined biological and chemo-catalytic routes,along with the use of different parallel pathways,are identified as key to producing all components of a cost-effective,100%SAF.展开更多
Prostate cancer(PCa),one of the leading causes of cancer-related mortality in men worldwide,presents significant challenges due to its heterogeneity and the presence of cancer stem cells(CSCs),which contribute to ther...Prostate cancer(PCa),one of the leading causes of cancer-related mortality in men worldwide,presents significant challenges due to its heterogeneity and the presence of cancer stem cells(CSCs),which contribute to therapy resistance and metastasis.Advances in three-dimensional(3D)bioprinting have ushered in a new era of precision medicine by enabling the recreation of complex tumor mi-croenvironments.This review highlights the transformative potential of 3D bioprinting technology in modelling prostate cancer stem cells(PCSCs)to identify therapeutic vulnerabilities and develop targeted treatments.By integrating bioinks with PCSCs and their niche components,3D bioprinting offers a robust platform to investigate the molecular and cellular mechanisms underlying PCa progression and resistance.Furthermore,it allows high-throughput drug scree-ning,cellular cross talks,facilitating the discovery of novel interventions aimed at eradicating CSCs while preserving healthy tissue.The review also discusses the challenges of scalability,bioink optimization,and clinical translation,alongside emerging technologies such as organ-on-chip systems and bioprinted metastatic models.This review underscores the promise of bioprinting as a disruptive in-novation in cancer care,capable of redefining therapeutic approaches and offering hope for better patient outcomes in PCa.展开更多
The effects of solid solution on the deformation behavior of binary Mg-xZn(x=0,1,2 wt%)alloys featuring a designated texture that enables extension twinning under tension parallel to the basal pole in most grains,were...The effects of solid solution on the deformation behavior of binary Mg-xZn(x=0,1,2 wt%)alloys featuring a designated texture that enables extension twinning under tension parallel to the basal pole in most grains,were investigated using in-situ neutron diffraction and the EVPSC-TDT model.Neutron diffraction was used to quantitatively track grain-level lattice strains and diffraction intensity changes(related to mechanical twinning)in differently oriented grains of each alloy during cyclic tensile/compressive loadings.These measurements were accurately captured by the model.The stress-strain curves of Mg-1 wt%Zn and Mg-2 wt%Zn alloys show as-expected solid solution strengthening from the addition of Zn compared to pure Mg.The macroscopic yielding and hardening behaviors are explained by alternating slip and twinning modes as calculated by the model.The solid solution's influence on individual deformation modes,including basal〈a〉slip,prismatic〈a〉slip,and extension twinning,was then quantitatively assessed in terms of activity,yielding behavior,and hardening response by combining neutron diffraction results with crystal plasticity predictions.The Mg-1 wt%Zn alloy displays distinct yielding and hardening behavior due to solid solution softening of prismatic〈a〉slip.Additionally,the dependence of extension twinning,in terms of the twinning volume fraction,on Zn content exhibits opposite trends under tensile and compressive loadings.展开更多
Background Sustained lipolysis exacerbates subclinical ketosis(SCK)in dairy cows and is associated with inflammation and adipose tissue macrophage(ATM)infiltration.While ATM involvement in adipose homeostasis and infl...Background Sustained lipolysis exacerbates subclinical ketosis(SCK)in dairy cows and is associated with inflammation and adipose tissue macrophage(ATM)infiltration.While ATM involvement in adipose homeostasis and inflammation in early lactation is recognized,a comprehensive exploration of ATM polarization phenotypes in SCK cows is lacking.This study aimed to characterize ATM polarization and its link to lipolysis and inflammation in SCK cows.Results Subcutaneous adipose tissue samples were obtained from dairy cows to analyze protein expression and gene profiles.Compared with healthy cows,SCK cows had higher serum BHBA and NEFA,smaller adipocytes,and increased expression of lipolytic enzymes(LIPE,ATGL),indicating enhanced lipolysis.Decreased levels of FASN,PPARγ,p-SMAD3,and TGFβsuggested impaired adipogenesis.Inflammatory markers(TNF-α,IFN-γ,TLR4,Caspase1)and NFκB signaling activity were elevated.ATM infiltration was supported by increased CD9,CD68,TREM2,and CXCL1 expression.Protein abundance of M1 polarization markers(iNOS,CD86 and CCL2)in ATMs were associated with greater levels of NOS2,IL1B,CD86 and CCL2 mRNA expression in SCK cows;fluorescence intensity of NOS2 and CD86 also was elevated,alongside a higher proportion of CD68+/CD86+immunopositive cells within adipose tissue.ELISA further quantified increased concentrations of IL-1β and CCL2.Conversely,the abundance of ATM M2 polarization markers,including CD206,IL-10,KLF4,and Arg1,at both the protein and mRNA levels demonstrated a decline.Meanwhile,the proportion of CD68+/CD206+immune response cells was relatively low in SCK cows.Conclusions Overall,the present study indicated an augmented macrophage presence within adipose tissue during subclinical ketosis,with a predominance of pro-inflammatory macrophages(M1 ATM).This observation suggested a vicious cycle wherein macrophage infiltration and pro-inflammatory polarization coincide with enhanced lipolysis and an amplified inflammatory cascade.展开更多
The advancement of efficient,cheap,and durable catalysts for oxygen reduction reaction(ORR)to substitute Pt/C in metal-air batteries is of paramount importance.However,traditional solvent-based methods fall short in t...The advancement of efficient,cheap,and durable catalysts for oxygen reduction reaction(ORR)to substitute Pt/C in metal-air batteries is of paramount importance.However,traditional solvent-based methods fall short in terms of environmental benign and scalability.Herein,a solvent-free organic-inorganic selfassembly approach is explored to construct cobalt single atom and cobalt nanocluster decorated nitrogendoped porous carbon spheres(Co-SA/NC@NCS).The solvent-free synthesis demonstrates an impressively high yield(282 g/L)and the resultant Co-SA/NC@NCS possesses a high N content(6.9 wt%).Density functional theory calculations disclose that the Co-SAs and Co-NCs are able to optimize the surface oxygen adsorption capability and enhance the conductivity of the NCS,thereby facilitating the ORR performance.The sol vent-free synthesis is also feasible for the synthesis of other non-noble metal element(Fe,Ni,and Zn)decorated nitrogen-doped porous carbon spheres.展开更多
The increasing frequency and intensity of drought caused by climate change necessitate the implementation of effective ways to increase the ability of wheat to withstand drought, with humic acid being a promising appr...The increasing frequency and intensity of drought caused by climate change necessitate the implementation of effective ways to increase the ability of wheat to withstand drought, with humic acid being a promising approach. Therefore, a pot experiment was conducted to determine the efficacy of exogenous humic acid on wheat under water deficit stress via a completely randomized design (CRD) with three replications. The impacts of four growing conditions, i.e., well water (65% field capacity), water deficit stress (35% field capacity), soil application of humic acid (44 mg kg−1 soil) under water deficit stress and foliar feeding of humic acid (200 ppm) under water deficit stress, were investigated on two wheat varieties (BWMRI Gom 1 and BWMRI Gom 3). The results demonstrated that water deficit stress substantially decreased the studied morphological and physiological traits, yield components and yield, in both genotypes, with the exception of the proline content of flag leaves. Compared with soil application, foliar feeding of humic acid promoted the ability of wheat to overcome stress conditions better. In the present study, humic acid as a soil application increased the grain yield by 9.13% and 13.86% and the biological yield by 9.94% and 5.19%, whereas foliar treatment increased the grain output by 24.76% and 25.19% and the biological yield by 19.23% and 6.50% in BWMRI Gom 1 and BWMRI Gom 3, respectively, under water deficit stress. Therefore, exogenous foliar humic acid treatment was more effective than soil application in alleviating the effects of drought stress on wheat.展开更多
Hemoglobin is a vital protein in red blood cells responsible for transporting oxygen throughout the body.Its accurate measurement is crucial for diagnosing and managing conditions such as anemia and diabetes,where abn...Hemoglobin is a vital protein in red blood cells responsible for transporting oxygen throughout the body.Its accurate measurement is crucial for diagnosing and managing conditions such as anemia and diabetes,where abnormal hemoglobin levels can indicate significant health issues.Traditional methods for hemoglobin measurement are invasive,causing pain,risk of infection,and are less convenient for frequent monitoring.PPG is a transformative technology in wearable healthcare for noninvasive monitoring and widely explored for blood pressure,sleep,blood glucose,and stress analysis.In this work,we propose a hemoglobin estimation method using an adaptive lightweight convolutional neural network(HMALCNN)from PPG.The HMALCNN is designed to capture both fine-grained local waveform characteristics and global contextual patterns,ensuring robust performance across acquisition settings.We validated our approach on two multi-regional datasets containing 152 and 68 subjects,respectively,employing a subjectindependent 5-fold cross-validation strategy.The proposed method achieved root mean square errors(RMSE)of 0.90 and 1.20 g/dL for the two datasets,with strong Pearson correlations of 0.82 and 0.72.We conducted extensive posthoc analyses to assess clinical utility and interpretability.A±1 g/dL clinical error tolerance evaluation revealed that 91.3%and 86.7%of predictions for the two datasets fell within the acceptable clinical range.Hemoglobin range-wise analysis demonstrated consistently high accuracy in the normal and low hemoglobin categories.Statistical significance testing using the Wilcoxon signed-rank test confirmed the stability of performance across validation folds(p>0.05 for both RMSE and correlation).Furthermore,model interpretability was enhanced using Gradient-weighted Class Activation Mapping(Grad-CAM),supporting the model’s clinical trustworthiness.The proposed HMALCNN offers a computationally efficient,clinically interpretable,and generalizable framework for noninvasive hemoglobin monitoring,with strong potential for integration into wearable healthcare systems as a practical alternative to invasive measurement techniques.展开更多
基金funded by FEDER/Ministerio de Ciencia,Innovación y Universidades Agencia Estatal de Investigación/Project(PID2020-119729GB-100,REF/AEI/10.13039/501100011033)(to EP)a predoctoral fellowship from the Spanish Ministry of Universities(FPU)and Amigos de la Universidad de Navarra(to NSS)“Programa MRR Investigo 2023”(to MGB and MMD)。
文摘Sirtuin 2 is a member of the sirtuin family nicotinamide adenine dinucleotide(NAD~+)-dependent deacetylases, known for its regulatory role in different processes, including inflammation. In this context, sirtuin 2 has been involved in the modulation of key inflammatory signaling pathways and transcription factors by deacetylating specific targets, such as nuclear factor κB and nucleotide-binding oligomerization domain-leucine-rich-repeat and pyrin domain-containing protein 3(NLRP3). However, whether sirtuin 2-mediated pathways induce a pro-or an anti-inflammatory response remains controversial. Sirtuin 2 has been implicated in promoting inflammation in conditions such as asthma and neurodegenerative diseases, suggesting that its inhibition in these conditions could be a potential therapeutic strategy. Conversely, arthritis and type 2 diabetes mellitus studies suggest that sirtuin 2 is essential at the peripheral level and, thus, its inhibition in these pathologies would not be recommended. Overall, the precise role of sirtuin 2 in inflammation appears to be context-dependent, and further investigation is needed to determine the specific molecular mechanisms and downstream targets through which sirtuin 2 influences inflammatory processes in various tissues and pathological conditions. The present review explores the involvement of sirtuin 2 in the inflammation associated with different pathologies to elucidate whether its pharmacological modulation could serve as an effective strategy for treating this prevalent symptom across various diseases.
基金financial support from the National Natural Science Foundation of China(Grant No.61971201)。
文摘High-resolution transmission electron microscopy(HRTEM)promises rapid atomic-scale dynamic structure imaging.Yet,the precision limitations of aberration parameters and the challenge of eliminating aberrations in Cs-corrected transmission electron microscopy constrain resolution.A machine learning algorithm is developed to determine the aberration parameters with higher precision from small,lattice-periodic crystal images.The proposed algorithm is then validated with simulated HRTEM images of graphene and applied to the experimental images of a molybdenum disulfide(MoS_(2))monolayer with 25 variables(14 aberrations)resolved in wide ranges.Using these measured parameters,the phases of the exit-wave functions are reconstructed for each image in a focal series of MoS_(2)monolayers.The images were acquired due to the unexpected movement of the specimen holder.Four-dimensional data extraction reveals time-varying atomic structures and ripple.In particular,the atomic evolution of the sulfur-vacancy point and line defects,as well as the edge structure near the amorphous,is visualized as the resolution has been improved from about 1.75?to 0.9 A.This method can help salvage important transmission electron microscope images and is beneficial for the images obtained from electron microscopes with average stability.
基金financially supported by the National Natural Science Foundation of China(No.52202228,52402298)funded by the Science Research Project of Hebei Education Department(No.BJK2022011)+3 种基金the Central Funds Guiding the Local Science and Technology Development of Hebei Province(No.236Z4404G)the Beijing Tianjin Hebei Basic Research Cooperation Special Project(No.E2024202273)the Science and Technology Correspondent Project of Tianjin(24YDTPJC00240)supported by the U.S.Department of Energy’s Office of Science,Office of Basic Energy Science,Materials Sciences and Engineering Division。
文摘Nickel-rich(Ni≥90%)layered oxides materials have emerged as a promising candidate for nextgeneration high-energy-density lithium-ion batteries(LIBs).However,their widespread application is hindered by structural fatigue and lattice oxygen loss.In this work,an epitaxial surface rock-salt nanolayer is successfully developed on the LiNi_(0.9)Co_(0.1)O_(2)sub-surface via heteroatom anchoring utilizing high-valence element molybdenum modification.This in-situ formed conformal buffer phase with a thickness of 1.2 nm effectively suppresses the continuous interphase side-reactions,and thus maintains the excellent structure integrity at high voltage.Furthermore,theoretical calculations indicate that the lattice oxygen reversibility in the anion framework of the optimized sample is obviously enhanced due to the higher content of O 2p states near the Fermi level than that of the pristine one.Meanwhile,the stronger Mo-O bond further reduces cell volume alteration,which improves the bulk structure stability of modified materials.Besides,the detailed charge compensation mechanism suggests that the average oxidation state of Ni is reduced,which induces more active Li+participating in the redox reactions,boosting the cell energy density.As a result,the uniquely designed cathode materials exhibit an extraordinary discharge capacity of 245.4 mAh g^(-1)at 0.1 C,remarkable rate performance of 169.3 mAh g^(-1)at 10 C at 4.5 V,and a high capacity retention of 70.5% after 1000 cycles in full cells at a high cut-off voltage of 4.4 V.This strategy provides an valuable insight into constructing distinctive heterostructure on highperformance Ni-rich layered cathodes for LIBs.
基金supported by the National Natural Science Foundation of China(No.82171599 and No.32270901)the National Key Research and Developmental Program of China(2022YFC2702601 and 2022YFA0806303)the Global Select Project(DJKLX-2022010)of the Institute of Health and Medicine,Hefei Comprehensive National Science Center.
文摘Male infertility can result from impaired sperm motility caused by multiple morphological abnormalities of the flagella(MMAF).Distinct projections encircling the central microtubules of the spermatozoal axoneme play pivotal roles in flagellar bending and spermatozoal movement.Mammalian sperm-associated antigen 17(SPAG17)encodes a conserved axonemal protein of cilia and flagella,forming part of the C1a projection of the central apparatus,with functions related to ciliary/flagellar motility,skeletal growth,and male fertility.This study investigated two novel homozygous SPAG17 mutations(M1:NM_206996.2,c.829+1G>T,p.Asp212_Glu276del;and M2:c.2120del,p.Leu707*)identified in four infertile patients from two consanguineous Pakistani families.These patients displayed the MMAF phenotype confirmed by Papanicolaou staining and scanning electron microscopy assays of spermatozoa.Quantitative real-time polymerase chain reaction(PCR)of patients’spermatozoa also revealed a significant decrease in SPAG17 mRNA expression,and immunofluorescence staining showed the absence of SPAG17 protein signals along the flagella.However,no apparent ciliary-related symptoms or skeletal malformations were observed in the chest X-rays of any of the patients.Transmission electron microscopy of axoneme cross-sections from the patients showed incomplete C1a projection and a higher frequency of missing microtubule doublets 1 and 9 compared with those from fertile controls.Immunofluorescence staining and Western blot analyses of spermatogenesis-associated protein 17(SPATA17),a component of the C1a projection,and sperm-associated antigen 6(SPAG6),a marker of the spring layer,revealed disrupted expression of both proteins in the patients’spermatozoa.Altogether,these findings demonstrated that SPAG17 maintains the integrity of spermatozoal flagellar axoneme,expanding the phenotypic spectrum of SPAG17 mutations in humans.
文摘Acridid populations have increased significantly in recent years, causing damage to crops. Having biocontrol tools is important as it will help reduce the use of insecticides. This study reports the presence of Paragordius varius in grasshoppers for the first time in Irapuato, Guanajuato, Mexico. Samples were taken from the grass around a water pond. A total of 1,225 grasshoppers were dissected to observe the presence of the worm. Seven species of grasshoppers were identified, with the most abundant species being Melanoplus differentialis. The parasitoid Paragordius varius, a nematomorph, parasitized male M. differentialis in greater numbers. This work is the first record of this parasitoid in Mexico and contributes to the knowledge of the biological control of acridids in Mexico.
基金was supported by the U.S.Department of Energy(DOE),Office of Science,Office of Basic Energy Sciences,Division of Chemical Sciences,Geosciences,and Biosciences,Condensed Phase and Interfacial Molecular Science program,FWP 16248.
文摘MgATP is a stable complex formed by the chelation of Mg^(2+)with deprotonated adenosine-5'-triphosphate(ATP).In the cellular environment,MgATP plays a critical role in ATP hydrolysis,releasing substantial energy to support essential biological functions.To understand the structure and stabilization mechanism of MgATP,we conducted a joint negative ion photoelectron spectroscopic and computational study of the[ATP^(4-)·Mg^(2+)]^(2-)complex dianion,using[ATP^(4-)·2H^(+)]^(2-)as a reference.The experimentally determined adiabatic and vertical detachment energies(ADE and VDE)of[ATP^(4-)·Mg^(2+)]^(2-)at 20 K are 3.51±0.05 eV and 3.82±0.05 eV,respectively.The major spectral features of[ATP^(4-)·Mg^(2+)]^(2-)are attributed to two theoretically identified isomers with unfolded geometries,which are stabilized primarily by electrostatic interactions between Mg^(2+)and the triphosphate and ribose groups,with four deprotonated oxygens forming a pseudo-tetrahedral coordination.In contrast,[ATP^(4-)·2H^(+)]^(2-)exhibits a fundamentally different stabilization mechanism.Although most of the fifteen identified[ATP^(4-)·2H^(+)]^(2-)isomers also adopt unfolded geometries,they are primarily stabilized by intramolecular hydrogen bonds within the triphosphate group and between triphosphate and ribose groups.The interaction between ATP^(4-)and two protons is found to be much weaker than that with Mg^(2+),and[ATP^(4-)·2H^(+)]^(2-)exhibits substantial structural flexibility compared to[ATP^(4-)·Mg^(2+)]^(2-)due to the conformational constraint of the triphosphate chain by Mg^(2+).Thirteen[ATP^(4-)·2H^(+)]^(2-)isomers with unfolded geometries likely account for the major high-EBE(electron-binding-energy)spectral features.Notably,for the first time,a low EBE and temperature-dependent spectral feature is observed and attributed to two folded isomers of[ATP^(4-)·2H^(+)]^(2-),which exist at 20 K but disappear at room temperature.This study provides valuable molecular-level insights into cellular MgATP that resides within the hydrophobic pockets of proteins.
基金sponsored by the US Department of Energy Fossil Energy and Carbon Management Program,project FEAA157 under contract DE-AC05-00OR22725 with UTBattelle,LLC.
文摘Coal is a versatile energy resource and was a driver of the industrial revolution that transformed the economies of Europe and North America and the trajectory of civilization.In this work,a technoeconomic analysis was performed for a coal-to-carbonfiber manufacture process developed at the University of Kentucky’s Center for Applied Energy Research.According to this process,coal,with decant oil as the solvent,was converted to mesophase pitch via solvent extraction,and the mesophase pitch was subsequently converted to carbon fiber.The total cost to produce carbon fibers from coal and decant oil via the solvent extraction process was estimated to be$11.50/kg for 50,000-tow pitch carbon fiber with a production volume of 3750 MT/year.The estimated carbon fiber cost was significantly lower than the current commercially available PAN-based carbon fiber price($20–$30/kg).With decant oil recycling rates of 50%and 70%in the solvent extraction process,the manufacturing cost of carbon fiber was estimated to be$9.90/kg and$9.50/kg of carbon fiber,respectively.A cradle-to-gate energy assessment revealed that carbon fiber derived from coal exhibited an embodied energy of 510 MJ/kg,significantly lower than that of conventionally produced carbon fiber from PAN.This notable difference is primarily attributed to the substantially higher conversion rate of coal-based mesophase pitch fibers into carbon fiber,surpassing PAN fibers by 1.6 times.These findings indicate that using coal for carbon fiber production through solvent extraction methods could offer a more energy-efficient and cost-competitive alternative to the traditional PAN based approach.
文摘This paper presents our endeavors in developing the large-scale, ultra-high-resolution E3SM Land Model (uELM), specifically designed for exascale computers furnished with accelerators such as Nvidia GPUs. The uELM is a sophisticated code that substantially relies on High-Performance Computing (HPC) environments, necessitating particular machine and software configurations. To facilitate community-based uELM developments employing GPUs, we have created a portable, standalone software environment preconfigured with uELM input datasets, simulation cases, and source code. This environment, utilizing Docker, encompasses all essential code, libraries, and system software for uELM development on GPUs. It also features a functional unit test framework and an offline model testbed for comprehensive numerical experiments. From a technical perspective, the paper discusses GPU-ready container generations, uELM code management, and input data distribution across computational platforms. Lastly, the paper demonstrates the use of environment for functional unit testing, end-to-end simulation on CPUs and GPUs, and collaborative code development.
基金supported by the National Key Research and Development Program of China,No.2021ZD0202503(to AHT)the National Natural Science Foundation of China,Nos.31872759(to AHT)and 32070707(to CF)+1 种基金Shenzhen Science and Technology Program,No.RCJC20210609104333007(to ZW)Shenzhen-Hong Kong Institute of Brain Science,Shenzhen Fundamental Research Institutions,No.2021SHIBS0002(to ZW).
文摘Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and memory.Kinesin-4 KIF21A helps organize the microtubule-actin network at the cell cortex by interacting with KANK1;however,whether KIF21A modulates dendritic structure and function in neurons remains unknown.In this study,we found that KIF21A was distributed in a subset of dendritic spines,and that these KIF21A-positive spines were larger and more structurally plastic than KIF21A-negative spines.Furthermore,the interaction between KIF21A and KANK1 was found to be critical for dendritic spine morphogenesis and synaptic plasticity.Knockdown of either KIF21A or KANK1 inhibited dendritic spine morphogenesis and dendritic branching,and these deficits were fully rescued by coexpressing full-length KIF21A or KANK1,but not by proteins with mutations disrupting direct binding between KIF21A and KANK1 or binding between KANK1 and talin1.Knocking down KIF21A in the hippocampus of rats inhibited the amplitudes of long-term potentiation induced by high-frequency stimulation and negatively impacted the animals’cognitive abilities.Taken together,our findings demonstrate the function of KIF21A in modulating spine morphology and provide insight into its role in synaptic function.
基金supported by the National Nature Science Foundation of China(NSFC)(Grant No.11974033)Xuqiang Liu acknowledges support from the National Postdoctoral Foundation Project of China under Grant No.GZC20230215+2 种基金the National Nature Science Foundation of China under Grants No.12404001The XRD measurements at room and high temperatures were performed at the 4W2 HPStation of the Beijing Synchrotron Radiation Facility(BSRF)and beamline 15U1 of the Shanghai Synchrotron Radiation Facility(SSRF)In situ high-pressure,low-temperature XRD measurements were conducted at sector 16 ID-B,HPCAT of the Advanced Photon Source,and were supported by DOE-NNSA under Award No.DE-NA0001974.
文摘High-pressure β-Sn germanium may transform into diverse metastable allotropes with distinctive nanostructures and unique physical properties via multiple pathways under decompression.However,the mechanism and transition kinetics remain poorly understood.Here,we investigate the formation of metastable phases and nanostructures in germanium via controllable transition pathways of β-Sn Ge under rapid decompression at different rates.High-resolution transmission electron microscopy reveals three distinct metastable phases with the distinctive nanostructures:an almost perfect st12 Ge crystal,nanosized bc8/r8 structures with amorphous boundaries,and amorphous Ge with nanosized clusters (0.8–2.5 nm).Fast in situ x-ray diffraction and x-ray absorption measurements indicate that these nanostructured products form in certain pressure regions via distinct kinetic pathways and are strongly correlated with nucleation rates and electronic transitions mediated by compression rate,temperature,and stress.This work provides deep insight into the controllable synthesis of metastable materials with unique crystal symmetries and nanostructures for potential applications.
基金supported by the National Natural Science Foundation of China(32272872,32172726).
文摘Intensive dairying has diminished infectious disease resistance in dairy cattle and increased the risk of disorders affecting milk quality and productive life.Development of novel health monitoring technologies,optimization of disease treatment protocols using novel biomarkers,and development of antibiotic substitutes are necessary to further enhance the productivity of dairy cattle.Extracellular vesicles(EVs)are key mediators of cellular communication and are essential for maintaining intracellular homeostasis and regulating various physiological and pathological processes.Establishing a network of mechanisms by which EVs regulate physiological processes in dairy cattle will contribute to the development of new technologies for early disease diagnosis and disease treatment.This review summarizes the molecular characterization and advances in the study of EVs in dairy cattle and focuses on the reported mechanisms of action.Prospects and limitations for the application of EVs in monitoring health status,disease treatment and assisted reproduction are discussed.
基金supported by the National SKA Program of China(No.2020SKA0110401)the National Natural Science Foundation of China(NSFC,grant No.12103044).
文摘In this paper, we propose a novel method using artificial neural networks(ANNs) to reconstruct the global 21 cm signal from measurements of the 21 cm power spectrum. The 21 cm global signal provides crucial information on cosmic evolution from the Dark Ages through cosmic dawn and the Epoch of Reionization. Single-dish telescopes directly measure the global signal, whereas interferometric experiments primarily measure spatial fluctuations,represented by the 21 cm power spectrum. While no direct mathematical relationship exists between these two observables-since they probe fundamentally independent Fourier modes-they are indirectly linked through their common dependence on underlying astrophysical and cosmological parameters. The ANN effectively learns this implicit, model-dependent relationship, enabling it to predict the global signal from the power spectrum. We demonstrate that the ANN accurately recovers the global 21 cm signal across a broad redshift range(z = 7.5–35)even under realistic observational noise scenarios corresponding to SKA-1 observations. The reconstruction accuracy depends significantly on the spatial scales(wavenumber k) included, with larger-scale modes yielding better results due to their stronger sensitivity to global astrophysical processes. Although the ANN method does not provide a model-independent verification of anomalous observations(e.g., the Experiment to Detect the Global Epoch of Reionization Signature absorption trough), it offers a computationally efficient and robust tool to infer the global signal within the context of standard astrophysical and cosmological models.
基金Department of Biotechnology(DBT,Govt of India)(BT/PR31315/MED/32/667/2019)DBT along with Wadhwani Research Center for Bioengineering,IIT Bombay(BT/INF/22/SP23026/2017)Department of Biotechnology(DBT,Govt of India)(BT/INF/22/SP17358/2016).
文摘Background:Targeted T-cell therapy has emerged as a promising strategy for the treatment of hematological malignancies.However,its application to solid tumors presents significant challenges due to the limited accessibility and heterogeneity.Localized delivery of tumor-specific T-cells using biomaterials has shown promise,however,procedures required for genetic modification and generation of a sufficient number of tumor-specific T-cells ex vivo remain major obstacles due to cost and time constraints.Methods:Polyethylene glycol(PEG)-based three-dimensional(3D)scaffolds were developed and conjugated with positively charged poly-L-lysine(PLL)using carbamide chemistry for efficient loading of lentiviruses(LVs)carrying tumor antigen-specific T-cell receptors(TCRs).The physical and biological properties of the scaffold were extensively characterized.Further,the scaffold loaded with OVA-TCR LVs was implanted in B16F10 cells expressing ovalbumin(B16-OVA)tumor model to evaluate the anti-tumor response and the presence of transduced T-cells.Results:Our findings demonstrate that the scaffolds do not induce any systemic inflammation upon subcutaneous implantation and effectively recruit T-cells to the site.In B16-OVA melanoma tumor-bearing mice,the scaffolds efficiently transduce host T-cells with OVA-specific TCRs.These genetically modified T-cells exhibit homing capability towards the tumor and secondary lymphoid organs,resulting in a significant reduction of tumor size and systemic increase in anti-tumor cytokines.Immune cell profiling revealed a significantly high percentage of transduced T-cells and a notable reduction in suppressor immune cells within the tumors of mice implanted with these scaffolds.Conclusions:Our scaffold-based T-cell therapy presents an innovative in situ localized approach for programming T-cells to target solid tumors.This approach offers a viable alternative to in vitro manipulation of T-cells,circumventing the need for large-scale in vitro generation and culture of tumor-specific T-cells.It offers an off-the-shelf alternative that facilitates the use of host cells instead of allogeneic cells,thereby,overcoming a major hurdle.
基金supported by the Center for Bioenergy Innovation(CBI)supported by the Office of Biological and Environmental Research in the DOE Office of Science and led by Oak Ridge National Laboratory.Oak Ridge National Laboratory is managed by UT-Battelle,LLC for the US DOE under Contract Number DE-AC05-00OR22725+2 种基金authored in part by the Na-tional Renewable Energy Laboratory,operated by Alliance for Sustainable Energy,LLC,for the U.S.Department of Energy(DOE)under Contract No.DE-LC-000L054provided by the U.S.Department of Energy(DOE),Office of Energy Efficiency and Renewable Energy(EERE),and Bioenergy Technologies Office(BETO)at the Pacific Northwest National Laboratory(PNNL)under Contract No.DE-AC05-76RL01830supported by Laboratory Directed Research and Development(LDRD)funding from Argonne National Laboratory,provided by the Director,Office of Science,of the U.S.Department of Energy under Contract No.DE-AC02-06CH11357。
文摘Sustainable aviation fuel(SAF)production from biomass and biowaste streams is an attractive option for decarbonizing the aviation sector,one of the most-difficult-to-electrify transportation sectors.Despite ongoing commercialization efforts using ASTM-certified pathways(e.g.,lipid conversion,Fischer-Tropsch synthesis),production capacities are still inadequate due to limited feedstock supply and high production costs.New conversion technologies that utilize lignocellulosic feedstocks are needed to meet these challenges and satisfy the rapidly growing market.Combining bio-and chemo-catalytic approaches can leverage advantages from both methods,i.e.,high product selectivity via biological conversion,and the capability to build C-C chains more efficiently via chemical catalysis.Herein,conversion routes,catalysis,and processes for such pathways are discussed,while key challenges and meaningful R&D opportunities are identified to guide future research activities in the space.Bio-and chemo-catalytic conversion primarily utilize the carbohydrate fraction of lignocellulose,leaving lignin as a waste product.This makes lignin conversion to SAF critical in order to utilize whole biomass,thereby lowering overall production costs while maximizing carbon efficiencies.Thus,lignin valorization strategies are also reviewed herein with vital research areas identified,such as facile lignin depolymerization approaches,highly integrated conversion systems,novel process configurations,and catalysts for the selective cleavage of aryl C-O bonds.The potential efficiency improvements available via integrated conversion steps,such as combined biological and chemo-catalytic routes,along with the use of different parallel pathways,are identified as key to producing all components of a cost-effective,100%SAF.
基金Supported by GSBTM,DST Government of Gujarat for Financial Support to the Prostate Cancer Research Project at GSFC University,Vadodara,No.GSBTM/RSS/E-FILE/30/2024/0021/04306791.
文摘Prostate cancer(PCa),one of the leading causes of cancer-related mortality in men worldwide,presents significant challenges due to its heterogeneity and the presence of cancer stem cells(CSCs),which contribute to therapy resistance and metastasis.Advances in three-dimensional(3D)bioprinting have ushered in a new era of precision medicine by enabling the recreation of complex tumor mi-croenvironments.This review highlights the transformative potential of 3D bioprinting technology in modelling prostate cancer stem cells(PCSCs)to identify therapeutic vulnerabilities and develop targeted treatments.By integrating bioinks with PCSCs and their niche components,3D bioprinting offers a robust platform to investigate the molecular and cellular mechanisms underlying PCa progression and resistance.Furthermore,it allows high-throughput drug scree-ning,cellular cross talks,facilitating the discovery of novel interventions aimed at eradicating CSCs while preserving healthy tissue.The review also discusses the challenges of scalability,bioink optimization,and clinical translation,alongside emerging technologies such as organ-on-chip systems and bioprinted metastatic models.This review underscores the promise of bioprinting as a disruptive in-novation in cancer care,capable of redefining therapeutic approaches and offering hope for better patient outcomes in PCa.
基金supported by the National Research Foundation grant funded by the Korean government(No,2023R1A2C2007190,RS-2024-00398068)partially funded by the Natural Science Foundation of Shandong Province,China(No.ZR2022QE206).
文摘The effects of solid solution on the deformation behavior of binary Mg-xZn(x=0,1,2 wt%)alloys featuring a designated texture that enables extension twinning under tension parallel to the basal pole in most grains,were investigated using in-situ neutron diffraction and the EVPSC-TDT model.Neutron diffraction was used to quantitatively track grain-level lattice strains and diffraction intensity changes(related to mechanical twinning)in differently oriented grains of each alloy during cyclic tensile/compressive loadings.These measurements were accurately captured by the model.The stress-strain curves of Mg-1 wt%Zn and Mg-2 wt%Zn alloys show as-expected solid solution strengthening from the addition of Zn compared to pure Mg.The macroscopic yielding and hardening behaviors are explained by alternating slip and twinning modes as calculated by the model.The solid solution's influence on individual deformation modes,including basal〈a〉slip,prismatic〈a〉slip,and extension twinning,was then quantitatively assessed in terms of activity,yielding behavior,and hardening response by combining neutron diffraction results with crystal plasticity predictions.The Mg-1 wt%Zn alloy displays distinct yielding and hardening behavior due to solid solution softening of prismatic〈a〉slip.Additionally,the dependence of extension twinning,in terms of the twinning volume fraction,on Zn content exhibits opposite trends under tensile and compressive loadings.
基金supported by grants from National Natural Science Foundation of China(32125038)National Key Research and Development Program of China(grant number 2023YFD1801100 and 2023YFD1800804)+1 种基金the Key Research and Development Program of the Xinjiang Uygur Autonomous Region(No.2024B02016)the 2115 Talent Development Program of China Agricultural University.Authors declare that no conflicts of interest exist.
文摘Background Sustained lipolysis exacerbates subclinical ketosis(SCK)in dairy cows and is associated with inflammation and adipose tissue macrophage(ATM)infiltration.While ATM involvement in adipose homeostasis and inflammation in early lactation is recognized,a comprehensive exploration of ATM polarization phenotypes in SCK cows is lacking.This study aimed to characterize ATM polarization and its link to lipolysis and inflammation in SCK cows.Results Subcutaneous adipose tissue samples were obtained from dairy cows to analyze protein expression and gene profiles.Compared with healthy cows,SCK cows had higher serum BHBA and NEFA,smaller adipocytes,and increased expression of lipolytic enzymes(LIPE,ATGL),indicating enhanced lipolysis.Decreased levels of FASN,PPARγ,p-SMAD3,and TGFβsuggested impaired adipogenesis.Inflammatory markers(TNF-α,IFN-γ,TLR4,Caspase1)and NFκB signaling activity were elevated.ATM infiltration was supported by increased CD9,CD68,TREM2,and CXCL1 expression.Protein abundance of M1 polarization markers(iNOS,CD86 and CCL2)in ATMs were associated with greater levels of NOS2,IL1B,CD86 and CCL2 mRNA expression in SCK cows;fluorescence intensity of NOS2 and CD86 also was elevated,alongside a higher proportion of CD68+/CD86+immunopositive cells within adipose tissue.ELISA further quantified increased concentrations of IL-1β and CCL2.Conversely,the abundance of ATM M2 polarization markers,including CD206,IL-10,KLF4,and Arg1,at both the protein and mRNA levels demonstrated a decline.Meanwhile,the proportion of CD68+/CD206+immune response cells was relatively low in SCK cows.Conclusions Overall,the present study indicated an augmented macrophage presence within adipose tissue during subclinical ketosis,with a predominance of pro-inflammatory macrophages(M1 ATM).This observation suggested a vicious cycle wherein macrophage infiltration and pro-inflammatory polarization coincide with enhanced lipolysis and an amplified inflammatory cascade.
基金supported by the National Natural Science Foundation of China(No.52072283)the program of China Scholarship Council(No.202306950008)。
文摘The advancement of efficient,cheap,and durable catalysts for oxygen reduction reaction(ORR)to substitute Pt/C in metal-air batteries is of paramount importance.However,traditional solvent-based methods fall short in terms of environmental benign and scalability.Herein,a solvent-free organic-inorganic selfassembly approach is explored to construct cobalt single atom and cobalt nanocluster decorated nitrogendoped porous carbon spheres(Co-SA/NC@NCS).The solvent-free synthesis demonstrates an impressively high yield(282 g/L)and the resultant Co-SA/NC@NCS possesses a high N content(6.9 wt%).Density functional theory calculations disclose that the Co-SAs and Co-NCs are able to optimize the surface oxygen adsorption capability and enhance the conductivity of the NCS,thereby facilitating the ORR performance.The sol vent-free synthesis is also feasible for the synthesis of other non-noble metal element(Fe,Ni,and Zn)decorated nitrogen-doped porous carbon spheres.
基金funded byDepartment of Crop Physiology and Ecology,HajeeMohammad Danesh Science and Technology University,Dinajpur 5200 Bangladesh and Taif University,Saudi Arabia,Project No.TU-DSPP-2024-07.
文摘The increasing frequency and intensity of drought caused by climate change necessitate the implementation of effective ways to increase the ability of wheat to withstand drought, with humic acid being a promising approach. Therefore, a pot experiment was conducted to determine the efficacy of exogenous humic acid on wheat under water deficit stress via a completely randomized design (CRD) with three replications. The impacts of four growing conditions, i.e., well water (65% field capacity), water deficit stress (35% field capacity), soil application of humic acid (44 mg kg−1 soil) under water deficit stress and foliar feeding of humic acid (200 ppm) under water deficit stress, were investigated on two wheat varieties (BWMRI Gom 1 and BWMRI Gom 3). The results demonstrated that water deficit stress substantially decreased the studied morphological and physiological traits, yield components and yield, in both genotypes, with the exception of the proline content of flag leaves. Compared with soil application, foliar feeding of humic acid promoted the ability of wheat to overcome stress conditions better. In the present study, humic acid as a soil application increased the grain yield by 9.13% and 13.86% and the biological yield by 9.94% and 5.19%, whereas foliar treatment increased the grain output by 24.76% and 25.19% and the biological yield by 19.23% and 6.50% in BWMRI Gom 1 and BWMRI Gom 3, respectively, under water deficit stress. Therefore, exogenous foliar humic acid treatment was more effective than soil application in alleviating the effects of drought stress on wheat.
基金funded by the Deanship of Graduate Studies and Scientific Research at Qassim University for financial support(QU-APC-2025).
文摘Hemoglobin is a vital protein in red blood cells responsible for transporting oxygen throughout the body.Its accurate measurement is crucial for diagnosing and managing conditions such as anemia and diabetes,where abnormal hemoglobin levels can indicate significant health issues.Traditional methods for hemoglobin measurement are invasive,causing pain,risk of infection,and are less convenient for frequent monitoring.PPG is a transformative technology in wearable healthcare for noninvasive monitoring and widely explored for blood pressure,sleep,blood glucose,and stress analysis.In this work,we propose a hemoglobin estimation method using an adaptive lightweight convolutional neural network(HMALCNN)from PPG.The HMALCNN is designed to capture both fine-grained local waveform characteristics and global contextual patterns,ensuring robust performance across acquisition settings.We validated our approach on two multi-regional datasets containing 152 and 68 subjects,respectively,employing a subjectindependent 5-fold cross-validation strategy.The proposed method achieved root mean square errors(RMSE)of 0.90 and 1.20 g/dL for the two datasets,with strong Pearson correlations of 0.82 and 0.72.We conducted extensive posthoc analyses to assess clinical utility and interpretability.A±1 g/dL clinical error tolerance evaluation revealed that 91.3%and 86.7%of predictions for the two datasets fell within the acceptable clinical range.Hemoglobin range-wise analysis demonstrated consistently high accuracy in the normal and low hemoglobin categories.Statistical significance testing using the Wilcoxon signed-rank test confirmed the stability of performance across validation folds(p>0.05 for both RMSE and correlation).Furthermore,model interpretability was enhanced using Gradient-weighted Class Activation Mapping(Grad-CAM),supporting the model’s clinical trustworthiness.The proposed HMALCNN offers a computationally efficient,clinically interpretable,and generalizable framework for noninvasive hemoglobin monitoring,with strong potential for integration into wearable healthcare systems as a practical alternative to invasive measurement techniques.
