Regulating Non-Equilibrium Solvation Structure in Locally Concentrated Ionic Liquid Electrolytes for Wide-Temperature and High-Voltage Lithium Metal Batteries.

The development of high-voltage lithium metal batteries (LMBs) encounters significant challenges due to aggressive electrode chemistry. Recently, locally concentrated ionic liquid electrolytes (LCILEs) have garnered attention for their exceptional stability with both Li anodes and high-voltage cathodes. However, there remains a limited understanding of how diluents in LCILEs affect the thermodynamic stability of the solvation structure and transportation dynamics of Li+ ions. Herein, we propose a wide-temperature LCILEs with 1,3-dichloropropane (DCP13) diluent to construct a non-equilibrium solvation structure under external electric field, wherein the DCP13 diluent enters the Li+ ion solvation sheath to enhance Li+ ion transport and suppress oxidative side reactions at high-nickel cathode (LiNi0.9Co0.05Mn0.05O2, NCM90).Consequently, a Li/NCM90 cell utilizing this LCILE achieves a high capacity retention of 94% after 240 cycles at 4.3 V, also operates stably at high cut-off voltages from 4.4 to 4.6 V and over a wide temperature range from -20 to 60 °C. Additionally, an Ah-level pouch cell with this LCILE simultaneously achieves high-energy-density and stable cycling, manifesting the practical feasibility. This work redefines the role of diluents in LCILEs, providing inspiration for electrolyte design in developing high-energy-density batteries.

A percolation-type criticality threshold controls immune protein coating of surfaces.

When a material enters the body, it is immediately attacked by hundreds of proteins, organized into complex networks of binding interactions and reactions. How do such complex systems interact with a material, "deciding" whether to attack? We focus on the "complement" system of ∼40 blood proteins that bind microbes, nanoparticles, and medical devices, initiating inflammation. We show a sharp threshold for complement activation upon varying a fundamental material parameter, the surface density of potential complement attachment points. This sharp threshold manifests at scales spanning single nanoparticles to macroscale pathologies, shown here for diverse engineered and living materials. Computational models show these behaviors arise from a minimal subnetwork of complement, manifesting percolation-type critical transitions in the complement response. This criticality switch explains the "decision" of a complex signaling network to interact with a material, and elucidates the evolution and engineering of materials interacting with the body.

Characterization and expression analysis of the MADS-box gene AGL8 in cotton: insights into gene function differentiation in plant growth and stress resistance.

BACKGROUND: AGAMOUS-LIKE 8 (AGL8) belongs to the MADS-box family, which plays important roles in transcriptional regulation, sequence-specific DNA binding and other biological processes and molecular functions. The genome of cotton, a representative polyploid plant, contains multiple AGL8 genes. However, their functional differentiation is still unclear. METHODS AND RESULTS: In this study, a comprehensive genomic analysis of AGL8 genes was conducted. Cotton AGL8s were subdivided into four subgroups (Groups 1, 2, 3, and 4) based on phylogenetic analysis, and different subgroups of AGL8s presented different characteristics, including different structures and conserved motifs. With respect to the promoter regions of the GhAGL8 genes, we successfully predicted cis-elements that respond to phytohormone signal transduction and the stress response of plants. Transcriptome data and real-time quantitative PCR validation indicated that three genes, namely, GH_D07G0744, GH_A03G0856 and GH_A07G0749, were highly induced by methyl jasmonate (MeJA), salicylic acid (SA), and abscisic acid (ABA), which indicated that they function in plant resistance to abiotic and biotic stresses. CONCLUSIONS: The information from the gene structure, number and types of conserved domains, tissue-specific expression levels, and expression patterns under different treatments highlights the differences in sequence and function of the cotton AGL8 genes. Different AGL8s play roles in vegetative growth, reproductive development, and plant stress resistance. These results lay a foundation for further study of GhAGL8s in cotton.

Recent advances in understanding and manipulating magnetic and electronic properties of EuM2X2(M= Zn, Cd;X= P, As).

Over the past five years, significant progress has been made in understanding the magnetism and electronic properties of CaAl2Si2-type EuM2X2(M= Zn, Cd;X= P, As) compounds. Prior theoretical work and experimental studies suggested that EuCd2As2had the potential to host rich topological phases, particularly an ideal magnetic Weyl semimetal state when the spins are polarized along thecaxis. However, this perspective is challenged by recent experiments utilizing samples featuring ultra-low carrier densities, as well as meticulous calculations employing various approaches. Nonetheless, the EuM2X2family still exhibit numerous novel properties that remain to be satisfactorily explained, such as the giant nonlinear anomalous Hall effect and the colossal magnetoresistance effect. Moreover, EuM2X2compounds can be transformed from semiconducting antiferromagnets to metallic ferromagnets by introducing a small number of carriers or applying external pressure, and a further increase in the ferromagnetic transition temperature can be achieved by reducing the unit cell volume. These features make the EuM2X2family a fertile platform for studying the interplay between magnetism and charge transport, and an excellent candidate for applications in spintronics. This paper presents a comprehensive review of the magnetic and transport behaviors of EuM2X2compounds with varying carrier densities, as well as the current insights into these characteristics. An outlook for future research opportunities is also provided.

Autophagy-enabled protein degradation: Key to platelet activation and ANGII production in patients with type 2 diabetes mellitus.

Background: Type 2 diabetes mellitus (T2DM) presents a thrombotic environment, contributing to diabetic macroangiopathy and microangiopathy. In this study, the regulation of microthrombosis in T2DM was assessed. Methods: Platelets from T2DM patients and healthy controls were analyzed using 4D label-free proteomics and bioinformatics. The role of autophagy in T2DM platelet activation and conversion of platelet-derived angiotensinogen (AGT) was investigated. Results: The results showed that complement and coagulation cascades, platelet activation, metabolic pathways, endocytosis, autophagy, and other protein digestion-related pathways were enriched. The levels of the key protein AGT were increased in T2DM platelets. Chloroquine (CQ) inhibited ADP- or arachidonic acid (AA)-stimulated platelet aggregation and granule release in a dose-dependent manner, while the effects were less pronounced or even reversed for the proteasome inhibitor PYR-41 and the endocytosis inhibitor Pitstop 2. This indicated the dependence of platelet activation and the accompanying protein digestion on the autophagy-lysosome pathway. Mitophagy occurred in fresh T2DM platelets and ADP- or storage-stimulated platelets; mitophagy was inhibited by CQ. However, the mitophagy inhibitor Mdivi-1 failed to show effects similar to those of CQ. AGT, which could be transformed into ANGII in vitro by ADP-stimulated platelets, was upregulated in T2DM platelets and in MEG-01 cell-derived platelets cultured in a high-glucose medium. Finally, microthrombosis was alleviated as indicated by a reduction in the levels of red blood cells in the liver, spleen, heart, and kidney tissues of db/db mice treated with CQ or valsartan. Conclusion: In platelets, macroautophagy promotes protein digestion, subsequently facilitating platelet activation, ANGII-mediated vasoconstriction, and microthrombosis. Our results suggested that lysosome is a promising therapeutic target for antithrombotic treatment in T2DM.

Introgression drives adaptation to the plateau environment in a subterranean rodent.

BACKGROUND: Introgression has repeatedly been shown to play an important role in the adaptation of species to extreme environments, yet how introgression enables rodents with specialized subterranean lifestyle to acclimatize to high altitudes is still unclear. Myospalacinae is a group of subterranean rodents, among which the high-altitude plateau zokors (Eospalax baileyi) and the low-altitude Gansu zokors (E. cansus) are sympatrically distributed in the grassland ecosystems of the Qinghai-Tibet Plateau (QTP). Together, they provide a model for the study of the role of introgression in the adaptation of low-altitude subterranean rodents to high altitudes. RESULTS: Applying low-coverage whole-genome resequencing and population genetics analyses, we identified evidence of adaptive introgression from plateau zokors into Gansu zokors, which likely facilitated the adaptation of the latter to the high-altitude environment of the QTP. We identified positively selected genes with functions related to energy metabolism, cardiovascular system development, calcium ion transport, and response to hypoxia which likely made critical contributions to adaptation to the plateau environment in both plateau zokors and high-altitude populations of Gansu zokors. CONCLUSIONS: Introgression of genes associated with hypoxia adaptation from plateau zokors may have played a role in the adaptation of Gansu zokors to the plateau environment. Our study provides new insights into the understanding of adaptive evolution of species on the QTP and the importance of introgression in the adaptation of species to high-altitude environments.

Molecular insights into kaempferol derivatives as potential inhibitors for CDK2 in colon cancer: pharmacophore modeling, docking, and dynamic analysis.

Cyclin-dependent kinase 2 (CDK2) has been recognized as one of the crucial factors in cell cycle regulation and has been proposed as a potential target for cancer therapies, particularly for colorectal cancer (CRC). Due to the increased incidence rate of CRC and challenges associated with existing treatment options, there is a need for efficient and selective anti-cancer compounds. The current work aims to explore the ability of novel kaempferol derivatives as CDK2 inhibitors by performing conceptual pharmacophore modeling, molecular docking, and molecular dynamic analysis. Kaempferol and its derivatives were obtained from PubChem, and the optimized 3D structures of the compounds were generated using Maestro Ligprep. Subsequently, a pharmacophore model was developed to identify compounds with high fitness values, resulting in the selection of several kaempferol derivatives for further study. We evaluated the ADMET properties of these compounds to assess their therapeutic potential. Molecular docking was conducted using Maestro and BIOVIA Discovery Studio version 4.0 to predict the binding affinities of the compounds to CDK2. The top candidates were subjected to MM-GBSA analysis to predict their binding free energies. Molecular dynamics simulations using GROMACS were performed to assess the thermodynamic stability of the ligand-protein complexes. The results revealed several kaempferol derivatives with high predicted binding affinities to CDK2 and favorable ADMET properties. Specifically, compounds 5281642, 5318980, and 14427423 demonstrated binding free energies of -30.26, -38.66, and -34.2 kcal/mol, respectively. Molecular dynamics simulations indicated that these ligand-protein complexes remained stable throughout the simulation period, with RMSD values remaining below 2 Å. In conclusion, the identified kaempferol derivatives show potential as CDK2 inhibitors based on computational predictions and demonstrate stability in molecular dynamics simulations, suggesting their future application in CRC treatment by targeting CDK2. These computational findings encourage further experimental validation and development of kaempferol derivatives as anti-cancer agents.

Mn-Fe dual-metal Assemblages on Carbon-coated Al2O3 Spheres for Catalytic Ozonation Oxidation: Structure, Performance, and Reaction Mechanism.

Catalysts with high catalytic activity and low production cost are important for industrial application of heterogeneous catalytic ozonation (HCO). In this study, we designed a carbon-coated aluminum oxide carrier (C-Al2O3) and reinforced it with Mn-Fe bimetal assemblages to prepare a high-performance catalyst Mn-Fe/C-Al2O3. The results showed that the carbon embedding significantly improved the abundance of surface oxygen functional groups, conductivity, and adsorption capacity of γ-Al2O3, while preserving its exceptional mechanical strength as a carrier. The prepared Mn-Fe/C-Al2O3 catalyst exhibited satisfactory catalytic ozonation activity and stability in the degradation of p-nitrophenol (PNP). Electron paramagnetic resonance (EPR) and quenching experiments reveal that radical (•OH and •O2-) and nonradical oxidation (1O2) dominated the PNP degradation process. Theoretical calculations corroborated that the anchored atomic Fe and Mn sites regulated the local electronic structure of the catalyst. This modulation effectively promoted the activation of O3 molecules, resulting in the generation of atomic oxygen species (AOS) and reactive oxygen species (ROS). The economic analysis on Mn-Fe/C-Al2O3 revealed that it was a cost-competitive catalyst for HCO. This study not only deepens the understanding on the reaction mechanism of HCO with transition metal/carbon composite catalysts, also provides a high-performance and cost-competitive ozone catalyst for prospective application.

The Current Status and Future Directions on Nanoparticles for Tumor Molecular Imaging.

Molecular imaging is an advanced technology that utilizes specific probes or markers in conjunction with cutting-edge imaging techniques to observe and analyze the localization, distribution, activity, and interactions of biomolecules within living organisms. Tumor molecular imaging, by enabling the visualization and quantification of molecular characteristics of tumor cells, facilitates a deeper and more comprehensive understanding of tumors, providing valuable insights for early diagnosis, treatment monitoring, and cancer biology research. However, the image quality of molecular imaging still requires improvement, and nanotechnology has significantly propelled the advancement of molecular imaging. Currently, nanoparticle-based tumor molecular imaging technologies encompass radionuclide imaging, fluorescence imaging, magnetic resonance imaging, ultrasound imaging, photoacoustic imaging, and multimodal imaging, among others. As our understanding of the tumor microenvironment deepens, the design of nanoparticle probes for tumor molecular imaging has also evolved, offering new perspectives and expanding the applications of tumor molecular imaging. Beyond diagnostics, there is a marked trend towards integrated diagnosis and therapy, with image-guided treatment playing a pivotal role. This includes image-guided surgery, photodynamic therapy, and chemodynamic therapy. Despite continuous advancements and innovative developments in molecular imaging, many of these remain in the experimental stage and require breakthroughs before they can be fully integrated into clinical practice.

Construction of machine learning diagnostic models for cardiovascular pan-disease based on blood routine and biochemical detection data.

BACKGROUND: Cardiovascular disease, also known as circulation system disease, remains the leading cause of morbidity and mortality worldwide. Traditional methods for diagnosing cardiovascular disease are often expensive and time-consuming. So the purpose of this study is to construct machine learning models for the diagnosis of cardiovascular diseases using easily accessible blood routine and biochemical detection data and explore the unique hematologic features of cardiovascular diseases, including some metabolic indicators. METHODS: After the data preprocessing, 25,794 healthy people and 32,822 circulation system disease patients with the blood routine and biochemical detection data were utilized for our study. We selected logistic regression, random forest, support vector machine, eXtreme Gradient Boosting (XGBoost), and deep neural network to construct models. Finally, the SHAP algorithm was used to interpret models. RESULTS: The circulation system disease prediction model constructed by XGBoost possessed the best performance (AUC: 0.9921 (0.9911-0.9930); Acc: 0.9618 (0.9588-0.9645); Sn: 0.9690 (0.9655-0.9723); Sp: 0.9526 (0.9477-0.9572); PPV: 0.9631 (0.9592-0.9668); NPV: 0.9600 (0.9556-0.9644); MCC: 0.9224 (0.9165-0.9279); F1 score: 0.9661 (0.9634-0.9686)). Most models of distinguishing various circulation system diseases also had good performance, the model performance of distinguishing dilated cardiomyopathy from other circulation system diseases was the best (AUC: 0.9267 (0.8663-0.9752)). The model interpretation by the SHAP algorithm indicated features from biochemical detection made major contributions to predicting circulation system disease, such as potassium (K), total protein (TP), albumin (ALB), and indirect bilirubin (NBIL). But for models of distinguishing various circulation system diseases, we found that red blood cell count (RBC), K, direct bilirubin (DBIL), and glucose (GLU) were the top 4 features subdividing various circulation system diseases. CONCLUSIONS: The present study constructed multiple models using 50 features from the blood routine and biochemical detection data for the diagnosis of various circulation system diseases. At the same time, the unique hematologic features of various circulation system diseases, including some metabolic-related indicators, were also explored. This cost-effective work will benefit more people and help diagnose and prevent circulation system diseases.

Robotic and Laparoscopic Adrenalectomy for Pheochromocytoma: An International Multicenter Study.

BACKGROUND AND OBJECTIVE: Robotic adrenalectomy (RA) has attracted interest as an alternative to laparoscopic adrenalectomy (LA) for patients with pheochromocytoma, although its beneficial effects are uncertain. Our aim was to compare RA and LA outcomes for these patients. METHODS: Data for patients who underwent RA or LA for pheochromocytoma in 46 international centers between 2012 and 2022 were reviewed. We analyzed baseline characteristics and postoperative complications at discharge, 90 d, and 1 yr. We conducted propensity score matching (PSM; 1:1 ratio) and multivariable analyses to evaluate outcomes and risk factors for the occurrence of complications and higher Comprehensive Complication Index (CCI). KEY FINDINGS AND LIMITATIONS: Of 1755 patients, 1613 (91.9%) underwent LA and 142 (8.1%) underwent RA. Estimated blood loss, conversion rate, complication rate, and CCI at discharge, 90 d, and 1 yr were similar between the groups. However, RA was associated with a longer operative time in comparison to LA (100 vs 123 min; p < 0.001), but not after PSM (p = 0.120). Multivariable analysis revealed that Charlson comorbidity index (odds ratio [OR] 1.17, 95% confidence interval [CI] 1.07-1.29; p = 0.001), and tumor size per 1-cm increment (OR 1.13, 95% CI 1.07-1.21; p < 0.001) were independently associated with the incidence of complications, but there was no significant difference in complication rates between the LA and RA groups (OR 1.09, 95% CI 0.63-1.87; p = 0.767). After PSM, RA was associated with a lower rate of severe (grade ≥3a) complications in comparison to LA (p = 0.023). CONCLUSIONS AND CLINICAL IMPLICATIONS: RA is a safe alternative to LA and yields similar outcomes for patients with pheochromocytoma. RA may be associated with a lower likelihood of severe complications. Further studies are warranted to determine the role of robotic surgery in pheochromocytoma. PATIENT SUMMARY: Pheochromocytoma is a rare tumor in the adrenal gland and the gold-standard treatment is surgical removal. We assessed patient outcomes after robot-assisted surgery compared with laparoscopic surgery and found that outcomes are similar, but the rate of severe complications may be lower if a surgical robot is used.

Promoting Cathodic Kinetics and Anodic Stability in Practical Room-Temperature Sodium-Sulfur Batteries with Bifunctional Electrolytes.

The development of room-temperature (RT) sodium-sulfur (Na-S) batteries is severely hindered due to the slow kinetics of the S cathode and the instability of the Na-metal anode. To overcome this, we introduced a dual-functional electrolyte cosolvent, trifluoromethanesulfonamide (TFMSA). Short-chain Na2Sx (1 ≤ x ≤ 2) can be effectively dissolved due to the strong H-S bond interaction between TFMSA and sulfides, which changes the S conversion process, thereby effectively enhancing the conversion kinetics of the cathode. Meanwhile, TFMSA can generate a stable solid electrolyte interphase on the Na-metal surface to protect it from soluble polysulfide attack. Therefore, the RT Na-S batteries using the ether electrolyte show a high initial discharge capacity of 896.6 mAh g-1 and a capacity retention rate of 73% after 150 cycles at 0.2C, and the pouch cell also demonstrates its practical performance. This work proposes a dual-functional electrolyte cosolvent selection principle to inspire the practical application of high-performance RT Na-S batteries.

In-Situ Construction of Fe-Doped NiOOH on the 3D Ni(OH)2 Hierarchical Nanosheet Array for Efficient Electrocatalytic Oxygen Evolution Reaction.

Accessible and superior electrocatalysts to overcome the sluggish oxygen evolution reaction (OER) are pivotal for sustainable and low-cost hydrogen production through electrocatalytic water splitting. The iron and nickel oxohydroxide complexes are regarded as the most promising OER electrocatalyst attributed to their inexpensive costs, easy preparation, and robust stability. In particular, the Fe-doped NiOOH is widely deemed to be superior constituents for OER in an alkaline environment. However, the facile construction of robust Fe-doped NiOOH electrocatalysts is still a great challenge. Herein, we report the facile construction of Fe-doped NiOOH on Ni(OH)2 hierarchical nanosheet arrays grown on nickel foam (FeNi@NiA) as efficient OER electrocatalysts through a facile in-situ electrochemical activation of FeNi-based Prussian blue analogues (PBA) derived from Ni(OH)2. The resultant FeNi@NiA heterostructure shows high intrinsic activity for OER due to the modulation of the overall electronic energy state and the electrical conductivity. Importantly, the electrochemical measurement revealed that FeNi@NiA exhibits a low overpotential of 240 mV at 10 mA/cm2 with a small Tafel slope of 62 mV dec-1 in 1.0 M KOH, outperforming the commercial RuO2 electrocatalysts for OER.

SlLTPg1, a tomato lipid transfer protein, positively regulates in response to biotic stresses.

Late blight, caused by Phytophthora infestans (P. infestans), is among the most devastating diseases affecting tomato and other Solanaceae species. Lipid transfer proteins (LTPs) represent a class of small, basic proteins that play a crucial role in combating biotic stresses. Previous studies have shown that SlLTPg1 most strongly responds after P. infestans infestation among the LTPs family in tomato. However, the function of SlLTPg1 in disease resistance remains unclear. Here, we constructed transient overexpression and VIGS-silenced plants of SlLTPg1. Our results revealed that SlLTPg1 plays a regulatory role in enhancing tomato resistance against P. infestans. This enhancement was attributed to the upregulation of defense-related genes and reactive oxygen species (ROS) scavenging genes, as well as increased enzymatic antioxidant activities. Importantly, we found that the SlLTPg1 protein significantly inhibited the growth of Fusarium oxysporum (F. oxysporum) by observing the zone of inhibition. Interestingly, we found smaller lesion diameters and upregulated expression levels of PR genes in transient overexpression SlLTPg1 of tobacco. Therefore, we further constructed transgenic tobacco lines of SlLTPg1, presenting evidence that overexpression of SlLTPg1 could positively regulate the resistance of tobacco to F. oxysporum. These findings revealed the role of SlLTPg1 in tomato resistance to P. infestans and tobacco resistance to F. oxysporum. Moreover, we propose SlLTPg1 as a potential candidate gene for augmenting broad-spectrum plant resistance against pathogens.

Marginated Neutrophils in the Lungs Effectively Compete for Nanoparticles Targeted to the Endothelium, Serving as a Part of the Reticuloendothelial System.

Nanomedicine has long pursued the goal of targeted delivery to specific organs and cell types but has yet to achieve this goal with the vast majority of targets. One rare example of success in this pursuit has been the 25+ years of studies targeting the lung endothelium using nanoparticles conjugated to antibodies against endothelial surface molecules. However, here we show that such "endothelial-targeted" nanocarriers also effectively target the lungs' numerous marginated neutrophils, which reside in the pulmonary capillaries and patrol for pathogens. We show that marginated neutrophils' uptake of many of these "endothelial-targeted" nanocarriers is on par with endothelial uptake. This generalizes across diverse nanomaterials and targeting moieties and was even found with physicochemical lung tropism (i.e., without targeting moieties). Further, we observed this in ex vivo human lungs and in vivo healthy mice, with an increase in marginated neutrophil uptake of nanoparticles caused by local or distant inflammation. These findings have implications for nanomedicine development for lung diseases. These data also suggest that marginated neutrophils, especially in the lungs, should be considered a major part of the reticuloendothelial system (RES), with a special role in clearing nanoparticles that adhere to the lumenal surfaces of blood vessels.

Can digital industrialization promote energy conservation development in China? Empirical evidence based on national big data comprehensive pilot zone policy.

Digital industrialization represented by big data provides substantial support for the high-quality development of the digital economy, but its impact on urban energy conservation development requires further research. To this end, based on the panel data of Chinese cities from 2010 to 2019 and taking the establishment of the national big data comprehensive pilot zone (NBDCPZ) as a quasi-natural experiment, this paper explores the impact, mechanism, and spatial spillover effect of digital industrialization represented by big data on urban energy conservation development using the Difference-in-Differences (DID) method. The results show that digital industrialization can help achieve urban energy conservation development, which still holds after a series of robustness tests. Mechanism analysis reveals that digital industrialization impacts urban energy conservation development by driving industrial sector output growth, promoting industrial upgrading, stimulating green technology innovation, and alleviating resource misallocation. Heterogeneity analysis indicates that the energy conservation effect of digital industrialization is more significant in the central region, intra-regional demonstration comprehensive pilot zones, large cities, non-resource-based cities, and high-level digital infrastructure cities. Additionally, digital industrialization can promote energy conservation development in neighboring areas through spatial spillover effect. This paper enriches the theoretical framework concerning the relationship between digital industrialization and energy conservation development. The findings have significant implications for achieving the coordinated development of digitalization and conservation.

Nanocarriers' repartitioning of drugs between blood subcompartments as a mechanism of improving pharmacokinetics, safety, and efficacy.

For medical emergencies, such as acute ischemic stroke, rapid drug delivery to the target site is essential. For many small molecule drugs, this goal is unachievable due to poor solubility that prevents intravenous administration, and less obviously, by extensive partitioning to plasma proteins and red blood cells (RBCs), which greatly slows delivery to the target. Here we study these effects and how they can be solved by loading into nanoscale drug carriers. We focus on fingolimod, a small molecule drug that is FDA-approved for treatment of multiple sclerosis, which has also shown promise in the treatment of stroke. Unfortunately, fingolimod has poor solubility and very extensive partitioning to plasma proteins and RBCs (in whole blood, 86% partitions to RBCs, 13.96% to plasma proteins, and 0.04% is free). We develop a liposomal formulation that slows the partitioning of fingolimod to RBCs and plasma proteins, enables intravenous delivery, and additionally prevents fingolimod toxicity to RBCs. The liposomal formulation nearly completely prevented fingolimod adsorption to plasma proteins (association with plasma proteins was 98.4 ± 0.4% for the free drug vs. 5.6 ± 0.4% for liposome-loaded drug). When incubated with whole blood in vitro, the liposomal formulation greatly slowed partitioning of fingolimod to RBCs and also eliminated deleterious effects of fingolimod on RBC rigidity, morphology, and hemolysis. In vivo, the liposomal formulation delayed fingolimod partitioning to RBCs for over 30 min, a critical time window for stroke. Fingolimod-loaded liposomes showed improved efficacy in a mouse model of post-stroke neuroinflammation, completely sealing the leaky blood-brain barrier (114 ± 11.5% reduction in albumin leak into the brain for targeted liposomes vs. 38 ± 16.5% reduction for free drug). This effect was only seen for liposomes modified with antibodies to enable targeted delivery to the site of action, and not in unmodified, long-circulating liposomes. Thus, loading fingolimod into liposomes prevented partitioning to RBCs and associated toxicities and enabled targeted delivery. This paradigm can be used for tuning the blood distribution of small molecule drugs for the treatment of acute illnesses requiring rapid pharmacologic intervention.

Research on the castor oil pressing extraction mechanism based on multi-physics coupling simulation.

Castor oil has been widely used in various fields due to its properties, leading to large attention for its extraction mechanism. To research the castor oil extraction mechanism during pressing, a self-developed uniaxial compression device combined with an in situ observation is established. The effects of pressure, loading speed, and creep time are investigated, and a finite element model coupling with multi-physics is established for castor oil pressing extraction, verified by the seed cake experimental compression strain matching with numerical simulation under the same condition. Simulation results indicated that the pressing oil extraction process can be divided into two stages, Darcy's speed shows the first sharp decreasing stage and the second gradual increasing stage during porosity and pressure interaction. In the first stage, porosity is dominant on Darcy's speed. With porosity decreasing, the pressure effect on Darcy's speed exceeds porosity in the second stage. With seed thickness increasing, Darcy's speed first increases and then decreases. With loading speed increasing, Darcy's speed increases. Darcy's speed decreases constantly with creep time increasing. This study can provide basic theoretical and practical guidance for oil extraction.

Prevention of postpancreatectomy hemorrhage after laparoscopic pancreaticoduodenectomy by wrapping ligamentum teres hepatis surrounding hepatic portal artery.

Postpancreatectomy hemorrhage (PPH) is an important risk factor for postoperative complications after laparoscopic pancreaticoduodenectomy (LPD). Recent studies have reported that the use of ligamentum teres hepatis (LTH) in LPD may reduce the risk of PPH. Therefore, this study aims to investigate whether wrapping the hepatic hilar artery with the LTH can reduce PPH after LPD. We reviewed the data of 131 patients who underwent LPD in our team from April 2018 to December 2023. The patients were divided into Groups A (60 patients) and B (71 patients) according to whether the hepatic portal artery was wrapped or not. The perioperative data of the two groups were compared to evaluate the effect of LTH wrapping the hepatic hilar artery on LPD. The platelet count of Group A was (225.25 ± 87.61) × 10^9/L, and that of Group B was (289.38 ± 127.35) × 10^9/L, with a statistically significant difference (p < 0.001). The operation time of group A [300.00 (270.00, 364.00)] minutes was shorter than that of group B [330.00 (300.00, 360.00)] minutes, p = 0.037. In addition, A set of postoperative hospital stay [12.00 (10.00, 15.00)] days shorter than group B [15.00 (12.00, 19.50)] days, p < 0.001. No PPH occurred in Group A, while 8 patients in Group B had PPH (7 cases of gastroduodenal artery hemorrhage and 1 case of proper hepatic artery hemorrhage), p = 0.019. The new technique of wrapping the hepatic hilar artery through the LTH can effectively reduce the occurrence of PPH after LPD.

Radiation-induced YAP/TEAD4 binding confers non-small cell lung cancer radioresistance via promoting NRP1 transcription.

Despite the importance of radiation therapy as a non-surgical treatment for non-small cell lung cancer (NSCLC), radiation resistance has always been a concern, due to poor patient response and prognosis. Therefore, it is crucial to uncover novel targets to enhance radiotherapy and investigate the mechanisms underlying radiation resistance. Previously, we demonstrated that NRP1 was connected to radiation resistance in NSCLC cells. In the present study, bioinformatics analysis of constructed radiation-resistant A549 and H1299 cell models revealed that transcription coactivator YAP is a significant factor in cell proliferation and metastasis. However, there has been no evidence linking YAP and NRP1 to date. In this research, we have observed that YAP contributes to radiation resistance in NSCLC cells by stimulating cell proliferation, migration, and invasion. Mechanistically, YAP dephosphorylation after NSCLC cell radiation. YAP acts as a transcription co-activator by binding to the transcription factor TEAD4, facilitating TEAD4 to bind to the NRP1 promoter region and thereby increasing NRP1 expression. NRP1 has been identified as a new target gene for YAP/TEAD4. Notably, when inhibiting YAP binds to TEAD4, it inhibits NRP1 expression, and Rescue experiments show that YAP/TEAD4 influences NRP1 to regulate cell proliferation, metastasis and leading to radiation resistance generation. According to these results, YAP/TEAD4/NRP1 is a significant mechanism for radioresistance and can be utilized as a target for enhancing radiotherapy efficacy.