Search

Abstract The aim is to address the limitations of conventional sliding mode control for PMSM, namely the problems of sliding mode oscillation, load disturbance, and poor control accuracy. An improved sliding mode control strategy for PMSM is proposed based on the novel convergence rate and extended state observer. Firstly, an integral sliding mode velocity loop controller is designed based on the novel convergence rate to solve the sliding mode vibration problem. The stability of the proposed control strategy is derived by the Lyapunov criterion. Secondly, an extended state observer capable of estimating the disturbance torque is designed for the purpose of disturbance compensation. The disturbance torque estimate is then used as a feed-forward signal for the sliding mode velocity loop controller. A fast second-order sliding mode controller is used for the current loop to avoid the potential introduction of noise and disturbances. The simulation results show that compared to alternative control strategies, the proposed control strategy enables the PMSM to respond effectively to start-up and load disturbances, significantly reduces the sliding mode jitter, and improves both the torque estimation accuracy and the system control accuracy.

Prokaryotes play a crucial role in marine ecosystem health and drive biogeochemical processes. The northern Ninety East Ridge (NER) of the Indian Ocean, a pivotal yet understudied area for these cycles, has been the focus of our study. We employed high-throughput 16S rRNA gene sequencing to analyze 35 water samples from five stations along the ridge, categorized into three depth- and dissolved oxygen-level-based groups. Our approach uncovered a clear stratification of microbial communities, with key bioindicators such as Prochlorococcus MIT9313, Sva0996 marine group, and Candidatus Actinomarina in the upper layer; Ketobacter, Pseudophaeobacter, Nitrospina, and SAR324 clade in the middle layer; and Methylobacterium-Methylorubrum, Sphingomonas, Sphingobium, and Erythrobacter in the deep layer. Methylobacterium-Methylorubrum emerged as the most abundant bacterial genus, while Nitrosopumilaceae predominated among archaeal communities. The spatial and depth-wise distribution patterns revealed that Ketobacter was unique to the northern NER, whereas Methylobacterium-Methylorubrum, UBA10353, SAR324 clade, SAR406, Sva0996_marine_group, Candidatus Actinomarina were ubiquitous across various marine regions, exhibiting niche differentiation at the OTU level. Environmental factors, especially dissolved oxygen (DO), silicate, nitrate, and salinity, significantly influence community structure. These findings not only reveal the novelty and adaptability of the microbial ecosystem in the northern NER but also contribute to the broader understanding of marine microbial diversity and its response to environmental heterogeneity.

Abstract Recombinant adeno-associated viruses (rAAVs) have emerged as promising gene therapy vectors due to their proven efficacy and safety in clinical applications. In non-human primates (NHPs), rAAVs are administered via suprachoroidal injection at a higher dose. However, high doses of rAAVs tend to increase additional safety risks. Here, we present a novel AAV capsid (AAVv128), which exhibits significantly enhanced transduction efficiency for photoreceptors and retinal pigment epithelial (RPE) cells, along with a broader distribution across the layers of retinal tissues in different animal models (mice, rabbits, and NHPs) following intraocular injection. Notably, the suprachoroidal delivery of AAVv128-anti-VEGF vector completely suppresses the Grade IV lesions in a laser-induced choroidal neovascularization (CNV) NHP model for neovascular age-related macular degeneration (nAMD). Furthermore, cryo-EM analysis at 2.1 Å resolution reveals that the critical residues of AAVv128 exhibit a more robust advantage in AAV binding, the nuclear uptake and endosome escaping. Collectively, our findings highlight the potential of AAVv128 as a next generation ocular gene therapy vector, particularly using the suprachoroidal delivery route.

With inspiration from natural systems, various soft actuators and robots have been explored in recent years with versatile applications in biomedical and engineering fields. Soft active materials with rich stimulus-responsive characteristics have been an ideal candidate to devise these soft machines by using different manufacturing technologies. Among these technologies, three-dimensional (3D) printing shows advantages in fabricating constructs with multiple materials and sophisticated architectures. In this Review, we aim to provide an overview of recent progress on 3D printing of soft materials, robotics performances, and representative applications. Typical 3D printing techniques are briefly introduced, followed by state-of-the-art advances in 3D printing of hydrogels, shape memory polymers, liquid crystalline elastomers, and their hybrids as soft actuators and robots. From the perspective of material properties, the commonly used printing techniques and action-generation principles for typical printed constructs are discussed. Actuation performances, locomotive behaviors, and representative applications of printed soft materials are summarized. The relationship between printing structures and action performances of soft actuators and robots is also briefly discussed. Finally, the advantages and limitations of each soft material are compared, and the remaining challenges and future directions in this field are prospected.

Tetrazole is widely utilized as a bioisostere for carboxylic acid in the field of medicinal chemistry and drug development, enhancing the drug-like characteristics of various molecules. Typically, tetrazoles are introduced from their nitrile precursors through late-stage functionalization. In this work, we propose a novel strategy involving the use of diversely protected, unprecedented tetrazole aldehydes as building blocks. This approach facilitates the incorporation of the tetrazole group into multicomponent reactions or other chemistries, aiding in the creation of a variety of complex, drug-like molecules. These innovative tetrazole building blocks are efficiently and directly synthesized using a Passerini three-component reaction (PT-3CR), employing cost-effective and readily available materials. We further showcase the versatility of these new tetrazole building blocks by integrating the tetrazole moiety into various multicomponent reactions (MCRs), which are already significantly employed in drug discovery. This technique represents a unique and complementary method to existing tetrazole synthesis processes. It aims to meet the growing demand for tetrazole-based compound libraries and novel scaffolds, which are challenging to synthesize through other methods.

Abstract Background Neoadjuvant therapy followed by surgery has become the standard of care for locally advanced esophageal squamous cell carcinoma (ESCC) and accurate pathological response assessment is critical to assess the therapeutic efficacy. However, it can be laborious and inconsistency between different observers may occur. Hence, we aim to develop an interpretable deep-learning model for efficient pathological response assessment following neoadjuvant therapy in ESCC. Methods This retrospective study analyzed 337 ESCC resection specimens from 2020–2021 at the Pudong-Branch (Cohort 1) and 114 from 2021–2022 at the Puxi-Branch (External Cohort 2) of Fudan University Shanghai Cancer Center. Whole slide images (WSIs) from these two cohorts were generated using different scanning machines to test the ability of the model in handling color variations. Four pathologists independently assessed the pathological response. The senior pathologists annotated tumor beds and residual tumor percentages on WSIs to determine consensus labels. Furthermore, 1850 image patches were randomly extracted from Cohort 1 WSIs and binarily classified for tumor viability. A deep-learning model employing knowledge distillation was developed to automatically classify positive patches for each WSI and estimate the viable residual tumor percentages. Spatial heatmaps were output for model explanations and visualizations. Results The approach achieved high concordance with pathologist consensus, with an R^2 of 0.8437, a RAcc_0.1 of 0.7586, a RAcc_0.3 of 0.9885, which were comparable to two senior pathologists (R^2 of 0.9202/0.9619, RAcc_0.1 of 8506/0.9425, RAcc_0.3 of 1.000/1.000) and surpassing two junior pathologists (R^2 of 0.5592/0.5474, RAcc_0.1 of 0.5287/0.5287, RAcc_0.3 of 0.9080/0.9310). Visualizations enabled the localization of residual viable tumor to augment microscopic assessment. Conclusion This work illustrates deep learning's potential for assisting pathological response assessment. Spatial heatmaps and patch examples provide intuitive explanations of model predictions, engendering clinical trust and adoption (Code and data will be available at https://github.com/WinnieLaugh/ESCC_Percentage once the paper has been conditionally accepted). Integrating interpretable computational pathology could help enhance the efficiency and consistency of tumor response assessment and empower precise oncology treatment decisions.

Abstract Deep learning‐based image registration (DLIR) has been widely developed, but it remains challenging in perceiving small and large deformations. Besides, the effectiveness of the DLIR methods was also rarely validated on the downstream tasks. In the study, a multi‐scale complexity‐aware registration network (MSCAReg‐Net) was proposed by devising a complexity‐aware technique to facilitate DLIR under a single‐resolution framework. Specifically, the complexity‐aware technique devised a multi‐scale complexity‐aware module (MSCA‐Module) to perceive deformations with distinct complexities, and employed a feature calibration module (FC‐Module) and a feature aggregation module (FA‐Module) to facilitate the MSCA‐Module by generating more distinguishable deformation features. Experimental results demonstrated the superiority of the proposed MSCAReg‐Net over the existing methods in terms of registration accuracy. Besides, other than the indices of Dice similarity coefficient (DSC) and percentage of voxels with non‐positive Jacobian determinant (|Jϕ|≤0), a comprehensive evaluation of the registration performance was performed by applying this method on a downstream task of multi‐atlas hippocampus segmentation (MAHS). Experimental results demonstrated that this method contributed to a better hippocampus segmentation over other DLIR methods, and a comparable segmentation performance with the leading SyN method. The comprehensive assessment including DSC, |Jϕ|≤0, and the downstream application on MAHS demonstrated the advances of this method.

Abstract Creatures, such as Venus flytrap and hummingbirds, capable of rapid predation through snap‐through transition, provide paradigms for the design of soft actuators and robots with fast actions. However, these artificial “snappers” usually need contact stimulations to trigger the flipping. Reported here is a constrained anisotropic poly(N‐isopropylacrylamide) hydrogel showing fast snapping upon light stimulation. This hydrogel is prepared by flow‐induced orientation of nanosheets (NSs) within a rectangular tube. The precursor containing gold nanoparticles is immediately exposed to UV light for photopolymerization to fix the ordered structure of NSs. Two ends of the slender gel are clamped to form a buckle with bistability nature, which snaps to the other side upon laser irradiation. Systematic experiments are conducted to investigate the influences of power intensity and irradiation angle of the laser, as well as thickness and buckle height of the gel, on the snapping behaviors. The fast snapping is further used to kick a plastic bead and control the switch state. Furthermore, synergetic or oscillated snapping of the gel with two buckles of opposite directions is realized by inclined irradiation of a laser or horizontal irradiation with two lasers, respectively. Such light‐steered snapping of hydrogels should merit designing soft robots, energy harvests, etc.

Layered double hydroxides (LDHs) are a class of promising cathode materials for supercapacitors. However, the bad cycling performance has always been the Achilles’ heel of LDHs‐based supercapacitors. In this contribution, a nonelectrochemical active element Scandium (Sc) is doped into NiCo‐LDHs to greatly improve the intrinsic cycling performance of active materials. The trimetallic NiCoSc‐LDHs exhibit an ultralong cycle lifespan with 40 000 charge–discharge cycles (exceeding 50 days) and a high specific capacity of 196 mAh g−1 (1695 F g−1). Sc doping greatly changes the degradation mode of NiCo‐LDHs from rapid decay in thousands of cycles to a two‐stage performance evolution, which consists of a superlong activation process of about 10 000 cycles and then extremely slow degradation. Moreover, Sc doping enhances the electrochemical activity of Ni3+, so as to not only avoid its Jahn–Teller distortion, but also perform as a structural stabilizer to alleviate the local strain of host layer. The assembled asymmetric supercapacitor delivers an ultralong cycling lifespan with 101% capacity retention even after 50 000 cycles. This work presents a new pathway to significantly improve the electrochemical performance, especially the cycling stability of LDH‐based electrodes for high‐performance supercapacitors.

The prevalence of calcific aortic valve disease (CAVD) remains substantial while there is currently no medical therapy available. Forkhead box O1 (FOXO1) is known to be involved in the pathogenesis of cardiovascular diseases, including vascular calcification and atherosclerosis; however, its specific role in calcific aortic valve disease remains to be elucidated. In this study, we identified FOXO1 significantly down-regulated in the aortic valve interstitial cells (VICs) of calcified aortic valves by investigating clinical specimens and GEO database analysis. FOXO1 silencing or inhibition promoted VICs osteogenic differentiation in vitro and aortic valve calcification in Apoe−/− mice, respectively. We identified that FOXO1 facilitated the ubiquitination and degradation of RUNX2, which process was mainly mediated by SMAD-specific E3 ubiquitin ligase 2 (SMURF2). Our discoveries unveil a heretofore unacknowledged mechanism involving the FOXO1/SMURF2/RUNX2 axis in CAVD, thereby proposing the potential therapeutic utility of FOXO1 or SMURF2 as viable strategies to impede the progression of CAVD.

Abstract Electric field-induced second harmonic generation allows electrically controlling nonlinear light-matter interactions crucial for emerging integrated photonics applications. Despite its wide presence in materials, the figures-of-merit of electric field-induced second harmonic generation are yet to be elevated to enable novel device functionalities. Here, we show that the polar skyrmions, a topological phase spontaneously formed in PbTiO3/SrTiO3 ferroelectric superlattices, exhibit a high comprehensive electric field-induced second harmonic generation performance. The second-order nonlinear susceptibility and modulation depth, measured under non-resonant 800 nm excitation, reach ~54.2 pm V−1 and ~664% V−1, respectively, and high response bandwidth (higher than 10 MHz), wide operating temperature range (up to ~400 K) and good fatigue resistance (>1010 cycles) are also demonstrated. Through combined in-situ experiments and phase-field simulations, we establish the microscopic links between the exotic polarization configuration and field-induced transition paths of the skyrmions and their electric field-induced second harmonic generation response. Our study not only presents a highly competitive thin-film material ready for constructing on-chip devices, but opens up new avenues of utilizing topological polar structures in the fields of photonics and optoelectronics.

Abstract Steering soft robots in a self-regulated manner remains a grand challenge, which often requires continuous symmetry breaking and recovery steps for persistent motion. Although structural morphology is found significant for robotic functions, geometric topology has rarely been considered and appreciated. Here we demonstrate a series of knotbots, namely hydrogel-based robots with knotted structures, capable of autonomous rolling and spinning/rotating motions. With symmetry broken by external stimuli and restored by self-regulation, the coupling between self-constraint-induced prestress and photothermal strain animates the knotbots continuously. Experiments and simulations reveal that nonequilibrium processes are regulated dynamically and cooperatively by self-constraints, active deformations, and self-shadowing effect of the photo-responsive gel. The active motions enable the knotbots to execute tasks including gear rotation and rod climbing. This work paves the way to devise advanced soft robots with self-regulated sustainable motions by harnessing the topology.

Abstract The northeastern Indian Ocean exhibits distinct hydrographic characteristics influenced by various local and remote forces. Variations in these driving factors may alter the physiochemical properties of seawater, such as dissolved oxygen levels, and affect the diversity and function of microbial communities. How the microbial communities change across water depths spanning a dissolved oxygen gradient has not been well understood. Here we employed both 16S rDNA amplicon and metagenomic sequencing approaches to study the microbial communities collected from different water depths along the E87 transect in the northeastern Indian Ocean. Samples were collected from the surface, Deep Chlorophyll Maximum (DCM), Oxygen Minimum Zone (OMZ), and bathypelagic layers. Proteobacteria were prevalent throughout the water columns, while Thermoproteota were found to be abundant in the aphotic layers. A total of 675 non-redundant metagenome-assembled genomes (MAGs) were constructed, spanning 21 bacterial and 5 archaeal phyla. The community structure and genomic information provided by this dataset offer valuable resources for the analysis of microbial biogeography and metabolism in the northeastern Indian Ocean.

To study the impact of faults on the enrichment and mobility of shale oil in the Gulong area, representative rock samples were selected in this paper. Based on geochemical data and chemical kinetics methods, coupled with shale oil enrichment and mobility analysis techniques, the shale oil generation quantity and in situ oil content were evaluated from the perspectives of shale oil generation and micro migration, and the mobility of shale oil was revealed. At the same time, the hydrocarbon expulsion efficiency (HEE) of shale was qualitatively and quantitatively characterized, combined with the development of faults. The research results indicate that the study area mainly develops organic-rich felsic (ORF)/organic-containing felsic (OCF) shale, their proportion in both wells exceeds 65%, and the resource amount is the largest in this type of lithofacies. The development of a fault controls the enrichment of shale oil, and the in situ oil content and oil saturation index (OSI) of the shale in well Y58, which is close to the fault, are significantly worse than those in well S2. Well Y58 has 9.52 mg/g and 424.83 mg/g TOC respectively, while well S2 has 11.34 mg/g and 488.73 mg/g TOC respectively. The fault enhanced the migration of shale oil, increasing the efficiency of oil expulsion. As a result, the components with weak polarity or small molecules, such as saturated hydrocarbons and low carbon number n-alkanes, are prone to migration, reducing the mobility of shale oil.

Microbial communities within oxygen minimum zones (OMZs) play crucial roles in the marine biogeochemical cycling. Arabian Sea (AS) has one of the largest OMZs among the global oceans, however, knowledge about the microbial ecology of the AS OMZ remained limited. In the present study, 44 water samples collected from six stations across the AS, spanning from the deep chlorophyll maximum (DCM) layer to 4000m depth were analyzed. High-throughput sequencing of 16S rRNA genes revealed the structural diversity of bacterial and archaeal communities, influenced primarily by depth and dissolved oxygen (DO) levels. Distinct community compositions were observed across different oxygen gradients, with shifts in the relative abundance of key taxa. Notably, Desulfosarcinaceae, UBA10353, Nitrospina, SUP05, Sva0996_marine_group, Microtrichaceae, and Nitrosopumilus emerged as bioindicator taxa in the AS hypoxic zones. Co-occurrence network analysis identified SAR324, Alteromonadaceae, and Sphingomonadaceae as keystone taxa. The spatial and depth-wise distribution patterns revealed that Desulfosarcinaceae was predominantly found in the hypoxic zones of the Arabian Sea, whereas UBA10353, Nitrospina, SUP05, Microtrichaceae and SAR324 were ubiquitous across AS, Bay of Bengal (BOB), and Eastern Tropical North Pacific (ETNP) OMZs, with OTU-level niche differentiation observed for the latter two. Functional profiling using FAPROTAX predicted higher metabolic potential for nitrogen and sulfur in the OMZ compared to other layers of the AS. Our findings provide valuable insights into the distribution, structure, and diversity of microbial communities in the AS OMZ, highlighting the ecological roles of key taxa in hypoxic environments. The established sequence database offers a foundation for further research into the complex interactions within these microbial ecosystems.

High-efficiency electromagnetic interference (EMI) shielding composite films (EMI shielding effectiveness (SE) value > 100 dB) with a small thickness are imminently desired for eliminating the serious electromagnetic wave pollution. Herein, asymmetric sandwiched silver-coated four-needle zinc oxide whisker/nanofibrillated cellulose/Ti3C2Tx (F-ZnO&Ag/NFC/Ti3C2Tx) composite films consisting of the loose F-ZnO&Ag sedimentary layer and compact upper Ti3C2Tx layer were successful fabricated by a facile one-pot vacuum filtration method in combination with gravity-induced delamination. Arising from the favorable electrical conductivity and unique asymmetric sandwich structure, electromagnetic waves can be trapped and dissipated in the F-ZnO&Ag skeletons and strongly multiply reflected between top Ti3C2Tx layer and bottom F-ZnO&Ag layers. Thereby, F-ZnO&Ag/NFC/Ti3C2Tx-30.4 exhibits the ultrahigh averaged EMI SET of 103.9 dB (the maximal value of 123.8 dB) at a low thickness of merely 209 μm, which is far superior to that of almost all the reported NFC composites at the similar thickness to date. In the real EMI shielding application test, composite films are confirmed to block signal transmission and switch off the toy car system. Such simple and high-efficiency asymmetric sandwich structure design makes a great progress towards preparing and adjusting thin EMI shielding composite films for the promising application prospects in advanced electronics and communication technology.

The ischemia–reperfusion process of a donor heart during heart transplantation leads to severe mitochondrial dysfunction, which may be the main cause of donor heart dysfunction after heart transplantation. Pyruvate carboxylase (PC), an enzyme found in mitochondria, is said to play a role in the control of oxidative stress and the function of mitochondria. This research examined the function of PC and discovered the signaling pathways controlled by PC in myocardial IRI. We induced IRI using a murine heterotopic heart transplantation model in vivo and a hypoxia–reoxygenation cell model in vitro and evaluated inflammatory responses, oxidative stress levels, mitochondrial function, and cardiomyocyte apoptosis. In both in vivo and in vitro settings, we observed a significant decrease in PC expression during myocardial IRI. PC knockdown aggravated IRI by increasing MDA content, LDH activity, TUNEL-positive cells, serum cTnI level, Bax protein expression, and the level of inflammatory cytokines and decreasing SOD activity, GPX activity, and Bcl-2 protein expression. PC overexpression yielded the opposite findings. Additional research indicated that reducing PC levels could block the Wnt/β-catenin pathway and glutamine metabolism by hindering the movement of β-catenin to the nucleus and reducing the activity of complex I and complex II, as well as ATP levels, while elevating the ratios of NADP+/NADPH and GSSG/GSH. Overall, the findings indicated that PC therapy can shield the heart from IRI during heart transplantation by regulating glutamine metabolism through the Wnt/β-catenin pathway.

Human–machine interactions (HMIs) have penetrated into various academic and industrial fields, such as robotics, virtual reality, and wearable electronics. However, the practical application of most human–machine interfaces faces notable obstacles due to their complex structure and materials, high power consumption, limited effective skin adhesion, and high cost. Herein, we report a self-powered, skin adhesive, and flexible human–machine interface based on a triboelectric nanogenerator (SSFHMI). Characterized by its simple structure and low cost, the SSFHMI can easily convert touch stimuli into a stable electrical signal at the trigger pressure from a finger touch, without requiring an external power supply. A skeleton spacer has been specially designed in order to increase the stability and homogeneity of the output signals of each TENG unit and prevent crosstalk between them. Moreover, we constructed a hydrogel adhesive interface with skin-adhesive properties to adapt to easy wear on complex human body surfaces. By integrating the SSFHMI with a microcontroller, a programmable touch operation platform has been constructed that is capable of multiple interactions. These include medical calling, music media playback, security unlocking, and electronic piano playing. This self-powered, cost-effective SSFHMI holds potential relevance for the next generation of highly integrated and sustainable portable smart electronic products and applications.

Background: This study investigated the impact of salvianolic acids, derived from Danshen, on melanoma cell growth. Specifically, we assessed the ability of salvianolic acid A (Sal A) to modulate melanoma cell proliferation. Methods: We used human melanoma A2058 and A375 cell lines to investigate the effects of Sal A on cell proliferation and death by measuring bromodeoxyuridine incorporation and lactate dehydrogenase release. We assessed cell viability and cycle progression using water soluble tetrazolium salt-1 (WST-1) mitochondrial staining and propidium iodide. Additionally, we used a phospho-kinase array to investigate intracellular kinase phosphorylation, specifically measuring the influence of Sal A on checkpoint kinase-2 (Chk-2) via western blot analysis. Results: Sal A inhibited the growth of A2058 and A375 cells dose-responsively and induced cell cycle arrest at the G2/M phase. Notably, Sal A selectively induces Chk-2 phosphorylation without affecting Chk-1, thereby degrading Chk-2-regulated genes Cdc25A and Cdc2. However, Sal A does not affect the Chk1-Cdc25C pathway. Conclusions: Salvianolic acids, especially Sal A, effectively hinder melanoma cell growth by inducing Chk-2 phosphorylation and disrupting G2/M checkpoint regulation.

In many oceanic regions, anthropogenic warming will coincide with iron (Fe) limitation. Interactive effects between warming and Fe limitation on phytoplankton physiology and biochemical function are likely, as temperature and Fe availability affect many of the same essential cellular pathways. However, we lack a clear understanding of how globally significant phytoplankton such as the picocyanobacteria Synechococcus will respond to these co-occurring stressors, and what underlying molecular mechanisms will drive this response. Moreover, ecotype-specific adaptations can lead to nuanced differences in responses between strains. In this study, Synechococcus isolates YX04-1 (oceanic) and XM-24 (coastal) from the South China Sea were acclimated to Fe limitation at two temperatures, and their physiological and proteomic responses were compared. Both strains exhibited reduced growth due to warming and Fe limitation. However, coastal XM-24 maintained relatively higher growth rates in response to warming under replete Fe, while its growth was notably more compromised under Fe limitation at both temperatures compared with YX04-1. In response to concurrent heat and Fe stress, oceanic YX04-1 was better able to adjust its photosynthetic proteins and minimize the generation of reactive oxygen species while reducing proteome Fe demand. Its intricate proteomic response likely enabled oceanic YX04-1 to mitigate some of the negative impact of warming on its growth during Fe limitation. Our study highlights how ecologically-shaped adaptations in Synechococcus strains even from proximate oceanic regions can lead to differing physiological and proteomic responses to these climate stressors.

Purpose: To investigate the pharmacokinetics and tissue distribution of VGB racemate and its single enantiomers, and explore the potential of clinic development for single enantiomer S-VGB. Methods: In the pharmacokinetics study, male Sprague-Dawley rats were gavaged with VGB racemate or its single enantiomers dosing 50, 100 or 200 mg/kg, and the blood samples were collected during 12 h at regular intervals. In the experiment of tissue distribution, VGB and its single enantiomers were administered intravenously dosing 200 mg/kg, and the tissues including heart, liver, spleen, lung and kidney, eyes, hippocampus, and prefrontal cortex were separated at different times. The concentrations of R-VGB and S-VGB in the plasma and tissues were measured using HPLC. Results: Both S-VGB and R-VGB could be detected in the plasma of rats administered with VGB racemate, reaching Cmax at approximately 0.5 h with t1/2 2–3 h. There was no significant pharmacokinetic difference between the two enantiomers when VGB racemate was given 200 mg/kg and 100 mg/kg. However, when given at the dose of 50 mg/kg, S-VGB presented a shorter t1/2 and a higher Cl/F than R-VGB, indicating a faster metabolism of S-VGB. Furthermore, when single enantiomer was administered respectively, S-VGB presented a slower metabolism than R-VGB, as indicated by a longer t1/2 and MRT but a lower Cmax. Moreover, compared with the VGB racemate, the single enantiomers S-VGB and R-VGB had shorter t1/2 and MRT, higher Cmax and AUC/D, and lower Vz/F and Cl/F, indicating the stronger oral absorption and faster metabolism of single enantiomer. In addition, regardless of VGB racemate administration or single enantiomer administration, S-VGB and R-VGB had similar characteristics in tissue distribution, and the content of S-VGB in hippocampus, prefrontal cortex and liver was much higher than that of R-VGB. Conclusions: Although there is no transformation between S-VGB and R-VGB in vivo, those two enantiomers display certain disparities in the pharmacokinetics and tissue distribution, and interact with each other. These findings might be a possible interpretation for the pharmacological and toxic effects of VGB and a potential direction for the development and optimization of the single enantiomer S-VGB.

[This corrects the article DOI: 10.1371/journal.pone.0268007.].

Enhancing the alkalinity of the ocean is a promising approach for CO2 removal by promoting marine carbon sequestration. Olivine is a key candidate material for enhancing alkalinity owing to its release of silicates when dissolved in seawater. These released compounds serve as crucial nutrients for phytoplankton such as diatoms to foster their growth, which in turn accelerates olivine dissolution and further enhances carbon sequestration. In this study, we investigated the short-term synergistic CO2 removal effects of an olivine–diatom coculture system. Over a 6-day incubation period, the olivine dissolution was 92% to 144% higher in the olivine–diatom groups compared with the olivine-only groups. The olivine-only groups achieved a CO2 removal efficiency of 5.15% to 5.49%, while the olivine–diatom groups achieved a CO2 removal efficiency of 8.84% to 14.44%. Adding olivine was found to increase the total alkalinity by 70 to 100 μM and the diatom abundance by 26.4% to 58.4%. Diatom growth and the fixed carbon content were greatly enhanced, particularly during the later silicate-depleted stage when the Si:C ratio significantly exceeded that of groups without olivine. This mutually beneficial olivine–diatom coculture system offers a highly efficient CO2 removal strategy for addressing climate change. The results of this study contribute to our understanding of carbonate and biological carbon pump processes.

Metal(loid) pollution has emerged as a pressing environmental issue in agriculture, garnering extensive public attention. Metal(loid)s are potentially toxic substances that infiltrate the soil through diverse pathways, leading to food chain contamination via plant uptake and subsequent animal exposure. This poses a serious threat to environmental quality, food security, and human health. Hence, the remediation of metal(loid)-contaminated agricultural soil is an urgent concern demanding immediate attention. Presently, the majority of research papers concentrate on established, isolated remediation technologies, often overlooking comprehensive field management approaches. It is imperative to provide a comprehensive summary of remediation technologies and identify future development directions. This review aims to comprehensively summarize a range of soil remediation and enhancement technologies, incorporating insights from multiple disciplines including physics, chemistry, biology, and their interdisciplinary intersections. The review examines the mechanisms of action, suitable scenarios, advantages, disadvantages, and benefits associated with each remediation technology. Particularly relevant is the examination of metal(loid) sources, as well as the mechanisms behind both established and innovative, efficient remediation and enhancement technologies. Additionally, the future evolution of remediation technologies are considered with the aim of offering a scientific research foundation and inspiration to fellow researchers. This is intended to facilitate the advancement of remediation technologies and establish a robust foundation for sustainable development of soil. [ABSTRACT FROM AUTHOR]

In many oceanic regions, anthropogenic warming will coincide with iron (Fe) limitation. Interactive effects between warming and Fe limitation on phytoplankton physiology and biochemical function are likely, as temperature and Fe availability affect many of the same essential cellular pathways. However, we lack a clear understanding of how globally significant phytoplankton such as the picocyanobacteria Synechococcus will respond to these co-occurring stressors, and what underlying molecular mechanisms will drive this response. Moreover, ecotype-specific adaptations can lead to nuanced differences in responses between strains. In this study, Synechococcus isolates YX04-1 (oceanic) and XM-24 (coastal) from the South China Sea were acclimated to Fe limitation at two temperatures, and their physiological and proteomic responses were compared. Both strains exhibited reduced growth due to warming and Fe limitation. However, coastal XM-24 maintained relatively higher growth rates in response to warming under replete Fe, while its growth was notably more compromised under Fe limitation at both temperatures compared with YX04-1. In response to concurrent heat and Fe stress, oceanic YX04-1 was better able to adjust its photosynthetic proteins and minimize the generation of reactive oxygen species while reducing proteome Fe demand. Its intricate proteomic response likely enabled oceanic YX04-1 to mitigate some of the negative impact of warming on its growth during Fe limitation. Our study highlights how ecologically-shaped adaptations in Synechococcus strains even from proximate oceanic regions can lead to differing physiological and proteomic responses to these climate stressors. [ABSTRACT FROM AUTHOR]

TCP is a widely distributed, essential plant transcription factor that regulates plant growth and development. An in-depth study of TCP genes in Dendrobium nobile, a crucial parent in genetic breeding and an excellent model material to explore perianth development in Dendrobium, has not been conducted. We identified 23 DnTCP genes unevenly distributed across 19 chromosomes and classified them as Class I PCF (12 members), Class II: CIN (10 members), and CYC/TB1 (1 member) based on the conserved domain and phylogenetic analysis. Most DnTCPs in the same subclade had similar gene and motif structures. Segmental duplication was the predominant duplication event for TCP genes, and no tandem duplication was observed. Seven genes in the CIN subclade had potential miR319 and -159 target sites. Cis-acting element analysis showed that most DnTCP genes contained many developmental stress-, light-, and phytohormone-responsive elements in their promoter regions. Distinct expression patterns were observed among the 23 DnTCP genes, suggesting that these genes have diverse regulatory roles at different stages of perianth development or in different organs. For instance, DnTCP4 and DnTCP18 play a role in early perianth development, and DnTCP5 and DnTCP10 are significantly expressed during late perianth development. DnTCP17, 20, 21, and 22 are the most likely to be involved in perianth and leaf development. DnTCP11 was significantly expressed in the gynandrium. Specially, MADS-specific binding sites were present in most DnTCP genes putative promoters, and two Class I DnTCPs were in the nucleus and interacted with each other or with the MADSbox. The interactions between TCP and the MADS-box have been described for the first time in orchids, which broadens our understanding of the regulatory network of TCP involved in perianth development in orchids. [ABSTRACT FROM AUTHOR]

Background: Early identification of patients at high risk of operative mortality is important for acute type A aortic dissection (TAAD). We aimed to investigate whether patients with distinct risk stratifications respond differently to anti-inflammatory pharmacotherapy. Methods: From 13 cardiovascular hospitals, 3110 surgically repaired TAAD patients were randomly divided into a training set (70%) and a test set (30%) to develop and validate a risk model to predict operative mortality using extreme gradient boosting. Performance was measured by the area under the receiver operating characteristic curve (AUC). Subgroup analyses were performed by risk stratifications (low versus middle-high risk) and anti-inflammatory pharmacotherapy (absence versus presence of ulinastatin use). Results: A simplified risk model was developed for predicting operative mortality, consisting of the top ten features of importance: platelet-leukocyte ratio, D-dimer, activated partial thromboplastin time, urea nitrogen, glucose, lactate, base excess, hemoglobin, albumin, and creatine kinase-MB, which displayed a superior discrimination ability (AUC: 0.943, 95 % CI 0.928–0.958 and 0.884, 95 % CI 0.836–0.932) in the derivation and validation cohorts, respectively. Ulinastatin use was not associated with decreased risk of operative mortality among each risk stratification, however, ulinastatin use was associated with a shorter mechanical ventilation duration among patients with middle-high risk (defined as risk probability >5.0 %) (β −1.6 h, 95 % CI [−3.1, −0.1] hours; P = 0.048). Conclusion: This risk model reflecting inflammatory, coagulation, and metabolic pathways achieved acceptable predictive performances of operative mortality following TAAD surgery, which will contribute to individualized anti-inflammatory pharmacotherapy.

Highly porous and nanostructured metal-organic frameworks (MOFs) have fascinated enormous interest as electrode active materials for electrochemical energy storage systems, whereas their practical applications are significantly hindered by their relative inferior energy density and cyclability. In this study, MoS2 with layered structure was successfully incorporated onto hierarchical Ni-MOFs via a facile hydrothermal approach. Moreover, sodium cations were introduced to improve electronic conductivity. The resulting nanocomposites (sodium ions and MoS2 incorporated Ni-MOFs) exhibited hierarchical porous structures with varying dimensions, offering increased volume for charge storage and diffusion channels for electrolyte ions. Benefiting from the unique topological architectures, the as-synthesized porous nanocomposites delivered an excellent supercapacitive performance, achieving a superlative energy of 33.33 Wh kg−1 and a power density of 3390 W kg−1. Furthermore, the as-fabricated symmetric supercapacitor device delivered a remarkable cycling durability where the acquired outstanding capacitance retention was 97.42% and coulombic efficiency was 97.82% respectively over more than 10,000 cycles in an aqueous electrolyte.