Enhancement of motor functional recovery in thoracic spinal cord injury: voluntary wheel running versus forced treadmill exercise.

JOURNAL/nrgr/04.03/01300535-202503000-00028/figure1/v/2024-06-17T092413Z/r/image-tiff Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery and morphological changes following thoracic contusive spinal cord injury. After a 7-day recovery period after spinal cord injury, mice were assigned to either a trained group (10 weeks of voluntary running wheel or forced treadmill exercise) or an untrained group. Bi-weekly assessments revealed that the exercise-trained group, particularly the voluntary wheel exercise subgroup, displayed significantly improved locomotor recovery, more plasticity of dopaminergic and serotonin modulation compared with the untrained group. Additionally, exercise interventions led to gait pattern restoration and enhanced transcranial magnetic motor-evoked potentials. Despite consistent injury areas across groups, exercise training promoted terminal innervation of descending axons. In summary, voluntary wheel exercise shows promise for enhancing outcomes after thoracic contusive spinal cord injury, emphasizing the role of exercise modality in promoting recovery and morphological changes in spinal cord injuries. Our findings will influence future strategies for rehabilitation exercises, restoring functional movement after spinal cord injury.

Chondroitinase ABC combined with Schwann cell transplantation enhances restoration of neural connection and functional recovery following acute and chronic spinal cord injury.

JOURNAL/nrgr/04.03/01300535-202505000-00029/figure1/v/2024-07-28T173839Z/r/image-tiff Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties. A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury. A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity, and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar, thus limiting axonal reentry into the host spinal cord. Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury. We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders, Schwann cells migrated for considerable distances in both rostral and caudal directions. Such Schwann cell migration led to enhanced axonal regrowth, including the serotonergic and dopaminergic axons originating from supraspinal regions, and promoted recovery of locomotor and urinary bladder functions. Importantly, the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury, even when treatment was delayed for 3 months to mimic chronic spinal cord injury. These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.

Carbon emissions in China's steel industry from a life cycle perspective: Carbon footprint insights.

China is the most important steel producer in the world, and its steel industry is one of the most carbon-intensive industries in China. Consequently, research on carbon emissions from the steel industry is crucial for China to achieve carbon neutrality and meet its sustainable global development goals. We constructed a carbon dioxide (CO2) emission model for China's iron and steel industry from a life cycle perspective, conducted an empirical analysis based on data from 2019, and calculated the CO2 emissions of the industry throughout its life cycle. Key emission reduction factors were identified using sensitivity analysis. The results demonstrated that the CO2 emission intensity of the steel industry was 2.33 ton CO2/ton, and the production and manufacturing stages were the main sources of CO2 emissions, accounting for 89.84% of the total steel life-cycle emissions. Notably, fossil fuel combustion had the highest sensitivity to steel CO2 emissions, with a sensitivity coefficient of 0.68, reducing the amount of fossil fuel combustion by 20% and carbon emissions by 13.60%. The sensitivities of power structure optimization and scrap consumption were similar, while that of the transportation structure adjustment was the lowest, with a sensitivity coefficient of less than 0.1. Given the current strategic goals of peak carbon and carbon neutrality, it is in the best interest of the Chinese government to actively promote energy-saving and low-carbon technologies, increase the ratio of scrap steel to steelmaking, and build a new power system.

Acarbose enhances the efficacy of immunotherapy against solid tumours by modulating the gut microbiota.

The crucial role of gut microbiota in shaping immunotherapy outcomes has prompted investigations into potential modulators. Here we show that oral administration of acarbose significantly increases the anti-tumour response to anti-PD-1 therapy in female tumour-bearing mice. Acarbose modulates the gut microbiota composition and tryptophan metabolism, thereby contributing to changes in chemokine expression and increased T cell infiltration within tumours. We identify CD8+ T cells as pivotal components determining the efficacy of the combined therapy. Further experiments reveal that acarbose promotes CD8+ T cell recruitment through the CXCL10-CXCR3 pathway. Faecal microbiota transplantation and gut microbiota depletion assays indicate that the effects of acarbose are dependent on the gut microbiota. Specifically, acarbose enhances the efficacy of anti-PD-1 therapy via the tryptophan catabolite indoleacetate, which promotes CXCL10 expression and thus facilitates CD8+ T cell recruitment, sensitizing tumours to anti-PD-1 therapy. The bacterial species Bifidobacterium infantis, which is enriched by acarbose, also improves response to anti-PD-1 therapy. Together, our study endorses the potential combination of acarbose and anti-PD-1 for cancer immunotherapy.

NDR1/FBXO11 promotes phosphorylation-mediated ubiquitination of ß-catenin to suppress metastasis in prostate cancer.

Background: Prostate cancer progression hinges on ß-catenin's stability and activity, a key factor in epithelial-mesenchymal transition (EMT) and metastasis. This study delves into NDR1-dependent phosphorylation's impact on ß-catenin via FBXO11, an E3 ubiquitin ligase, in prostate cancer cells. Methods: Human prostate cancer cell lines underwent various in vitro assays, including real-time PCR, Western blotting, immunoprecipitation, immunofluorescence, and protein stability assays, to explore ß-catenin's interactions and post-translational modifications. NDR1 modulation's in vivo efficacy was assessed using a nude mice lung metastasis model. Small-molecule screening identified a potential NDR1 activator, aNDR1, tested for its effects on metastasis via in vitro and in vivo assays. Results: NDR1 phosphorylated ß-catenin at Ser33/37, facilitating its interaction with FBXO11. This led to FBXO11-mediated ubiquitination and cytoplasmic degradation of ß-catenin, while the NDR1-FBXO11 complex impeded ß-catenin nuclear translocation by inducing JNK2 ubiquitination. Thus, NDR1 and FBXO11 jointly regulate ß-catenin activity in prostate cancer cells through dual phosphorylation-driven ubiquitination, potentially suppressing EMT. Reduced NDR1 expression inhibited FBXO11 and ß-catenin phosphorylation, diminishing ß-catenin and JNK2 ubiquitination, promoting EMT and enhancing prostate cancer cell metastasis. The inhibitory effects of aNDR1 on prostate cancer metastasis were validated. Conclusion: The NDR1/FBXO11 axis outlines a non-canonical ß-catenin degradation pathway crucial in regulating EMT and prostate cancer cell metastasis. NDR1 activation, particularly with aNDR1, could offer a promising therapeutic avenue against prostate cancer metastasis.

PNLDC1 catalysis and postnatal germline function are required for piRNA trimming, LINE1 silencing, and spermatogenesis in mice.

PIWI-interacting RNAs (piRNAs) play critical and conserved roles in transposon silencing and gene regulation in the animal germline. Three distinct piRNA populations are present during mouse spermatogenesis: fetal piRNAs in fetal/perinatal testes, pre-pachytene and pachytene piRNAs in postnatal testes. PNLDC1 is required for piRNA 3' end maturation in multiple species. However, whether PNLDC1 is the bona fide piRNA trimmer and the physiological role of 3' trimming of different piRNA populations in spermatogenesis in mammals remain unclear. Here, by inactivating Pnldc1 exonuclease activity in vitro and in mice, we reveal that the PNLDC1 trimmer activity is essential for spermatogenesis and male fertility. PNLDC1 catalytic activity is required for both fetal and postnatal piRNA 3' end trimming. Despite this, postnatal piRNA trimming but not fetal piRNA trimming is critical for LINE1 transposon silencing. Furthermore, conditional inactivation of Pnldc1 in postnatal germ cells causes LINE1 transposon de-repression and spermatogenic arrest in mice, indicating that germline-specific postnatal piRNA trimming is essential for transposon silencing and germ cell development. Our findings highlight the germ cell-intrinsic role of PNLDC1 and piRNA trimming in mammals to safeguard the germline genome and promote fertility.

Changes in insulin utilization in China from 2020 to 2022.

AIM: To assess the variation in patterns of use of insulin and other antidiabetic medicines across China, both geographically and over time. MATERIALS AND METHODS: Nationally, we calculated the relative change in antidiabetic medicine purchases between the first and last quarters of 2020 through 2022 based on the number of defined daily doses procured per quarter. We used annual data to analyse differences in antidiabetic medicine use and patterns across seven regions of China. Considering large regional variations, we used multifactor linear regression to preliminarily explore the possible factors influencing this variation. RESULTS: Nationally, the procurement of antidiabetic medicines and insulin increased from 2020 to 2022, while the proportion of insulin among antidiabetic medicines remained stable at approximately 22%. Among all insulins, premixed insulin (human) was ranked first. Of the three subgroups of insulin, analogues were the most preferred and had the largest procurement, but different categories showed different trends in terms of purchases and proporation. Regionally, the growth rate of antidiabetic medicines, the proportion of insulin procurement and the preferred types of insulin across the seven regions were different. Regarding preliminary influencing factors, the level of education and owning a domestically funded producer had a positive effect on insulin procurement. CONCLUSIONS: From 2020 to 2022, the procurement of insulin increased, which may be due to the increased attention for diabetes from the country and residents.However, the proportion of insulin among all antidiabetic medicines was essentially unchanged, while the use of some non-insulin hypoglycemic drugs increased significantly, especially the SGLT2i and GLP-1 RA. Given the economic and cultural diversity, Insulin procurement and utilization patterns varied greatly across the regions. Owning domestic enterprises potentially influences the procurement of insulin. Enhancing education to further improve the self-management of patients with diabetes is essential.

Role of Exercise on Neuropathic Pain in Preclinical Models: Perspectives for Neuroglia.

The benefits of exercise on neuropathic pain (NP) have been demonstrated in numerous studies. In recent studies, inflammation, neurotrophins, neurotransmitters, and endogenous opioids are considered as the main mechanisms. However, the role of exercise in alleviating NP remains unclear. Neuroglia, widely distributed in both the central and peripheral nervous systems, perform functions such as support, repair, immune response, and maintenance of normal neuronal activity. A large number of studies have shown that neuroglia play an important role in the occurrence and development of NP, and exercise can alleviate NP by regulating neuroglia. This article reviewed the involvement of neuroglia in the development of NP and their role in the exercise treatment of NP, intending to provide a theoretical basis for the exercise treatment strategy of NP.

Sustainable Natural Resources for Aphid Management: ß-Ionone and Its Derivatives as Promising Ecofriendly Botanical-Based Products.

ß-Ionone, sustainably derived from Petunia hybrida as a natural bioresource, was identified as a lead compound for integrated aphid management. A series of ß-ionone derivatives containing ester groups were designed and synthesized for the purpose of discovering renewable botanical-based products. The odorant-binding protein (OBP) binding test indicated that ß-ionone and its derivatives displayed binding affinities with Acyrthosiphon pisum OBP9 (ApisOBP9) and Harmonia axyridis OBP15 (HaxyOBP15). Bioactivity assays revealed that most ß-ionone derivatives exhibited a higher repellent activity than that of ß-ionone. ß-Ionone and derivatives 4g and 4l displayed attractiveness to H. axyridis. Specifically, 4g was a highly promising derivative, possessing good repellent activity against A. pisum and attractiveness to H. axyridis. Molecular dynamics simulations revealed that integrating the hydrophobic ester group into the ß-ionone framework strengthened the van der Waals interactions of 4g with ApisOBP9/HaxyOBP15, improving the binding affinity with OBPs and producing higher push-pull activity than ß-ionone; 4g also had low toxicity toward nontarget organisms. Thus, 4g is a potential ecofriendly, botanical-based option for aphid management.

Selection of Reference Genes of Flower Development in Ludisia discolor.

Background: RT-qPCR is a powerful strategy for recognizing the most appropriate reference genes, which can successfully minimize experimental mistakes through accurate normalization. Ludisia discolor, recognized for its ornamental value, features little, distinctive blossoms with twisted lips and gynostemium showing chiral asymmetry, together with striking blood-red fallen leaves periodically marked with golden blood vessels. Methods and Results: To ensure the accuracy of qRT-PCR, selecting appropriate reference genes for quantifying target gene expression levels is essential. This study aims to identify stable reference genes during the development of L. discolor. In this study, the entire floral buds, including the lips and gynostemium from different development stages, were taken as materials. Based upon the transcriptome information of L. discolor, nine housekeeping genes, ACT, HIS, EF1-α1, EF1-α2, PP2A, UBQ1, UBQ2, UBQ3, and TUB, were selected in this research study as prospect interior referral genes. The expression of these nine genes were found by RT-qPCR and afterwards comprehensively examined by four software options: geNorm, NormFinder, BestKeeper, and ΔCt. The outcomes of the analysis showed that ACT was the most steady gene, which could be the most effective inner referral gene for the expression evaluation of flower advancement in L. discolor. Conclusions: The results of this study will contribute to the molecular biology research of flower development in L. discolor and closely related species.

Tissue inhibitor of metalloproteinase (TIMP)-1 predicts failure of recovery of ejection fraction in acute heart failure with reduced ejection fraction.

BACKGROUND: Heart failure (HF) with improved ejection fraction (HFimpEF) is a recently identified phenotype of HF, which had better cardiovascular outcomes compared with persistent HF with reduced ejection fraction (HFrEF). The present study aimed to investigate the predictive value of tissue inhibitor of metalloproteinase (TIMP)-1 and matrix metalloproteinases-9 (MMP-9) in the recovery of left ventricular ejection fraction (LVEF). METHODS: Subjects who presented with acute decompensated HF and reduced LVEF of ≤40% were eligible for this study. HFimpEF was defined by a follow-up LVEF >40% and a ≥10% improvement in LVEF. Overnight fasting N-terminal pro-brain natriuretic peptide (NT-proBNP), MMP-9 and TIMP-1 were measured within 24 hours before discharge. The study participants were followed for up to 5 years. RESULTS: Among a total of 91 participants (70.1±16.2 years, baseline LVEF 28.9±7.6%), 19 (20.8%) of them had HFimpEF and 72 (79.2%) had persistent HFrEF at 6 months. The receiver operating characteristic curve analyses showed the area under curve measures for TIMP-1, MMP-9 and NT-proBNP in the prediction of HFimpEF were 0.69, 0.52 and 0.65, respectively. TIMP-1 was negatively correlated with HFimpEF as continuous variables (OR per 1-SD and 95% CI 0.99 (0.98 to 1.00)) and categorical variables (cut-off value 200.68 ng/mL, OR and 95% CI 0.16 (0.05 to 0.54)) after adjustment of confounding factors. During a mean follow-up duration 34.8 months, patients with HFimpEF will have better long-term survival than those with persistent HFrEF. CONCLUSIONS: In subjects with decompensated HFrEF, TIMP-1, but not MMP-9 was associated with the reverse remodelling in LVEF. In addition, patients with HFimpEF would have better long-term survival.

ELK4 targets CHMP6 to inhibit ferroptosis and enhance malignant properties of skin cutaneous melanoma cells.

Ferroptosis, a key factor in tumor progression, is poorly understood at the molecular level. This study investigates how ELK4 and CHMP6 regulate skin cutaneous melanoma (SKCM) cell proliferation and ferroptosis. Analysis of TCGA data reveals high expression of ELK4 and CHMP6 in SKCM. Overexpression of ELK4 or CHMP6 enhances cell proliferation, invasion, and migration while reducing ROS and Fe2 + levels. It also increases GPX4 and xCT expression and decreases ACSL4 levels in SKCM cells. The opposite effects are observed with ELK4 or CHMP6 knockdown. ELK4 binds to the CHMP6 promoter, promoting CHMP6 transcription. Knockdown of CHMP6 reverses the oncogenic effects of ELK4 overexpression. In conclusion, ELK4 enhances proliferation, invasion, and migration while inhibiting ferroptosis in SKCM cells by upregulating CHMP6 transcription. This study sheds light on the intricate mechanisms involved in SKCM progression and identifies potential therapeutic targets in melanoma treatment.

Mixture effect of parental exposure to triazophos and fenvalerate on the early development of zebrafish offspring.

Triazophos (TRI) and fenvalerate (FEN) have been extensively used in the world and frequently coexist in the water environments, might pose health risk to aquatic species. However, investigations of their mixture toxic effects on offspring after parental exposure have been neglected, especially for aquatic vertebrates such fish. To address this knowledge gap, parental zebrafish (F0 generation) were exposed to TRI, FEN and their mixture for 60 days, as well as the embryos (F1 generation) were hatched without or with continued corresponding exposures at the same concentrations until 7 days post fertilization. The results exhibited that exposure to TRI and FEN altered the expression levels of biomarkers associated with several biological processes, such as apoptosis and inflammatory response. Compared to individual exposure in the F1 generation, the co-exposure to TRI and FEN resulted in increased the expression of T4 and cc-chem mRNA and decreased the expression of ROS, trα, il-8, and gpx mRNA when the F0 generation was similarly exposed. These results revealed that the co-exposure to TRI and FEN has detrimental effects on fish progeny following parental exposure, even if the progeny are not directly exposed to the pesticides, and such negative effects may be intensified if the offspring continue to be exposed. This study enhances the understanding of the harmful impacts of parental exposure to the pesticide mixture on descendants and holds implications for the ecological risk assessment of pesticide mixtures in aquatic vertebrates. Further mechanistic studies are necessary to gain a deeper insight into the mixture effects of pesticides and other kinds of pollutants on subsequent offspring following parental exposure.

Main-group element-boosted oxygen electrocatalysis of Cu-N-C sites for zinc-air battery with cycling over 5000 h.

Developing highly active and durable air cathode catalysts is crucial yet challenging for rechargeable zinc-air batteries. Herein, a size-adjustable, flexible, and self-standing carbon membrane catalyst encapsulating adjacent Cu/Na dual-atom sites is prepared using a solution blow spinning technique combined with a pyrolysis strategy. The intrinsic activity of the Cu-N4 site is boosted by the neighboring Na-containing functional group, which enhances O2 adsorption and optimizes the rate-determining step of O2 activation (*O2 → *OOH) during the oxygen reduction reaction process. Meanwhile, the Cu-N4 sites are encapsulated within carbon nanofibers and anchored by the carbon matrix to form a C2-Cu-N4 configuration, thereby reinforcing the stability of the Cu centers. Moreover, the introduction of Na-containing functional groups on the carbon atoms significantly reduces the positive charge on their outer shell C atoms, rendering the carbon skeletons less susceptible to corrosion by oxygen species and further preventing the dissolution of Cu centers. Under these multi-type regulations, the zinc-air battery with Cu/Na-carbon membrane catalyst as the air cathode demonstrates long-term discharge/charge cycle stability of over 5000 h. This considerable stability improvement represents a critical step towards developing Cu-N4 active sites modified with the neighboring main-group metal-containing functional groups to overcome the durability barriers of zinc-air batteries for future practical applications.

On-chip multifunctional metasurfaces with full-parametric multiplexed Jones matrix.

On-chip metasurface for guided wave radiation works as an upgrade of conventional grating couplers, enriching the interconnection between guided wave and free-space optical field. However, the number of controllable parameters in equivalent Jones matrix of on-chip metasurface is limited that restricts the channels for multiplexing. Here, a supercell design based on detour phase and geometric phase has been proposed to reach full-parametric modulation of Jones matrix. As proof of concept, four independent sets of amplitude-phase channels have been experimentally demonstrated through a single on-chip metasurface. Moreover, through joint modulation of three phase mechanisms including detour phase, geometric phase and propagation phase, the Jones matrix could be decoupled from forward- and backward-propagating guided waves for direction multiplexing. This work paves the way for guided wave radiation towards high-capacity multiplexing and may further extend its application in optical communications, optical displays and augmented/virtual reality.

GLT-1 downregulation in hippocampal astrocytes induced by type 2 diabetes contributes to postoperative cognitive dysfunction in adult mice.

AIMS: Type 2 diabetes mellitus (T2DM) is related to an increased risk of postoperative cognitive dysfunction (POCD), which may be caused by neuronal hyperexcitability. Astrocyte glutamate transporter 1 (GLT-1) plays a crucial role in regulating neuron excitability. We investigated if T2DM would magnify the increased neuronal excitability induced by anesthesia/surgery (A/S) and lead to POCD in young adult mice, and if so, determined whether these effects were associated with GLT-1 expression. METHODS: T2DM model was induced by high fat diet (HFD) and injecting STZ. Then, we evaluated the spatial learning and memory of T2DM mice after A/S with the novel object recognition test (NORT) and object location test (OLT). Western blotting and immunofluorescence were used to analyze the expression levels of GLT-1 and neuronal excitability. Oxidative stress reaction and neuronal apoptosis were detected with SOD2 expression, MMP level, and Tunel staining. Hippocampal functional synaptic plasticity was assessed with long-term potentiation (LTP). In the intervention study, we overexpressed hippocampal astrocyte GLT-1 in GFAP-Cre mice. Besides, AAV-Camkllα-hM4Di-mCherry was injected to inhibit neuronal hyperexcitability in CA1 region. RESULTS: Our study found T2DM but not A/S reduced GLT-1 expression in hippocampal astrocytes. Interestingly, GLT-1 deficiency alone couldn't lead to cognitive decline, but the downregulation of GLT-1 in T2DM mice obviously enhanced increased hippocampal glutamatergic neuron excitability induced by A/S. The hyperexcitability caused neuronal apoptosis and cognitive impairment. Overexpression of GLT-1 rescued postoperative cognitive dysfunction, glutamatergic neuron hyperexcitability, oxidative stress reaction, and apoptosis in hippocampus. Moreover, chemogenetic inhibition of hippocampal glutamatergic neurons reduced oxidative stress and apoptosis and alleviated postoperative cognitive dysfunction. CONCLUSIONS: These findings suggest that the adult mice with type 2 diabetes are at an increased risk of developing POCD, perhaps due to the downregulation of GLT-1 in hippocampal astrocytes, which enhances increased glutamatergic neuron excitability induced by A/S and leads to oxidative stress reaction, and neuronal apoptosis.

OsNF-YB7 inactivates OsGLK1 to inhibit chlorophyll biosynthesis in rice embryo.

As a master regulator of seed development, Leafy Cotyledon 1 (LEC1) promotes chlorophyll (Chl) biosynthesis in Arabidopsis, but the mechanism underlying this remains poorly understood. Here, we found that loss of function of OsNF-YB7, a LEC1 homolog of rice, leads to chlorophyllous embryo, indicating that OsNF-YB7 plays an opposite role in Chl biosynthesis in rice compared with that in Arabidopsis. OsNF-YB7 regulates the expression of a group of genes responsible for Chl biosynthesis and photosynthesis by directly binding to their promoters. In addition, OsNF-YB7 interacts with Golden 2-Like 1 (OsGLK1) to inhibit the transactivation activity of OsGLK1, a key regulator of Chl biosynthesis. Moreover, OsNF-YB7 can directly repress OsGLK1 expression by recognizing its promoter in vivo, indicating the involvement of OsNF-YB7 in multiple regulatory layers of Chl biosynthesis in rice embryo. We propose that OsNF-YB7 functions as a transcriptional repressor to regulate Chl biosynthesis in rice embryo.

Comparative Analysis of Adaptation Behaviors of Different Types of Drivers to Steer-by-Wire Systems.

As one of the advanced automotive chassis technologies, the steer-by-wire system offers a high level of precision, responsiveness, and controllability in the driving experience. It can also adjust and optimize parameters to adapt to the preferences of different drivers. However, when faced with the steer-by-wire system, both experienced drivers and novice drivers are in the novice stage, exhibiting learning or adaptation behaviors when using this steering system. In this paper, a small-scale pilot evaluation was conducted by means of a questionnaire survey and driving-simulator experiment, and the learning behavior and adaptability of four experienced and four novice drivers to the steer-by-wire system were analyzed when using the traditional steering system. The study found that experienced drivers show significant changes in their adaptation to the steering system, mainly due to their habitual driving with traditional steering systems. In contrast, novice drivers show no significant changes in their adaptation to the steering system, which is attributed to their lack of driving experience and skills, resulting in less sensitivity to changes in the steering system. Additionally, the study found that novice drivers under the steer-by-wire system grasp control over speed and steering-wheel angle more quickly. This research provides a reference for improving drivers' learning and adaptation abilities to the steer-by-wire system and optimizing the design of the steer-by-wire system.

Long-term expanded hepatic progenitor cells ameliorate D-GalN/LPS-induced acute liver failure through repolarizing M1 macrophage to M2-Like phenotype via activation of the IL-10/JAK2/STAT3 signaling pathway.

Acute liver failure (ALF) is a devastating liver disease characterized by the rapid deterioration of hepatocytes, which causes a series of clinical complications, including hepatic dysfunction, coagulopathy, encephalopathy, and multiorgan failure. Cell-based therapy is a promising alternative as it can bridge patients until their livers regenerate, releasing immunomodulatory molecules to suppress inflammation. This study reports an iPSCs-derived long-term expanded hepatic progenitor cell (LTHepPCs), which can differentiate into hepatocyte-like cells (HLCs) in vivo. When introduced into drug-induced ALF models, LTHepPCs mitigate liver damage by modulating the local immune microenvironment. This is achieved by shifting macrophages/Kupffer cells towards an anti-inflammatory state, resulting in a decrease in the expression of inflammatory cytokines such as TNF-a, IL-1ß, and IL-8, and an increase in the expression of anti-inflammatory cytokines such as IL-10 and ARG-1. In vitro co-culturing of THP-1 or mBMDMs with LTHepPCs suggested that LTHepPCs could activate the anti-inflammatory state of macrophages/Kupffer cells via the IL-10/JAK2/STAT3 signaling pathway. Therefore, LTHepPC transplantation is a promising therapy for ALF patients.

Transport and retention of COVID-19-related antiviral drugs in saturated porous media under various hydrochemical conditions.

Antiviral drugs have garnered considerable attention, particularly in the global battle against the COVID-19 pandemic, amid heightened concerns regarding environmentally acquired antiviral resistance. A comprehensive understanding of their transport in subsurface environments is imperative for accurately predicting their environmental fate and risks. This study investigated the mobility and retention characteristics of six COVID-19 antiviral drugs in saturated quartz sand columns. Results showed that the mobility of the drugs was primarily contingent on their hydrophobicity, with ribavirin and favipiravir exhibiting the highest transportability, while arbidol displaying the greatest retention. The transport characteristics of ribavirin and favipiravir remained largely unaffected by pH, whereas the retention of the other four antivirals remained consistently minimal under alkaline conditions. Elevating ionic strength marginally facilitated the transport of these antivirals, while the presence of Ca2+ notably enhanced their retention in quartz sand compared to Na+. Ribavirin and remdesivir warrant particular attention due to their relatively high transportability and propensity for environmentally acquired antiviral resistance. These findings contribute to an enhanced understanding of the leachate potential and transport of COVID-19-related antivirals in sandy porous media, furnishing fundamental data for predicting their environmental fate and associated risks.