TLR4 TIR domain and nucleolin GAR domain synergistically mediate RSV infection and induce neuronal inflammatory damage in SH-SY5Y cells.

Previous research results of our group showed that Toll-like receptor 4 (TLR4) and nucleolin synergistically mediate respiratory syncytial virus (RSV) infection in human central neuron cells, but the specific mechanism remains unclear. Here we designed and synthesized lentiviruses with TIR (674-815 aa), TLR4 (del 674-815 aa), GAR (645-707 aa), and NCL (del 645-707 aa) domains, and obtained stable overexpression cell lines by drug screening, and subsequently infected RSV at different time points. Laser confocal microscopy and coimmunoprecipitation were used for the observation of co-localization and interaction of TIR/GAR domains. Western blot analysis was used for the detection of p-NF-κB and LC3 protein expression. Real-time PCR was used for the detection of TLR4/NCL mRNA expression. ELISA assay was used to measure IL-6, IL-1ß, and TNF-α concentrations and flow cytometric analysis was used for the study of apoptosis. Our results suggest that overexpression of TIR and GAR domains can exacerbate apoptosis and autophagy, and that TIR and GAR domains can synergistically mediate RSV infection and activate the NF-κB signaling pathway, which regulates the secretion of downstream inflammatory factors, such as IL-6, IL-1ß, and TNF-α, and ultimately leads to neuronal inflammatory injury.

Utility of polygenic scores across diverse diseases in a hospital cohort for predictive modeling.

Polygenic scores estimate genetic susceptibility to diseases. We systematically calculated polygenic scores across 457 phenotypes using genotyping array data from China Medical University Hospital. Logistic regression models assessed polygenic scores' ability to predict disease traits. The polygenic score model with the highest accuracy, based on maximal area under the receiver operating characteristic curve (AUC), is provided on the GeneAnaBase website of the hospital. Our findings indicate 49 phenotypes with AUC greater than 0.6, predominantly linked to endocrine and metabolic diseases. Notably, hyperplasia of the prostate exhibited the highest disease prediction ability (P value = 1.01 × 10-19, AUC = 0.874), highlighting the potential of these polygenic scores in preventive medicine and diagnosis. This study offers a comprehensive evaluation of polygenic scores performance across diverse human traits, identifying promising applications for precision medicine and personalized healthcare, thereby inspiring further research and development in this field.

XIOSIS: an X-ray-based intra-operative image-guided platform for oncology smart material delivery.

Image-guided interventional oncology procedures can greatly enhance the outcome of cancer treatment. As an enhancing procedure, oncology smart material delivery can increase cancer therapy's quality, effectiveness, and safety. However, the effectiveness of enhancing procedures highly depends on the accuracy of smart material placement procedures. Inaccurate placement of smart materials can lead to adverse side effects and health hazards. Image guidance can considerably improve the safety and robustness of smart material delivery. In this study, we developed a novel generative deep-learning platform that highly prioritizes clinical practicality and provides the most informative intra-operative feedback for image-guided smart material delivery. XIOSIS generates a patient-specific 3D volumetric computed tomography (CT) from three intraoperative radiographs (X-ray images) acquired by a mobile C-arm during the operation. As the first of its kind, XIOSIS (i) synthesizes the CT from small field-of-view radiographs;(ii) reconstructs the intra-operative spacer distribution; (iii) is robust; and (iv) is equipped with a novel soft-contrast cost function. To demonstrate the effectiveness of XIOSIS in providing intra-operative image guidance, we applied XIOSIS to the duodenal hydrogel spacer placement procedure. We evaluated XIOSIS performance in an image-guided virtual spacer placement and actual spacer placement in two cadaver specimens. XIOSIS showed a clinically acceptable performance, reconstructed the 3D intra-operative hydrogel spacer distribution with an average structural similarity of 0.88 and Dice coefficient of 0.63 and with less than 1 cm difference in spacer location relative to the spinal cord.

Dialdehyde cellulose (DAC) and polyethyleneimine (PEI) coated polyvinylidene fluoride (PVDF) membrane for simultaneously removing emulsified oils and anionic dyes.

Developing high-efficiency membrane for oil and dye removal is very urgent, because wastewater containing them can cause great damage to human and environment. In this study, a coated membrane was fabricated by applying DAC and PEI onto the commercial PVDF microfiltration membrane for supplying the demand. The coated membrane presents superhydrophlic and superoleophobic properties with a water contact angle of 0o and underwater oil contact angle exceed 150°, as well as excellent low underwater oil adhesion performance. The coated membrane shows high separation efficiency exceeded 99.0% and flux 350.0 L·m-2·h-1 when used for separating for six kinds of oil including pump oil, sunflower oil, n-hexadecane, soybean oil, diesel and kerosene in water emulsions. Additionally, the coated membrane can effectively remove anionic dyes, achieving rejection rates of 94.7%, 93.4%, 92.3%, 90.7% for the CR, MB, RB5, AR66, respectively. More importantly, the membrane was able to simultaneously remove emulsified oil and soluble anionic dyes in wastewater containing both of them. Therefore, this novel coated membrane can be a promising candidate for treating complex wastewater.

Deformable registration of preoperative MR and intraoperative long-length tomosynthesis images for guidance of spine surgery via image synthesis.

PURPOSE: Improved integration and use of preoperative imaging during surgery hold significant potential for enhancing treatment planning and instrument guidance through surgical navigation. Despite its prevalent use in diagnostic settings, MR imaging is rarely used for navigation in spine surgery. This study aims to leverage MR imaging for intraoperative visualization of spine anatomy, particularly in cases where CT imaging is unavailable or when minimizing radiation exposure is essential, such as in pediatric surgery. METHODS: This work presents a method for deformable 3D-2D registration of preoperative MR images with a novel intraoperative long-length tomosynthesis imaging modality (viz., Long-Film [LF]). A conditional generative adversarial network is used to translate MR images to an intermediate bone image suitable for registration, followed by a model-based 3D-2D registration algorithm to deformably map the synthesized images to LF images. The algorithm's performance was evaluated on cadaveric specimens with implanted markers and controlled deformation, and in clinical images of patients undergoing spine surgery as part of a large-scale clinical study on LF imaging. RESULTS: The proposed method yielded a median 2D projection distance error of 2.0 mm (interquartile range [IQR]: 1.1-3.3 mm) and a 3D target registration error of 1.5 mm (IQR: 0.8-2.1 mm) in cadaver studies. Notably, the multi-scale approach exhibited significantly higher accuracy compared to rigid solutions and effectively managed the challenges posed by piecewise rigid spine deformation. The robustness and consistency of the method were evaluated on clinical images, yielding no outliers on vertebrae without surgical instrumentation and 3% outliers on vertebrae with instrumentation. CONCLUSIONS: This work constitutes the first reported approach for deformable MR to LF registration based on deep image synthesis. The proposed framework provides access to the preoperative annotations and planning information during surgery and enables surgical navigation within the context of MR images and/or dual-plane LF images.

Analysis of Risk Factors for Velopharyngeal Insufficiency and Palatal Fistula After Sommerlad-Furlow Palatoplasty.

This study aimed to introduce a surgery technique-Sommerlad-Furlow palatoplasty (SFP) and analyze the risk factors of velopharyngeal insufficiency (VPI) and palatal fistula after SFP. Cases after SFP under the age of 5 between 2011 and 2021 were reviewed, and the cases with complete follow-up information were included. Univariate and multivariate logistic regression were used to evaluate the effects of surgical age, surgery technique, surgeon's experience, and cleft type on velopharyngeal function and the occurrence of palatal fistula. SFP is a safe and effective procedure to increase the palatal length and reconstruct the levator veli palatini sling. The speech outcome after SFP was associated with cleft type and age at operation. Age = 1.285 years is the best cutoff value. The fistula occurrence was associated with cleft type only.

Identification of Sulfur-Containing Chlorinated Paraffin Structural Analogues in Human Serum: Origination from Biotransformation or Bioaccumulation?

Chlorinated paraffins (CPs) are manufactured and used in high quantities and have diverse structural analogues. It is generally recognized that sulfur-containing structural analogues of CPs are mainly derived from sulfate-conjugated phase II metabolism. In this study, we non-targeted identified three classes of sulfur-containing CP structural analogues (CPs-S) in human serum, including 44 CP sulfates (CPs-SO4H/CPs-SO4H-OH), 14 chlorinated benzene sulfates (CBs-SO4H), and 19 CP sulfite esters (CPs-SO3/CPs-S2O6), which were generated during the production of commercial mixtures of CPs and, thus, bioaccumulated via environmental exposures. We first wrote a program to screen CPs-S, which were baseline-separated from CPs according to their polar functional groups. Then, mass spectral analyses of alkalization-acidification liquid-liquid extracts of serum samples and Orbitrap mass spectrometry analyses in the presence and absence of tetraphenylphosphonium chloride (Ph4PCl), respectively, were performed to determine the ionization forms ([M + Cl]- or [M - H]-) of CPs-S. The presence of fragment ions (SO4H-, SO3-, SO2Cl-, and HSO3-) revealed the structures of CPs-S, which were validated by their detections in commercial mixtures of CPs. The estimated total concentrations of CPs-S in the human serum samples were higher than the concentrations of medium- and long-chain CPs. The profiles of CPs-S in human serum were similar to those detected in CP commercial mixtures and rats exposed to the commercial mixtures, but CPs-S were not detected in human liver S9 fractions or rat tissues after exposure to CP standards. These results, together with the knowledge of the processes used to chemically synthesize CPs, demonstrate that CPs-S in humans originates from environmental bioaccumulation.

A critical size volumetric muscle loss model in mouse masseter with impaired mastication on nutrition.

Orofacial muscle defect due to congenital anomalies, tumour ablation or traumatic accident that exceeds endogenous regeneration capacity may lead to sustained deficits in masticatory function and nutrition intake. Functional recovery has always been the goal of muscle tissue repair, but currently, there is no suitable model for quantitative analyses of either functional consequences or treatment efficacy of orofacial muscle defect. This study proposed a critical size volumetric muscle loss (VML) model in mouse masseter with impaired mastication on nutrition. Full-thickness VML defects in diameter of 1.0, 1.5, 2.0 and 3.0 mm were generated in the centre of the mouse masseter using a biopsy punch to determine the critical size for functional impairment. In the VML region, myogenesis was dampened but fibrogenesis was activated, as long with a reduction in the density of the neuromuscular junction and an increase in vascular density. Accordingly, persistent fibrosis was observed in the centre region of VML in all diameters. The 2.0 mm diameter was the critical threshold to masticatory function impairment after VML in the masseter. VML of 3.0 mm diameter led to a significant impact on nutrition intake and body weight gain. Autologous muscle graft effectively relieved the fibrosis and functional deficit after VML injury in the masseter. This model serves as a reliable tool in studying functional recovery strategies for orofacial muscle defects.

Theory of Defect-Induced Crystal Field Perturbations in Rare-Earth Magnets.

We present a theory describing the single-ion anisotropy of rare-earth (RE) magnets in the presence of point defects. Taking the RE-lean 1∶12 magnet class as a prototype, we use first-principles calculations to show how the introduction of Ti substitutions into SmFe_{12} perturbs the crystal field, generating new coefficients due to the lower symmetry of the RE environment. We then demonstrate that these perturbations can be described extremely efficiently using a screened point charge model. We provide analytical expressions for the anisotropy energy that can be straightforwardly implemented in atomistic spin dynamics simulations, meaning that such simulations can be carried out for an arbitrary arrangement of point defects. The significant crystal field perturbations calculated here demonstrate that a sample that is single phase from a structural point of view can nonetheless have a dramatically varying anisotropy profile at the atomistic level if there is compositional disorder, which may influence localized magnetic objects like domain walls or skyrmions.

Integrative Metabolomics and Proteomics Allow the Global Intracellular Characterization of Bacillus subtilis Cells and Spores.

Reliable and comprehensive multi-omics analysis is essential for researchers to understand and explore complex biological systems more completely. Bacillus subtilis (B. subtilis) is a model organism for Gram-positive spore-forming bacteria, and in-depth insight into the physiology and molecular basis of spore formation and germination in this organism requires advanced multilayer molecular data sets generated from the same sample. In this study, we evaluated two monophasic methods for polar and nonpolar compound extraction (acetonitrile/methanol/water; isopropanol/water, and 60% ethanol) and two biphasic methods (chloroform/methanol/water, and methyl tert-butyl ether/methanol/water) on coefficients of variation of analytes, identified metabolite composition, and the quality of proteomics profiles. The 60% EtOH protocol proved to be the easiest in sample processing and was more amenable to automation. Collectively, we annotated 505 and 484 metabolites and identified 1665 and 1562 proteins in B. subtilis vegetative cells and spores, respectively. We also show differences between vegetative cells and spores from a multi-omics perspective and demonstrate that an integrative multi-omics analysis can be implemented from one sample using the 60% EtOH protocol. The results obtained by the 60% EtOH protocol provide comprehensive insight into differences in the metabolic and protein makeup of B. subtilis vegetative cells and spores.

Quaternization drives spleen-to-lung tropism conversion for mRNA-loaded lipid-like nanoassemblies.

Background: As the overwhelming majority of advanced mRNA delivery systems are preferentially accumulated in the liver, there is an accelerating growth in the demand for the development of non-liver mRNA delivery platforms. Methods: In this study, we prepared cationic lipid-like nanoassemblies through a N-quaternizing strategy. Their physicochemical properties, in vitro mRNA delivery efficiency, and organ tropism in mice were investigated. Results: Introduction of quaternary ammonium groups onto lipid-like nanoassemblies not only enhances their mRNA delivery performance in vitro, but also completely alters their tropism from the spleen to the lung after intravenous administration in mice. Quaternized lipid-like nanoassemblies exhibit ultra-high specificity to the lung and are predominantly taken up by pulmonary immune cells, leading to over 95% of exogenous mRNA translation in the lungs. Such mRNA delivery carriers are stable even after more than one-year storage at ambient temperature. Conclusions: Quaternization provides an alternative method for design of new lung-targeted mRNA delivery systems without incorporation of targeting ligands, which should extend the therapeutic applicability of mRNA to lung diseases.

Negative Effects of Butachlor on the Growth and Physiology of Four Aquatic Plants.

The increasing use of herbicides in intelligent agricultural production is driven by the time-consuming nature of manual weeding, as well as its ephemeral effectiveness. However, herbicides like butachlor degrade slowly and can be washed away by rainwater, ultimately flowing into the farm ponds and posing risks to aquatic plants. To identify and recommend superior restoration strategies that effectively address the challenges posed by butachlor, we investigated the impacts of butachlor on the growth and physiology of four common aquatic plants (i.e., Hydrilla verticillata, Ceratophyllum demersum, Potamogeton maackianus, and Myriophyllum aquaticum) and their potential role in mitigating environmental damage by reducing residual herbicide levels. Our findings indicated that M. aquaticum was tolerant to butachlor, exhibiting higher growth rates than other species when exposed to various butachlor concentrations. However, the concentration of butachlor negatively impacted the growth of H. verticillata, C. demersum, and P. maackianus, with higher concentrations leading to more significant inhibitory effects. After a 15-day experimental period, aquatic plants reduced the butachlor residuals in culture mediums across concentrations of 0.5 mg/L, 1 mg/L, and 2 mg/L compared to non-plant controls. Our findings classified P. maackianus as butachlor-sensitive and M. aquaticum as butachlor-tolerant species. This investigation represents novel research aimed at elucidating the contrasting effects of different concentrations of butachlor on four common aquatic species in the agricultural multi-pond system.

Microglia regulate sleep through calcium-dependent modulation of norepinephrine transmission.

Sleep interacts reciprocally with immune system activity, but its specific relationship with microglia-the resident immune cells in the brain-remains poorly understood. Here, we show in mice that microglia can regulate sleep through a mechanism involving Gi-coupled GPCRs, intracellular Ca2+ signaling and suppression of norepinephrine transmission. Chemogenetic activation of microglia Gi signaling strongly promoted sleep, whereas pharmacological blockade of Gi-coupled P2Y12 receptors decreased sleep. Two-photon imaging in the cortex showed that P2Y12-Gi activation elevated microglia intracellular Ca2+, and blockade of this Ca2+ elevation largely abolished the Gi-induced sleep increase. Microglia Ca2+ level also increased at natural wake-to-sleep transitions, caused partly by reduced norepinephrine levels. Furthermore, imaging of norepinephrine with its biosensor in the cortex showed that microglia P2Y12-Gi activation significantly reduced norepinephrine levels, partly by increasing the adenosine concentration. These findings indicate that microglia can regulate sleep through reciprocal interactions with norepinephrine transmission.

Alkylphenols disrupt estrogen homeostasis via diradical cross-coupling reactions: A novel pathway of endocrine disruption.

Estrogen, being an essential class of sex hormone, is an important target of endocrine disruption chemicals. It is well known that environmental disruptors could activate or inhibit estrogen receptors, acting as agonists or antagonists, and thus affect the circulating estrogen concentrations. Here, we report enzyme-mediated diradical cross-coupling reactions between alkylphenols (e.g., 2,4-di-tert-butylphenol [DBP], 4-nonylphenol [4-NP], and 4-tert-octylphenol [4-t-OP]) and estrogens (e.g., estradiol [E2]) that generate coupling metabolites and disrupt estrogen homeostasis. Among the phenolic xenobiotics, the screening of metabolic products revealed that alkylphenols had the highest reaction activities and generated coupling metabolites with high abundances (DBP-O-E2, 4-t-OP-O-E2, and 4-NP-O-E2). The coupling reactions were catalyzed by cytochrome P450 3A4 (CYP3A4) and verified by the detection of the coupling products in general populations. In vitro and in vivo exposures together with CYP3A4 inhibition demonstrated that cross-coupling reactions of phenols and E2 significantly reduced the normal levels of E2. We further established a unique spin-trapping-based high-throughput screening method to show the existence of diradicals in the coupling reaction. Density functional theory calculations revealed that spin aromatic delocalization was the fundamental cause of the high rebound barrier and sufficient lifetime of phenoxy radicals that enabled phenolic cross-coupling triggered by cytochrome P450. The identified mechanistic details for diradical cross-coupling reactions provide a novel pathway for phenolic chemicals to disrupt estrogen homeostasis.

Electrochemical sulfate production from sulfide-containing wastewaters and integration with electrochemical nitrogen recovery.

Electrochemical methods can help manage sulfide in wastewater, which poses environmental and health concerns due to its toxicity, malodor, and corrosiveness. In addition, sulfur could be recovered as fertilizer and commodity chemicals from sulfide-containing wastewaters. Wastewater characteristics vary widely among wastewaters; however, it remains unclear how these characteristics affect electrochemical sulfate production. In this study, we evaluated how four characteristics of influent wastewaters (electrolyte pH, composition, sulfide concentration, and buffer strength) affect sulfide removal (sulfide removal rate, sulfide removal efficiency) and sulfate production metrics (sulfate production rate, sulfate production selectivity). We identified that electrolyte pH (3 × difference, i.e., 25.1 to 84.9 µM h-1 in average removal rate within the studied pH range) and sulfide concentration (16 × difference, i.e., 82.1 to 1347.2 µM h-1 in average removal rate) were the most influential factors for electrochemical sulfide removal. Sulfate production was most sensitive to buffer strength (6 × difference, i.e., 4.4 to 27.4 µM h-1 in average production rate) and insensitive to electrolyte composition. Together, these results provide recommendations for the design of wastewater treatment trains and the feasibility of applying electrochemical methods to varying sulfide-containing wastewaters. In addition, we investigated a simultaneous multi-nutrient (sulfur and nitrogen) process that leverages electrochemical stripping to further enhance the versatility and compatibility of electrochemical nutrient recovery.

MXene-Decorated Nanofibrous Membrane with Programmed Antibacterial and Anti-Inflammatory Effects via Steering NF-κB Pathway for Infectious Cutaneous Regeneration.

Although antibiotic is still the main choice for antibacteria both in hospital and community, phototherapy has become a possibly one of the alternative approaches in the treatment of microbe-associated infections nowadays because of its considerable potential in effective eradication of pathogenic bacteria. However, overwhelming reactive oxygen species (ROS) generated from phototherapy inevitably provoke an inflammatory response, complicating the healing process. To address this outstanding issue, a MXene-decorated nanofibrious is devised that not only yield localized heat but also elevate ROS levels under near-infrared laser exposure ascribed to the synergistic photothermal/photodynamic effect, for potent bacterial inactivation. After being further loaded with aspirin, the nanofibrous membranes exhibit benign cytocompatibility, boosting cell growth and suppressing the (nuclear factor kappa-B ( NF-κB) signaling pathways through RNA sequencing analysis, indicating an excellent anti-inflammatory effect. Interestingly, in vivo investigations also corroborate that the nanofibrous membranes accelerate infectious cutaneous regeneration by efficiently killing pathogenic bacteria, promoting collagen deposition, boosting angiogenesis, and dampening inflammatory reaction via steering NF-κB pathway. As envisaged, this work furnishes a decorated nanofibrous membrane with programmed antibacterial and anti-inflammatory effects for remedy of refractory bacteria-invaded wound regeneration.

Molecular physiological characterization of the dynamics of persister formation in Staphylococcus aureus.

Bacteria possess the ability to enter a growth-arrested state known as persistence in order to survive antibiotic exposure. Clinically, persisters are regarded as the main causative agents for chronic and recurrent infectious diseases. To combat this antibiotic-tolerant population, a better understanding of the molecular physiology of persisters is required. In this study, we collected samples at different stages of the biphasic kill curve to reveal the dynamics of the cellular molecular changes that occur in the process of persister formation. After exposure to antibiotics with different modes of action, namely, vancomycin and enrofloxacin, similar persister levels were obtained. Both shared and distinct stress responses were enriched for the respective persister populations. However, the dynamics of the presence of proteins linked to the persister phenotype throughout the biphasic kill curve and the molecular profiles in a stable persistent population did show large differences, depending on the antibiotic used. This suggests that persisters at the molecular level are highly stress specific, emphasizing the importance of characterizing persisters generated under different stress conditions. Additionally, although generated persisters exhibited cross-tolerance toward tested antibiotics, combined therapies were demonstrated to be a promising approach to reduce persister levels. In conclusion, this investigation sheds light on the stress-specific nature of persisters, highlighting the necessity of tailored treatment approaches and the potential of combined therapy.

Sclerosis rim volume ratio and Japanese Investigation Committee classification as predictive factors for femoral head collapse progression after non-vascularized fibular grafting in osteonecrosis patients.

OBJECTIVE: The purpose of this retrospective cohort study was to determine the relationship between sclerosis rim volume ratio (SVR) and the progression of femoral head collapse after non-vascularized fibular grafting (NVFG) surgery in patients with osteonecrosis of the femoral head (ONFH), investigating risk factors associated with femoral head collapse progression and establishing a predictive model to enhance clinical decision-making. METHODS: ONFH patients who underwent NVFG between January 2008 and December 2021 were analyzed retrospectively to assess the risk of post-operative collapse progression (collapse >2 mm). A logistic regression model was used to evaluate the independent risk factors associated with collapse progression, including age, sex, etiology, affected side, Japanese Investigation Committee classification (JIC), and the sclerosis rim volume ratio (SVR). SVR values was collected from three weight-bearing columns, namely SVR1, SVR2, and SVR3, respectively. RESULTS: 57 patients with 64 hips who had undergone NVFG and were followed up for at least one year were included. During the follow-up, collapse＞2 mm occurred in 30 hips (46.88%). Multivariable analysis revealed that JIC (p =0.037) and SVR1 (p = 0.04) were independent risk factors for collapse progression after NVFG. The results of the receiver operating characteristic (ROC) analysis indicated that the aforementioned indices provided a satisfactory prediction of early femoral head collapse progression in ONFH patients after NVFG. The regression model using the above two indicators as a composite index showed satisfactory performance in predicting early postoperative femoral head collapse progression, with an area under the curve (AUC) of 84.6%. CONCLUSIONS: SVR is significant predictor of post-operative collapse progression following NVFG, and the composite index provides an optimal predictive value for femoral head collapse progression after surgery.

Interleukin-10 gene intervention ameliorates liver fibrosis by enhancing the immune function of natural killer cells in liver tissue.

BACKGROUND AND AIMS: Interleukin 10 (IL-10) and natural killer (NK) cells have the potential to combat liver fibrosis. However, whether NK cells play an important role in the anti-fibrotic effects of IL-10 is not sufficiently elucidated. In this study, we investigated the regulatory effects of IL-10 on NK cells during liver fibrosis. METHODS: Fibrotic mice induced with carbon tetrachloride were treated with or without IL-10 in the presence or absence of NK cells. Liver damage and fibrosis were assessed using hematoxylin and eosin and Sirius Red staining and serum transaminase and liver hydroxyproline assays, respectively. NK cell distribution, quantity, activation, cytotoxicity, development, and origin were analyzed using immunohistochemistry, immunofluorescence, and flow cytometry. Enzyme-linked immunosorbent assay was used to determine chemokine levels. RESULTS: In the presence of NK cells, IL-10 gene intervention improved liver fibrosis and enhanced NK cell accumulation and function in the liver, as evidenced by increased NKG2D, interferon-γ, and CD107a expression. Furthermore, IL-10 promoted the migration of circulating NK cells to the fibrotic liver and elevated C-C motif ligand 5 levels. However, depletion of NK cells exacerbated liver fibrosis and impaired the anti-fibrotic effect of IL-10. CONCLUSIONS: The anti-fibrotic effect of IL-10 relies on the enhancement of NK cell immune function, including activation, cytotoxicity, development, and migration. These results provide valuable insights into the mechanisms through which IL-10 regulates NK cells to limit the progression of liver fibrosis.

Engineered organoids for biomedical applications.

As miniaturized and simplified stem cell-derived 3D organ-like structures, organoids are rapidly emerging as powerful tools for biomedical applications. With their potential for personalized therapeutic interventions and high-throughput drug screening, organoids have gained significant attention recently. In this review, we discuss the latest developments in engineering organoids and using materials engineering, biochemical modifications, and advanced manufacturing technologies to improve organoid culture and replicate vital anatomical structures and functions of human tissues. We then explore the diverse biomedical applications of organoids, including drug development and disease modeling, and highlight the tools and analytical techniques used to investigate organoids and their microenvironments. We also examine the latest clinical trials and patents related to organoids that show promise for future clinical translation. Finally, we discuss the challenges and future perspectives of using organoids to advance biomedical research and potentially transform personalized medicine.