Bacterial load in meconium.

The spike-in plasmid method was utilized to perform an analysis on meconium and second-pass feces, yielding both relative and absolute quantitative results. With the absolute quantitative data, the abundance of bacteria in 17 meconium samples and 17 second-pass fecal samples were found to be 1.14 × 107 and 1.59 × 109 copies/g, respectively. The mode of delivery can significantly influence the alterations and compositions of gut bacteria in a newborn within 72 h.

Exploring ways to improve China's ecological well-being amidst air pollution challenges using mixed methods.

Ecological well-being performance (EWP), a novel concept in sustainable development research, diverges from traditional ecological efficiency in terms of perspectives, core content, and driving factors. However, research on EWP remains insufficiently comprehensive, particularly the corresponding theoretical and methodological investigations into driving pathways. To address this gap, this study develops an "economy-environment-health" framework, incorporating air pollution and associated health losses into the evaluation system, and employs a two-stage Super-NSBM and Window DEA model for reevaluating EWP. The study further investigates the primary pathways of EWP, focusing on environmental regulations, technological innovation, and structural adjustments through both quantitative and qualitative methods. Quantitative spatial econometric analysis reveals that factors such as market-driven environmental regulations, green invention patents, and industrial and energy consumption structures significantly enhance EWP. While examining the "net effects" contributions of individual variables using spatial econometric models, the fsQCA method is employed to identify four effective driving paths for EWP from a configurational perspective. These paths are 1) technological innovation and structural adjustment under environmental regulations with public participation; 2) a combination of environmental regulation, technological innovation, and structural adjustment; 3) structural adjustment with minimal influence from environmental regulations and technological innovation; and 4) structural adjustment directed by market-incentive environmental regulations.

Chromones and biflavonoids from Garcinia pedunculata and Garcinia nujiangensis and their anti-inflammatory activity.

Plants of the Garcinia genus were rich in structurally diverse and naturally bioactive components, while limited studies have been reported for Garcinia pedunculata Roxb. and G. nujiangensis C. Y. Wu & Y. H. Li. Four previously undescribed compounds including three chromones, garpedunchromones A-C (1-3), and one biflavonoid, nujiangbiflavone A (14), along with fifteen known analogs (4-13, 15-19) were isolated from G. pedunculata and G. nujiangensis. The structures of the isolated compounds were determined based on their HRESIMS data, extensive NMR spectroscopic analyses, and ECD calculations. The chromone derivatives were isolated from Garcinia for the first time. Compound 14 was a rare biflavonoid with C-3─C-6″ linkage. The biological evaluation of these isolates against NO production was conducted in the LPS-induced RAW 264.7 cells, resulting in the identification of a series of potent NO inhibitors, of which garpedunchromone B (2) was the most active with an IC50 value of 18.11 ± 0.96 µM. In the network pharmacology studies, the potential targets of compounds and inflammation were obtained from PharmMapper and GeneCards database. GO and KEGG enrichment analysis revealed that the overlapped targets were closely related to the major pathogenic processes linked to inflammation. Garpedunchromone B and proteins binding sites were being predicted.

A new mouse-fixation device for IOP measurement in awake mice.

Glaucoma is an irreversible blinding eye disease. The mechanisms underlying glaucoma are complex. Up to now, no successful remedy has been found to completely cure the condition. High intraocular pressure (IOP) is an established risk factor for glaucoma and the only known modifiable factor for glaucoma treatment. Mice have been widely used to study glaucoma pathogenesis. IOP measurement is an important tool for monitoring the potential development of glaucomatous phenotypes in glaucoma mouse models. Currently, there are two methods of IOP measurement in mice: invasive and non-invasive. As the invasive method can cause corneal damage and inflammation, and most of the noninvasive method involves the use of anesthetics. In the course of our research, we designed a mouse fixation device to facilitate non-invasive measurements of mouse IOPs. Using this device, mouse IOPs can be accurately measured in awake mice. This device will help researchers to accurately assess mouse IOP without the use of anesthetics.

CLPs-miR-103a-2-5p inhibits proliferation and promotes cell apoptosis in AML cells by targeting LILRB3 and Nrf2/HO-1 axis, regulating CD8 + T cell response.

BACKGROUND: LILRB3, a member of the leukocyte immunoglobulin-like receptor B (LILRB) family, has immunosuppressive functions and directly regulates cancer development, which indicates that LILRB3 is an attractive target for cancer diagnosis and therapy. Novel therapeutic treatments for acute myeloid leukemia (AML) are urgent and important, and RNA therapeutics including microRNAs (miRNAs) could be an effective option. Here, we investigate the role of dysregulated miRNA targeting LILRB3 in the AML microenvironment. METHODS: Potential miRNAs binding to the 3'-untranslated region (3'-UTR) of the LILRB3 mRNA were predicted by bioinformatics websites. Then, we screened miRNAs targeting LILRB3 by quantitative real-time PCR, and the dual luciferase reporter assay. The expression of LILRB3 and microRNA (miR)-103a-2-5p in AML were determined and then their interactions were also analyzed. In vitro, the effects of miR-103a-2-5p were determined by CCK8, colony formation assay, and transwell assay, while cell apoptosis and cell cycle were analyzed by flow cytometry. Cationic liposomes (CLPs) were used for the delivery of miR-103a-2-5p in the AML mouse model, which was to validate the potential roles of miR-103a-2-5p in vivo. RESULTS: LILRB3 was upregulated in AML cells while miR-103a-2-5p was dramatically downregulated. Thus, a negative correlation was found between them. MiR-103a-2-5p directly targeted LILRB3 in AML cells. Overexpressed miR-103a-2-5p significantly suppressed the mRNA and protein levels of LILRB3, thereby inhibiting AML cell growth and reducing CD8 + T cell apoptosis. In addition, overexpressed miR-103a-2-5p reduced both the relative expression of Nrf2/HO-1 pathway-related proteins and the ratio of GSH/ROS, leading to the excessive intracellular ROS that may promote AML cell apoptosis. In the mouse model, the delivery of miR-103a-2-5p through CLPs could inhibit tumor growth. CONCLUSIONS: MiR-103a-2-5p serves as a tumor suppressor that could inhibit AML cell proliferation and promote their apoptosis by downregulating LILRB3 expression, suppressing the Nrf2/HO-1 axis, and reducing the ratio of GSH/ROS. Besides, our findings indicate that miR-103a-2-5p may enhance the CD8 + T cell response by inhibiting LILRB3 expression. Therefore, the delivery of miR-103a-2-5p through CLPs could be useful for the treatment of AML.

Excess glucocorticoids inhibit murine bone turnover via modulating the immunometabolism of the skeletal microenvironment.

Elevated bone resorption and diminished bone formation have been recognized as the primary features of glucocorticoid-associated skeletal disorders. However, the direct effects of excess glucocorticoids on bone turnover remain unclear. Here, we explored the outcomes of exogenous glucocorticoid treatment on bone loss and delayed fracture healing in mice and found that reduced bone turnover was a dominant feature, resulting in a net loss of bone mass. The primary effect of glucocorticoids on osteogenic differentiation was not inhibitory; instead, they cooperated with macrophages to facilitate osteogenesis. Impaired local nutrient status - notably, obstructed fatty acid transportation - was a key factor contributing to glucocorticoid-induced impairment of bone turnover in vivo. Furthermore, fatty acid oxidation in macrophages fueled the ability of glucocorticoid-liganded receptors to enter the nucleus and then promoted the expression of BMP2, a key cytokine that facilitates osteogenesis. Metabolic reprogramming by localized fatty acid delivery partly rescued glucocorticoid-induced pathology by restoring a healthier immune-metabolic milieu. These data provide insights into the multifactorial metabolic mechanisms by which glucocorticoids generate skeletal disorders, thus suggesting possible therapeutic avenues.

Cascade signal amplification strategy for the electrochemical aptasensing of nucleic acid: Combination of dual-output toehold-mediated DNA strand displacement, DNA walker and Exo III.

BACKGROUND: Sensitive and selective analysis of low content nucleic acid sequences plays an important role in pathogen analysis, disease diagnosis and biomedicine. The electrochemical biosensor based on toehold-mediated strand displacement reaction (TMSD) is highly attractive in nucleic acid detection due to their improved sensitivity and rapid response. But the traditional TMSD carried out on the electrode always with low displacement efficiency and complicated electrode operation, resulting in compromised sensing performance. There is a great need to construct a novel TMSD based electrochemical detection strategy to overcome such challenges in nucleic acid detecting. RESULT: Herein, a triple signal amplification electrochemical aptasensor was developed for ultrasensitive detection of CYFRA21-1 DNA. The dual-output toehold mediated strand displacement reaction (dTMSD) can convert one input to two strands output within one strand displacement cycle. So that it possesses a higher efficiency for improving the sensitivity in comparison with the single-output TMSD. And the fuel strand was configured with a tail to realize successive DNA circuits through self-propelling as a DNA walker. All the above processes were carried out on magnetic beads, which is conducive to achieving effective sample purification and minimizing the background signals. Besides, Exonuclease III was further amplified signal. As a result, through the cascade use of above three technologies, the proposed biosensing strategy realized sensitive detection of target DNA with a low detection limit of 0.35 fM (S/N = 3) and wide linear range (0.5 fM-500 pM). SIGNIFICANCE: The proposed novel dTMSD combining multiple signal amplification strategies for electrochemical detection of CYFRA21-1 DNA with easy operation not only possesses excellent sensitivity and selectivity, but also has potential application value for monitoring DNA in serum. Meanwhile, the development of highly sensitive and specific CYFRA21-1 DNA detection methods is very important for the prevention and treatment of lung cancer.

The Association of Preoperative Diabetes With Postoperative Delirium in Older Patients Undergoing Major Orthopedic Surgery: A Prospective Matched Cohort Study.

BACKGROUND: Postoperative delirium (POD) is a common form of postoperative brain dysfunction, especially in the elderly. However, its risk factors remain largely to be determined. This study aimed to investigate whether (1) preoperative diabetes is associated with POD after elective orthopedic surgery and (2) intraoperative frontal alpha power is a mediator of the association between preoperative diabetes and POD. METHODS: This was a prospective matched cohort study of patients aged 60 years or more, with a preoperative diabetes who underwent elective orthopedic surgery. Nondiabetic patients were matched 1:1 to diabetic patients in terms of age, sex, and type of surgery. Primary outcome was occurrence of POD, assessed using the 3-minute Diagnostic Confusion Assessment Method (3D-CAM) once daily from 6 pm to 8 pm during the postoperative days 1-7 or until discharge. Secondary outcome was the severity of POD which was assessed for all participants using the short form of the CAM-Severity. Frontal electroencephalogram (EEG) was recorded starting before induction of anesthesia and lasting until discharge from the operating room. Intraoperative alpha power was calculated using multitaper spectral analyses. Mediation analysis was used to estimate the proportion of the association between preoperative diabetes and POD that could be explained by intraoperative alpha power. RESULTS: A total of 138 pairs of eligible patients successfully matched 1:1. After enrollment, 6 patients in the diabetes group and 4 patients in the nondiabetes group were excluded due to unavailability of raw EEG data. The final analysis included 132 participants with preoperative diabetes and 134 participants without preoperative diabetes, with a median age of 68 years and 72.6% of patients were female. The incidence of POD was 16.7% (22/132) in patients with preoperative diabetes vs 6.0% (8/134) in patients without preoperative diabetes. Preoperative diabetes was associated with increased odds of POD after adjustment of age, sex, body mass index, education level, hypertension, arrhythmia, coronary heart disease, and history of stroke (odds ratio, 3.2; 95% confidence interval [CI], 1.4-8.0; P = .009). The intraoperative alpha power accounted for an estimated 20% (95% CI, 2.6-60%; P = .021) of the association between diabetes and POD. CONCLUSIONS: This study suggests that preoperative diabetes is associated with an increased risk of POD in older patients undergoing major orthopedic surgery, and that low intraoperative alpha power partially mediates such association.

Lovastatin/SN38 co-loaded liposomes amplified ICB therapeutic effect via remodeling the immunologically-cold colon tumor and synergized stimulation of cGAS-STING pathway.

Current immune checkpoint blockade (ICB) immunotherapeutics have revolutionized cancer treatment. However, many cancers especially the "immunologically cold" tumors, do not respond to ICB, prompting the search for additional strategies to achieve durable responses. The cGAS-STING pathway, as an essential immune response pathway, has been demonstrated for a potent target to sensitize ICB immunotherapy. However, the low efficiency of conventional STING agonists limits their clinical application. Recent studies have shown that DNA topoisomerase I (TOPI) inhibitor chemodrug SN38 can activate the cGAS-STING pathway and induce an immune response through DNA damage, while the traditional statins medication lovastatin was found to inhibit DNA damage repair, which may in turn upregulate the damaged DNA level. Herein, we have developed a liposomal carrier co-loaded with SN38 and lovastatin (SL@Lip), which can be accumulated in tumors and efficiently released SN38 and lovastatin, addressing the problem of weak solubility of these two drugs. Importantly, lovastatin can increase DNA damage and enhance the activation of cGAS-STING pathway, coordinating with SN38 chemotherapy and exhibiting the enhanced combinational immunotherapy of PD-1 antibody by remodeling the tumor microenvironment in mouse colorectal cancer of both subcutaneous and orthotopic xenograft models. Overall, this study demonstrates that lovastatin-assisted cGAS-STING stimulation mediated by liposomal delivery system significantly strengthened both chemotherapy and immunotherapy of colorectal cancer, providing a clinically translational strategy for combinational ICB therapy in the "immunologically cold" tumors.

Electrochemically and Thermally Stable Inorganics-Rich Solid Electrolyte Interphase for Robust Lithium Metal Batteries.

Severe dendrite growth and high-level activity of the lithium metal anode lead to a short life span and poor safety, seriously hindering the practical applications of lithium metal batteries. With a trisalt electrolyte design, an F-/N-containing inorganics-rich solid electrolyte interphase on a lithium anode is constructed, which is electrochemically and thermally stable over long-term cycles and safety abuse conditions. As a result, its Coulombic efficiency can be maintained over 98.98% for 400 cycles. An 85.0% capacity can be retained for coin-type full cells with a 3.14 mAh cm-2 LiNi0.5 Co0.2 Mn0.3 O2 cathode after 200 cycles and 1.0 Ah pouch-type full cells with a 4.0 mAh cm-2 cathode after 72 cycles. During the thermal runaway tests of a cycled 1.0 Ah pouch cell, the onset and triggering temperatures were increased from 70.8 °C and 117.4 °C to 100.6 °C and 153.1 °C, respectively, indicating a greatly enhanced safety performance. This work gives novel insights into electrolyte and interface design, potentially paving the way for high-energy-density, long-life-span, and thermally safe lithium metal batteries.

Developing a novel SARS-CoV-2 risk index to predict the prognostic and therapeutic effects in acute myeloid leukemia.

There is growing evidence of a strong association between SARS-CoV-2 and cancer prognosis and treatment outcome. However, there are no reliable SARS-CoV-2 assessment models to accurately predict prognostic and therapeutic effects in acute myeloid leukemia (AML). Here, differentially expressed genes associated with SARS-CoV-2 were detected, and multiple Cox regression methods were used to construct a SARS-CoV-2 risk index (SC2RI). Then, RT-qPCR was used to validate the gene expression levels in the AML samples. Finally, we explored how the SC2RI affected prognosis, immune infiltration, immunotherapy, and drug sensitivity in AML. We found that CYB5R3 and CLIP4 had been confirmed as hub genes in AML and were used to generate the SC2RI. The datasets indicated that the SC2RI had a superior predictive impact on the prognosis of AML. In addition, high expression of immune checkpoints and numerous immunological infiltrations were substantially correlated with a high SC2RI. However, it responded poorly to immune checkpoint blockade, which may be related to T-cell dysfunction, lack of effective antigens, and deficiency of synaptic capacity. Moreover, a high SC2RI was less susceptible to mTOR-related pathway medications but more sensitive to cell cycle suppressors. Therefore, categorization based on SC2RI could enhance the prognostic prediction of AML and help identify novel therapeutic approaches.

A Polymer Acceptor with Grafted Small Molecule Acceptor Unit for Efficient All Polymer Organic Solar Cells.

A polymer acceptor, named PX-1, is  designed and synthesized using a polymerization strategy with grafted small molecule acceptors. This design approach allows for the freedom of end groups while maintaining efficient terminal packing, enhancing π-π interactions, and facilitating charge transport. All-polymer organic solar cells based on PM6: PX-1 demonstrate a promising efficiency of 13.55%. The result presents an alternative pathway for the design of high-efficiency polymer acceptors through the careful regulation of small molecule acceptor monomers and linker units.

Advancements in Nanoenabled Membrane Distillation for a Sustainable Water-Energy-Environment Nexus.

The emergence of nano innovations in membrane distillation (MD) has garnered increasing scientific interest. This enables the exploration of state-of-the-art nano-enabled MD membranes with desirable properties, which significantly improve the efficiency and reliability of the MD process and open up opportunities for achieving a sustainable water-energy-environment (WEE) nexus. This comprehensive review provides broad coverage and in-depth analysis of recent innovations in nano-enabled MD membranes, focusing on their role in achieving desirable properties, such as strong liquid-repellence, high resistance to scaling, fouling, and wetting, as well as efficient self-heating and self-cleaning functionalities. The recent developments in nano-enhanced photothermal-catalytic applications for water-energy co-generation within a single MD system are also discussed. Furthermore, the bottlenecks are identified that impede the scale-up of nanoenhanced MD membranes and a future roadmap is proposed for their sustainable commercialiation. This holistic overview is expected to inspire future research and development efforts to fully harness the potential of nano-enabled MD membranes to achieve sustainable integration of water, energy, and the environment.

Electrospun nanofibrous membranes for membrane distillation application-A dynamic life cycle assessment (dLCA) approach.

Membrane distillation (MD) for water desalination and purification has been gaining prominence to address the issues relating to water security and the destruction of aquatic ecosystems globally. Recent advances in electrospun membranes for MD application have improved antifouling and anti-wetting performance. However, the environmental impacts associated with producing novel electrospun membranes still need to be clarified. It is imperative to quantify and analyze the tradeoffs between membrane performance and impacts at the early stages of research on these novel membranes. Life Cycle Assessment (LCA) is an appropriate tool to systematically account for environmental performance, all the way from raw material extraction to the disposal of any product, process, or technology. The inherent lack of detailed datasets for emerging technologies contributes to significant uncertainties, making the adoption of traditional LCA challenging. A dynamic LCA (dLCA) is performed to guide the sustainable design and selection of emerging electrospun poly (vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) electrospun membrane (E-PH) and hybridizing polydimethylsiloxane (PDMS) on E-PH membrane (E-PDMS) for dyeing wastewater treatment technologies. The associated environmental impacts are related to the high energy demands required for fabricating electrospun nanofibrous membranes. After LCA analysis, the E-PDMS membrane emerges as a promising membrane, due to the relatively low impact/benefit ratio and the high performance achieved in treating dyeing wastewater.

The counterbalance of endothelial glycocalyx and high wall shear stress to low-density lipoprotein concentration polarization in mouse ear skin arterioles.

BACKGROUND AND AIMS: Atherosclerosis preferentially occurs at regions in arterial branching, curvature, and stenosis, which may be explained by the geometric predilection of low-density lipoprotein (LDL) concentration polarization that has been investigated in major arteries in previous studies. Whether this also happens in arterioles remains unknown. METHODS: Herein, a radially non-uniform distribution of LDL particles and a heterogeneous endothelial glycocalyx layer in the mouse ear arterioles, as shown by fluorescein isothiocyanate labeled wheat germ agglutinin (WGA-FITC), were successfully observed by a non-invasive two-photon laser-scanning microscopy (TPLSM) technique. The stagnant film theory was applied as the fitting function to evaluate LDL concentration polarization in arterioles. RESULTS: The concentration polarization rate (CPR, the ratio of the number of polarized cases to that of total cases) in the inner walls of curved and branched arterioles was 22% and 31% higher than the outer counterparts, respectively. Results from the binary logistic regression and multiple linear regression analysis showed that endothelial glycocalyx thickness increases CPR and the thickness of the concentration polarization layer (CPL). Flow field computation indicates no obvious disturbances or vortex in modeled arterioles with different geometries and the mean wall shear stress is about 7.7-9.0 Pa. CONCLUSIONS: These findings suggest a geometric predilection of LDL concentration polarization in arterioles for the first time, and the existence of an endothelial glycocalyx, acting together with a relatively high wall shear stress in arterioles, may explain to some extent why atherosclerosis rarely occurs in these regions.

KRAS mutations upregulate Runx1 to promote occurrence of head and neck squamous cell carcinoma.

Gene mutations play an important role in head and neck squamous cell carcinoma (HNSCC) by not only promoting the occurrence and progression of HNSCC but also affecting sensitivity to treatment and prognosis. KRAS is one of the most frequently mutated oncogenes, which has been reported to have a mutation rate from 1.7% to 12.7% and may lead to poor prognosis in HNSCC, but its role remains unclear. Here, we found that the KRAS mutation can promote HNSCC generation through synergism with 4-Nitroquinoline-1-Oxide(4NQO). Mechanistically, KRAS mutations can significantly upregulate Runx1 to promote oral epithelial cell proliferation and migration and inhibit apoptosis. Runx1 inhibitor Ro 5-3335 can effectively inhibit KRAS-mutated HNSCC progression both in vitro and in vivo. These findings suggest that the KRAS mutation plays an important role in HNSCC and that Runx1 may be a novel therapeutic target for KRAS-mutated HNSCC.

Bioinspired Tumor-Targeting and Biomarker-Activatable Cell-Material Interfacing System Enhances Osteosarcoma Treatment via Biomineralization.

Osteosarcoma is an aggressive malignant tumor that primarily develops in children and adolescents. The conventional treatments for osteosarcoma often exert negative effects on normal cells, and chemotherapeutic drugs, such as platinum, can lead to multidrug resistance in tumor cells. Herein, this work reports a new bioinspired tumor-targeting and enzyme-activatable cell-material interface system based on DDDEEK-pY-phenylboronic acid (SAP-pY-PBA) conjugates. Using this tandem-activation system, this work selectively regulates the alkaline phosphatase (ALP) triggered anchoring and aggregation of SAP-pY-PBA conjugates on the cancer cell surface and the subsequent formation of the supramolecular hydrogel. This hydrogel layer can efficiently kill osteosarcoma cells by enriching calcium ions from tumor cells and forming a dense hydroxyapatite layer. Owing to the novel antitumor mechanism, this strategy neither hurts normal cells nor causes multidrug resistance in tumor cells, thereby showing an enhanced tumor treatment effect than the classical antitumor drug, doxorubicin (DOX). The outcome of this research demonstrates a new antitumor strategy based on a bioinspired enzyme-responsive biointerface combining supramolecular hydrogels with biomineralization.

Injectable magnesium oxychloride cement foam-derived scaffold for augmenting osteoporotic defect repair.

HYPOTHESIS: Cement augmentation has been widely applied to promote osteoporotic fracture healing, whereas the existing calcium-based products suffer from the excessively slow degradation, which may impede bone regeneration. Magnesium oxychloride cement (MOC) shows promising biodegradation tendency and bioactivity, which is expected to be a potential alternative to the classic calcium-based cement for hard-tissue-engineering applications. EXPERIMENTS: Here, a hierarchical porous MOC foam (MOCF)-derived scaffold with favorable bio-resorption kinetic and superior bioactivity is fabricated through Pickering foaming technique. Then, a systematic characterization in terms of material properties and in vitro biological performance have been conducted to evaluate the feasibility of the as-prepared MOCF scaffold to be a bone-augmenting material for treating osteoporotic defects. FINDINGS: The developed MOCF shows excellent handling performance in the paste state, while exhibiting sufficient load-bearing capacity after solidification. In comparison with the traditional bone cement, calcium deficient hydroxyapatite (CDHA), our porous MOCF scaffold demonstrates a much higher biodegradation tendency and better cell recruitment ability. Additionally, the eluted bioactive ions by MOCF commits to a biologically inductive microenvironment, where the in vitro osteogenesis is significantly enhanced. It is anticipated that this advanced MOCF scaffold will be competitive for clinical therapies to augment osteoporotic bone regeneration.

Exosomal miR-146b-5p derived from cancer-associated fibroblasts promotes progression of oral squamous cell carcinoma by downregulating HIPK3.

OBJECTIVES: Cancer-associated fibroblasts (CAFs) are vital constituents of the tumor microenvironment (TME) and play a predominant role in oral squamous cell carcinoma (OSCC) progression. We aimed to investigate the effect and mechanism of exosomal miR-146b-5p derived from CAFs on the malignant biological behavior of OSCC. MATERIALS AND METHODS: Illumina small RNA (sRNA) sequencing was conducted to determine the differential expression patterns of microRNAs (miRNAs) in exosomes derived from CAFs and normal fibroblasts (NFs). Transwell and cell counting kit-8 (CCK-8) assays and xenograft tumor models in nude mice were used to investigate the effect of CAF exosomes and miR-146b-p on the malignant biological behavior of OSCC. Reverse transcription quantitative real-time PCR (qRT-PCR), luciferase reporter, western blotting (WB) and immunohistochemistry assays were employed to investigate the underlying mechanisms involved in CAF exosomes that promote OSCC progression. RESULTS: We demonstrated that CAF-derived exosomes were taken up by OSCC cells and enhanced the proliferation, migration, and invasion ability of OSCC. Compared with NFs, the expression of miR-146b-5p was increased in exosomes and their parent CAFs. Further studies showed that the decreased expression of miR-146b-5p inhibited the proliferation, migration and invasion ability of OSCC cells in vitro and the growth of OSCC cells in vivo. Mechanistically, miR-146b-5p overexpression led to the suppression of HIKP3 by directly targeting the 3'-UTR of HIPK3, as confirmed by luciferase assay. Reciprocally, HIPK3 knockdown partially reversed the inhibitory effect of the miR-146b-5p inhibitor on the proliferation, migration, and invasion ability of OSCC cells and restored their malignant phenotype. CONCLUSIONS: Our results revealed that CAF-derived exosomes contained higher levels of miR-146b-5p than NFs, and miR-146b-5p overexpression in exosomes promoted the malignant phenotype of OSCC by targeting HIPK3. Therefore, inhibiting exosomal miR-146b-5p secretion may be a promising therapeutic modality for OSCC.

Water-Immiscible Coacervate as a Liquid Magnetic Robot for Intravascular Navigation.

Developing magnetic ultrasoft robots to navigate through extraordinarily narrow and confined spaces like capillaries in vivo requires synthesizing materials with excessive deformability, responsive actuation, and rapid adaptability, which are difficult to achieve with the current soft polymeric materials, such as elastomers and hydrogels. We report a magnetically actuatable and water-immiscible (MAWI) coacervate based on the assembled magnetic core-shell nanoparticles to function as a liquid robot. The degradable and biocompatible millimeter-sized MAWI coacervate liquid robot can remain stable under changing pH and salt concentrations, release loaded cargoes on demand, squeeze through an artificial capillary network within seconds, and realize intravascular targeting in vivo guided by an external magnetic field. We believe the proposed "coacervate-based liquid robot" can implement demanding tasks beyond the capability of conventional elastomer or hydrogel-based soft robots in the field of biomedicine and represents a distinct design strategy for high-performance ultrasoft robots.