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Two-dimensional transition metal carbides (MXenes) have attracted a great interest of the research community as a relatively recently discovered large class of materials with unique electronic and optical properties. Understanding of adhesion between MXenes and various substrates is critically important for MXene device fabrication and performance. We report results of direct atomic force microscopy (AFM) measurements of adhesion of two MXenes (Ti 3 C 2 T x and Ti 2 CT x ) with a SiO 2 coated Si spherical tip. The Maugis-Dugdale theory was applied to convert the AFM measured adhesion force to adhesion energy, while taking into account surface roughness. The obtained adhesion energies were compared with those for mono-, bi-, and tri-layer graphene, as well as SiO 2 substrates. The average adhesion energies for the MXenes are 0.90 ± 0.03 J m −2 and 0.40 ± 0.02 J m −2 for thicker Ti 3 C 2 T x and thinner Ti 2 CT x , respectively, which is of the same order of magnitude as that between graphene and silica tip. The adhesion of two-dimensional transition metal carbides (MXenes) is important for potential MXene device fabrication and performance. Here, the authors show that adhesion of MXenes depends on their monolayer thickness and, in contrast to graphene, does not show number-of-monolayers dependency.

Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide. Patient‐derived organoid (PDO) has great potential in precision oncology, but low success rate, time‐consuming culture, and lack of tumor microenvironment (TME) limit its application. Mesenchymal stromal cells (MSC) accumulate in primary site to support tumor growth and recruit immune cells to form TME. Here, MSC and peripheral blood mononuclear cells (PBMC) coculture is used to construct HCC organoid‐on‐a‐chip mimicking original TME and provide a high‐throughput drug‐screening platform to predict outcomes of anti‐HCC immunotherapies. HCC‐PDOs and PBMC are co‐cultured with MSC and Cancer‐associated fibroblasts (CAF). MSC increases success rate of biopsy‐derived PDO culture, accelerates PDO growth, and promotes monocyte survival and differentiation into tumor‐associated macrophages. A multi‐layer microfluidic chip is designed to achieve high‐throughput co‐culture for drug screening. Compared to conventional PDOs, MSC‐PDO‐PBMC and CAF‐PDO‐PBMC models show comparable responses to chemotherapeutic or targeted anti‐tumor drugs but more precise prediction potential in assessing patients’ responses to anti‐PD‐L1 drugs. Moreover, this microfluidic platform shortens PDO growth time and improves dimensional uniformity of organoids. In conclusion, the study successfully constructs microengineered organoid‐on‐a‐chip to mimic TME for high‐throughput drug screening, providing novel platform to predict immunotherapy response of HCC patients.

Triggering receptors expressed on myeloid cells 2 (TREM2) is considered a protective factor to protect host from bacterial infection, while how it elicits this role is unclear. In the present study, we demonstrate that deficiency of triggering receptors expressed on myeloid cells 2 (TREM2) significantly enhanced macrophage pyroptosis induced by four common pyogenic bacteria including Staphylococcus aureus , Pseudomonas aeruginosa , Streptococcus pneumoniae , and Escherichia coli . TREM2 deficiency also decreased bacterial killing ratio of macrophage, while Caspase-1 or GSDMD inhibition promoted macrophage-mediated clearance to these bacteria. Further study demonstrated that the effect of TREM2 on macrophage pyroptosis and bacterial eradication mainly dependents on the activated status of NLRP3 inflammasome. Moreover, as the key downstream of TREM2, β-catenin phosphorylated at Ser675 by TREM2 signal and accumulated in nucleus and cytoplasm. β-catenin mediated the effect of TREM2 on NLRP3 inflammasome and macrophage pyroptosis by reducing NLRP3 expression, and inhibiting inflammasome complex assembly by interacting with ASC. Collectively, TREM2/β-catenin inhibits NLRP3 inflammasome to regulate macrophage pyroptosis, and enhances macrophage-mediated pyogenic bacterial clearance.

Electrochemical reduction of CO2 to syngas (CO and H2) offers an efficient way to mitigate carbon emissions and store intermittent renewable energy in chemicals. Herein, the hierarchical one‐dimensional/three‐dimensional nitrogen‐doped porous carbon (1D/3D NPC) is prepared by carbonizing the composite of Zn‐MOF‐74 crystals in situ grown on a commercial melamine sponge (MS), for electrochemical CO2 reduction reaction (CO2RR). The 1D/3D NPC exhibits a high CO/H2 ratio (5.06) and CO yield (31 mmol g−1 h−1) at −0.55 V, which are 13.7 times and 21.4 times those of 1D porous carbon (derived from Zn‐MOF‐74) and N‐doped carbon (carbonized by MS), respectively. This is attributed to the unique spatial environment of 1D/3D NPC, which increases the adsorption capacity of CO2 and promotes electron transfer from the 3D N‐doped carbon framework to 1D carbon, improving the reaction kinetics of CO2RR. Experimental results and charge density difference plots indicate that the active site of CO2RR is the positively charged carbon atom adjacent to graphitic N on 1D carbon and the active site of HER is the pyridinic N on 1D carbon. The presence of pyridinic N and pyrrolic N reduces the number of electron transfer, decreasing the reaction kinetics and the activity of CO2RR. The CO/H2 ratio is related to the distribution of N species and the specific surface area, which are determined by the degree of spatial confinement effect. The CO/H2 ratios can be regulated by adjusting the carbonization temperature to adjust the degree of spatial confinement effect. Given the low cost of feedstock and easy strategy, 1D/3D NPC catalysts have great potential for industrial application. The hierarchical one‐dimensional/three‐dimensional nitrogen‐doped porous carbon (1D/3D NPC) was prepared by carbonizing the composite of Zn‐MOF‐74 crystals in situ grown on a commercial melamine sponge, for electrochemical CO2 reduction reaction (CO2RR). The 1D/3D NPC exhibits a high CO/H2 ratio (5.06) and CO yield (31 mmol g−1 h−1) at −0.55 V, which is 13.7 times and 21.4 times of 1D porous carbon (derived from Zn‐MOF‐74) and N‐doped carbon (carbonized by MS), respectively. This is attributed to the spatial confinement effect of 3D N‐doped carbon framework on 1D porous carbon, which significantly improves the reaction kinetics of CO2RR by increasing specific surface areas, CO2 adsorption, mass transport, and facilitating electron transfer from the 3D N‐doped carbon framework to 1D carbon.

Immune checkpoint combination therapy, particularly dual LAG-3/PD-1 blockade, demonstrates superior clinical efficacy over monotherapy in cancers like melanoma, yet its mechanistic synergy requires further validation. In this study, we established a cell co-culture model by co-culturing LAG-3 + PD-1 + Jurkat cells induced by phytohemagglutinin (PHA) and human tumor cells with high expression of LAG-3 and PD-1 major ligands to characterize the combination effect of LBL-007 with anti-PD-1 antibodies and the mechanism of action in cancer immunotherapy. The results showed that the combination of LBL-007 and anti-PD-1 antibodies in the cell co-culture model enhanced the ability of activated Jurkat cells to kill tumor cells compared with monotherapy. Furthermore, this combination also inhibited the apoptosis of Jurkat cells and promoted IL-2, IL-10, and TNF secretion from Jurkat cells. Tumor cell death via apoptosis induced by activated Jurkat cells was observed, which was enhanced by combined LBL-007 and anti-PD-1 antibody treatment. The combination of LBL-007 and anti-PD-1 antibodies delayed tumor growth and promoted tumor cell apoptosis compared with monotherapy in human LAG-3 transgenic mice subjected to transplantation with colorectal tumor cells. Taken together, the combination of LBL-007 and anti-PD-1 antibodies plays an enhanced antitumor role by improving T cell viability and activity as well as by promoting T cell-induced apoptosis, thereby suggesting this combination as a potential effective strategy for cancer immunotherapy.

Background Vibrio vulnificus exists as one of the most serious foodborne pathogens for humans, and rapid and sensitive detection methods are needed to control its infections. As an emerging method, The Loop-Mediated Isothermal Amplification (LAMP) assay has been applied to the early detection of various foodborne pathogens due to its high efficiency, but sample preprocessing still prolongs the complete detection. To optimize the detection process, our study established a novel sample preprocessing method that was more efficient compared to common methods. Result Using V. vulnificus as the detecting pathogen, the water-lysis-based detecting LAMP method shortened the preprocessing time to ≤ 1 min with 100% LAMP specificity; the detection limits of the LAMP assay were decreased to 1.20 × 10 2 CFU/mL and 1.47 × 10 3 CFU/g in pure culture and in oyster, respectively. Furthermore, the 100% LAMP specificity and high sensitivity of the water-lysis method were also obtained on detecting V. parahaemolyticus , V. alginolyticus , and P. mirabilis , revealing its excellent LAMP adaption with improvement in sensitivity and efficiency. Conclusion Our study provided a novel LAMP preprocessing method that was more efficient compared to common methods and possessed the practical potential for LAMP application in the future.

Background Adenosine-to-inosine (A-to-I) RNA editing is a process that contributes to the diversification of proteins that has been shown to be essential for neurotransmission and other neuronal functions. However, the spatiotemporal and diversification properties of RNA editing in the brain are largely unknown. Here, we applied in situ sequencing to distinguish between edited and unedited transcripts in distinct regions of the mouse brain at four developmental stages, and investigate the diversity of the RNA landscape. Results We analyzed RNA editing at codon-altering sites using in situ sequencing at single-cell resolution, in combination with the detection of individual ADAR enzymes and specific cell type marker transcripts. This approach revealed cell-type-specific regulation of RNA editing of a set of transcripts, and developmental and regional variation in editing levels for many of the targeted sites. We found increasing editing diversity throughout development, which arises through regional- and cell type-specific regulation of ADAR enzymes and target transcripts. Conclusions Our single-cell in situ sequencing method has proved useful to study the complex landscape of RNA editing and our results indicate that this complexity arises due to distinct mechanisms of regulating individual RNA editing sites, acting both regionally and in specific cell types.

Background Rheumatoid arthritis (RA) affects ankle joints in up to one half of patients with established disease, causing inflammation and damage. Arthroscopic synovectomy removes inflamed tissue to improve joint function, but long-term outcomes and the potential role of adjunctive therapies are limited. Materials and methods A total of 176 patients who had a preoperative diagnosis of RA according to the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria, radiographic Larsen grade ≤ 3, and who underwent arthroscopic synovectomy from May 2013 to May 2019 were prospectively enrolled. Weight-bearing anteroposterior and lateral plain radiographs of the ankle were performed annually after initial surgery. The Larsen grade was used to evaluate the progression of ankle joint damage in RA, and patient-reported outcomes (American Orthopaedic Foot and Ankle Society [AOFAS] Ankle–Hindfoot Scale and the Foot and Ankle Outcome Score [FAOS]) were collected annually. The primary outcome measure was 5-year AOFAS score. Baseline characteristics, including age, body mass index (BMI), duration of symptoms before surgery, Larsen grade before surgery, and other potentially related factors, including number of platelet-rich plasma (PRP) injections and change in BMI from baseline, were recorded. Results There were 138 patients included, all with minimum 5-year follow-up data. The overall reoperation rate was 13% (95% confidence interval [CI] 6.8–18.9%; 18 of 138). According to multivariable analysis, 5-year AOFAS scores were associated with number of PRP injections (correlation coefficient = 2.09 [95% CI 1.47–2.71]; P  < 0.001), duration of symptoms before surgery (correlation coefficient = 0.42 [95% CI 0.14–0.70]; P  = 0.01), Larsen grade before surgery (correlation coefficient = 0.28 [95% CI 0.06–0.49]; P  = 0.034), and mean BMI change from baseline (correlation coefficient = −1.23 [95% CI −1.57 to −0.89]; P  < 0.001). When comparing the number of PRP injections (0, 1–2, or ≥ 3), patients who had serial PRP injections (≥ 3) had diminished functional and radiographic deterioration over time. Conclusions Arthroscopic synovectomy improves symptoms for ankle RA and appears to slow—but not halt—radiographic deterioration over 5 years. Serial PRP injections and reduction in BMI from baseline could be associated with better clinical outcomes and slower joint degeneration, which needs to be verified by randomized controlled trials. Level of evidence Level II, prospective cohort study. Trial registration Research Registry, researchregistry10878. Registered 24 November 2024—retrospectively registered, http://researchregistry.knack.com/researchregistry10878

N-Acyl Homoserine Lactones (N-AHLs) are an important group of small quorum-sensing molecules generated and released into the surroundings by Gram-negative bacteria. N-AHLs play a crucial role in various infection-related biological processes of marine species, including survival, colonization, invasion, and pathogenesis. With the increasing problem of antibiotic abuse and subsequently the emergence of drug-resistant bacteria, studies on AHLs are therefore expected to bring potential new breakthroughs for the prevention and treatment of infections. This article starts from AHLs generation in marine , and then discusses the advantages, disadvantages, and trends in the future development of various detection methods for AHLs characterization. In addition to a detailed classification of the various marine -derived AHL types that have been reported over the years, the regulatory mechanisms of AHLs and their roles in marine biofilms, pathogenicity and interaction with host cells are also highlighted. Intervention measures for AHLs in different stages are systematically reviewed, and the prospects of their future development and application are examined.

Purpose To investigate the treatment outcomes of subtalar arthroereisis (SA) in progressive collapsing foot deformity (PCFD) patients, to assess the clinical efficacy in PCFD patients after HyProCure removal, and to evaluate safety and effectiveness of SA. Methods In this retrospective study, 202 cases (213 feet) of PCFD patients treated with SA from June 2015 to December 2022 were selected. General data and surgical information were recorded, and clinical efficacy was evaluated through imaging and clinical indicators. Furthermore, for 36 patients (36 feet) who underwent secondary surgery to remove HyProCure, imaging and clinical evaluation indicators at 1-year post-removal were recorded. Complications were also documented. Results The main complications were sinus tarsi pain (91.37%), with partial relief or disappearance of symptoms in some patients after conservative treatment. The imaging indicators improved significantly after SA ( P  < 0.01), and AOFAS score and VAS were significantly improved ( P  < 0.01), with a 100% excellent rate in patients one year after SA. For patients who removed HyProCure, the imaging indicators exhibited a significant improvement at preoperation and post-SA ( P  < 0.01), and no statistical difference was observed between post-SA and post-removal ( P  > 0.05). Regarding clinical indicators, AOFAS score at post-SA was difference compared with preoperation and post-removal separately ( P  < 0.01). However, the difference in VAS between preoperation and post-SA was not statistically significant ( P  > 0.05). Notably, there was a significant improvement at post-removal compared with post-SA ( P  < 0.01). Conclusion PCFD patients showed significant improvement in imaging and clinical evaluations after SA, with no significant flatfoot recurrence in patients who had HyProCure removed. Therefore, the application of HyProCure in SA can be considered a safe and effective surgical treatment for PCFD patients.