In-situ polymerized solid/quasi-solid polymer electrolyte for lithium-metal batteries: recent progress and perspectives.

In pursuit of high energy density, lithium metal batteries (LMBs) are undoubtedly the best choice. However, leakage and inevitable dendrite growth in liquid electrolytes seriously hinder its practical application. Solid/quasi-solid state electrolytes have emerged as an answer to solve the above issues. Especially, polymer electrolytes with excellent interface compatibility, high flexibility, and ease of machining have become a research hotspot for LMBs. Nevertheless, the interface contact between polymer electrolyte and inorganic electrode materials and the low ionic conductivity restrict its development. On account of these, in situ polymerized polymer electrolyte is proposed. Polymer solid electrolytes produced through in situ polymerization promote robust interface contact between the electrolyte and electrode while simplifying the preparation steps. This review summarized the latest research progress in in situ polymerized solid electrolytes for LMBs. These electrolytes were divided into three parts according to their polymerization methods: thermally induced polymerization, chemical initiator polymerization, ionizing radiation polymerization, and so on. Furthermore, we concluded the major challenges and future trends of in situ polymerized solid electrolytes for LMBs. It's hoped that this review will provide meaningful guidance on designing high-performance polymer solid electrolytes for LMBs.

Facile One-Pot Preparation of Polypyrrole-Incorporated Conductive Hydrogels for Human Motion Sensing.

Conductive hydrogels have been widely used in soft robotics, as well as skin-attached and implantable bioelectronic devices. Among the candidates of conductive fillers, conductive polymers have become popular due to their intrinsic conductivity, high biocompatibility, and mechanical flexibility. However, it is still a challenge to construct conductive polymer-incorporated hydrogels with a good performance using a facile method. Herein, we present a simple method for the one-pot preparation of conductive polymer-incorporated hydrogels involving rapid photocuring of the hydrogel template followed by slow in situ polymerization of pyrrole. Due to the use of a milder oxidant, hydrogen peroxide, for polypyrrole synthesis, the photocuring of the hydrogel template and the growing of polypyrrole proceeded in an orderly manner, making it possible to prepare conductive polymer-incorporated hydrogels in one pot. The preparation process is facile and extensible. Moreover, the obtained hydrogels exhibit a series of properties suitable for biomedical strain sensors, including good conductivity (2.49 mS/cm), high stretchability (>200%), and a low Young's modulus (~30 kPa) that is compatible with human skin.

Targeting the IKs Channel PKA Phosphorylation Axis to Restore Its Function in High-Risk LQT1 Variants.

BACKGROUND: The KCNQ1+KCNE1 (IKs) potassium channel plays a crucial role in cardiac adaptation to stress, in which ß-adrenergic stimulation phosphorylates the IKs channel through the cyclic adenosine monophosphate (cAMP)/PKA (protein kinase A) pathway. Phosphorylation increases the channel current and accelerates repolarization to adapt to an increased heart rate. Variants in KCNQ1 can cause long-QT syndrome type 1 (LQT1), and those with defective cAMP effects predispose patients to the highest risk of cardiac arrest and sudden death. However, the molecular connection between IKs channel phosphorylation and channel function, as well as why high-risk LQT1 mutations lose cAMP sensitivity, remain unclear. METHODS: Regular patch clamp and voltage clamp fluorometry techniques were utilized to record pore opening and voltage sensor movement of wild-type and mutant KCNQ1/IKs channels. The clinical phenotypic penetrance of each LQT1 mutation was analyzed as a metric for assessing their clinical risk. The patient-specific-induced pluripotent stem-cell model was used to test mechanistic findings in physiological conditions. RESULTS: By systematically elucidating mechanisms of a series of LQT1 variants that lack cAMP sensitivity, we identified molecular determinants of IKs channel regulation by phosphorylation. These key residues are distributed across the N-terminus of KCNQ1 extending to the central pore region of IKs. We refer to this pattern as the IKs channel PKA phosphorylation axis. Next, by examining LQT1 variants from clinical databases containing 10 579 LQT1 carriers, we found that the distribution of the most high-penetrance LQT1 variants extends across the IKs channel PKA phosphorylation axis, demonstrating its clinical relevance. Furthermore, we found that a small molecule, ML277, which binds at the center of the phosphorylation axis, rescues the defective cAMP effects of multiple high-risk LQT1 variants. This finding was then tested in high-risk patient-specific induced pluripotent stem cell-derived cardiomyocytes, where ML277 remarkably alleviates the beating abnormalities. CONCLUSIONS: Our findings not only elucidate the molecular mechanism of PKA-dependent IKs channel phosphorylation but also provide an effective antiarrhythmic strategy for patients with high-risk LQT1 variants.

The long-term effectiveness and mechanism of oncolytic virotherapy combined with anti-PD-L1 antibody in colorectal cancer patient.

Colorectal cancer (CRC) is known to be resistant to immunotherapy. In our phase-I clinical trial, one patient achieved a 313-day prolonged response during the combined treatment of oncolytic virotherapy and immunotherapy. To gain a deeper understanding of the potential molecular mechanisms, we performed a comprehensive multi-omics analysis on this patient and three non-responders. Our investigation unveiled that, initially, the tumor microenvironment (TME) of this responder presented minimal infiltration of T cells and natural killer cells, along with a relatively higher presence of macrophages compared to non-responders. Remarkably, during treatment, there was a progressive increase in CD4+ T cells, CD8+ T cells, and B cells in the responder's tumor tissue. This was accompanied by a significant upregulation of transcription factors associated with T-cell activation and cytotoxicity, including GATA3, EOMES, and RUNX3. Furthermore, dynamic monitoring of peripheral blood samples from the responder revealed a rapid decrease in circulating tumor DNA (ctDNA), suggesting its potential as an early blood biomarker of treatment efficacy. Collectively, our findings demonstrate the effectiveness of combined oncolytic virotherapy and immunotherapy in certain CRC patients and provide molecular evidence that virotherapy can potentially transform a "cold" TME into a "hot" one, thereby improving sensitivity to immunotherapy.

Long-term survivals of immune checkpoint inhibitors as neoadjuvant and adjuvant therapy in dMMR/MSI-H colorectal and gastric cancers.

BACKGROUND: The long-term survival benefit of immune checkpoint inhibitors (ICIs) in neoadjuvant and adjuvant settings is unclear for colorectal cancers (CRC) and gastric cancers (GC) with deficiency of mismatch repair (dMMR) or microsatellite instability-high (MSI-H). METHODS: This retrospective study enrolled patients with dMMR/MSI-H CRC and GC who received at least one dose of neoadjuvant ICIs (neoadjuvant cohort, NAC) or adjuvant ICIs (adjuvant cohort, AC) at 17 centers in China. Patients with stage IV disease were also eligible if all tumor lesions were radically resectable. RESULTS: In NAC (n = 124), objective response rates were 75.7% and 55.4%, respectively, in CRC and GC, and pathological complete response rates were 73.4% and 47.7%, respectively. The 3-year disease-free survival (DFS) and overall survival (OS) rates were 96% (95%CI 90-100%) and 100% for CRC (median follow-up [mFU] 29.4 months), respectively, and were 84% (72-96%) and 93% (85-100%) for GC (mFU 33.0 months), respectively. In AC (n = 48), the 3-year DFS and OS rates were 94% (84-100%) and 100% for CRC (mFU 35.5 months), respectively, and were 92% (82-100%) and 96% (88-100%) for GC (mFU 40.4 months), respectively. Among the seven patients with distant relapse, four received dual blockade of PD1 and CTLA4 combined with or without chemo- and targeted drugs, with three partial response and one progressive disease. CONCLUSION: With a relatively long follow-up, this study demonstrated that neoadjuvant and adjuvant ICIs might be both associated with promising DFS and OS in dMMR/MSI-H CRC and GC, which should be confirmed in further randomized clinical trials.

A Pressure and Proximity Sensor Based on Laser-Induced Graphene.

Smart wearable devices are extensively utilized across diverse domains due to their inherent advantages of flexibility, portability, and real-time monitoring. Among these, flexible sensors demonstrate exceptional pliability and malleability, making them a prominent focus in wearable electronics research. However, the implementation of flexible wearable sensors often entails intricate and time-consuming processes, leading to high costs, which hinder the advancement of the entire field. Here, we report a pressure and proximity sensor based on oxidized laser-induced graphene (oxidized LIG) as a dielectric layer sandwiched by patterned LIG electrodes, which is characterized by high speed and cost-effectiveness. It is found that in the low-frequency range of fewer than 0.1 kHz, the relative dielectric constant of the oxidized LIG layer reaches an order of magnitude of 104. The pressure mode of this bimodal capacitive sensor is capable of detecting pressures within the range of 1.34 Pa to 800 Pa, with a response time of several hundred milliseconds. The proximity mode involves the application of stimulation using an acrylic probe, which demonstrates a detection range from 0.05 mm to 37.8 mm. Additionally, it has a rapid response time of approximately 100 ms, ensuring consistent signal variations throughout both the approach and withdrawal phases. The sensor fabrication method proposed in this project effectively minimizes expenses and accelerates the preparation cycle through precise control of laser processing parameters to shape the electrode-dielectric layer-electrode within a single substrate material. Based on their exceptional combined performance, our pressure and proximity sensors exhibit significant potential in practical applications such as motion monitoring and distance detection.

Electrochemical Sensors Based on Self-Assembling Peptide/Carbon Nanotube Nanocomposites for Sensitive Detection of Bisphenol A.

In this study, a cationic amphiphilic self-assembling peptide (SAP) Z23 was designed, and a simple bisphenol a (BPA) sensor, based on SAP Z23/multiwalled carbon nanotubes (Z23/MWCNTs) composite, was successfully fabricated on the surface of a glassy carbon electrode (GCE). The composite material was formed by π-π stacking interaction between the aromatic group on the hydrophobic side of Z23 and the side-wall of MWCNTs, with the charged hydrophilic group of Z23 exposed. During the electrocatalytic process of BPA, a synergistic effect was observed between Z23 and MWCNTs. The current response of the sensor based on composite material was 3.24 times that of the MWCNTs-modified electrode, which was much higher than that of the peptide-based electrode. Differential pulse voltammetry (DPV) was used to optimize the experimental conditions affecting the analytical performance of the modified electrode. Under optimal conditions, the linear range of the sensor was from 10 nM to 100 µM by amperometric measurement with sensitivity and limit of detection (LOD) at 6.569 µAµM-1cm-2 and 1.28 nM (S/N = 3), respectively. Consequently, the sensor has excellent electrochemical performance and is easy to fabricate, making it a good prospect in the field of electrochemical detection in the future.

S100A9+CD14+ monocytes contribute to anti-PD-1 immunotherapy resistance in advanced hepatocellular carcinoma by attenuating T cell-mediated antitumor function.

BACKGROUND: The paucity of reliable biomarkers for predicting immunotherapy efficacy in patients with advanced hepatocellular carcinoma (HCC) has emerged as a burgeoning concern with the expanding use of immunotherapy. This study endeavors to delve into the potential peripheral biomarkers capable of prognosticating efficacy in HCC patients who are poised to receive anti-PD-1 monotherapy within the phase III clinical trial, KEYNOTE394. Additionally, we sought to elucidate the underlying molecular mechanisms for resistance to immune checkpoint blockade (ICB) and propose innovative combination immunotherapy strategies for future clinical application. METHODS: Patient blood samples were collected for single-cell RNA sequencing to evaluate the immune cell signature before receiving ICB therapy. Subsequently, in vitro assays and in vivo murine model experiments were conducted to validate the mechanism that S100A9+CD14+ monocytes play a role in ICB resistance. RESULTS: Our study demonstrates a notable enrichment of S100A9+CD14+ monocytes in the peripheral blood of patients exhibiting suboptimal responses to anti-PD-1 therapy. Moreover, we identified the Mono_S100A9 signature as a predictive biomarker, indicative of reduced efficacy in immunotherapy and decreased survival benefits across various tumor types. Mechanistically, S100A9 activates PD-L1 transcription by directly binding to the CD274 (PD-L1) gene promoter, thereby suppressing T-cell proliferation and cytotoxicity via the PD-1/PD-L1 axis, consequently diminishing the therapeutic effectiveness of subsequent anti-PD-1 treatments. Furthermore, our in vivo studies revealed that inhibiting S100A9 can synergistically enhance the efficacy of anti-PD-1 drugs in the eradication of hepatocellular carcinoma. CONCLUSIONS: Our study underscores the significance of S100A9+CD14+ monocytes in predicting inadequate response to ICB treatment and provides insights into the monocyte cell-intrinsic mechanisms of resistance to ICB therapy. We also propose a combined therapeutic approach to enhance ICB efficacy by targeting S100A9.

A multiomics analysis-assisted deep learning model identifies a macrophage-oriented module as a potential therapeutic target in colorectal cancer.

Colorectal cancer (CRC) is a common malignancy involving multiple cellular components. The CRC tumor microenvironment (TME) has been characterized well at single-cell resolution. However, a spatial interaction map of the CRC TME is still elusive. Here, we integrate multiomics analyses and establish a spatial interaction map to improve the prognosis, prediction, and therapeutic development for CRC. We construct a CRC immune module (CCIM) that comprises FOLR2+ macrophages, exhausted CD8+ T cells, tolerant CD8+ T cells, exhausted CD4+ T cells, and regulatory T cells. Multiplex immunohistochemistry is performed to depict the CCIM. Based on this, we utilize advanced deep learning technology to establish a spatial interaction map and predict chemotherapy response. CCIM-Net is constructed, which demonstrates good predictive performance for chemotherapy response in both the training and testing cohorts. Lastly, targeting FOLR2+ macrophage therapeutics is used to disrupt the immunosuppressive CCIM and enhance the chemotherapy response in vivo.

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A 70-year-old man had radical surgery for colon cancer one year before the symptoms of memory loss and decreasing cognitive function. Subsequent magnetic resonance imaging revealed a brain mass, which was surgically resected and confirmed to be metastatic intestinal adenocarcinoma. Immunohistochemistry of the primary tumor and brain metastasis showed mismatch repair deficiency. The patient received adjuvant chemotherapy after surgery. However, the brain metastasis relapsed one month after the last chemotherapy. Genetic testing on the resected colon tumor samples confirmed microsatellite instability-high with a high tumor mutation burden by 77.7 muts/Mb. The patient was subsequently treated with programmed death-1 (PD-1) monoclonal antibody pembrolizumab (keytruda). The brain metastatic lesions were completely shrunk, and a complete clinical response was achieved.

Nano-enhanced immunotherapy: Targeting the immunosuppressive tumor microenvironment.

The tumor microenvironment (TME), which is mostly composed of tumor cells, immune cells, signaling molecules, stromal tissue, and the vascular system, is an integrated system that is conducive to the formation of tumors. TME heterogeneity makes the response to immunotherapy different in different tumors, such as "immune-cold" and "immune-hot" tumors. Tumor-associated macrophages, myeloid-derived suppressor cells, and regulatory T cells are the major suppressive immune cells and their different phenotypes interact and influence cancer cells by secreting different signaling factors, thus playing a key role in the formation of the TME as well as in the initiation, growth, and metastasis of cancer cells. Nanotechnology development has facilitated overcoming the obstacles that limit the further development of conventional immunotherapy, such as toxic side effects and lack of targeting. In this review, we focus on the role of three major suppressive immune cells in the TME as well as in tumor development, clinical trials of different drugs targeting immune cells, and different attempts to combine drugs with nanomaterials. The aim is to reveal the relationship between immunotherapy, immunosuppressive TME and nanomedicine, thus laying the foundation for further development of immunotherapy.

Hydrogen Peroxide and Dopamine Sensors Based on Electrodeposition of Reduced Graphene Oxide/Silver Nanoparticles.

In this work, silver nanoparticles (AgNPs)/reduced graphene oxide (rGO) nanocomposites were electrodeposited on glassy carbon electrodes (GCE) to construct electrochemical sensors for the detection of hydrogen peroxide (H2O2) and dopamine (DA). The AgNPs were synthesized on graphene oxide (GO) by the hydrothermal method, followed by the reduction of the GO during the electrodeposition process, resulting in the formation of the nanocomposites on the surface of the electrodes. The generation of AgNPs on the graphene sheets was verified by scanning electron microscopy (SEM) and electrochemical impedance spectroscopy (EIS). The AgNPs/rGO/GCE showed a linear response to H2O2 in the range of 5 µM to 620 µM, with a sensitivity of 49 µA mM-1cm-2 and a limit of detection (LOD) of 3.19 µA. The linear response of the AgNPs/rGO/GCE to DA ranged from 1 µM to 276 µM, the sensitivity was 7.86 µA mM-1cm-2, and the LOD was 0.18 µM. Furthermore, DA and H2O2 were detected simultaneously in the same solution without interferences, and the sensors displayed good stability over time. The preparation method for the sensors is relatively eco-friendly, convenient, and efficient, exhibiting great potential for sensitive detection of DA and H2O2.

The Pathological Factors Involved in Current In Vitro Atherosclerotic Models.

Cardiovascular disease stemmed from atherosclerosis (AS) is well recognized to be the predominant cause of global death. To comprehensively clarify the pathogenesis of AS, exploit effective drugs, as well as develop therapeutic solutions, various atherosclerotic models were constructed in vitro and widely utilized by the scientific community. Compared with animal models, the in vitro atherosclerotic models play a prominent role not only in the targeted research of single pathological factor related to AS in the human derived system, but also in the combined study on multipathological factors leading to AS, thereby contributing tremendously to the in-depth elucidation of atherosclerotic pathological process. In the current review, a variety of pathological factors incorporated into the existing atherosclerotic models in vitro are broadly elaborated, including the pathological mechanism, in vitro simulation approaches, and the desired improvement perspectives for reproducing each pathological factor. In addition, this review also summarizes the advantages and disadvantages of current atherosclerotic models as well as their potential functionality. Finally, the promising aspects for future atherosclerotic models in vitro with potential advances are also discussed.

Development of a whole-slide-level segmentation-based dMMR/pMMR deep learning detector for colorectal cancer.

To investigate whole-slide-level prediction in the field of artificial intelligence identification of dMMR/pMMR from hematoxylin and eosin (H&E) in colorectal cancer (CRC), we established a segmentation-based dMMR/pMMR deep learning detector (SPEED). Our model was approximately 1,700 times faster than that of the classification-based model. For the internal validation cohort, our model yielded an overall AUC of 0.989. For the external validation cohort, the model exhibited a high performance, with an AUC of 0.865. The human‒machine strategy further improved the model performance for external validation by an AUC up to 0.988. Our whole-slide-level prediction model provided an approach for dMMR/pMMR detection from H&E whole slide images with excellent predictive performance and less computer processing time in patients with CRC.

RUNX-3-expressing CAR T cells targeting glypican-3 in patients with heavily pretreated advanced hepatocellular carcinoma: a phase I trial.

Background: Glypican-3 (GPC3) is a well-characterized hepatocellular carcinoma (HCC)-associated antigen and a promising target for HCC treatment. CT017 CAR T cells were engineered to co-express CAR-GPC3 and runt-related transcription factor 3 (RUNX3), which triggers CD8+ T-cell infiltration into the cancer microenvironment. Methods: This single-center, single-arm, open-label, phase I clinical study enrolled heavily pretreated patients with GPC3-positive HCC between August 2019 and December 2020 (NCT03980288). Patients were treated with CT017 CAR T cells at a dose of 250 × 106 cells. The primary objective was to assess the safety and tolerability of this first-in-human product. Findings: Six patients received 7 infusions (one patient received 2 infusions) at the 250 × 106 cells dose. Three patients received CT017 monotherapy, and three patients received CT017-tyrosine kinase inhibitor (TKI) combination therapy at the first infusion. One patient received CT017-TKI combination therapy at the second infusion after CT017 monotherapy. All patients experienced cytokine release syndrome (CRS), with 50% (3/6) at Grade 2, 50% (3/6) at Grade 3, and all events resolved after treatment. No immune effector cell-associated neurotoxicity syndrome was observed. Dose escalation was not performed due to the investigator's decision regarding safety. Of six evaluable patients, one achieved partial response and two had stable disease for a 16.7% objective response rate, 50% disease control rate, 3.5-month median progression-free survival, 3.2-month median duration of disease control, and 7.9-month median overall survival (OS) with 7.87-month median follow-up. The longest OS was 18.2 months after CT017 infusion. Interpretation: Current preliminary phase I data showed a manageable safety profile and promising antitumor activities of CT017 for patients with advanced HCC. These results need to be confirmed in a robust clinical trial. Funding: This study was funded by CARsgen Therapeutics Co., Ltd.

Advances in Alzheimer's Disease-Associated Aß Therapy Based on Peptide.

Alzheimer's disease (AD) urgently needs innovative treatments due to the increasing aging population and lack of effective drugs and therapies. The amyloid fibrosis of AD-associated ß-amyloid (Aß) that could induce a series of cascades, such as oxidative stress and inflammation, is a critical factor in the progression of AD. Recently, peptide-based therapies for AD are expected to be great potential strategies for the high specificity to the targets, low toxicity, fast blood clearance, rapid cell and tissue permeability, and superior biochemical characteristics. Specifically, various chiral amino acids or peptide-modified interfaces draw much attention as effective manners to inhibit Aß fibrillation. On the other hand, peptide-based inhibitors could be obtained through affinity screening such as phage display or by rational design based on the core sequence of Aß fibrosis or by computer aided drug design based on the structure of Aß. These peptide-based therapies can inhibit Aß fibrillation and reduce cytotoxicity induced by Aß aggregation and some have been shown to relieve cognition in AD model mice and reduce Aß plaques in mice brains. This review summarizes the design method and characteristics of peptide inhibitors and their effect on the amyloid fibrosis of Aß. We further describe some analysis methods for evaluating the inhibitory effect and point out the challenges in these areas, and possible directions for the design of AD drugs based on peptides, which lay the foundation for the development of new effective drugs in the future.

A Novel Closed-Loop Control to Solve Light Source Power Fluctuations in the Fiber-Optic Gyroscope.

The performance of a gyroscope is directly affected by the fluctuations in the light source power (LSP) in an interferometric fiber-optic gyroscope (IFOG). Therefore, it is important to compensate for fluctuations in the LSP. When the feedback phase generated by the step wave completely cancels the Sagnac phase in real-time, the error signal of the gyroscope is linearly related to the differential signal of the LSP, otherwise, the error signal of the gyroscope is uncertain. Herein, we present two compensation methods to compensate for the error of the gyroscope when the error is uncertain, which are double period modulation (DPM) and triple period modulation (TPM). Compared with the TPM, DPM has better performance, but it increases the requirements for the circuit. TPM has lower requirements for the circuit and is more suitable for small fiber- coil applications. The experimental results show that, when the frequency of the LSP fluctuation is relatively low (1 kHz and 2 kHz), DPM and TPM do not differ significantly in terms of performance; both of them can achieve an improvement of about 95% in bias stability. When the frequency of the LSP fluctuation is relatively high (4 kHz, 8 kHz and 16 kHz), DPM and TPM can achieve about 95% and 88% improvement in bias stability, respectively.

Visualization of Cell Membrane Tension Regulated by the Microfilaments as a "Shock Absorber" in Micropatterned Cells.

The extracellular stress signal transmits along the cell membrane-cytoskeleton-focal adhesions (FAs) complex, regulating the cell function through membrane tension. However, the mechanism of the complex regulating membrane tension is still unclear. This study designed polydimethylsiloxane stamps with specific shapes to change the actin filaments' arrangement and FAs' distribution artificially in live cells, visualized the membrane tension in real time, and introduced the concept of information entropy to describe the order degree of the actin filaments and plasma membrane tension. The results showed that the actin filaments' arrangement and FAs' distribution in the patterned cells were changed significantly. The hypertonic solution resulted in the plasma membrane tension of the pattern cell changing more evenly and slowly in the zone rich in cytoskeletal filaments than in the zone lacking filaments. In addition, the membrane tension changed less in the adhesive area than in the non-adhesive area when destroying the cytoskeletal microfilaments. This suggested that patterned cells accumulated more actin filaments in the zone where FAs were difficult to generate to maintain the stability of the overall membrane tension. The actin filaments act as shock absorbers to cushion the alternation in membrane tension without changing the final value of membrane tension.

Rapid Prototyping Flexible Capacitive Pressure Sensors Based on Porous Electrodes.

Flexible pressure sensors are widely applied in tactile perception, fingerprint recognition, medical monitoring, human-machine interfaces, and the Internet of Things. Among them, flexible capacitive pressure sensors have the advantages of low energy consumption, slight signal drift, and high response repeatability. However, current research on flexible capacitive pressure sensors focuses on optimizing the dielectric layer for improved sensitivity and pressure response range. Moreover, complicated and time-consuming fabrication methods are commonly applied to generate microstructure dielectric layers. Here, we propose a rapid and straightforward fabrication approach to prototyping flexible capacitive pressure sensors based on porous electrodes. Laser-induced graphene (LIG) is produced on both sides of the polyimide paper, resulting in paired compressible electrodes with 3D porous structures. When the elastic LIG electrodes are compressed, the effective electrode area, the relative distance between electrodes, and the dielectric property vary accordingly, thereby generating a sensitive pressure sensor in a relatively large working range (0-9.6 kPa). The sensitivity of the sensor is up to 7.71%/kPa-1, and it can detect pressure as small as 10 Pa. The simple and robust structure allows the sensor to produce quick and repeatable responses. Our pressure sensor exhibits broad potential in practical applications in health monitoring, given its outstanding comprehensive performance combined with its simple and quick fabrication method.

Induction of Tumor Ferroptosis-Dependent Immunity via an Injectable Attractive Pickering Emulsion Gel.

The combination of ferroptosis inducers and immune checkpoint blockade can enhance antitumor effects. However, the efficacy in tumors with low immunogenicity requires further investigation. In this work, a water-in-oil Pickering emulsion gel is developed to deliver (1S, 3R)-RSL-3 (RSL-3), a ferroptosis inducer dissolved in iodized oil, and programmed death-1 (PD-1) antibody, the most commonly used immune checkpoint inhibitor dissolved in water, with optimal characteristics (RSL-3 + PD-1@gel). Tumor lipase degrades the continuous oil phase, which results in the slow release of RSL-3 and PD-1 antibody and a notable antitumor effect against low-immunogenic hepatocellular carcinoma and pancreatic cancer. Intriguingly, the RSL-3 + PD-1@gel induces ferroptosis of tumor cells, resulting in antitumor immune response via accumulation of helper T lymphocyte cells and cytotoxic T cells. Additionally, the single-cell sequence profiling analysis during tumor treatment reveals the induction of ferroptosis in tumor cells together with strong antitumor immune response in ascites.