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1.
Sensors (Basel) ; 24(12)2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38931691

ABSTRACT

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.

2.
J Exp Clin Cancer Res ; 43(1): 72, 2024 Mar 08.
Article in English | MEDLINE | ID: mdl-38454445

ABSTRACT

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.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Animals , Mice , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/genetics , Monocytes/metabolism , Liver Neoplasms/drug therapy , Liver Neoplasms/metabolism , B7-H1 Antigen/metabolism , T-Lymphocytes/metabolism , Immunotherapy , Tumor Microenvironment , Calgranulin B/metabolism
3.
Sensors (Basel) ; 24(5)2024 Feb 23.
Article in English | MEDLINE | ID: mdl-38474999

ABSTRACT

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.


Subject(s)
Benzhydryl Compounds , Nanocomposites , Nanotubes, Carbon , Phenols , Electrochemical Techniques/methods , Nanotubes, Carbon/chemistry , Limit of Detection , Nanocomposites/chemistry , Electrodes
4.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 53(1): 58-63, 2024 Feb 15.
Article in English, Chinese | MEDLINE | ID: mdl-38413220

ABSTRACT

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.


Subject(s)
Adenocarcinoma , Antineoplastic Agents, Immunological , Brain Neoplasms , Colonic Neoplasms , Colorectal Neoplasms , Neoplastic Syndromes, Hereditary , Male , Humans , Aged , Programmed Cell Death 1 Receptor/genetics , Programmed Cell Death 1 Receptor/therapeutic use , Antibodies, Monoclonal/therapeutic use , Mutation , Antineoplastic Agents, Immunological/therapeutic use
5.
Cell Rep Med ; 5(2): 101399, 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38307032

ABSTRACT

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.


Subject(s)
Colorectal Neoplasms , Deep Learning , Folate Receptor 2 , Humans , CD8-Positive T-Lymphocytes , Multiomics , Macrophages , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Tumor Microenvironment/genetics
6.
Biomaterials ; 305: 122463, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38232643

ABSTRACT

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.


Subject(s)
Nanostructures , Neoplasms , Humans , Tumor Microenvironment , Immunotherapy , Neoplasms/drug therapy , Nanomedicine
7.
Sensors (Basel) ; 24(2)2024 Jan 07.
Article in English | MEDLINE | ID: mdl-38257448

ABSTRACT

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.

8.
Article in English | MEDLINE | ID: mdl-38258801

ABSTRACT

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.

9.
iScience ; 26(12): 108468, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-38077136

ABSTRACT

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.

10.
Int J Mol Sci ; 24(17)2023 Aug 23.
Article in English | MEDLINE | ID: mdl-37685916

ABSTRACT

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.


Subject(s)
Alzheimer Disease , Animals , Mice , Alzheimer Disease/drug therapy , Amyloid beta-Peptides , Aging , Amino Acids , Amyloidogenic Proteins
11.
EClinicalMedicine ; 63: 102175, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37680942

ABSTRACT

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.

12.
Sensors (Basel) ; 23(10)2023 May 09.
Article in English | MEDLINE | ID: mdl-37430503

ABSTRACT

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.

13.
Biology (Basel) ; 12(6)2023 Jun 20.
Article in English | MEDLINE | ID: mdl-37372173

ABSTRACT

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.

14.
Biosensors (Basel) ; 13(5)2023 May 14.
Article in English | MEDLINE | ID: mdl-37232907

ABSTRACT

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.


Subject(s)
Graphite , Humans , Porosity , Electrodes
15.
Adv Mater ; 35(35): e2303542, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37192546

ABSTRACT

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.

16.
Chem Commun (Camb) ; 59(29): 4368-4371, 2023 Apr 06.
Article in English | MEDLINE | ID: mdl-36946304

ABSTRACT

We have developed a reactive oxygen species (ROS) sensor based on nanopores modified with GGGCEG(GPGGA)4CEG. The formation of an intramolecular disulfide bond oxidized by ROS leads to conformation changes in GGGCEG(GPGGA)4CEG, which then induces an obvious change in the size of the nanopores and a corresponding ionic current change. This work allows the accurate and dynamic monitoring of ROS through the combination of (GPGGA)4 and nanopores.

17.
Cell Rep Med ; 4(4): 100987, 2023 04 18.
Article in English | MEDLINE | ID: mdl-36990096

ABSTRACT

Immunometabolism in the tumor microenvironment (TME) and its influence on the immunotherapy response remain uncertain in colorectal cancer (CRC). We perform immunometabolism subtyping (IMS) on CRC patients in the training and validation cohorts. Three IMS subtypes of CRC, namely, C1, C2, and C3, are identified with distinct immune phenotypes and metabolic properties. The C3 subtype exhibits the poorest prognosis in both the training cohort and the in-house validation cohort. The single-cell transcriptome reveals that a S100A9+ macrophage population contributes to the immunosuppressive TME in C3. The dysfunctional immunotherapy response in the C3 subtype can be reversed by combination treatment with PD-1 blockade and an S100A9 inhibitor tasquinimod. Taken together, we develop an IMS system and identify an immune tolerant C3 subtype that exhibits the poorest prognosis. A multiomics-guided combination strategy by PD-1 blockade and tasquinimod improves responses to immunotherapy by depleting S100A9+ macrophages in vivo.


Subject(s)
Colorectal Neoplasms , Multiomics , Humans , Programmed Cell Death 1 Receptor , Immunotherapy , Macrophages , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Tumor Microenvironment
18.
JCO Precis Oncol ; 7: e2200463, 2023 03.
Article in English | MEDLINE | ID: mdl-36996375

ABSTRACT

PURPOSE: To investigate the efficacy of PD-1/PD-L1 inhibitors plus chemotherapy versus anti-PD-1/PD-L1 monotherapy in advanced microsatellite instability (MSI)/mismatch repair-deficient (dMMR) gastrointestinal cancers. METHODS: We retrospectively recruited patients with MSI/dMMR gastrointestinal cancer who received anti-PD-1/PD-L1 with or without chemotherapy and compared objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) of PD-1/PD-L1 inhibitor plus chemotherapy (chemo-anti-PD-1/PD-L1 group) and PD-1/PD-L1 inhibitor alone (anti-PD-1/PD-L1 group). Propensity score-based overlap weighting analysis was conducted to adjust the baseline covariable imbalance. Sensitivity analysis was performed to confirm the stability of the results by propensity score matching and multivariable Cox and logistic regression models. RESULTS: A total of 256 patients were eligible, with 68 and 188 receiving chemo-anti-PD-1/PD-L1 and anti-PD-1/PD-L1, respectively. The chemo-anti-PD-1/PD-L1 group showed significant improvements versus the anti-PD-1/PD-L1 group in ORR (61.8% v 38.8%; P = .001), DCR (92.6% v 74.5%; P = .002), PFS (median PFS [mPFS], not reached [NR] v 27.9 months; P = .004), and OS (median OS [mOS], NR v NR; P = .014). After overlap weighting, the improvements tended to be more significant with chemo-anti-PD-1/PD-L1 versus anti-PD-1/PD-L1 in ORR (62.5% v. 38.3%; P < .001), DCR (93.8% v 74.2%; P < .001), PFS (mPFS, NR v 26.0 months; P = .004), and OS (mOS, NR v NR; P = .010). These results were solidified through sensitivity analysis. CONCLUSION: Chemo-anti-PD-1/PD-L1 is superior to anti-PD-1/PD-L1 in MSI/dMMR gastrointestinal cancers with improved efficacy.


Subject(s)
Colorectal Neoplasms , Immune Checkpoint Inhibitors , Humans , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/therapeutic use , B7-H1 Antigen/genetics , Retrospective Studies , Microsatellite Instability , Colorectal Neoplasms/drug therapy
19.
Heliyon ; 9(2): e13629, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36846668

ABSTRACT

Background: KMT2D mutation (KMT2DMT) was found to play an important role in cancer immunity and response to immune checkpoint inhibitors (ICIs). The present study aims to investigate the association between KMT2D exon 39 mutation (K-ex39MT) and molecular and clinical characteristics in colorectal adenocarcinoma (CRAD). Methods: We performed profiling of KMT2DMT and K-ex39MT via Kaplan-Meier analysis, cBioportal, Immune-related functional analysis and correlation analysis with TCGA and MSK cohorts to explore their effects on the prognosis, immune landscape, molecular characteristics and drug sensitivity in CRAD. Panel gene sequencing of 30 in-house CRAD tissues and multiple immunofluorescences (mIF) were also used. Results: In multi-cancer, patients with KMT2DMT have a worse overall survival (OS), and CRAD with K-ex39MT exhibited a greater degree of immune cellular infiltration. For CRAD, compared with KMT2D exon39 wild type (K-ex39WT), K-ex39MT patients had higher tumor mutational burden (TMB) and lower copy number alteration (CNA), and were accompanied by more immune cell infiltration including activated T cells, NK cells, Treg cells and exhausted T cells and enrichment of immune-related genes and pathways. In drug sensitivity prediction, K-ex39MT patients have a lower CTX-S score and IC50 of 5-Fluorouracil and irinotecan, and higher Tumor Immune Dysfunction and Rejection (TIDE) dysfunction score. Conclusions: CRAD patients with K-ex39MT have more abundant immune cell infiltration and enrichment of immune-related pathways and signatures. And they may be more sensitive to some chemotherapies but less to cetuximab.

20.
Sensors (Basel) ; 23(4)2023 Feb 08.
Article in English | MEDLINE | ID: mdl-36850522

ABSTRACT

An interferometric fiber-optic gyroscope (IFOG) demodulates a rotation signal via interferometric light intensity. However, the working environments of IFOGs typically involve great uncertainty. Fluctuations in temperature, air pressure, electromagnetic field, and the power system all cause the power of the superluminescent diode (SLD) light source to fluctuate as well. In this invited paper, we studied the effects of SLD power fluctuation on the dynamic and static performance characteristics of a gyro system through the use of a light-power feedback loop. Fluctuations of 0.5 mA, 1 mA, and 5 mA in the SLD source entering the IFOG caused zero-bias stability to be 69, 135, and 679 times worse. We established an effective method to monitor power fluctuations of SLD light sources and to compensate for their effects without increasing hardware complexity or system cost. In brief, we established a real-time power-sensing and -compensating system. Experimental results showed that for every 0.1 mA increase in the fluctuation amplitude of the driving current, the zero-bias stability became 4 to 7 times worse, which could be reduced about 95% through the use of SLD power compensation.

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