Ganoderma lucidum Polysaccharide Supplementation Significantly Activates T-Cell-Mediated Antitumor Immunity and Enhances Anti-PD-1 Immunotherapy Efficacy in Colorectal Cancer.

Ganoderma lucidum polysaccharide (GLP) is a prebiotic with immunomodulatory effects. However, the therapeutic potential of GLP in tumor immunotherapy has not been fully explored, especially in T cell-mediated antitumor immunity. In this study, we found that GLP significantly inhibited tumor growth and activated antitumor immunity in colorectal cancer (CRC). In the spleens and tumor tissues, the proportion of cytotoxic CD8+T cells and Th1 helper cells increased, while immunosuppressive Tregs decreased. Additionally, microbiota dysbiosis was alleviated by GLP, and short-chain fatty acid production was increased. Meanwhile, GLP decreased the ratio of kynurenine and tryptophan (Kyn/Trp) in the serum, which contributed to antitumor immunity of T cells. More importantly, the combination of GLP and the immune checkpoint inhibitor anti-PD-1 monoclonal antibody further enhanced the efficacy of anti-PD-1 immunotherapy. Thus, GLP as a prebiotic has the potential to be used in tumor immunotherapy.

Photoelectrochemical aptasensing of lincomycin based on a AgI-carboxylated multiwalled carbon nanotubes-BiOI Z-scheme heterojunction.

Lincomycin (LIN) is a common antibiotic that is widely used in animal husbandry and other fields, and the residual problem caused by its abuse has attracted widespread attention. Herein, a novel AgI-carboxylated multiwalled carbon nanotubes (cMWCNT)-BiOI Z-scheme heterojunction material was synthesized via a one-pot hydrothermal method, modified on a fluorine-doped tin oxide (FTO) electrode surface, and used for detecting LIN. The photocurrent on the AgI-cMWCNT-BiOI/FTO photoelectrode is 4.6 times that on the control AgI-BiOI/FTO photoelectrode. An amino-functionalized LIN aptamer was fixed on the AgI-cMWCNT-BiOI/FTO photoelectrode by the cross-linking reaction between chitosan and glutaraldehyde, and then Ru(NH3)63+ was electrostatically attached to the LIN aptamer to increase the photocurrent response to the LIN binding. When LIN binds competitively with Ru(NH3)63+ to the aptamer, the photocurrent signal can be quantitatively decreased. Under optimized conditions, the anodic photocurrent at 0 V vs KCl-saturated calomel electrode in 0.1 M phosphate buffer (pH 7.0) containing 0.100 M ascorbic acid was linear with the common logarithm of LIN concentration from 10.0 pM to 500 nM, with a limit of detection of 2.8 pM (S/N = 3). Satisfactory recovery results were obtained in the analysis of cow milk samples.

Cell metabolism-based optimization strategy of CAR-T cell function in cancer therapy.

Adoptive cell therapy (ACT) using chimeric antigen receptor (CAR)-modified T cells has revolutionized the field of immune-oncology, showing remarkable efficacy against hematological malignancies. However, its success in solid tumors is limited by factors such as easy recurrence and poor efficacy. The effector function and persistence of CAR-T cells are critical to the success of therapy and are modulated by metabolic and nutrient-sensing mechanisms. Moreover, the immunosuppressive tumor microenvironment (TME), characterized by acidity, hypoxia, nutrient depletion, and metabolite accumulation caused by the high metabolic demands of tumor cells, can lead to T cell "exhaustion" and compromise the efficacy of CAR-T cells. In this review, we outline the metabolic characteristics of T cells at different stages of differentiation and summarize how these metabolic programs may be disrupted in the TME. We also discuss potential metabolic approaches to improve the efficacy and persistence of CAR-T cells, providing a new strategy for the clinical application of CAR-T cell therapy.

Photoelectrochemical aptasensing of oxytetracycline based on a BiVO4-carboxylated graphene-WO3 Z-scheme heterojunction.

A new BiVO4-carboxylated graphene (cG)-WO3 Z-scheme heterojunction was constructed on a fluorine-doped tin oxide (FTO) substrate electrode by ultrasonic mixing and cast-coating for determination of oxytetracycline (OTC). Since cG can absorb visible light and well match with the energy levels of WO3 and BiVO4 to promote the charge separation and transfer, the photocurrent on the BiVO4-cG-WO3/FTO photoelectrode is 4.4 times that on the control BiVO4-WO3/FTO photoelectrode. An amino-functionalized OTC aptamer was fixed on the BiVO4-cG-WO3/FTO photoelectrode by the 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide mediated amide reaction, and then hexaammonium ruthenium(III) (Ru(NH3)63+) was attached to the OTC aptamer to increase the photocurrent response to the OTC binding. Under the optimized conditions, the photocurrent on the BiVO4-cG-WO3/FTO photoelectrode at 0 V vs SCE was linear with the common logarithm of OTC concentration from 0.01 nM to 500 nM, with a limit of detection of 3.1 pM (S/N = 3). Satisfactory recovery results were obtained in the analysis of real water samples.

Sandwich photoelectrochemical biosensing of concanavalin A based on CdS/AuNPs/NiO Z-scheme heterojunction and lectin-sugar binding.

A CdS/AuNPs/NiO Z-scheme heterojunction was prepared on a fluorine-doped tin oxide (FTO) electrode by hydrothermal synthesis of NiO on FTO, electrodeposition of AuNPs on NiO/FTO electrode and then cast-coating of CdS quantum dots. The CdS/AuNPs/NiO/FTO electrode gave a notably increased photocurrent versus NiO/FTO, CdS/FTO, AuNPs/NiO/FTO, CdS/AuNPs/FTO and CdS/NiO/FTO electrodes. The CdS/AuNPs/NiO/FTO electrode was further cast-coated with chitosan to immobilize d-mannose by Schiff base reaction, and concanavalin A (ConA) and then horseradish peroxidase (HRP) were captured on the electrode surface by lectin-sugar binding. 4-Chloro-1-naphthol (4-CN) was oxidized to form an insoluble precipitate catalyzed by HRP in the presence of H2O2, and the presence of precipitate on the photoelectrode inhibited the photocurrent in the presence of holes scavenger ascorbic acid. The relevant electrodes were characterized by electrochemistry, quartz crystal microbalance (QCM), UV-vis spectrophotometry, scanning electron microscopy/energy dispersive spectroscopy, and transmission electron microscopy. The QCM revealed that the collection efficiency (η) of the 4-CN-electrooxidation precipitate on the electrode can be as high as 91.8%. Under the optimal conditions, the decline of photocurrent responded linearly to the common logarithm of ConA concentration from 50 pM to 500 nM, with a limit of detection of 17 pM (S/N = 3). Satisfactory results were obtained in the detection of real soybean samples.

Anodic Stripping Voltammetric Analysis of Trace Arsenic(III) on a Au-Stained Au Nanoparticles/Pyridine/Carboxylated Multiwalled Carbon Nanotubes/Glassy Carbon Electrode.

A Au-stained Au nanoparticle (Aus)/pyridine (Py)/carboxylated multiwalled carbon nanotubes (C-MWCNTs)/glassy carbon electrode (GCE) was prepared for the sensitive analysis of As(III) by cast-coating of C-MWCNTs on a GCE, electroreduction of 4-cyanopyridine (cPy) to Py, adsorption of gold nanoparticles (AuNPs), and gold staining. The Py/C-MWCNTs/GCE can provide abundant active surface sites for the stable loading of AuNPs and then the AuNPs-initiated Au staining in HAuCl4 + NH2OH solution, giving a large surface area of Au on the Aus/Py/C-MWCNTs/GCE for the linear sweep anodic stripping voltammetry (LSASV) analysis of As(III). At a high potential-sweep rate of 5 V s-1, sharp two-step oxidation peaks of As(0) to As(III) and As(III) to As(V) were obtained to realize the sensitive dual-signal detection of As(III). Under optimal conditions, the ASLSV peak currents for oxidation of As(0) to As(III) and of As(III) to As(V) are linear with a concentration of As(III) from 0.01 to 8 µM with a sensitivity of 0.741 mA µM-1 and a limit of detection (LOD) of 3.3 nM (0.25 ppb) (S/N = 3), and from 0.01 to 8.0 µM with a sensitivity of 0.175 mA µM-1 and an LOD of 16.7 nM (1.20 ppb) (S/N = 3), respectively. Determination of As(III) in real water samples yielded satisfactory results.

Six-Year BDS-2 Broadcast Navigation Message Analysis from 2013 to 2018: Availability, Anomaly, and SIS UREs Assessment.

The second-generation of the Beidou Navigation Satellite System (BDS-2) has been officially providing positioning, navigation, and timing (PNT) services within the Asia-Pacific region for six years, starting from 2013. A comprehensive analysis of BDS-2 satellite broadcast navigation message performance during the past six years is highly demanded, not only for the regional service but also for the global service announced in December 2018. Therefore, this study focuses on the performance assessment of six-year BDS-2 broadcast navigation messages from 2013 to 2018 in three aspects: Message availability, anomaly detection, and signal-in-space user range errors (SIS UREs). Firstly, our results, based on International GNSS service (IGS) Multi-GNSS Experiment (MGEX) navigation files, indicate that the BDS-2 Geosynchronous Earth Orbit (GEO) and Inclined Geosynchronous Satellite Orbit (IGSO) satellites have >98.51% broadcast navigation message availability, and the Medium Earth Orbit (MEO) satellites has a ~90.03% availability. Secondly, the comparison between broadcast navigation messages and IGS precise products reveals that the User Range Accuracy Index (URAI) contained in the broadcast message could not reflect satellite performance correctly. Another satellite status indicator, space vehicle (SV) health, can only partially detect a satellite anomaly. The anomaly detection result using IGS precise products for reference shows 20241 anomalies out of 651038 broadcast navigation messages within six years. Finally, compared with the IGSO and MEO satellites, the orbit qualities of GEO satellites are significantly worse due to their large along-track orbit error. The clock performance of all satellites are at the comparable level. The satellite orbit type (GEO/IGSO/MEO) does not impact the orbit-only URE, global-average URE, and worst-case URE.