Dietary arginine regulates the growth performance, antioxidant capacity, and immune response in Culter alburnus.

Culter alburnus is sensitive to stressors. Arginine is a precursor of nitric oxide, which can effectively relieve the level of oxidative stress and improve the antioxidant and immune capacity of fish. The effect of different arginine levels on topmouth culter (Culter alburnus) fry development performance, liver antioxidant capacity, and immune parameters were investigated in this study. Five diets (1.96%, ARG1, control group; 2.28%, ARG2; 2.52%, ARG3; 2.81%, ARG4; 3.09%, ARG5) were used to feed fry (initial weight 0.31 ± 0.01 g) for 8 weeks. The data showed that the final weight (FW), weight gain rate (WGR), and specific growth rate (SGR) of the ARG3 and ARG4 groups were significantly improved, while the feed conversion ratio (FCR) reduced significantly. Compared with the ARG1 group, all groups remarkably reduced the crude ash content of the whole body. The activity of hepatic superoxide dismutase (SOD) and the content of hepatic glutathione (GSH) were significantly increased in the ARG3 and ARG4 groups, while the malondialdehyde (MDA) content was significantly decreased. Compared with the ARG1 group, arginine levels in ARG2, ARG3, and ARG4 groups up-regulated the expression levels of Nrf2, down-regulated the gene expression level of Keap1 in the liver. And the expression of Nrf2/Keap1 pathway downstream genes Mn-SOD and CAT was up-regulated in ARG2 and ARG3 groups. Furthermore, the expression levels of MyD88 and IL-1ß were down-regulated, and the anti-inflammatory gene TGF-ß expression levels were up-regulated in the ARG2, ARG3, and ARG4 groups. Additionally, compared to the ARG1 group, there was a significant increase in the relative expression levels of the C3 and C4 genes in the ARG4 group. In conclusion, 2.28-2.81% dietary arginine levels improved the growth performance, promoted antioxidant capacity, and enhance immune response. The optimal level of arginine was determined by the quadratic regression analysis of SGR and FCR to be 2.55% of diet (5.43% of dietary protein) and 2.53% of diet (5.38% of dietary protein), accordingly.

Cancer Immunotherapy Based on Cell Membrane-Coated Nanocomposites Augmenting cGAS/STING Activation by Efferocytosis Blockade.

Innate immunity triggered by the cGAS/STING pathway has the potential to improve cancer immunotherapy. Previously, the authors reported that double-stranded DNA (dsDNA) released by dying tumor cells can trigger the cGAS/STING pathway. However, owing to efferocytosis, dying tumor cells are engulfed and cleared before the damaged dsDNA is released; hence, immunologic tolerance and immune escape occur. Herein, a cancer-cell-membrane biomimetic nanocomposites that exhibit tumor-immunotherapeutic effects are synthesized by augmenting the cGAS/STING pathway and suppressing efferocytosis. Once internalized by cancer cells, a combined chemo/chemodynamic therapy would be triggered, which damages their nuclear and mitochondrial DNA. Furthermore, the releasing Annexin A5 protein could inhibit efferocytosis effect and promote immunostimulatory secondary necrosis by preventing phosphatidylserine exposure, resulting in the burst release of dsDNA. These dsDNA fragments, as molecular patterns to immunogenic damage, escape from the cancer cells, activate the cGAS/STING pathway, enhance cross-presentation inside dendritic cells, and promote M1-polarization of tumor-associated macrophages. In vivo experiments suggest that the proposed nanocomposite could recruit cytotoxic T-cells and facilitate long-term immunological memory. Moreover, when combined with immune-checkpoint blockades, it could augment the immune response. Therefore, this novel biomimetic nanocomposite is a promising strategy for generating adaptive antitumor immune responses.

FPR3 reprograms glycolytic metabolism and stemness in gastric cancer via calcium-NFATc1 pathway.

Aerobic glycolysis accelerates tumor proliferation and progression, and inhibitors or drugs targeting abnormal cancer metabolism have been developing. Cancer stem-like cells (CSCs) significantly contribute to tumor initiation, metastasis, therapy resistance, and recurrence. Formyl peptide receptor 3 (FPR3), a member of FPR family, involves in inflammation, tissue repair, and angiogenesis. However, studies in exploring the regulatory mechanisms of aerobic glycolysis and CSCs by FPR3 in gastric cancer (GC) remain unknown. Here, we demonstrated that overexpressed FPR3 suppressed glycolytic capacity and stemness of tumor cells, then inhibited GC cells proliferation. Mechanistically, FPR3 impeded cytoplasmic calcium ion flux and hindered nuclear factor of activated T cells 1 (NFATc1) nuclear translocation, leading to the transcriptional inactivation of NFATc1-binding neurogenic locus notch homolog protein 3 (NOTCH3) promoter, subsequently obstructing NOTCH3 expression and the AKT/mTORC1 signaling pathway, and ultimately downregulating glycolysis. Additionally, NFATc1 directly binds to the sex determining region Y-box 2 (SOX2) promoter and modifies stemness in GC. In conclusion, our work illustrated that FPR3 played a negative role in GC progression by modulating NFATc1-mediated glycolysis and stemness in a calcium-dependent manner, providing potential insights into cancer therapy.

Lactate/GPR81 recruits regulatory T cells by modulating CX3CL1 to promote immune resistance in a highly glycolytic gastric cancer.

Lactate plays an important role in shaping immune tolerance in tumor microenvironment (TME) and correlates with poor prognosis in various solid tumors. Overcoming the immune resistance in an acidic TME may improve the anti-tumor immunity. Here, this study elucidated that via G-protein-coupled receptor 81 (GPR81), lactate could modulate immune tolerance in TME by recruiting regulatory T cells (Tregs) in vitro and in vivo. A high concentration of lactate was detected in cell supernatant and tissues of gastric cancer (GC), which was modulated by lactic dehydrogenase A (LDHA). GPR81 was the natural receptor of lactate and was overexpressed in different GC cell lines and samples, which correlated with poor outcomes in GC patients. Lactate/GPR81 signaling could promote the infiltration of Tregs into TME by inducing the expression of chemokine CX3CL1. GPR81 deficiency could decrease the infiltration of Tregs into TME, thereby inhibiting GC progression by weakening the inhibition of CD8+T cell function in a humanized mouse model. In conclusion, targeting the lactate/GPR81 signaling may potentially serve as a critical process to overcome immune resistance in highly glycolytic GC.

Icariside I enhances the effects of immunotherapy in gastrointestinal cancer via targeting TRPV4 and upregulating the cGAS-STING-IFN-I pathway.

Gastrointestinal cancer is among the most common cancers worldwide. Immune checkpoint inhibitor-based cancer immunotherapy has become an innovative approach in cancer treatment; however, its efficacy in gastrointestinal cancer is limited by the absence of infiltration of immune cells within the tumor microenvironment. Therefore, it is therefore urgent to develop a novel therapeutic drug to enhance immunotherapy. In this study, we describe a previously unreported potentiating effect of Icariside I (ICA I, GH01), the main bioactive compound isolated from the Epimedium species, on anti-tumor immune responses. Mechanistically, molecular docking and SPR assay result show that ICA I binding with TRPV4. ICA I induced intracellular Ca2+ increasing and mitochondrial DNA release by targeting TRPV4, which triggered cytosolic ox-mitoDNA release. Importantly, these intracellular ox-mitoDNA fragments were taken up by immune cells in the tumor microenvironment, which amplified the immune response. Moreover, our study shows the remarkable efficacy of sequential administration of ICA I and anti-α-PD-1 mAb in advanced tumors and provides a strong scientific rationale for recommending such a combination therapy for clinical trials. ICA I enhanced the anti-tumor effects with PD-1 inhibitors by regulating the TRPV4/Ca2+/Ox-mitoDNA/cGAS/STING axis. We expect that these findings will be translated into clinical therapies, which will benefit more patients with cancer in the near future.

SCD1 promotes the stemness of gastric cancer stem cells by inhibiting ferroptosis through the SQLE/cholesterol/mTOR signalling pathway.

Cancer stem cells (CSCs) play a substantial role in cancer onset and recurrence. Anomalous iron and lipid metabolism have been documented in CSCs, suggesting that ferroptosis, a recently discovered form of regulated cell death characterised by lipid peroxidation, could potentially exert a significant influence on CSCs. However, the precise role of ferroptosis in gastric cancer stem cells (GCSCs) remains unknown. To address this gap, we screened ferroptosis-related genes in GCSCs using The Cancer Genome Atlas and corroborated our findings through quantitative polymerase chain reaction and western blotting. These results indicate that stearoyl-CoA desaturase (SCD1) is a key player in the regulation of ferroptosis in GCSCs. This study provides evidence that SCD1 positively regulates the transcription of squalene epoxidase (SQLE) by eliminating transcriptional inhibition of P53. This mechanism increases the cholesterol content and the elevated cholesterol regulated by SCD1 inhibits ferroptosis via the mTOR signalling pathway. Furthermore, our in vivo studies showed that SCD1 knockdown or regulation of cholesterol intake affects the stemness of GCSCs and their sensitivity to ferroptosis inducers. Thus, targeting the SCD1/squalene epoxidase/cholesterol signalling axis in conjunction with ferroptosis inducers may represent a promising therapeutic approach for the treatment of gastric cancer based on GCSCs.

Strain engineering of electrocatalysts for hydrogen evolution reaction.

As the key half reaction of water-splitting electrolysis, the hydrogen evolution reaction (HER) that occurs at the cathode directly determines the overall efficiency of hydrogen production. To improve the efficiency of electrochemical water splitting for hydrogen generation, efficient and robust catalysts need to be developed. Strain engineering, which represents an effective and promising category of strategies, can regulate the electronic structures of catalysts by modulating the lattice strain and ultimately optimizing the HER dynamics. This work critically reviews the recent progress of strain engineering in HER and provides future perspectives for this area. The methods and characterization techniques are also introduced in detail. Hopefully this review can provide guidelines for the design and manufacturing of advanced catalysts for HER and other heterogeneous catalysis reactions such as chemical sensing, CO2 reduction and NH3 synthesis.

A cloth-based single-working-electrode electrochemiluminescence sensor for simultaneous detection of diabetes complication markers.

As one of the most common noninfectious diseases, diabetes and diabetic complications (DDC) have attracted great attention in the field of life and health. However, simultaneous detection of DDC markers usually requires labor- and time-consuming steps. Here, a novel cloth-based single-working-electrode electrochemiluminescence (SWE-ECL) sensor was designed for the simultaneous detection of multiple DDC markers. For this sensor, three independent ECL cells are distributed on the SWE, which is a simplification of the configuration of traditional sensors for simultaneous detection. In this way, the modification processes and ECL reactions occur at the back of the SWE, eliminating the adverse effects caused by human intervention on the electrode. Under optimized conditions, glucose, uric acid and lactate were determined, with corresponding linear dynamic ranges of 80-4000 µM, 45-1200 µM and 60-2000 µM, and detection limits of 54.79 µM, 23.95 µM and 25.82 µM, respectively. In addition, the cloth-based SWE-ECL sensor exhibited good specificity and satisfactory reproducibility, and its actual application potential was verified by measuring complex human serum samples. Overall, this work developed a simple, sensitive, low-cost and rapid method for the simultaneous quantitative determination of multiple markers related to DDC and demonstrated a new route for multiple-marker detection.

Progress and Perspectives of Single-Atom Catalysts for Gas Sensing.

Single-atom catalysts (SACs) attract extensive attention in the field of heterogeneous catalysis in recent years due to the maximum atom utilization and unique physical and chemical properties. The gas sensing is actually a heterogeneous catalysis process but the SACs are new to this area. Although SACs show huge potential in gas sensing, the SACs gas sensing area currently is still at the infancy stage. This work critically reviews the recent advances and current status of single-atom gas sensing materials. General synthesis routes, characterization methods, and sensing performance indexes are introduced. At the end, the challenges and future prospects on SACs gas sensing are presented from the authors' perspectives. This work is anticipated to provide insights and guideline for the chemical sensing community.

A microfluidic cloth-based photoelectrochemical analytical device for the detection of glucose in saliva.

Photoelectrochemical (PEC) detection is a widely used detection method that uses light to stimulate and photocurrent signals to detect the target. Due to the disengagement of the excitation unit and the detection unit, the PEC background signal is reduced, and the detection sensitivity is improved. In this work, we report the first demonstration of PEC detection for microfluidic cloth-based analytical devices (µCADs). Using PEC µCADs integrated with cadmium sulfide quantum dots (CdS QDs) and multiwalled carbon nanotubes (MWCNTs), the nonenzymatic, sensitive and rapid measurement of glucose in saliva has been achieved. For the cloth-based device, the PEC reaction zone and cloth-based electrodes can be fabricated by inexpensive wax-based and carbon ink-based screen-printing, respectively. By the layer-by-layer method, the as-prepared poly (dimethyl diadly ammonium chloride-functionalized) MWCNTs (PDDA-MWCNTs) and CdS QDs are successively adsorbed onto the working electrode surface of the cloth-based device. In the presence of an excitation source and glucose, the CdS QDs generate a strong oxidizing electron hole that can then continuously oxidize glucose to produce an electrical signal for glucose detection. Under optimized conditions, a linear dependence is obtained between the PEC signal and glucose concentrations in the range of 0.05-1000 µM with a detection limit of 15.99 nM. In the detection range, the cloth-based device also shows acceptable selectivity, reproducibility, and long-term stability. Moreover, the method has been implemented for the detection of glucose in real saliva samples, suggesting good potential for biochemical applications.

Safety and short-term outcomes of laparoscopic surgery for advanced gastric cancer after neoadjuvant immunotherapy: A retrospective cohort study.

Background: Immune checkpoint inhibitors (ICIs) have been increasingly used for the treatment of advanced gastric cancer (AGC). However, the safety and the short-term outcomes of laparoscopic gastrectomy for patients with AGC after neoadjuvant immunotherapy (NAI) remain unknown. Methods: We retrospectively analyzed the patients with AGC who underwent laparoscopic surgery after neoadjuvant therapy between 1 January 2019 and 31 October 2021. We further compared the differences in postoperative complications, overall response rate, adverse events, surgical parameters, and postoperative recovery between two cohorts: the NAI group (NAI plus chemotherapy) and the neoadjuvant chemotherapy (NAC) group. Multivariable regression analyses were used to determine the risk factors for the overall response rate. Results: Overall, 80 patients were enrolled, of whom 30 cases were included in the NAI cohort and 50 were included in the NAC cohort. The overall rate of postoperative complications was 30.0% in both groups (p = 1.000). The overall response rate was 70.0% in the NAI cohort and 40% in the NAC cohort (p = 0.012). The adverse effects were found in 16 cases (53.3%) of the NAI cohort and 23 cases (46.0%) of the NAC cohort (p = 0.645). There was no statistical difference in intraoperative bleeding (50 ml vs. 50 ml, p = 0.983), operation time (320.9 min vs. 303.5 min, p = 0.382), dissected lymph node count (43.5 vs. 40.0, p = 0.364), first postoperative anal aerofluxus (3 days vs. 3 days, p = 0.091), first liquid diet (4 days vs. 5 days, p = 0.213), and postoperative length of stay in the hospital (8 days vs. 7 days, p = 0.508) between the two groups. NAI was estimated to be the independent protective factor [odds ratio (OR) 4.931, 95% confidence interval (CI) (1.385-17.559), p = 0.014] for odds to overall response rate, whereas vessel invasion was found to be the significant risk factor [OR 0.113, 95% CI (0.027-0.475), p = 0.003]. Conclusions: Laparoscopic surgery after NAI combined with chemotherapy is a safe therapeutic choice for AGC and may bring better short-term outcomes due to a higher overall response rate.