The FOXO1/G6PC axis promotes gastric cancer progression and mediates 5-fluorouracil resistance by targeting the PI3K/AKT/mTOR signaling pathway.

Gastric cancer (GC) is a prevalent malignancy of the digestive system. Distant metastasis and chemotherapy resistance are the crucial obstacles to prognosis in GC. Recent research has discovered that the glucose-6-phosphatase catalytic subunit (G6PC) plays an important role in tumor malignant development. However, little evidence has highlighted its role in GC. Herein, through a comprehensive analysis including profiling of tissue samples and functional validation in vivo and in vitro, we identify G6PC as a crucial factor in GC tumorigenesis. Importantly, we found that the FOXO1/G6PC axis could accelerate GC cell proliferation, metastasis, and 5-Fluorouracil (5-FU) resistance by targeting the PI3K/AKT/mTOR signaling pathway, implicating that as a prospective therapeutic approach in GC.

LS-HB-Mediated Photodynamic Therapy Inhibits Proliferation and Induces Cell Apoptosis in Melanoma.

Chlorin e6-C-15-ethyl ester (LS-HB), a newly identified photosensitizer, was isolated from chlorin e6. The mechanism of tumor cell death induced by photodynamic therapy with LS-HB (LS-HB-PDT) is still unknown. Here, we investigated the photophysical properties of LS-HB, evaluated the antitumor effect on melanoma in vitro and in vivo, and explored its possible mechanisms. LS-HB not only has an optimal spectral band of red wavelength (660 nm) for photosensitization but also has favorable photostability. More importantly, LS-HB-PDT elicited a potent dose-dependent phototoxic effect in vitro. We discovered that LS-HB located in the mitochondria of B16F10 cells was able to generate excess reactive oxygen species, which subsequently resulted in mitochondrial membrane potential loss and induced apoptosis via caspase-9 and caspase-3 pathways. Moreover, PDT with LS-HB markedly inhibited the growth of melanoma in vivo. Therefore, LS-HB is expected to be an effective potential photosensitizer in antitumor therapy.

pH-Responsive Liposomes Loaded with Targeting Procoagulant Proteins as Potential Embolic Agents for Solid Tumor-Targeted Therapy.

Selectively inducing tumor thrombosis and subsequent necrosis is a novel and promising antitumor strategy. We have previously designed a targeting procoagulant protein, called tTF-EG3287, which is a fusion of a truncated tissue factor (tTF) with EG3287, a short peptide against the neuropilin-1 (NRP1) binding site of vascular endothelial growth factor-A 165 (VEGF-A 165). However, off-target effects and high-dose requirements limit the further use of tTF-EG3287 in antitumor therapy. Therefore, we encapsulated tTF-EG3287 into poly(2-ethyl-2-oxazoline)-distearoyl phosphatidyl ethanolamine (PEOz-DSPE)-modified liposomes to construct pH-responsive liposomes as a novel vascular embolization agent, called tTF-EG3287@Liposomes. The liposomes had an average particle size of about 100 nm and showed considerable drug-loading capacity, encapsulation efficiency, and biocompatibility. Under the stimulation of acidic microenvironments (pH 6.5), the lipid membrane of tTF-EG3287@Liposomes collapsed, and the cumulative drug release rate within 72 h was 83 ± 1.26%. When administered to a mouse model of hepatocellular carcinoma (HCC), tTF-EG3287@Liposomes showed prolonged retention and enhanced accumulation in the tumor as well as a superior antitumor effec, compared with tTF-EG3287. This study demonstrates the potential of tTF-EG3287@Liposomes as a novel embolic agent for solid tumors and provides a new strategy for tumor-targeted infarction therapy.

Mitochondrial DNA variant spectrum and the association with chronic tic disorders.

BACKGROUND AND PURPOSE: Tic disorders (TDs) are childhood onset neuropsychiatric disorders characterized by single or multiple sudden, rapid, recurrent, and motor tics and/or vocal tics. Several nuclear genes that are involved in mitochondrial functions suggest a potential role of mitochondria in TDs. METHODS: To evaluate the association of mitochondrial DNA (mtDNA) variants with TDs, we screened the whole mitochondrial genomes in 493 TD patients and 109 age- and sex-matched healthy controls using next generation sequencing technology. RESULTS: A total of 1918 mtDNA variants including 1220 variants in patients only, 154 variants in controls only, and 544 variants shared by both cases and controls were identified. We found a higher number of overall mtDNA variants in TD patients (p = 0.00028). The variant density in MT-ATP6/8 and MT-CYB coding regions showed a significant difference between TD patients and controls (p = 0.0025 and p = 0.003, respectively). Furthermore, we observed a significant association of 15 common variants with TD based on an additive model, including m.14766C > T, m.14783 T > C, m.14905G > A, and m.15301G > A in MT-CYB; m.4769A > G, m.10398A > G, m.12705C > T, and m.12850A > G in MT-ND genes; m.7028C > T in MT-CO1; m.8701A > G in MT-ATP6; two variants with m.16223C > T, m.5580 T > C in noncoding regions; and three rRNA variants with m.1438A > G and m.750A > G in RNR1, and m.2352 T > C in RNR2. CONCLUSIONS: Our data provide evidence of mtDNA variants associated with TDs. The accumulation of the heteroplasmic levels may increase the risk of TDs. Replication studies with larger samples are necessary to understand the pathogenesis of TDs.

[Sagittaria sagittifolia polysaccharides regulates Nrf2/HO-1 to relieve liver injury caused by multiple heavy metals in vivo and in vitro].

This study explored whether Sagittaria sagittifolia polysaccharides(SSP) activates the nuclear factor erythroid-2-related factor2(Nrf2)/heme oxygenase-1(HO-1) signaling pathway to protect against liver damage jointly induced by multiple heavy metals. First, based on the proportion of dietary intake of six heavy metals in rice available in Beijing market, a heavy metal mixture was prepared for inducing mouse liver injury and HepG2 cell injury. Forty male Kunming mice were divided into five groups: control group, model group, glutathione positive control group, and low-and high-dose SSP groups, with eight mice in each group. After 30 days of intragastric administration, the liver injury in mice was observed by HE staining. In the in vitro experiment, MTT assay was conducted to detect the effects of SSP at 0.25, 0.5, 1, and 2 mg·mL~(-1) on HepG2 cell survival at different time points. The content of alanine transaminase(ALT) and aspartate aminotransferase(AST) in the 48-h cell culture fluid was measured using micro-plate cultivation method, followed by the detection of the change in reactive oxygen species(ROS) content by flow cytometry. The mRNA expression levels of Nrf2 and HO-1 in cells were determined by RT-PCR, and their protein expression by Western blot. HE staining results showed that compared with the model group, the SSP administration groups exhibited significantly alleviated inflammatory cell infiltration and fatty infiltration in the liver, with better outcomes observed in the high-dose SSP group. In the in vitro MTT assay, compared with the model group, SSP at four concentrations all significantly increased the cell survival rate, decreased the ALT, AST, and ROS content(P<0.05), and down-regulated Nrf2 and HO-1 mRNA and protein expression(P<0.05). SSP significantly improves inflammatory infiltration in the liver tissue of mice exposed to a variety of heavy metals and corrects the liver fat degeneration, which may be related to its regulation of the Nrf2/HO-1 signaling pathway, reduction of ROS, and alleviation of oxidative damage.

Role of alternative splicing events in endometrial cancer prognosis. / é€‰æ‹©æ€§å‰ªæŽ¥äº‹ä»¶åœ¨å­å®«å† è†œç™Œé¢„åŽä¸­çš„ä½œç”¨.

OBJECTIVES: Alternative splicing (AS), as a potent and pervasive mechanism of transcriptional regulation, can expand the genome's coding capacity. Growing evidence suggests that the AS events may be associated with various types of cancer. This study aims to explore the prognostic value of AS in endometrial cancer (EC). METHODS: Differently expressed AS (DEAS) events were screened by pairing the percent spliced in (PSI) value of tumor and paracancerous tissues in The Cancer Genome Atlas (TCGA) database, and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed on their parental gene analysis of organisms. Subsequently, univariate Cox analysis was used to identify the prognostic AS events and a stepwise multi-factor Cox regression analysis was performed to further construct prognostic models. Furthermore, the diagnostic value of the prognostic model was evaluated by receiver operating characteristic (ROC) curve and Kaplan-Meier analysis. Finally, the regulatory network of AS events and splicing factory in the model was also constructed. RESULTS: A total of 28 281 AS events were detected in EC. Of them, 42 DEAS were identified, and their parental genes were involved in tumor-related processes such as meiotic nuclear division, alpha-amino acid biosynthetic process, nuclear division, and so on. Univariate Cox analysis identified 2 289 prognostic-related AS events and constructed Cox prognostic models based on 7 different types and all types of AS events, in which the area under the curve of ROC of all types was as high as 0.882 and was better than that of 7 different splicing types. Finally, 12 splicing factors and AS events showed an obvious regulatory relationship. CONCLUSIONS: We use the whole genome analysis of AS events to establish a scientific prognostic prediction model for EC patients, which provides a reliable theoretical basis for the evaluation of EC clinical prognosis.

Deceleration of glycometabolism impedes IgG-producing B-cell-mediated tumor elimination by targeting SATB1.

B lymphocytes, known as antibody producers, mediate tumor cell destruction in the manner of antibody-dependent cell-mediated cytotoxicity; however, their anti-tumor function seems to be weakened during tumorigenesis, while the underlying mechanisms remain unclear. In this study, we found that IgG mediated anti-tumor effects, but IgG-producing B cells decreased in various tumors. Considering the underlying mechanism, glycometabolism was noteworthy. We found that tumor-infiltrating B cells were glucose-starved and accompanied by a deceleration of glycometabolism. Both inhibition of glycometabolism and deprivation of glucose through tumor cells, or glucose-free treatment, reduced the differentiation of B cells into IgG-producing cells. In this process, special AT-rich sequence-binding protein-1 (SATB1) was significantly silenced in B cells. Down-regulating SATB1 by inhibiting glycometabolism or RNA interference reduced the binding of signal transducer and activator of transcription 6 (STAT6) to the promoter of germline Cγ gene, subsequently resulting in fewer B cells producing IgG. Our findings provide the first evidence that glycometabolic inhibition by tumorigenesis suppresses differentiation of B cells into IgG-producing cells, and altering glycometabolism may be promising in improving the anti-tumor effect of B cells.

MicroRNAs 15A and 16-1 Activate Signaling Pathways That Mediate Chemotaxis of Immune Regulatory B cells to Colorectal Tumors.

BACKGROUND & AIMS: B cells infiltrate tumors, but little is known about how they affect tumor growth and progression. microRNA15A (MIR15A or miRNA15A) and microRNA16-1 (MIR16-1 or miRNA16-1) regulate cell proliferation, apoptosis, and drug resistance. We investigated their involvement in B-cell-mediated immune suppression by colorectal tumors. METHODS: Mice with disruptions of the gene cluster that encodes MIR15A and MIR16-1 (knockout mice), and control (C57BL/B6) mice were given azoxymethane with dextran sodium sulfate (AD) to induce formation of colorectal tumors. Mice were given anti-CD20 to delete B cells, or injections of agomir to increase MIR15A and MIR16-1. Proliferation of CD8+T cells was measured by carboxyfluorescein-succinimidyl-ester analysis. Colon tissues were collected from mice and analyzed by flow cytometry, microRNA (miRNA) sequencing, and for cytokine production. Intestinal epithelial cells (IECs) were isolated and transfected with miRNA mimics, to identify their targets. We analyzed miRNA expression patterns and quantified B cells in colorectal cancer tissue microarrays derived from 90 patients who underwent surgical resection, from July 2006 through April 2008, in Shanghai, China; expression data were compared with clinical outcomes. RESULTS: Tumors that developed in knockout mice following administration of AD were larger and contained greater numbers of B cells than tumors that grew in control mice. Most of the B cells in the tumors were positive for immunoglobulin A (IgA+). IgA+ B cells expressed high levels of immune regulatory molecules (programmed death ligand 1, interleukin 10, and transforming growth factor beta), and repressed the proliferation and activation of CD8+ T cells. Levels of MIR15A and MIR16-1 were reduced in colon tumors from mice, compared with nontumor colon tissue. Incubation of IECs with IL17A reduced expression of MIR15A and MIR16-1. Transgenic expression of MIR15A and MIR16-1 in IECs decreased activation of NF-κB and STAT1 by reducing expression of I-kappaB kinases; this resulted in reduced production of chemokine (C-X-C motif) ligands 9 and 10 and decreased chemotaxis of IgA+ B cells. Tumors in mice injected with AD and agomir grew more slowly than tumors in mice not given in agomir and contained fewer IgA+ B cells. We found a negative correlation between levels of MIR15A and MIR16-1 and numbers of IgA+B cells in human colorectal tumor tissues; high levels of MIR15A and MIR16-1 and low numbers of IgA+B cells were associated with longer survival times of patients. CONCLUSIONS: We found increased levels of MIR15A and MIR16-1 to reduce numbers of IgA+ B cells in colorectal tumor tissues and correlate with increased survival time of patients. In mice that lack MIR15A and MIR16-1, colon tumors grow more rapidly and contain increased numbers of IgA+ B cells. MIR15A and MIR16-1 appear to activate signaling pathways required for B-cell-mediated immune suppression.

MicroRNA 15a/16-1 suppresses aryl hydrocarbon receptor-dependent interleukin-22 secretion in CD4+ T cells and contributes to immune-mediated organ injury.

Interleukin-22 (IL-22), as a link between leukocytic and nonleukocytic cells, has gained increasing attention for its pronounced tissue-protective properties. MicroRNAs, emerging as crucial immune modulators, have been reported to be involved in the production and action of various cytokines. However, the precise control of IL-22 by microRNAs and its subsequent actions remained to be elucidated. In this study, we found a negative correlation between the expression of microRNA 15a/16-1 (miR-15a/16-1) and IL-22 in the model of concanavalin A-induced, immune-mediated liver injury. Knockout of miR-15a/16-1 ameliorated liver injury in an IL-22-dependent manner. Further results revealed that cluster of differentiation 4-positive (CD4+ ) T cells were the major source of IL-22 during liver injury and that the aryl hydrocarbon receptor was the direct target of miR-15a/16-1 in CD4+ T cells. In vivo and in vitro data showed that miR-15a/16-1 knockout CD4+ T cells produced more IL-22, while overexpression of miR-15a/16-1 down-regulated the IL-22 production by inhibiting the aryl hydrocarbon receptor. Moreover, transfer of miR-15a/16-1 knockout CD4+ T cells promoted tissue repair compared to wild-type CD4+ T cells by up-regulating IL-22. In addition, as a synergistic effect, IL-22 could down-regulate miR-15a/16-1 expression by activating phosphorylated signal transducer and activator of transcription 3-c-myc signaling, and the decrease of miR-15a/16-1 in damaged hepatocytes contributed to IL-22-mediated tissue repair by reducing cell apoptosis and promoting cell proliferation. As further proof, we demonstrated the role of miR-15a/16-1 in controlling IL-22 production and IL-22-mediated reconstruction of the intestinal epithelial barrier in a dextran sodium sulfate-induced colitis model. CONCLUSION: Our results suggest that miR-15a/16-1 acts as a essential regulator of IL-22 and that the miR-15a/16-1-aryl hydrocarbon receptor-IL-22 regulatory axis plays a central role in tissue repair; modulation of miR-15a/16-1 might hold promise in developing new strategies to enhance IL-22-mediated tissue repair. (Hepatology 2018;67:1027-1040).

Peyer's patches-derived CD11b+ B cells recruit regulatory T cells through CXCL9 in dextran sulphate sodium-induced colitis.

Regulatory T (Treg) cells play an essential role in the maintenance of intestinal homeostasis. In Peyer's patches (PPs), which comprise the most important IgA induction site in the gut-associated lymphoid tissue, Treg cells promote IgA isotype switching. However, the mechanisms underlying their entry into PPs and isotype switching facilitation in activated B cells remain unknown. This study, based on the dextran sulphate sodium (DSS)-induced colitis model, revealed that Treg cells are significantly increased in PPs, along with CD11b+ B-cell induction. Immunofluorescence staining showed that infiltrated Treg cells were located around CD11b+ B cells and produced transforming growth factor-ß, thereby inducing IgA+ B cells. Furthermore, in vivo and in vitro studies revealed that CD11b+ B cells in PPs had the capacity to recruit Treg cells into PPs rather than promoting their proliferation. Finally, we found that Treg cell recruitment was mediated by the chemokine CXCL9 derived from CD11b+ B cells in PPs. These findings demonstrate that CD11b+ B cells induced in PPs during colitis actively recruit Treg cells to accomplish IgA isotype switch in a CXCL9-dependent manner.

Dental pulp stem cells promote regeneration of damaged neuron cells on the cellular model of Alzheimer's disease.

Alzheimer's disease (AD) is an incurable neurodegenerative disease and many types of stem cells have been used in AD therapy with some favorable effects. In this study, we investigated the potential therapeutical effects of human dental pulp stem cells (hDPSCs) on AD cellular model which established by okadaic acid (OA)-induced damage to human neuroblastoma cell line, SH-SY5Y, in vitro for 24 h. After confirmed the AD cellular model, the cells were co-culture with hDPSCs by transwell co-culture system till 24 h for treatment. Then the cytomorphology of the hDPSCs-treated cells were found to restore gradually with re-elongation of retracted dendrites. Meanwhile, Cell Counting Kit-8 assay and Hoechst 33258 staining showed that hDPSCs caused significant increase in the viability and decrease in apoptosis of the model cells, respectively. Observation of DiI labeling also exhibited the prolongation dendrites in hDPSCs-treated cells which were obviously different from the retraction dendrites in AD model cells. Furthermore, specific staining of α-tubulin and F-actin demonstrated that the hDPSCs-treated cells had the morphology of restored neurons, with elongated dendrites, densely arranged microfilaments, and thickened microtubular fibrils. In addition, results from western blotting revealed that phosphorylation at Ser 396 of Tau protein was significantly suppressed by adding of hDPSCs. These results indicate that hDPSCs may promote regeneration of damaged neuron cells in vitro model of AD and may serve as a useful cell source for treatment of AD.

NKT cells mediate the recruitment of neutrophils by stimulating epithelial chemokine secretion during colitis.

Ulcerative colitis (UC) is a kind of inflammatory bowel diseases characterized by chronic inflammation and ulcer in colon, and UC patients have increased risk of getting colorectal cancer. NKT cells are cells that express both NK cell markers and semi-invariant CD1d-restricted TCRs, can regulate immune responses via secreting a variety of cytokines upon activation. In our research, we found that the NKT cell-deficient CD1d(-/-) mice had relieved colitis in the DSS-induced colitis model. Further investigations revealed that the colon of CD1d(-/-) mice expressed less neutrophil-attracting chemokine CXCL 1, 2 and 3, and had decreased neutrophil infiltration. Infiltrated neutrophils also produced less reactive oxygen species (ROS) and TNF-α, indicating they may cause less epithelial damage. In addition, colitis-associated colorectal cancer was also relieved in CD1d(-/-) mice. During colitis, NKT cells strongly expressed TNF-α, which could stimulate CXCL 1, 2, 3 expressions by the epithelium. In conclusion, NKT cells can regulate colitis via the NKT cell-epithelium-neutrophil axis. Targeting this mechanism may help to improve the therapy of UC and prevent colitis-associated colorectal cancer.

Radiology Resident Remediation: Five Important Questions to Ask.

OBJECTIVE: Residents needing remediation are difficult to recognize, assess, and address. The purposes of this article are to review common signs that a resident needs remediation and the causes of the deficiencies and to detail a checklist for preparing to approach the resident. CONCLUSION: Radiology residents who need remediation generally have either academic or professionalism deficits, and their remediation programs should be tailored to the deficit. Having a clear definition of the problem while eliciting the resident's thoughts on the nature of and solution to the problem are instrumental in the solution.

Optimization of enzyme complexes for efficient hydrolysis of corn stover to produce glucose.

Hydrolysis of cellulose to glucose is the critical step for transferring the lignocellulose to the industrial chemicals. For improving the conversion rate of cellulose of corn stover to glucose, the cocktail of celllulase with other auxiliary enzymes and chemicals was studied in this work. Single factor tests and Response Surface Methodology (RSM) were applied to optimize the enzyme mixture, targeting maximum glucose release from corn stover. The increasing rate of glucan-to-glucose conversion got the higher levels while the cellulase was added 1.7µl tween-80/g cellulose, 300µg ß-glucosidase/g cellulose, 400µg pectinase/g cellulose and 0.75mg/ml sodium thiosulphate separately in single factor tests. To improve the glucan conversion, the ß-glucosidase, pectinase and sodium thiosulphate were selected for next step optimization with RSM. It is showed that the maximum increasing yield was 45.8% at 377µg/g cellulose Novozyme 188, 171µg/g cellulose pectinase and 1mg/ml sodium thiosulphate.

Association study of two inflammation-related polymorphisms with susceptibility to hepatocellular carcinoma: a meta-analysis.

BACKGROUND: Inflammation is a response of body tissues to injury or irritation. Small RNAs, such as miR-146a and miR-499, participate in various processes of tumorigenesis. A recent study indicates that inflammation and abnormal immune responses may promote malignant progression in cancer development, indicating that inflammation-related polymorphisms such as miR-146a rs2910164 and miR-499 rs3746444 are crucial. However, studies on the association of these two polymorphisms with hepatocellular carcinoma (HCC) are inconclusive and inconsistent. We aimed at accessing the combined result of reported studies and make a more precise estimate of the relationship. METHODS: Meta-analysis was performed on the associations between the miR-146a rs2910164 C > G and miR-499 rs3746444 T > C polymorphisms and hepatocellular carcinoma, using: allele contrast, dominant, and recessive models. A total of 12 studies(8 on miR-146a rs2910164 and 4 on miR-499 rs3746444) with three populations (Chinese, Korean, Turkish) were included in this study. RESULTS: Results show that both allele frequency and genotype distributions of miR-146a rs2910164 polymorphism are significantly associated with susceptibility to HCC (G versus C: OR = 1.153, 95% CI 1.083-1.228, P < 0.001; GC versus CC: OR = 1.165, 95% CI 1.054-1.286, P = 0.003; GG versus CC: OR = 1.361, 95% CI 1.192-1.553, P < 0.001; GG/GC versus CC: OR = 1.213, 95% CI 1.104-1.333, P < 0.001; GG versus GC/CC: OR = 1.210, 95% CI 1.080-1.356, P < 0.001). Our data suggest that people with G allele have a higher susceptibility to HCC as compared to those with C allele. However, meta-analysis failed to detect associations between miR-499 rs3746444 and HCC risk under each genetic model tested. Subgroup analysis showed that Chinese population with CC genotype are more vulnerable to HCC (OR = 2.171, 95% CI = 1.149-4.104, P = 0.017) than those with TT genotype. CONCLUSIONS: We conclude that rs2910164 in miR-146a may confer susceptibility to HCC, especially in the Chinese population. No significant association was found between miR-499 rs3746444 and HCC, but subgroup study showed that subjects with CC genotype are more vulnerable to HCC than TT genotype in the Chinese population.

Protoplast fusion enhances lignocellulolytic enzyme activities in Trichoderma reesei.

Protoplast fusion was used to obtain a higher production of lignocellulolytic enzymes with protoplast fusion in Trichoderma reesei. The fusant strain T. reesei JL6 was obtained from protoplast fusion from T. reesei strains QM9414, MCG77, and Rut C-30. Filter paper activity of T. reesei JL6 increased by 18% compared with that of Rut C-30. ß-Glucosidase, hemicellulase and pectinase activities of T. reesei JL6 were also higher. The former activity was 0.39 Uml(-1), while those of QM9414, MCG77, and Rut C-30 were 0.13, 0.11, and 0.16 Uml(-1), respectively. Pectinase and hemicellulase activities of JL6 were 5.4 and 15.6 Uml(-1), respectively, which were slightly higher than those of the parents. The effects of corn stover and wheat bran carbon sources on the cellulase production and growth curve of T. reesei JL6 were also investigated.

Channel reflection: Knowledge-driven data augmentation for EEG-based brain-computer interfaces.

A brain-computer interface (BCI) enables direct communication between the human brain and external devices. Electroencephalography (EEG) based BCIs are currently the most popular for able-bodied users. To increase user-friendliness, usually a small amount of user-specific EEG data are used for calibration, which may not be enough to develop a pure data-driven decoding model. To cope with this typical calibration data shortage challenge in EEG-based BCIs, this paper proposes a parameter-free channel reflection (CR) data augmentation approach that incorporates prior knowledge on the channel distributions of different BCI paradigms in data augmentation. Experiments on eight public EEG datasets across four different BCI paradigms (motor imagery, steady-state visual evoked potential, P300, and seizure classifications) using different decoding algorithms demonstrated that: (1) CR is effective, i.e., it can noticeably improve the classification accuracy; (2) CR is robust, i.e., it consistently outperforms existing data augmentation approaches in the literature; and, (3) CR is flexible, i.e., it can be combined with other data augmentation approaches to further improve the performance. We suggest that data augmentation approaches like CR should be an essential step in EEG-based BCIs. Our code is available online.

Physicochemical, structural and functional properties of pomelo peel pectin extracted by combination of pulsed electric field and cellulase hydrolysis.

In this study, pectin extracted from pomelo peel was investigated using three different combination methods of pulsed electric field (PEF) and cellulase. Three action sequences were performed, including PEF treatment followed by enzymatic hydrolysis, enzymatic hydrolysis followed by PEF treatment, and enzymatic hydrolysis simultaneously treated by PEF. The three corresponding pectins were namely PEP, EPP and SP. The physiochemical, molecular structural and functional properties of the three pectins were determined. The results showed that PEP had excellent physiochemical properties, with the highest yield (12.08 %), total sugar (80.17 %) and total phenol content (38.20 %). The monosaccharide composition and FT-IR analysis indicated that the three pectins were similar. The molecular weights of PEP, EPP and SP were 51.13, 88.51 and 40.00 kDa, respectively. PEP showed the best gel properties, emulsification stability and antioxidant capacity among the three products, due to its high galacturonic acid and total phenol content, appropriate protein and low molecular weight. The mechanism of PEF-assisted cellulase hydrolysis of pomelo peel was also revealed by SEM analysis. These results suggested that PEF pretreatment was the best method, which not only improved the efficiency of enzymatic extraction, but also reduced resource waste and increased financial benefits.

Astragalus polysaccharide ameliorates CD8+ T cell dysfunction through STAT3/Gal-3/LAG3 pathway in inflammation-induced colorectal cancer.

Chronic inflammation can promote cancer development as observed in inflammation-induced colorectal cancer (CRC). However, the poor treatment outcomes emphasize the need for effective treatment. Astragalus polysaccharide (APS), a vital component of the natural drug Astragalus, has anti-tumor effects by inhibiting cancer cell proliferation and enhancing immune function. In this study, we found that APS effectively suppressed CRC development through activating CD8+ T cells and reversing its inhibitory state in the tumor microenvironment (TME) of AOM/DSS inflammation-induced CRC mice. Network pharmacology and clinical databases suggested that the STAT3/ Galectin-3(Gal-3)/LAG3 pathway might be APS's potential target for treating CRC and associated with CD8+ T cell dysfunction. In vivo experiments showed that APS significantly reduced phosphorylated STAT3 and Gal-3 levels in tumor cells, as well as LAG3 in CD8+ T cells. Co-culture experiments with MC38 and CD8+ T cells demonstrated that APS decreased the expression of co-inhibitory receptor LAG3 in CD8+ T cells by targeting STAT3/Gal-3 in MC38 cells. Mechanism investigations revealed that APS specifically improved CD8+ T cell function through modulation of the STAT3/Gal-3/LAG3 pathway to inhibit CRC development, providing insights for future clinical development of natural anti-tumor drugs and immunotherapies as a novel strategy combined with immune checkpoint inhibitors (ICIs).

13-Methylpalmatine improves myocardial infarction injury by inhibiting CHOP-mediated cross-talk between endoplasmic reticulum and mitochondria.

Myocardial infarction (MI) is a leading cause of morbidity and mortality worldwide, and endoplasmic reticulum stress (ERS) and mitochondrial Ca2+ overload have been involved in apoptotic cardiomyocyte death during MI. 13-Methylpalmatine (13-Me-PLT) is a natural isoquinoline alkaloid isolated from Coptis chinensis and has not been systematically studied for their potential pharmacological effects in cardiovascular diseases. We conducted the present study to elucidate whether 13-Me-PLT modulates MI pathology in animal MI and cellular hypoxic models, employing state-of-the-art molecular techniques. The results demonstrated that 13-Me-PLT preserved post-ischemic cardiac function and alleviated cardiomyocyte apoptosis. 13-Me-PLT decreased ERS and the communication between ER and mitochondria, which serves as a protective mechanism against mitochondrial Ca2+ overload and structural and functional injuries to mitochondria. Our data revealed mitigating mitochondrial Ca2+ overload and apoptosis by inhibiting CHOP-mediated Ca2+ transfer between inositol 1,4,5-trisphosphate receptor (IP3R) in ER and VDAC1 in mitochondria as an underlying mechanism for 13-Me-PLT action. Furthermore, 13-Me-PLT produced superior effects in alleviating cardiac dysfunction and apoptosis post-MI to diltiazem and palmatine. Collectively, our research suggests that the CHOP/IP3R/VDAC1 signaling pathway mediates ER-mitochondrial Ca2+ transfer and 13-Me-PLT activates this axis to maintain cellular and organellar Ca2+ homeostasis, protecting against ischemic myocardial injury. These findings may offer an opportunity to develop new agents for the therapy of ischemic heart disease.