Advanced application of slightly acidic electrolyzed water for fresh-cut fruits and vegetables preservation.

Fresh-cut fruits and vegetables (F&V) play a pivotal role in modern diets due to their convenience and nutritional value. However, their perishable nature renders them susceptible to rapid spoilage, causing quality deterioration, safety risks, and economic losses along the supply chain. Traditional preservation methods, while effective to some extent, often fall short in maintaining the quality and safety of fresh-cut F&V. This comprehensive review examines the utilization of slightly acidic electrolyzed water (SAEW) as a novel preservation technique for fresh-cut F&V. The review encompasses the production mechanisms, sterilization principles, classifications and application of SAEW. It explores the effects of SAEW on microbial inactivation, quality parameters, and metabolic pathways in fresh-cut F&V. Additionally, it assesses the synergistic effects of SAEW when combined with other preservation methods. SAEW demonstrates remarkable potential in extending the shelf life of fresh-cut F&V by effectively inhibiting microbial growth, suppressing browning, preserving chemical content, and influencing various metabolic processes. Moreover, its synergy with different treatments enhances its overall efficacy in maintaining fresh-cut F&V quality. The review highlights the promising role of SAEW as an innovative preservation approach for fresh-cut F&V. However, challenges regarding its widespread implementation and potential limitations require further exploration. Overall, SAEW stands as a significant contender in ensuring the safety and quality of fresh-cut F&V paving the way for future research and application in the food industry.

Differences in clinical manifestations and the fecal microbiome between irritable bowel syndrome and small intestinal bacterial overgrowth.

BACKGROUND: Irritable bowel syndrome (IBS) and small intestinal bacterial overgrowth (SIBO) share similar abdominal symptoms; however, their differentiation remains controversial. AIMS: To illustrate the differences between the two conditions. METHODS: Patients and healthy controls completed questionnaires and provided stool samples for analysis. RESULTS: IBS presented with the most severe symptoms and was specifically characterized by intense abdominal pain and frequent episodes of diarrhea. Patients with IBS displayed more dysregulated taxonomy within the fecal microbiota than SIBO. Opportunistic pathogens, including Lachnoclostridium, Escherichia-Shigella, and Enterobacter were enriched in the IBS group which contributed to increased bacterial pathogenicity and positively correlated with abdominal pain and bloating, meanwhile, Lachnoclostridium and Escherichia-Shigella were found to be associated with metabolites affiliated to bile acids, alcohols and derivatives. Bacteria enriched in SIBO group correlated with constipation. The bacterial co-occurrence network within the SIBO group was the most intricate. Ruminococcaceae Group were defined as core bacteria in SIBO. Differential metabolites affiliated to androstane steroids and phenylacetic acids were associated with core bacteria. CONCLUSIONS: Our study elucidates the differences between IBS and SIBO in terms of symptoms, microbiota and functions, which provides insights into a better understanding of both diseases and evidence for different treatment strategies.

Enhancing Fresh-Cut Apple Preservation: Impact of Slightly Acidic Electrolyzed Water and Chitosan-Apple Essence Microencapsulation Coating on Browning and Flavor.

Fresh-cut apple preservation is a critical concern in the food industry due to the rapid deterioration of texture, color, and flavor. While our previous study introduced apple essence microencapsulation (AEM) to enhance flavor during storage, its impact on overall storage quality was minimal. Thus, this study explores the application of two preservation techniques, namely, slightly acidic electrolyzed water (SAEW) and chitosan-apple essence microencapsulation (CH-AEM) coating, to enhance the quality of fresh-cut apples. Our findings reveal that SAEW treatment significantly reduces the browning index (from 65.38 to 57.36) and respiratory rate (from 5.10% to 4.30% of CO2), and maintains a desirable aroma profile compared to uncoated treatment during 10 days of storage. Additionally, the CH-AEM coating acts as a protective barrier, further preserving the sensory characteristics of fresh-cut apples. Notably, the SAEW-CH-AEM group exhibits superior performance in firmness (8.14 N), respiratory rate (3.37% of CO2), ion leakage (34.86%), and juice yield (47.52%) after 10 days. Our research highlights the synergistic effect of combining these preservation strategies, providing a promising approach for extending the shelf life of fresh-cut apples while maintaining their visual appeal and aromatic quality. These results offer valuable insights for the fresh-cut produce industry, contributing to improved apple product preservation and consumer satisfaction.

Fecal Coprococcus, hidden behind abdominal symptoms in patients with small intestinal bacterial overgrowth.

BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is the presence of an abnormally excessive amount of bacterial colonization in the small bowel. Hydrogen and methane breath test has been widely applied as a non-invasive method for SIBO. However, the positive breath test representative of bacterial overgrowth could also be detected in asymptomatic individuals. METHODS: To explore the relationship between clinical symptoms and gut dysbiosis, and find potential fecal biomarkers for SIBO, we compared the microbial profiles between SIBO subjects with positive breath test but without abdominal symptoms (PBT) and healthy controls (HC) using 16S rRNA amplicon sequencing. RESULTS: Fecal samples were collected from 63 SIBO who complained of diarrhea, distension, constipation, or abdominal pain, 36 PBT, and 55 HC. For alpha diversity, the Shannon index of community diversity on the genus level showed a tendency for a slight increase in SIBO, while the Shannon index on the predicted function was significantly decreased in SIBO. On the genus level, significantly decreased Bacteroides, increased Coprococcus_2, and unique Butyrivibrio were observed in SIBO. There was a significant positive correlation between saccharolytic Coprococcus_2 and the severity of abdominal symptoms. Differently, the unique Veillonella in the PBT group was related to amino acid fermentation. Interestingly, the co-occurrence network density of PBT was larger than SIBO, which indicates a complicated interaction of genera. Coprococcus_2 showed one of the largest betweenness centrality in both SIBO and PBT microbiota networks. Pathway analysis based on the Kyoto Encyclopedia of Genes and Genome (KEGG) database reflected that one carbon pool by folate and multiple amino acid metabolism were significantly down in SIBO. CONCLUSIONS: This study provides valuable insights into the fecal microbiota composition and predicted metabolic functional changes in patients with SIBO. Butyrivibrio and Coprococcus_2, both renowned for their role in carbohydrate fermenters and gas production, contributed significantly to the symptoms of the patients. Coprococcus's abundance hints at its use as a SIBO marker. Asymptomatic PBT individuals show a different microbiome, rich in Veillonella. PBT's complex microbial interactions might stabilize the intestinal ecosystem, but further study is needed due to the core microbiota similarities with SIBO. Predicted folate and amino acid metabolism reductions in SIBO merit additional validation.

Eddy impacts on abundance and habitat distribution of a large predatory squid off Peru.

The pelagic cephalopod species jumbo flying squid Dosidicus gigas is ecologically and economically important in the Humboldt ecosystem off Peru. This squid species is sensitive to oceanic environmental changes, and regional oceanographical variability is one of the important factors driving its redistribution. Off Peruvian waters, mesoscale eddies are ubiquitous and dominate the biogeochemical processes in this region. This study first explored the role of mesoscale eddies in regulating the environments and their effects on the abundance and habitat distribution of D. gigas off Peru by analyzing squid distribution in eddy-centric coordinates and building a habitat suitability index (HSI) model. Results indicated that the abundance and habitat distribution of D. gigas in mesoscale eddies varied across months, with significant differences observed between anticyclonic eddies (AE) and cyclonic eddies (CE). In AE, a higher abundance and proportion of suitable habitat occurred. While in CE, the abundance was relatively low and the suitable habitat was relatively less, concentrating at the periphery of CE. Based on the HSI model results, sea surface temperature (SST) and 50 m water temperature (T50m) in AE were more favorable for D. gigas, which was 0.3-0.5 °C lower than that in CE, yielding high-quality habitats and higher abundance of D. gigas. Our findings emphasized that mesoscale eddies have a significant impact on water temperature conditions and nutrient concentrations off Peruvian waters.

Integrative Metabolomic and Transcriptomic Landscape during Akebia trifoliata Fruit Ripening and Cracking.

Akebia trifoliata fruit is prone to crack after ripening, but little is known about the mechanism underlying the cracking process. This study integrated transcriptomic and metabolomic data, revealing significant changes in 398 metabolites and 8414 genes during ripening and cracking, mainly impacting cell-wall metabolism. Multi-omics joint analysis indicated that genes related to polygalacturonase, pectate lyase, α-amylase, and glycogen phosphorylase were up-regulated after cracking, degrading cell wall and starch. Concurrently, diminished photosynthetic metabolism and heightened phenylpropanoid metabolism suggested alterations in cuticle structure, potentially impacting cell-wall robustness. Numerous auxin and abscisic acid signaling-related genes were expressed, and we assume that they contributed to the promoting peel growth. These alterations collectively might compromise peel strength and elevate expanding pressure, potentially leading to A. trifoliata cracking. Transcription factors, predominantly ethylene response factors and helix-loop-helix family members, appeared to regulate these metabolic shifts. These findings provide valuable insights into A. trifoliata cracking mechanisms; however, direct experimental validation of these assumptions is necessary to strengthen these conclusions and expedite their commercial utilization.

Lipopolysaccharides protect mesenchymal stem cell against cardiac ischemia-reperfusion injury by HMGB1/STAT3 signaling.

BACKGROUND: Myocardial ischemia-reperfusion (I/R) is a serious and irreversible injury. Bone marrow-derived mesenchymal stem cells (MSCs) is considered to be a potential therapy for I/R injury due to the paracrine effects. High-mobility group box 1 (HMGB1) is a novel mediator in MSC and regulates the response of inflammation injury. Signal Transduction and Transcription Activator 3 (STAT3) is a critical transcription factor and important for release of paracrine factors. However, the relationship between HMGB1 and STAT3 in paracrine effect of MSC remains unknown. METHODS: In vitro, hypoxia/reoxygenation injury model was established by AnaeroPack System and examined by Annexin V flow cytometry, CCK8 assay and morphology observation. Detection of apoptotic proteins and protein expression of HMGB1 and STAT3 by Western blot. RESULTS: The conditioned medium of MSCs with or without LPS pretreatment was cocultured with H9C2 cells for 24 h before hypoxia treatment and MSC showed obvious cardiomyocytes protect role, as evidence by decreased apoptosis rate and improved cells viability, and LPS pretreated MSC exhibited better protect role than untreated MSC. However, such effect was abolished in HMGB1 deficiency group, silencing HMGB1 decreased the secretion of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), insulin growth factor (IGF), cell viability, and the expression of STAT3. Furthermore, STAT3 silence attenuated the protective effect of LPS in MSC. CONCLUSIONS: These findings suggested that LPS improved MSC-mediated cardiomyocytes protection by HMGB1/STAT3 signaling.

miR-379-5p regulates the proliferation, cell cycle, and cisplatin resistance of oral squamous cell carcinoma cells by targeting ROR1.

OBJECTIVE: To analyze the regulatory mechanism microRNA miR-379-5p in oral squamous cell carcinoma (OSCC). METHODS: We collected serum samples from patients with OSCC and examined the expression of miR-379-5p and receptor tyrosine kinase-like orphan receptor 1 (ROR1) by real-time polymerase chain reaction and western blot. OSCC cells were purchased for molecular research, cell multiplication was tested using the BrdU assay, cell cycle was tested using flow cytometry, and resistance to cisplatin (DDP) was assessed using the MTT assay. RESULTS: miR-379-5p expression was downregulated and ROR1 expression was upregulated in the serum of OSCC patients, and the area under the curve for OSCC identified by miR-379-5p and ROR1 was not less than 0.800. In the cell function test, overexpression of miR-379-5p could suppress the proliferation, cell cycle, and DDP resistance of OSCC cells. miR-379-5p could negatively regulate ROR1. Inhibition of ROR1 expression had a similar effect after the re-expression of miR-379-5p. Co-overexpression of miR-379-5p and ROR1 counteracted the above inhibitory effects on the proliferation, cell cycle, and DDP resistance of OSCC cells. CONCLUSION: miR-379-5p in OSCC regulates the proliferation, cell cycle, and DDP resistance of tumor cells by targeting ROR1.

Berberine and rifaximin effects on small intestinal bacterial overgrowth: Study protocol for an investigator-initiated, double-arm, open-label, randomized clinical trial (BRIEF-SIBO study).

Introduction: Small intestinal bacterial overgrowth (SIBO) leads to non-specific abdominal discomfort and nutrient malabsorption. Currently, rifaximin is widely applied in SIBO based on its antibacterial and non-absorbable nature. Berberine is a natural component of many popular medicine plants that ameliorates intestinal inflammation in humans through its modification of the gut microbiota. Potential effect of berberine to the gut may provide therapeutic target for SIBO. We aimed to evaluate the effect of berberine compared with rifaximin on SIBO patients. Methods: This is an investigator-initiated, single-center, open-label, double-arm randomized controlled trial, termed BRIEF-SIBO (Berberine and rifaximin effects for small intestinal bacterial overgrowth). In total, 180 patients will be recruited and allocated to an intervention group (berberine) and a control group (rifaximin). Each participant will receive one 400 mg drug twice a day (800 mg daily) for 2 weeks. The total follow-up period is 6 weeks from the start of medication. The primary outcome is a negative breath test. The secondary outcomes include abdominal symptom relief and alteration in gut microbiota. Efficacy assessment will be performed every 2 weeks, as well as safety assessment during the treatment. The primary hypothesis is that berberine is not inferior to rifaximin for SIBO. Discussion: The BRIEF-SIBO study is the first clinical trial assessing the eradication effects of 2 weeks of berberine treatment in SIBO patients. The effect of berberine will be fully verified by using rifaximin as the positive control. The findings of this study may have implications for the management of SIBO, especially increasing the awareness of both physicians and patients who are suffering from long-term abdominal discomfort and avoiding excessive examination.

HIF-1α/IL-8 axis in hypoxic macrophages promotes esophageal cancer progression by enhancing PD-L1 expression.

Esophageal cancer (EC) is a malignancy with poor prognosis and high mortality. Hypoxic microenvironment has also been proved to be an important feature of tumors. Herein, we mainly studied the influence of hypoxia-treated tumor-associated macrophages (TAMs) on EC malignant phenotype and related molecular mechanism. In this paper, we found that hypoxic macrophages contributed to EC cell proliferation, cell cycle progression, and metastasis. Besides, the hypoxia treatment expedited the transformation of macrophages into M2 polarization. The level of interleukin (IL)-8 was boosted in macrophages after hypoxia treatment. Moreover, hypoxia treatment heightened IL-8 secretion by macrophages via positively regulating hypoxia-inducible factor-1α (HIF-1α) expression. The IL-8 secreted by hypoxic macrophages facilitated EC cell proliferation, cell cycle progression, and metastasis by elevating ligand of programmed death 1 (PD-L1) expression. In the end, IL-8 also expedited EC tumorigenesis in vivo. In conclusion, HIF-1α/IL-8 axis in hypoxic macrophages could expedite EC advancement by upregulating PD-L1 level, which might deliver a novel thought for EC cure.

Dynamic changes in mental health status related to the COVID-19 pandemic among health care workers and inpatients in China.

Background: Exposure to coronavirus disease 2019 (COVID-19) can cause severe mental health problems, the dynamics of which remain unclear. This study evaluated the mental status of frontline health care workers (FHWs) and suspected infected patients (SIPs) during different periods of the COVID-19 outbreak. Materials and methods: Demographic and psychological data were collected through a cross-sectional survey of 409 participants in a hospital from 20 January to 7 August 2020. COVID-19 outbreaks were divided into three periods owing to the time, place, and scale, including the national outbreak period (a nationwide pandemic period from 20 January to 8 April 2020), sporadic period (a stable period from 9 April to 10 June), and local epidemic period (a local pandemic in Beijing from 11 June to 7 August 2020). Acute psychological disorders (APDs), including symptoms of anxiety and depression, were assessed using the Zung Self-Rating Anxiety/Depression Scale (SAS/SDS). Results: A total of 206 FHWs and 203 SIPs completed the electronic questionnaire. Overall, the prevalence rates of anxiety and depression among SIPs were 3.9 and 19.4%, respectively, while significantly higher prevalence rates (17.7 and 25.1%) were found among FHWs, P-value < 0.05. Psychological status among SIPs did not differ significantly across the three periods. The FHWs were more vulnerable, as their SAS and SDS scores and almost all the dimension scores were significantly higher during the local epidemic period than during the national outbreak and sporadic periods (all P-values < 0.001). The prevalence of anxiety (34.41%) and depression (41.94%) was significantly higher during the local epidemic period (P < 0.001). Logistic and linear mixed models showed that age, sex, and doctor-patient ratio especially, independently influenced most dimension scores of SAS and SDS among FHWs (P < 0.05). Conclusion: Compared to the COVID-19 epidemic at the national level, the local epidemic had a greater influence on FHWs' mental health. More attention should be given to the workload of FHWs.

Circ_0001821 Affects Proliferation and the Cell Cycle in Esophageal Squamous Cell Carcinoma by Elevating BTRC-Mediated IKBA Ubiquitination.

Esophageal squamous cell carcinoma (ESCC) is a fatal human cancer featured with a tendency to metastasis and relapse. Increasing studies have emphasized the critical roles of circular RNAs (circRNA) in ESCC. This study targeted at a novel circRNA and uncovering its function and mechanisms in ESCC. Functional assays were implemented to evaluate proliferation and cell cycle of ESCC cells. Mechanistic analyses were conducted to explore the potential molecular mechanisms in ESCC cells. In vivo assay was also performed. Based on the collected data, circ_0001821 was highly expressed in ESCC cells. Circ_0001821 knockdown retarded ESCC cell proliferation and tumor growth, while promoting G2-M cell cycle arrest. With regard to its mechanism, RUNX3 promoted PVT1 transcription, further upregulating circ_0001821. Moreover, circ_0001821 sponged miR-423-5p to upregulate BTRC, thus promoting IKBA ubiquitination, and circ_0001821 decreased IKBA expression to activate NF-κB signaling pathway. Rescue assays demonstrated that circ_0001821 facilitated ESCC cell proliferation and cell cycle by downregulating IKBA. In summary, RUNX3-induced circ_0001821 switches on NF-κB signaling pathway via diminishing IKBA expression, functionally prompting ESCC cell proliferation and cell cycle. IMPLICATIONS: This study uncovered a novel molecular pathway in ESCC progression, which might provide potential biomarkers for ESCC diagnosis.

c-MYC and HIF1α promoter G-quadruplexes dependent metabolic regulation mechanism of berberine in colon cancer.

Background: G-quadruplexes are molecular switches regulating gene transcription. c-MYC and hypoxia-inducible factor 1-alpha (HIF1α) play important roles in cell proliferation, apoptosis, and metabolic regulation in colon cancer. Whether berberine can regulate metabolism by interacting with c-MYC and HIF1α G-quadruplexes in colon cancer needs to be explored. Methods: The binding mode of berberine with c-MYC and HIF1α G-quadruplexes were explored by ultraviolet and visible absorption spectroscopy and fluorescence spectroscopy. Circular dichroism (CD) spectroscopy was performed to evaluate the effects of berberine on the stability of c-MYC and HIF1α G-quadruplexes. After different concentrations of berberine acting on HCT116 cells for 24 h, cell proliferation and apoptosis were detected by MTT assay and flow cytometry; quantitative real-time polymerase chain reaction and western blot were performed to detect mRNA and protein expression of c-MYC and HIF1α; transcriptome sequencing was used to analyze the metabolic pathways. For the effects of berberine on colon cancer mouse model with dose of 50 mg·kg-1 for 14 days, tumor growth were monitored, hematoxylin and eosin staining and immunofluorescence staining were performed to analyze histopathology and protein expression of c-MYC and HIF1α, central carbon metabolism was detected in tumor tissues. Results: The binding ability of berberine with c-MYC G-quadruplex was different to that of berberine with HIF1α G-quadruplex. Both binding modes involved π-π stacking. The stoichiometric ratios were 1:1, 1:3, and 3:1 for berberine with c-MYC G-quadruplex and only 1:1 for berberine with HIF1α G-quadruplex. Temperature had a greater effect on the binding of berberine to c-MYC G-quadruplex. Berberine could improve the thermal stability of both c-MYC and HIF1α G-quadruplexes. Berberine inhibited the gene transcription and protein expression of c-MYC and HIF1α in colon cancer HCT116 cells. In vivo, berberine delayed tumor progression and inhibited the protein expression of c-MYC and HIF1α. Twelve differential metabolites such as decreased adenosine triphosphate were obtained, indicating that berberine could regulate the metabolic pathways of the tricarboxylic acid (TCA) cycle and glycolysis/gluconeogenesis, among others. Conclusions: Berberine may inhibit colon cancer by regulating the TCA cycle and glycolysis/gluconeogenesis based on the interaction with c-MYC and HIF1α G-quadruplexes.

CD16/PD-L1 bi-specific aptamer for cancer immunotherapy through recruiting NK cells and acting as immunocheckpoint blockade.

It is well established that natural killer (NK) cells can be used as an alternative candidate of T cells for adoptive cell therapy (ACT) due to its high killing capacity, off-the-shelf utility, and low toxicity. Though NK cells provide rapid and potent immune effects, they still suffer from insufficient infiltration and tumor immunosuppression environment, which result in unsatisfactory therapeutic efficiency. Herein, a highly stable CD16/PD-L1 bi-specific aptamer (defined as CP-bi-apt) with high affinity and selectivity was introduced to overcome these obstacles. This CP-bi-apt can mediate a significant antitumor immunity by recruiting CD16-positive NK cells to directly contact with PD-L1 high-expressed tumor cells. In addition, the induced up-regulation of PD-L1 on tumor cells can inevitably occur as an adaptive response to most of the immunotherapeutic strategies. The prepared CP-bi-apt can be further used as an immune checkpoint inhibitor to specifically bind to PD-L1, thus reducing the negative impact of PD-L1 over-expression on the therapeutic efficacy. Furthermore, this CP-bi-apt-based immunotherapy is simple, highly efficient, and has low side effects, showing a promising potential for clinical translation.

Helicobacter pylori infection is associated with reduced risk of Barrett's esophagus: a meta-analysis and systematic review.

BACKGROUND: Helicobacter pylori (Hp) is a class I carcinogen in gastric carcinogenesis, but its role in Barrett's esophagus (BE) is unknown. Therefore, we aimed to explore the possible relationship. METHODS: We reviewed observational studies published in English until October 2019. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for included studies. RESULTS: 46 studies from 1505 potential citations were eligible for inclusion. A significant inverse relationship with considerable heterogeneity was found between Hp (OR = 0.70; 95% CI, 0.51-0.96; P = 0.03) and BE, especially the CagA-positive Hp strain (OR = 0.28; 95% CI, 0.15-0.54; P = 0.0002). However, Hp infection prevalence was not significantly different between patients with BE and the gastroesophageal reflux disease (GERD) control (OR = 0.99; 95% CI, 0.82-1.19; P = 0.92). Hp was negatively correlated with long-segment BE (OR = 0.47; 95% CI, 0.25-0.90; P = 0.02) and associated with a reduced risk of dysplasia. However, Hp had no correlated with short-segment BE (OR = 1.11; 95% CI, 0.78-1.56; P = 0.57). In the present infected subgroup, Hp infection prevalence in BE was significantly lower than that in controls (OR = 0.69; 95% CI, 0.54-0.89; P = 0.005); however, this disappeared in the infection history subgroup (OR = 0.88; 95% CI, 0.43-1.78; P = 0.73). CONCLUSIONS: Hp, especially the CagA-positive Hp strain, and BE are inversely related with considerable heterogeneity, which is likely mediated by a decrease in GERD prevalence, although this is not observed in the absence of current Hp infection.

Identification of gene biomarkers and immune cell infiltration characteristics in rectal cancer.

BACKGROUND: Compared with colon cancer, the increase of morbidity is more significant for rectal cancer. The current study set out to identify novel and critical biomarkers or features that may be used as promising targets for early diagnosis and treatment monitoring of rectal cancer. METHODS: Microarray datasets of rectal cancer with a minimum sample size of 30 and RNA-sequencing datasets of rectal adenocarcinoma (READ) were downloaded from the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database. The method of robust rank aggregation was utilized to integrate differentially expressed genes (DEGs). The protein-protein interaction (PPI) network of the DEGs was structured using the STRING platform, and hub genes were identified using the Cytoscape plugin cytoHubba and an UpSet diagram. R software was employed to perform functional enrichment analysis. Receiver operating characteristic (ROC) curves based on the GEO data and Kaplan-Meier curves based on the TCGA data were drawn to assess the diagnostic and prognostic values of the hub genes. Immune cell infiltration analysis was conducted with CIBERSORT, and the diagnostic value and correlations between prognostic genes and infiltrated immune cells were analyzed by principal component analysis (PCA), ROC curves, and correlation scatter plots. RESULTS: A total of 137 robust DEGs were obtained by integrating datasets in GEO. Twenty-four hub genes, including CHGA, TTR, SAA1, SPP1, MMP1, TGFBI, COL1A1, and PCK1, were identified as a diagnostic gene biomarker group for rectal cancer, and SAA1, SPP1, and SI were identified as potential novel prognostic biomarkers. Functionally, the hub genes were mainly involved in the rectal cancer related interleukin (IL)-17 and proximal tubule bicarbonate reclamation pathways. Twelve sensitive infiltrated immune cells were identified, and were correlated with prognostic genes. CONCLUSIONS: The integrated gene biomarker group combined with immune cell infiltration can effectively indicate rectal cancer.

A highly stable multifunctional aptamer for enhancing antitumor immunity against hepatocellular carcinoma by blocking dual immune checkpoints.

T-lymphocytes play a potent role in cancer immunotherapy; while, limited tumor infiltrating lymphocytes (TILs) combined with severe immunosuppression always significantly hinder their antitumor immune responses, especially in solid tumors such as hepatocellular carcinoma (HCC). Here, we prepared a highly stable multifunctional aptamer for strengthening antitumor immunity against HCC solid tumors through a dual immune checkpoint blockade of CTLA-4 and PD-L1. The engineered multifunctional aptamer (termed P1/C4-bi-apt) can block both CTLA-4/B7 and PD-1/PD-L1 signaling pathways and thus enhance the antitumor immune responses. Furthermore, it can direct CTLA-4-positive T cells to infiltrate into tumors to further enhance the antitumor efficacy compared to a single blockage of CTLA-4 or PD-L1. As a result, the multifunctional aptamer can significantly inhibit tumor growth and thus improve the long-term survival of HCC-bearing mice. The designed multifunctional aptamer is simple, stable and easy to prepare, and it can significantly strengthen the functionality of T cells, holding great potential for HCC immunotherapy.

DDX10 promotes human lung carcinoma proliferation by U3 small nucleolar ribonucleoprotein IMP4.

BACKGROUND: Lung cancer is a common tumor and a leading cause of death worldwide. DEAD/H box RNA helicases (DDX) include several family members which regulate mRNA translation in cancer cells. In this study, we demonstrated that DEAD/H box RNA helicase 10 (DDX10) was significantly upregulated in lung cancer tissues compared with adjacent nontumor tissues. METHODS: DDX10 expression was knocked down with shRNA in order to investigate the impact on A549 lung cancer cell growth and related molecular mechanisms in vitro and in vivo. DDX10 expression in lung cancer was assessed using online databases and patient samples. RESULTS: DDX10 knockdown significantly inhibited the proliferation of lung cancer cells in vitro and in vivo. Furthermore, the bioinformatic tool indicated the putative downstream protein U3 small nucleolar ribonucleoprotein 4 (IMP4). Our data showed a positive correlation between IMP4 and DDX10. We found that IMP4 overexpression could reverse the effect of DDX10 knockdown on the proliferation and apoptosis of A549 cells. CONCLUSIONS: The findings of this study suggest that DDX10/IMP4 might be a novel target for lung cancer diagnosis and treatment.

A novel long-wavelength off-on fluorescence probe for nitroreductase analysis and hypoxia imaging.

Hypoxia is one of the most important features of various diseases including solid tumors. It is of significant clinical importance for hypoxia analysis in tumors, and the analysis of hypoxia can be moved away to the indirect detection of nitroreductase. Various fluorescence methods have been developed for the analysis of nitroreductase and tumor hypoxia due to their simplicity, non-invasiveness and excellent spatial-temporal resolution. Here, we synthesized a multifunctional fluorophore, which possesses larger π-conjugation structure, leading to the red-shift of absorption and fluorescence emission to long-wavelength region. This fluorophore (RCOH) can be further used to prepare the off-on hypoxia probe (RCO-NTR) by introducing the electron withdrawing group of nitrobenzyl, leading to the quenching of fluorescence emission through an electron transfer process. After reaction with NTR accompanied by NADH as an electron donor, the nitro group in the RCO-NTR probe can be reduced and then the RCOH fluorophore can be released through rearrangement and elimination, leading to the enhancement of fluorescence signal. Thus, the prepared RCO-NTR probe can be used for nitroreductase analysis, which can be further used for hypoxia imaging at both cellular and animal levels.

[Analysis of Influencing Factors of Preoperative Anxiety or Depression in Patients with Lung Cancer Surgery].

BACKGROUND: Preoperative anxiety/depression can bring physical and mental harm to the patients with lung cancer. There is little study on whether hospital waiting time before surgery can increase the psychological burden of patients with lung cancer. The aim of this study was to investigate the preoperative anxiety and depression of patients with lung cancer in our hospital, and to analyze the related influencing factors. METHODS: A total of 135 lung cancer inpatients in the Department of Thoracic Surgery of Beijing Friendship Hospital were studied. Their general information and anxiety/depression were recorded by general questionnaire, Zung self-rating anxiety scale (SAS) and self-rating depression scale (SDS). RESULTS: The score of SAS was 36.25 (30.00, 42.50) on the day of admission, and 37.50 (31.25, 43.75) on one day before operation. The score of self-rating depression scale (SDS) was 46.25 (40.00, 52.50) on the day of admission, and 47.50 (41.25, 53.75) on one day before operation. Compared with the Chinese norm, there were 0 patient suffered from anxiety on the day of admission, and one day before operation. There were 2 patients suffered from mild anxiety; 6 patients suffered from mild depression on the day of admission, and this number went up to 8 on the day before operation. Single factor analysis showed that the hospital waiting time before surgery was positively correlated with preoperative anxiety and depression, and the results were statistically significant (P<0.05). The generalized linear model analysis showed that other factors such as knowledge, gender, age and marital status had no significant correlation with preoperative anxiety and depression. CONCLUSIONS: The occurrence of preoperative anxiety in hospitalized patients with lung cancer is positively correlated to the hospital waiting time before surgery. The longer they stayed in the hospital before operation, the greater their risk of anxiety/depression. So medical staff should actively focus on the psychological condition of the patients with lung cancer, and it is strongly recommended that patients complete preoperative examination and preparation in the outpatient department, in order to reduce the waiting time before operation and reduced the risk of adverse psychological problems such as anxiety and depression.