Podocan unraveled: Understanding its role in tumor proliferation and smooth muscle regulation.

Podocan, a small leucine-rich repeat protein, is expressed in HIV-associated nephropathy, the cardiovascular system, and smooth muscle. Studies have linked PODN and PODNL to cancers such as osteosarcoma, glioma, and stomach cancer. Research has primarily focused on podocan's role in renal podocytes, injured smooth muscle cells, and various tumor cells. Bioinformatics studies have examined the role of PODN as a biomarker in tumors. Our research summarizes the modulatory role of podocan in smooth muscle and tumor proliferation through its suppression of cell proliferation and promotion of cell differentiation via various signaling pathways, including Wnt/ß-catenin, TGF-ß, and Akt/mTOR. We aim to provide a comprehensive overview of PODN's involvement in smooth muscle, cardiovascular system, and tumors by integrating current and past research. This review aims to enhance understanding and inform in the diagnosis, prognosis, and treatment of various diseases.

starTracer is an accelerated approach for precise marker gene identification in single-cell RNA-Seq analysis.

Revealing the heterogeneity among tissues is the greatest advantage of single-cell-sequencing. Marker genes not only act as the key to correctly identify cell types, but also the bio-markers for cell-status under certain experimental imputations. Current analysis methods such as Seurat and Monocle employ algorithms which compares one cluster to all the rest and select markers according to statistical tests. This pattern brings redundant calculations and thus, results in low calculation efficiency, specificity and accuracy. To address these issues, we introduce starTracer, a novel algorithm designed to enhance the efficiency, specificity and accuracy of marker gene identification in single-cell RNA-seq data analysis. starTracer operates as an independent pipeline, which exhibits great flexibility by accepting multiple input file types. The primary output is a marker matrix, where genes are sorted by the potential to function as markers, with those exhibiting the greatest potential positioned at the top. The speed improvement ranges by 2 ~ 3 orders of magnitude compared to Seurat, as observed across three independent datasets with lower false positive rate as observed in a simulated testing dataset with ground-truth. It's worth noting that starTracer exhibits increasing speed improvement with larger data volumes. It also excels in identifying markers in smaller clusters. These advantages solidify starTracer as an important tool for single-cell RNA-seq data, merging robust accuracy with exceptional speed.

First-line immune checkpoint inhibitors in low programmed death-ligand 1-expressing population.

Introduction: Inhibitors of programmed cell death 1 (PD1) and its ligand (PDL1) have exhibited favorable long-term survival in many types of advanced-stage cancer and current approvals have to date been granted in certain tumour types irrespective of PD-L1 status. Methods: We extracted the following information: study sample size, trial period, cancer types, intervention of treatment, type of PD-L1 antibody, immunohistochemistry (IHC) scoring method, number and percentage of PD-L1 < 1% population, and median follow- up time. PD-L1 expression was defined as percentage of number of PD-L1-stained tumor cells (TPS), area of tumor infiltrated by PD-L1-stained immune cells (IPS), number of PD-L1-stained cells (tumor cells, lymphocytes and macrophages; CPS). Different trials used distinct method to define low PD-L1 expression. The risk of bias of the included trials was assessed by using the Cochrane risk of bias tool for RCTs. Results: Here, a total of 34 trials were included to extract individual patient data (IPD) to evaluate the survival benefit of first line PD1/PDL1 inhibitors vs. standard-of-care (SOC) in patients with PDL1 < 1%. In term of anti-PD-1/PD-L1 monotherapy, OS (HR = 0.90, 0.81-1.01) and PFS (HR = 1.11, 0.97-1.27) between PD-1/PD-L1 inhibitor group and SOC group were comparable. In term of anti-PD-1/PD-L1 combination therapy, PD-1/PD-L1 inhibitor group exhibited longer OS (median 19.5 months vs. 16.3 months; HR = 0.83, 0.79-0.88, p < 0.001) and PFS than those of SOC group (median 8.11 months vs. 6.96 months; HR = 0.82, 0.77-0.87, p < 0.001).Subgroup analysis showed that survival benefit was mainly observed in non-small cell lung cancer (NSCLC) (HROS = 0.74; HRPFS = 0.69; p < 0.001), small-cell lung cancer (SCLC) (HROS = 0.58, p < 0.001; HRPFS = 0.55, p = 0.030), esophageal squamous cell carcinoma (ESCC) (HROS = 0.62, p = 0.005; HRPFS = 0.79, p < 0.001), melanoma (HROS = 0.53, p < 0.001) and nasopharyngeal carcinoma (NPC) (HRPFS = 0.35, p = 0.013). Conclusion: Anti-PD-1/PD-L1 combinational therapy rather than monotherapy exhibit survival benefit in the low PD-L1 population in the first-line setting, and the survival benefit was mainly observed in specific tumor types.

Multi-omics analysis of the prognostic and biological role of cuproptosis-related gene in gastric cancer.

Background: A considerable number of gastric cancer (GC) patients cannot receive benefits from current treatments. We aimed to identify possible biomarkers of cuproptosis-related genes (CRGs) in GC patients, which may help guide precision medicine-based decision-making. Methods: RNA sequencing data, copy number variations (CNVs) data, and single nucleotide variant (SNV) data were obtained from The Cancer Genome Atlas (TCGA) database and Gene Set Cancer Analysis (GSCA) database. Chi-squared test was adopted to screen differentially expressed CRGs (DE-CRGs) between samples from 14 kinds of carcinoma and adjacent tissue samples. Then, GC samples were divided into high- and low-expressed groups based on DE-CRGs for further survival analyses and the selection of biomarkers. Methylation sites related with biomarkers were acquired. The correlation between immune cells and biomarkers was verified. Finally, miRNA-mRNA, TFs-mRNA, and co-expression networks were established to detect factors with regulating effects on biomarkers. Results: Three CRGs including LIAS, GLS, and CDKN2A were identified as biomarkers in GC patients. Three methylation sites with a significant survival effect including cg13601799, 07562918, and 07253264 were acquired. Then, we found that B cells native was significantly correlated with CDKN2A, four immune cells such as T cells regulatory are significantly correlated with GLS, and two immune cells such as T cells CD4 memory activated were significantly correlated with LIAS. Moreover, 10 miRNAs in the miRNA-mRNA network and three transcription factors (TFs) in the TFs-mRNA network had a significant correlation with overall survival (OS). Finally, 20 enrichment functions were obtained on the basis of the co-expression network. Conclusions: Three biomarkers with a prognosis prediction value of GC were found, and multi-factor regulatory networks were constructed to screen out 13 factors with regulating influences of biomarkers.

Hyperactivation of mTOR/eIF4E Signaling Pathway Promotes the Production of Tryptophan-To-Phenylalanine Substitutants in EBV-Positive Gastric Cancer.

Although messenger RNA translation is tightly regulated to preserve protein synthesis and cellular homeostasis, chronic exposure to interferon-γ (IFN-γ) in several cancers can lead to tryptophan (Trp) shortage via the indoleamine-2,3-dioxygenase (IDO)- kynurenine pathway and therefore promotes the production of aberrant peptides by ribosomal frameshifting and tryptophan-to-phenylalanine (W>F) codon reassignment events (substitutants) specifically at Trp codons. However, the effect of Trp depletion on the generation of aberrant peptides by ribosomal mistranslation in gastric cancer (GC) is still obscure. Here, it is shows that the abundant infiltrating lymphocytes in EBV-positive GC continuously secreted IFN-γ, upregulated IDO1 expression, leading to Trp shortage and the induction of W>F substitutants. Intriguingly, the production of W>F substitutants in EBV-positive GC is linked to antigen presentation and the activation of the mTOR/eIF4E signaling pathway. Inhibiting either the mTOR/eIF4E pathway or EIF4E expression counteracted the production and antigen presentation of W>F substitutants. Thus, the mTOR/eIF4E pathway exposed the vulnerability of gastric cancer by accelerating the production of aberrant peptides and boosting immune activation through W>F substitutant events. This work proposes that EBV-positive GC patients with mTOR/eIF4E hyperactivation may benefit from anti-tumor immunotherapy.

Co-occurrence of ST412 Klebsiella pneumoniae isolates with hypermucoviscous and non-mucoviscous phenotypes in a short-term hospitalized patient.

Hypermucoviscosity (HMV) is a phenotype that is commonly associated with hypervirulence in Klebsiella pneumoniae. The factors that contribute to the emergence of HMV subpopulations remain unclear. In this study, eight K. pneumoniae strains were recovered from an inpatient who had been hospitalized for 20 days. Three of the isolates exhibited a non-HMV phenotype, which was concomitant with higher biofilm formation than the other five HMV isolates. All eight isolates were highly susceptible to serum killing, albeit HMV strains were remarkably more infective than non-HMV counterparts in a mouse model of infection. Whole genome sequencing (WGS) showed that the eight isolates belonged to the K57-ST412 lineage. Average nucleotide identity (FastANIb) analysis indicated that eight isolates share 99.96% to 99.99% similarity and were confirmed to be the same clone. Through comparative genomics analysis, 12 non-synonymous mutations were found among these isolates, eight of which in the non-HMV variants, including rmpA (c.285delG) and wbaP (c.1305T > A), which are assumed to be associated with the non-HMV phenotype. Mutations in manB (c.1318G > A), dmsB (c.577C > T) and tkt (c.1928C > A) occurred in HMV isolates only. RNA-Seq revealed transcripts of genes involved in energy metabolism, carbohydrate metabolism and membrane transport, including cysP, cydA, narK, tktA, pduQ, aceB, metN, and lsrA, to be significantly dysregulated in the non-HMV strains, suggesting a contribution to HMV phenotype development. This study suggests that co-occurrence of HMV and non-HMV phenotypes in the same clonal population may be mediated by mutational mechanisms as well as by certain genes involved in membrane transport and central metabolism. IMPORTANCE: K. pneumoniae with a hypermucoviscosity (HMV) phenotype is a community-acquired pathogen that is associated with increased invasiveness and pathogenicity, and underlying diseases are the most common comorbid risk factors inducing metastatic complications. HMV was earlier attributed to the overproduction of capsular polysaccharide, and more data point to the possibility of several causes contributing to this bacterial phenotype. Here, we describe a unique event in which the same clonal population showed both HMV and non-HMV characteristics. Studies have demonstrated that this process is influenced by mutational processes and genes related to transport and central metabolism. These findings provide fresh insight into the mechanisms behind co-occurrence of HMV and non-HMV phenotypes in monoclonal populations as well as potentially being critical in developing strategies to control the further spread of HMV K. pneumoniae.

Bacteriophage-resistant carbapenem-resistant Klebsiella pneumoniae shows reduced antibiotic resistance and virulence.

Phage therapy has shown great promise in the treatment of bacterial infections. However, the effectiveness of phage therapy is compromised by the inevitable emergence of phage-resistant strains. In this study, a phage-resistant carbapenem-resistant Klebsiella pneumoniae strain SWKP1711R, derived from parental carbapenem-resistant K. pneumoniae strain SWKP1711 was identified. The mechanism of bacteriophage resistance in SWKP1711R was investigated and the molecular determinants causing altered growth characteristics, antibiotic resistance, and virulence of SWKP1711R were tested. Compared to SWKP1711, SWKP1711R showed slower growth, smaller colonies, filamentous cells visible under the microscope, reduced production of capsular polysaccharide (CPS) and lipopolysaccharide, and reduced resistance to various antibiotics accompanied by reduced virulence. Adsorption experiments showed that phage vB_kpnM_17-11 lost the ability to adsorb onto SWKP1711R, and the adsorption receptor was identified to be bacterial surface polysaccharides. Genetic variation analysis revealed that, compared to the parental strain, SWKP1711R had only one thymine deletion at position 78 of the open reading frame of the lpcA gene, resulting in a frameshift mutation that caused alteration of the bacterial surface polysaccharide and inhibition of phage adsorption, ultimately leading to phage resistance. Transcriptome analysis and quantitative reverse transcriptase PCR revealed that genes encoding lipopolysaccharide synthesis, ompK35, blaTEM-1, and type II and Hha-TomB toxin-antitoxin systems, were all downregulated in SWKP1711R. Taken together, the evidence presented here indicates that the phenotypic alterations and phage resistance displayed by the mutant may be related to the frameshift mutation of lpcA and altered gene expression. While evolution of phage resistance remains an issue, our study suggests that the reduced antibiotic resistance and virulence of phage-resistant strain derivatives might be beneficial in alleviating the burden caused by multidrug-resistant bacteria.

Anti-Helicobacter pylori Treatment in Patients With Gastric Cancer After Radical Gastrectomy.

Importance: Whether anti-Helicobacter pylori treatment can provide survival benefits for patients with gastric cancer who are diagnosed with H pylori infection is an area with limited research. Objective: To explore the potential survival benefits of anti-H pylori treatment after radical gastrectomy in patients with gastric cancer and presurgical confirmation of H pylori infection. Design, Setting, and Participants: This retrospective cohort study was conducted using data from patients with gastric cancer treated between January 1, 2010, and December 31, 2018, and followed up for outcome ascertainment until May 19, 2021. Propensity score matching was performed in patients treated with or without anti-H pylori treatment. This study involved a single institute in a comprehensive cancer treatment and research center located in Guangzhou, Guangdong Province, China. The study included patients with gastric or esophagogastric junction adenocarcinoma who underwent curative gastrectomy with D2 lymphadenectomy and tested positive for H pylori infection. Data were analyzed from March to June 2023. Exposure: Anti-H pylori treatment, which primarily includes triple therapy regimens consisting of amoxicillin, clarithromycin, and omeprazole for 14 days. Main Outcomes and Measures: Clinical outcomes, including overall survival (OS) and disease-free survival (DFS), were analyzed by Kaplan-Meier method, log-rank test, and Cox proportional hazards regression model. Subgroup analysis based on crucial clinical information was also conducted. Results: All 1293 patients (median [IQR] age, 59 [50-65] years; 860 [66.5%] male) were divided into 2 groups, with 125 patients in the anti-H pylori treatment group and 1168 patients in the non-anti-H pylori treatment group based on whether they received anti-H pylori treatment during the perioperative period and the follow-up. Survival analysis showed that the 5-year OS rates were 94.1% (95% CI, 89.3%-99.2%) in the anti-H pylori group and 73.8% (95% CI, 70.7%-77.0%) in the non-anti-H pylori group, and the hazard ratio (HR) of these 2 groups was 0.33 (95% CI, 0.18-0.60; P < .001). The survival benefit remained after propensity score matching (HR, 0.50; 95% CI, 0.26-0.99; P = .048). Multivariable analysis for OS and DFS further showed the survival benefit of anti-H pylori treatment, with HRs of 0.38 (95% CI, 0.17-0.87; P = .02) and 0.48 (95% CI, 0.28-0.83; P = .008), respectively. Among patients with TNM stage II/III disease who received adjuvant chemotherapy, anti-H pylori treatment was associated with survival benefits (OS: HR, 0.49; 95% CI, 0.24-0.99; P = .046), whereas among those who did not receive adjuvant chemotherapy, anti-H pylori treatment was not associated with survival benefits (OS: HR, 0.29; 95% CI, 0.04-2.08; P = .22). Conclusions and Relevance: This cohort study indicates that anti-H pylori treatment may be associated with improved survival in patients with gastric cancer who have H pylori infections. The study reinforces the importance of including H pylori screening and treatment in the surgical treatment of these patients.

Design of public open space: Site features, playing, and physical activity.

Not enough studies have examined how specific design features of public open space, such as movable site features, are associated with people's physical activity level or playfulness. To fill this gap, this study uses deep learning-based methods to extract visitors' movement trajectories (n = 18,592) from a time-lapse video of a promenade in Hong Kong. The trajectories are classified into different groups based on a set of movement indicators. Multinomial logistic regression is used to examine the relationship between trajectory types and the level of interaction with different site features. A one-way analysis of variance (ANOVA) is also used to compare the average amount of physical activity among different trajectory types. The results show that interaction with semi-fixed or movable site features is associated with higher odds of people having "playful" trajectories than other types of trajectories. People with "sporty" trajectories and "playful" trajectories on average have the highest amount of physical activity.

TPI1 promotes MAPK/ERK-induced EMT, cell migration and invasion in lung adenocarcinoma.

BACKGROUND: Triosephosphate isomerase 1 (TPI1), as a widely involved glycolytic enzyme, plays a significant role in glucose metabolism and is highly expressed in various tumors. However, its role in lung adenocarcinoma (LUAD) remains incompletely understood. METHODS: Through bioinformatic analysis, we identified a positive association between high expression of TPI1 and metastasis in LUAD. Western blot, RT-qPCR, wound healing assays and transwell experiments, were employed to investigate potential mechanisms. RESULTS: In this study, bioinformatic analysis showed that high expression of TPI1 was associated with poor prognosis in LUAD patients. We examined the expression of TPI1 in 29 paired LUAD tissues and found that TPI1 expression was higher in LUAD tissues than in paired adjacent noncancerous tissues. Meanwhile, overexpression of TPI1 promoted the epithelial-mesenchymal transition (EMT) process in LUAD cells, while silencing TPI1 weakened the EMT process. Furthermore, TPI1 was shown to regulate EMT through the MAPK/ERK signaling pathway. CONCLUSION: TPI1 promotes LUAD metastasis by activating the MAPK/ERK signaling pathway.

One-step fabrication of eco-friendly multi-functional amphiphobic coatings for cellulose-based food packaging.

Plastic and fluorine-containing oil and water resistant packaging materials have been gradually replaced by non-toxic and harmless bio-based materials because of their hazard to environment and human health. In this study, chitosan/carnauba wax emulsions (CS/CWs) were firstly prepared by one-step and used as oil and water resistant coating for cellulose-based food packaging paper. The impacts of emulsion components on stability of the emulsions and barrier performance of the coated paper were investigated. The results showed that the viscosity, particle size and polydispersity index of the emulsions were greatly dependent on the concentration of CS and CW, and the coated paper had the best comprehensive performance in water and oil resistance when the concentration of CS was 3 % and the amount of CW was 90 % of the total solid content (CS3/CW90). The particle size of CS3/CW90 was in the range of 0.5-0.7 µm, and the Cobb60 value, water contact angle and the kit ratings of paper coated with CS3/CW90 achieved 7.5 g/m2, 130.9° and 12/12, respectively, and the coated paper also exhibited excellent thermal stability and high antibacterial rate of 99.1 %, demonstrating its great potential for application in multi-functional food packaging.

Combined Use of Tumor Markers in Gastric Cancer: A Novel Method with Promising Prognostic Accuracy and Practicality.

BACKGROUND: The effect of a single tumor marker on the prognosis of gastric cancer patients is not ideal. This study explored a novel prognostic assessment method for gastric cancer (GC) patients using a combination of three important tumor markers (CEA, CA72-4, and CA19-9). METHOD: Data from 1966 GC patients who underwent curative gastrectomy at Sun Yat-Sen University Cancer Center (Guangzhou, China) were included. Hazard ratios (HR) for all factors for overall survival (OS) were analyzed by Cox regression. A nomogram and calibration curve were used to establish the survival prediction model. The prediction accuracy was evaluated with the concordance index (C-index). RESULTS: All patients were divided into four groups (C0-C3) according to the number of elevated tumor markers. The 5-year OS rates of the patients in preoperative groups C0-C3 were 83.8% (81.3-86.4%), 72.8% (68.5-77.4%), 58.9% (50.4-68.9%), and 18.5% (4.0-33.0%), respectively, and those in postoperative groups C0-C3 were 82.1% (79.4-84.8%), 76.1% (72.2-80.3%), 57.6% (48.4-68.5%), and 16.8% (5.1-28.5%), respectively, with significant differences between each C0-C3 subgroup in both preoperative and postoperative cohorts. Multivariate analysis showed that preoperative (HR: 6.001, 95% CI: 3.523-10.221) and postoperative (HR: 8.149, 95% CI: 4.962-13.528) elevated tumor markers were independent risk factors for GC patients. The C-index for the combined use of tumor markers was 0.65-0.66, which was higher than that for using a single tumor marker (0.53-0.56). CONCLUSION: The combined use of tumor markers significantly improved the prognostic value compared with using a single tumor marker. The survival prediction model including the combined tumor markers was accurate and effective.

Characteristics of a ceftadine/avibatam resistance KPC-33-producing Klebsiella Pneumoniae strain with capsular serotype K19 belonging to ST15.

OBJECTIVES: The aim of this study was to characterize the blaKPC-33 in a ST15-K19 ceftazidime-avibactam (CAZ-AVI)-resistant Klebsiella pneumoniae strain after the antibiotic CAZ-AVI was approved for use in Wuxi No. 2 People's Hospital, China. METHODS: Antimicrobial susceptibility testing was performed by the microdilution broth method. Whole genome sequencing (WGS) was performed using PacBio II and MiSeq sequencers. High-quality reads were assembled using the SOAPdenovo and GapCloser v1.12, and genome annotation was performed using the NCBI Prokaryotic Genome Annotation Pipeline (PGAP). Genomic characteristics were analysed by using bioinformatics methods. RESULTS: K. pneumoniae strain KPHRJ showed resistance to CAZ-AVI. WGS analysis showed that strain KPHRJ had one 5 536 506 bp chromosome (57.25% G+C content) and one plasmid (133 451 bp, G+C 54.29%). KPHRJ was classified as ST15 and K19 serotype. Resistome analysis showed that KPHRJ carries seven antimicrobial resistance genes (ARGs). WGS analysis and conjugation experiments demonstrated that the blaKPC-33 gene was carried by plasmid pKPHRJ, flanked by two copies of IS26 mobile elements (IS26-ISKpn27-blaKPC-33-ISKpn6-korC-TnAs1-tetR-tetA-Tn3-IS26). Besides these acquired resistance genes, mutations in porin protein-coding genes, such as OmpK36 and OmpK37, which may reduce susceptibility to the CAZ-AVI, were also identified from the genome. CONCLUSION: Here, we present the WGS of a CAZ-AVI resistant K. pneumoniae isolate, strain KPHRJ, with capsular serotype K19 and belonging to ST15. CAZ-AVI resistance is likely conferred by a KPC-2 variant, blaKPC-33 and mutations in porin-coding genes. We speculate that the approval of the CAZ-AVI in hospital could contribute to the emergence of these genomic features by providing a selective pressure leading to the emergence of CAZ-AVI resistant bacteria.

Repurposed Fenoprofen Targeting SaeR Attenuates Staphylococcus aureus Virulence in Implant-Associated Infections.

Implant-associated infections (IAIs) caused by S. aureus can result in serious challenges after orthopedic surgery. Due to biofilm formation and antibiotic resistance, this refractory infection is highly prevalent, and finding drugs to attenuate bacterial virulence is becoming a rational alternative strategy. In S. aureus, the SaeRS two-component system (TCS) plays a key role in the production of over 20 virulence factors and the pathogenesis of the bacterium. Here, by conducting a structure-based virtual screening against SaeR, we identified that fenoprofen, a USA Food and Drug Administration (FDA)-approved nonsteroid anti-inflammatory drug (NSAID), had excellent inhibitory potency against the response regulator SaeR protein. We showed that fenoprofen attenuated the virulence of S. aureus without drug resistance. In addition, it was helpful in relieving osteolysis and restoring the walking ability of mice in vitro and in implant-associated infection models. More importantly, fenoprofen treatment suppressed biofilm formation and changed the biofilm structure, which caused S. aureus to form loose and porous biofilms that were more vulnerable to infiltration and elimination by leukocytes. Our results reveal that fenoprofen is a potent antivirulence agent with potential value in clinical applications and that SaeR is a drug target against S. aureus implant-associated infections.

Immobilization of the Polar Group into an Ultramicroporous Metal-Organic Framework Enabling Benchmark Inverse Selective CO2/C2H2 Separation with Record C2H2 Production.

One-step harvest of high-purity light hydrocarbons without the desorption process represents an advanced and highly efficient strategy for the purification of target substances. The separation and purification of acetylene (C2H2) from carbon dioxide (CO2) by CO2-selective adsorbents are urgently demanded yet are very challenging owing to their similar physicochemical properties. Here, we employ the pore chemistry strategy to adjust the pore environment by immobilizing polar groups into an ultramicroporous metal-organic framework (MOF), achieving one-step manufacture of high-purity C2H2 from CO2/C2H2 mixtures. Embedding methyl groups into prototype stable MOF (Zn-ox-trz) not only changes the pore environment but also improves the discrimination of guest molecules. The methyl-functionalized Zn-ox-mtz thus exhibits the benchmark reverse CO2/C2H2 uptake ratio of 12.6 (123.32/9.79 cm3 cm-3) and an exceptionally high equimolar CO2/C2H2 selectivity of 1064.9 at ambient conditions. Molecular simulations reveal that the synergetic effect of pore confinement and surfaces decorated with methyl groups provides high recognition of CO2 molecules through multiple van der Waals interactions. The column breakthrough experiments suggest that Zn-ox-mtz dramatically achieved the one-step purification capacity of C2H2 from the CO2/C2H2 mixture with a record C2H2 productivity of 2091 mmol kg-1, surpassing all of the CO2-selective adsorbents reported so far. In addition, Zn-ox-mtz exhibits excellent chemical stability under different pH values of aqueous solutions (pH = 1-12). Moreover, the highly stable framework and excellent inverse selective CO2/C2H2 separation performance showcase its promising application as a C2H2 splitter for industrial manufacture. This work paves the way to developing reverse-selective adsorbents for the challenging gas separation process.

Integrated insight into the molecular mechanisms of selenium-modulated, MPP+-induced cytotoxicity in a Parkinson's disease model.

OBJECTIVE: Parkinson's disease (PD) is a neurodegenerative disease that is associated with oxidative stress. Due to the anti-inflammatory and antioxidant functions of Selenium (Se), this molecule may have neuroprotective functions in PD; however, the involvement of Se in such a protective function is unclear. METHODS: 1-methyl-4-phenylpyridinium (MPP+), which inhibits mitochondrial respiration, is generally used to produce a reliable cellular model of PD. In this study, a MPP+-induced PD model was used to test if Se could modulate cytotoxicity, and we further capture gene expression profiles following PC12 cell treatment with MPP+ with or without Se by genome wide high-throughput sequencing. RESULTS: We identified 351 differentially expressed genes (DEGs) and 14 differentially expressed long non-coding RNAs (DELs) in MPP+-treated cells when compared to controls. We further document 244 DEGs and 27 DELs in cells treated with MPP+ and Se vs. cells treated with MPP+ only. Functional annotation analysis of DEGs and DELs revealed that these groups were enriched in genes that respond to reactive oxygen species (ROS), metabolic processes, and mitochondrial control of apoptosis. Thioredoxin reductase 1 (Txnrd1) was also identified as a biomarker of Se treatment. CONCLUSIONS: Our data suggests that the DEGs Txnrd1, Siglec1 and Klf2, and the DEL AABR07044454.1 which we hypothesize to function in cis on the target gene Cdkn1a, may modulate the underlying neurodegenerative process, and act a protective function in the PC12 cell PD model. This study further systematically demonstrated that mRNAs and lncRNAs induced by Se are involved in neuroprotection in PD, and provides novel insight into how Se modulates cytotoxicity in the MPP+-induced PD model.

Prognostic factors and the necessity of chemotherapy for stage II gastric cancer: a model based on multicenter retrospective study.

BACKGROUND: This study aimed to construct a prognostic model for prognosis prediction and assess the response to adjuvant chemotherapy (ACT) of stage II gastric cancer (GC) patients on high and low survival risk stratifications. METHODS: We retrospectively reviewed 547 stage II gastric cancer patients who underwent D2 radical gastrectomy from January 2009 to May 2017 in Sixth Affiliated Hospital of Sun Yat-Sen University (SAH-SYSU), the Fujian Medical University Union Hospital (FJUUH), and the Sun Yat-Sen University Cancer Center (SYSUCC).The propensity score matching (PSM) of all variables was performed to balance selective bias between ACT and surgery alone (SA) groups. Kaplan-Meier survival and multivariate Cox regression analyses were carried out to identify independent prognostic factors. Independent factors selected by the Cox regression were integrated into the nomogram. The nomogram points stratified patients into high-risk and low-risk groups by the optimal cut-off value. RESULTS: 278 patients were selected after PSM. Age, tumor site, T stage and lymph-nodes-examined (LNE) selected by Cox regression as independent prognostic factors were integrated into the nomogram. The nomogram performed well with a C-index of 0.76 and with C-indexes of 0.73 in and 0.71 in two validate cohorts. AUCs of the 3 year and 5 year ROC curves were 0.81 and 0.78. High- and low-risk groups stratified by the cut-off value demonstrated different responses to ACT. CONCLUSIONS: The nomogram performed well in prognosis prediction. Patients in high- and low-risk groups demonstrated different responses to ACT, and high-risk patients might need ACT.

Antibiotic treatment can exacerbate biofilm-associated infection by promoting quorum cheater development.

Quorum cheating, a socio-microbiological process that is based on mutations in cell density-sensing (quorum-sensing) systems, has emerged as an important contributor to biofilm-associated infection in the leading human pathogen Staphylococcus aureus. This is because inactivation of the staphylococcal Agr quorum-sensing system leads to pronounced biofilm formation, increasing resistance to antibiotics and immune defense mechanisms. Since biofilm infections in the clinic usually progress under antibiotic treatment, we here investigated whether such treatment promotes biofilm infection via the promotion of quorum cheating. Quorum cheater development was stimulated by several antibiotics used in the treatment of staphylococcal biofilm infections more strongly in biofilm than in the planktonic mode of growth. Sub-inhibitory concentrations of levofloxacin and vancomycin were investigated for their impact on biofilm-associated (subcutaneous catheter-associated and prosthetic joint-associated infection), where in contrast to a non-biofilm-associated subcutaneous skin infection model, a significant increase of the bacterial load and development of agr mutants was observed. Our results directly demonstrate the development of Agr dysfunctionality in animal biofilm-associated infection models and reveal that inappropriate antibiotic treatment can be counterproductive for such infections as it promotes quorum cheating and the associated development of biofilms.