Visualized Tracking and Multidimensional Assessing of Mitochondria-Associated Pyroptosis in Cancer Cells by a Small-Molecule Fluorescent Probe.

Pyroptosis is closely related to the development and treatment of various cancers; thus, comprehensive studies of the correlations between pyroptosis and its inductive or inhibitive factors can provide new ideas for the intervention and diagnosis of tumors. The dysfunction of mitochondria may induce pyroptosis in cancer cells, which can be reflected by the fluctuations of the microenvironmental parameters in mitochondria as well as the changes of mitochondrial DNA level and morphology, etc. To precisely track and assess the mitochondria-associated pyroptosis process, simultaneous visualization of changes in multiphysiological parameters in mitochondria is highly desirable. In this work, we reported a nonreaction-based, multifunctional small-molecule fluorescent probe Mito-DK with the capability of crosstalk-free response to polarity and mtDNA as well as mitochondrial morphology. Accurate assessment of mitochondria-associated pyroptosis induced by palmitic acid/H2O2 was achieved through monitoring changes in mitochondrial multiple parameters with the help of Mito-DK. In particular, the pyroptosis-inducing ability of an antibiotic doxorubicin and the pyroptosis-inhibiting capacity of an anticancer agent puerarin were evaluated by Mito-DK. These results provide new perspectives for visualizing mitochondria-associated pyroptosis and offer new approaches for screening pyroptosis-related anticancer agents.

Tunneling Interpenetrative Lithium Ion Conduction Channels in Polymer-in-Ceramic Composite Solid Electrolytes.

Polymer-in-ceramic composite solid electrolytes (PIC-CSEs) provide important advantages over individual organic or inorganic solid electrolytes. In conventional PIC-CSEs, the ion conduction pathway is primarily confined to the ceramics, while the faster routes associated with the ceramic-polymer interface remain blocked. This challenge is associated with two key factors: (i) the difficulty in establishing extensive and uninterrupted ceramic-polymer interfaces due to ceramic aggregation; (ii) the ceramic-polymer interfaces are unresponsive to conducting ions because of their inherent incompatibility. Here, we propose a strategy by introducing polymer-compatible ionic liquids (PCILs) to mediate between ceramics and the polymer matrix. This mediation involves the polar groups of PCILs interacting with Li+ ions on the ceramic surfaces as well as the interactions between the polar components of PCILs and the polymer chains. This strategy addresses the ceramic aggregation issue, resulting in uniform PIC-CSEs. Simultaneously, it activates the ceramic-polymer interfaces by establishing interpenetrating channels that promote the efficient transport of Li+ ions across the ceramic phase, the ceramic-polymer interfaces, and the intervening pathways. Consequently, the obtained PIC-CSEs exhibit high ionic conductivity, exceptional flexibility, and robust mechanical strength. A PIC-CSE comprising poly(vinylidene fluoride) (PVDF) and 60 wt % PCIL-coated Li3Zr2Si2PO12 (LZSP) fillers showcasing an ionic conductivity of 0.83 mS cm-1, a superior Li+ ion transference number of 0.81, and an elongation of ∼300% at 25 °C could be produced on meter-scale. Its lithium metal pouch cells show high energy densities of 424.9 Wh kg-1 (excluding packing films) and puncture safety. This work paves the way for designing PIC-CSEs with commercial viability.

Dual-modification of Ni-rich cathode materials through strontium titanate coating and thermal treatment.

Ni-rich layered structure ternary oxides, such as LiNi0.8Co0.1Mn0.1O2 (NCM811), are promising cathode materials for high-energy lithium-ion batteries (LIBs). However, a trade-off between high capacity and long cycle life still obstructs the commercialization of Ni-rich cathodes in modern LIBs. Herein, a facile dual modification approach for improving the electrochemical performance of NCM811 was enabled by a typical perovskite oxide: strontium titanate (SrTiO3). With a suitable thermal treatment, the modified cathode exhibited an outstanding electrochemical performance that could deliver a high discharge capacity of 188.5 mAh/g after 200 cycles under 1C with a capacity retention of 90%. The SrTiO3 (STO) protective layer can effectively suppress the side reaction between the NCM811 and the electrolyte. In the meantime, the pillar effect provided by interfacial Ti doping could effectively reduce the Li+/Ni2+ mixing ratio on the NCM811 surface and offer more efficient Li+ migration between the cathode and the coating layer after post-thermal treatment (≥600 °C). This dual modification strategy not only significantly improves the structural stability of Ni-rich layered structure but also enhances the electrochemical kinetics via increasing diffusion rate of Li+. The electrochemical measurement results further disclosed that the 3 wt% STO coated NCM811 with 600 °C annealing exhibits the best performance compared with other control samples, suggesting an appropriate temperature range for STO coated NCM811 cathode is critical for maintaining a stable structure for the whole system. This work may offer an effective option to enhance the electrochemical performance of Ni-rich cathodes for high-performance LIBs.

A dual-salt fluorescent probe for specific recognition of mitochondrial NADH and potential cancer diagnosis.

Reduced nicotinamide adenine dinucleotide (NADH) is a kind of coenzyme and widely works as a biomarker in cancer cells. It plays a crucial role in many cellular metabolic processes, especially NADH in mitochondria is indispensable for the mitochondrial respiration chain that produces ATP. Herein, we designed a fluorescent probe Mito-FCC based on an ethylene-bridging dual-salt structure, in which benzo[e]indolium fluorophore was used as the mitochondria-targeting group and 1-methylquinolinium moiety as the NADH recognition unit. Mito-FCC exhibited high sensitivity and selectivity for NADH with a rapid "turn-on" fluorescence signal. The dual-salt structure endowed the probe with a reliable mitochondria-targeted ability even after the recognition unit was reduced by NADH. With the help of the probe, the fluctuations of endogenous NADH induced by glucose or pyruvate were imaged. Besides, Mito-FCC had a capability to make a distinction between cancer cells and normal cells due that the content of NADH in cancer cells was distinctly higher than that in normal ones. Notably, the visualization of tumor in vivo through monitoring NADH using Mito-FCC was realized successfully. These experimental results showed that Mito-FCC hold a great perspective in study of mitochondrial function and potential diagnosis of cancer diseases.

KIAA1199 promotes oxaliplatin resistance and epithelial mesenchymal transition of colorectal cancer via protein O-GlcNAcylation.

Oxaliplatin is a commonly used platinum drug for colorectal cancer (CRC). However, the treatment of CRC by oxaliplatin usually fails because of drug resistance, which results in a huge challenge in the therapy of CRC. Elucidation of molecular mechanisms may help to overcome oxaliplatin resistance of CRC. In our study, we revealed that KIAA1199 can promote oxaliplatin resistance of CRC. Mechanistically, KIAA1199 prevents oxaliplatin mediated apoptosis via up-regulated PARP1 derived from reduced endoplasmic reticulum stress induced by protein O-GlcNAcylation. In the meantime, KIAA1199 can also trigger epithelial mesenchymal transition by stabilizing SNAI1 protein via O-GlcNAcylation. Therefore, KIAA1199 has great potential to be a novel biomarker, therapeutic target for oxaliplatin resistance and metastasis of CRC.

Clinical Characteristics and Prognostic Factors in Primary Breast Diffuse Large B-Cell Lymphoma.

Background: Primary breast diffuse large B-cell lymphoma (PB-DLBCL) is a rare subtype of non-Hodgkin lymphoma (NHL) with limited data on the clinical features and prognostic factors. Patients and Methods: A consecutive cohort of patients with PB-DLBCL was retrospectively analyzed in our hospital from February 1997 through July 2018. The primary endpoint is overall survival (OS) contributing to any cause. Results: A total of 76 patients were diagnosed with PB-DLBCL. The median age at diagnosis was 51 years (range: 25-80 years), with female prevalence (98.7%). Forty (52.6%) patients had right-sided breast involvement but no bilateral breast involvement at diagnosis. Overall, disease stages IE and IIE were seen in 55 (72.4%) and 21 (27.6%) patients, respectively. According to the stage-modified International Prognostic Index (IPI), 37 (48.7%) patients were classified in the very good risk group (IPI 0). Of the 72 patients available, the non-germinal center B-cell (non-GCB) subtype of DLBCL was observed in 66 (91.6%) patients. All patients received anthracycline-based chemotherapy, 56 (73.7%) with rituximab, 31 (40.8%) also with additional radiation therapy, and 14 (18.4%) patients received a prophylactic intrathecal injection. Seven (9.2%) patients had refractory disease. With a median follow-up of 6.8 years (range 0.4-25.0 years), 10 (13.2%) patients had a relapse in the central nervous system (CNS) site. The 5-year and 10-year OS of all the patients was 97.2% (95% CI: 99.3-89.5) and 84.8% (95% CI: 70.0-93.5), respectively. The median OS was not reached. The median progression-free survival (PFS) was 10.3 years for patients with PB-DLBCL. The 5-year PFS of all the patients was 76.3% (95% CI: 64.6-84.6). Univariate analysis revealed several prognostic factors, including stage-modified IPI, breast surgery, refractory disease, and CNS relapse. Multivariate analyses produced two independent prognostic factors for patients with PB-DLBCL, including stage-modified IPI score (2-3 versus 0) (hazard ratio: 19.114, 95% CI 1.841 to 198.451, p=0.013) and CNS relapse (hazard ratio: 5.522, 95% CI 1.059 to 28.788, p=0.043). Conclusion: In our cohort, PB-DLBCL clinical features are similar to prior literature reports. Stage-modified IPI score and CNS relapse were associated with overall survival.

Identification and Verification of Potential Biomarkers in Gastric Cancer By Integrated Bioinformatic Analysis.

Background: Gastric cancer (GC) is a common cancer with high mortality. This study aimed to identify its differentially expressed genes (DEGs) using bioinformatics methods. Methods: DEGs were screened from four GEO (Gene Expression Omnibus) gene expression profiles. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. A protein-protein interaction (PPI) network was constructed. Expression and prognosis were assessed. Meta-analysis was conducted to further validate prognosis. The receiver operating characteristic curve (ROC) was analyzed to identify diagnostic markers, and a nomogram was developed. Exploration of drugs and immune cell infiltration analysis were conducted. Results: Nine up-regulated and three down-regulated hub genes were identified, with close relations to gastric functions, extracellular activities, and structures. Overexpressed Collagen Type VIII Alpha 1 Chain (COL8A1), Collagen Type X Alpha 1 Chain (COL10A1), Collagen Triple Helix Repeat Containing 1 (CTHRC1), and Fibroblast Activation Protein (FAP) correlated with poor prognosis. The area under the curve (AUC) of ADAM Metallopeptidase With Thrombospondin Type 1 Motif 2 (ADAMTS2), COL10A1, Collagen Type XI Alpha 1 Chain (COL11A1), and CTHRC1 was >0.9. A nomogram model based on CTHRC1 was developed. Infiltration of macrophages, neutrophils, and dendritic cells positively correlated with COL8A1, COL10A1, CTHRC1, and FAP. Meta-analysis confirmed poor prognosis of overexpressed CTHRC1. Conclusion: ADAMTS2, COL10A1, COL11A1, and CTHRC1 have diagnostic values in GC. COL8A1, COL10A1, CTHRC1, and FAP correlated with worse prognosis, showing prognostic and therapeutic values. The immune cell infiltration needs further investigations.

Enhancing cyclic and in-air stability of Ni-Rich cathodes through perovskite oxide surface coating.

Ni-rich layered oxides, such as LiNi0.8Co0.1Mn0.1O2 (NCM811), are promising cathode materials for high-energy lithium-ion batteries. However, the relatively high reactivity of Ni in NCM811 cathodes results in severe capacity fading originating from the undesired side reactions that occur at the cathode-electrolyte interface during prolonged cycling. Therefore, the trade-off between high capacity and long cycle life can obstruct the commercialization process of Ni-rich cathodes in modern lithium-ion batteries (LIBs). In addition, high sensitivity toward air upon storage greatly limits the commercial application. Herein, a facile surface modification strategy is introduced to enhance the cycling and in-air storage stability of NCM811. The NCM811 with a uniform SrTiO3 (STO) nano-coating layer exhibited outstanding electrochemical performances that could deliver a high discharge capacity of 173.5 mAh⋅g-1 after 200 cycles under 1C with a capacity retention of 90%. In contrast, the uncoated NCM811 only provided 65% capacity retention of 130.8 mAh⋅g-1 under the same conditions. Structural evolution analysis suggested that the STO coating acted as a buffer layer to suppress the dissolution of transition metal ions caused by the HF attack from the electrolyte and promote the lithium diffusion during the charge-discharge process. In addition, the constructed STO layer prevented the exposure of NCM811 to H2O and CO2 and thus effectively improved the in-air storage stability. This work offers an effective way to enhance the performance stability of Ni-rich oxides for high-performance cathodes of lithium-ion batteries.

Diagnostic Value, Prognostic Value, and Immune Infiltration of LOX Family Members in Liver Cancer: Bioinformatic Analysis.

Background: Liver cancer (LC) is well known for its prevalence as well as its poor prognosis. The aberrant expression of lysyl oxidase (LOX) family is associated with liver cancer, but their function and prognostic value in LC remain largely unclear. This study aimed to explore the function and prognostic value of LOX family in LC through bioinformatics analysis and meta-analysis. Results: The expression levels of all LOX family members were significantly increased in LC. Area under the receiver operating characteristic curve (AUC) of LOXL2 was 0.946 with positive predictive value (PPV) of 0.994. LOX and LOXL3 were correlated with worse prognosis. Meta-analysis also validated effect of LOX on prognosis. Nomogram of these two genes and other predictors was also plotted. There was insufficient data from original studies to conduct meta-analysis on LOXL3. The functions of LOX family members in LC were mostly involved in extracellular and functions and structures. The expressions of LOX family members strongly correlated with various immune infiltrating cells and immunomodulators in LC. Conclusions: For LC patients, LOXL2 may be a potential diagnostic biomarker, while LOX and LOXL3 have potential prognostic and therapeutic values. Positive correlation between LOX family and infiltration of various immune cells and immunomodulators suggests the need for exploration of their roles in the tumor microenvironment and for potential immunotherapeutic to target LOX family proteins.

CD274 (PD-L1) Methylation is an Independent Predictor for Bladder Cancer Patients' Survival.

This study was carried out to demonstrate the prognostic value of CD274 (PD-L1 promoter gene) methylation in bladder cancer patients. UCSC Xena database was searched for relevant information on PD-L1 (CD274) methylation and PD-L1 mRNA expression in bladder cancer. 407 bladder patients were included in our analyses. Multivariate analysis revealed that PD-L1 methylation was an independent predictor for OS (P = 0.037). Moreover, PD-L1 methylation might be a prognostic biomarker for immunotherapy response. However, PD-L1 methylation and PD-L1 mRNA expression was not statistically associated with chemotherapy response. In conclusion, PD-L1 methylation was an independent prognostic factor for bladder cancer patients.

Membrane-Based In-Gel Loop-Mediated Isothermal Amplification (mgLAMP) System for SARS-CoV-2 Quantification in Environmental Waters.

Since the COVID-19 pandemic is expected to become endemic, quantification of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in ambient waters is critical for environmental surveillance and for early detection of outbreaks. Herein, we report the development of a membrane-based in-gel loop-mediated isothermal amplification (mgLAMP) system that is designed for the rapid point-of-use quantification of SARS-CoV-2 particles in environmental waters. The mgLAMP system integrates the viral concentration, in-assay viral lysis, and on-membrane hydrogel-based RT-LAMP quantification using enhanced fluorescence detection with a target-specific probe. With a sample-to-result time of less than 1 h, mgLAMP successfully detected SARS-CoV-2 below 0.96 copies/mL in Milli-Q water. In surface water, the lowest detected SARS-CoV-2 concentration was 93 copies/mL for mgLAMP, while the reverse transcription quantitative polymerase chain reaction (RT-qPCR) with optimal pretreatment was inhibited at 930 copies/mL. A 3D-printed portable device is designed to integrate heated incubation and fluorescence illumination for the simultaneous analysis of nine mgLAMP assays. Smartphone-based imaging and machine learning-based image processing are used for the interpretation of results. In this report, we demonstrate that mgLAMP is a promising method for large-scale environmental surveillance of SARS-CoV-2 without the need for specialized equipment, highly trained personnel, and labor-intensive procedures.

Single-Cell Phenotypic Analysis and Digital Molecular Detection Linkable by a Hydrogel Bead-Based Platform.

Cell heterogeneity, such as antibiotic heteroresistance and cancer cell heterogeneity, has been increasingly observed. To probe the underlying molecular mechanisms in the dynamically changing heterogeneous cells, a high throughput platform is urgently needed to establish single cell genotype-phenotype correlations. Herein, we report a platform combining single-cell viability phenotypic analysis with digital molecular detection for bacterial cells. The platform utilizes polyethylene glycol hydrogel that cross-links through a thiol-Michael addition, which is biocompatible, fast, and spontaneous. To generate uniform nanoliter-sized hydrogel beads (Gelbeads), we developed a convenient and disposable device made of needles and microcentrifuge tubes. Gelbead-based single cell viability and molecular detection assays were established. Enhanced thermal stability and uncompromised efficiency were achieved for digital polymerase chain reaction (PCR) and digital loop-mediated isothermal amplification (LAMP) within the Gelbeads. Reagent exchange for in situ PCR following viability phenotypic analyses was demonstrated. The combined analyses may address the genotypic differences between cellular subpopulations exhibiting distinct phenotypes. The platform promises unique perspectives in mechanism elucidation of environment-evolution interaction that may be extended to other cell types for medical research.

Rapid Detection Methods for Bacterial Pathogens in Ambient Waters at the Point of Sample Collection: A Brief Review.

The world is currently facing a serious health burden of waterborne diseases, including diarrhea, gastrointestinal diseases, and systemic illnesses. The control of these infectious diseases ultimately depends on the access to safe drinking water, properly managed sanitation, and hygiene practices. Therefore, ultrasensitive, rapid, and specific monitoring platforms for bacterial pathogens in ambient waters at the point of sample collection are urgently needed. We conducted a literature review on state-of-the-art research of rapid in-field aquatic bacteria detection methods, including cell-based methods, nucleic acid amplification detection methods, and biosensors. The detection performance, the advantages, and the disadvantages of the technologies are critically discussed. We envision that promising monitoring approaches should be automated, real-time, and target-multiplexed, thus allowing comprehensive evaluation of exposure risks attributable to waterborne pathogens and even emerging microbial contaminants such as antibiotic resistance genes, which leads to better protection of public health.

Synthesis and application of superabsorbent polymer microspheres for rapid concentration and quantification of microbial pathogens in ambient water.

Even though numerous methods have been developed for the detection and quantification of waterborne pathogens, the application of these methods is often hindered by the very low pathogen concentrations in natural waters. Therefore, rapid and efficient sample concentration methods are urgently needed. Here we present a novel method to pre-concentrate microbial pathogens in water using a portable 3D-printed system with super-absorbent polymer (SAP) microspheres, which can effectively reduce the actual volume of water in a collected sample. The SAP microspheres absorb water while excluding bacteria and viruses by size exclusion and charge repulsion. To improve the water absorption capacity of SAP in varying ionic strength waters (0-100 mM), we optimized the formulation of SAP to 180 g⋅L-1 Acrylamide, 75 g⋅L-1 Itaconic Acid and 4.0 g⋅L-1 Bis-Acrylamide for the highest ionic strength water as a function of the extent of cross-linking and the concentration of counter ions. Fluorescence microscopy and double-layer agar plating respectively showed that the 3D-printed system with optimally-designed SAP microspheres could rapidly achieve a 10-fold increase in the concentration of Escherichia coli (E. coli) and bacteriophage MS2 within 20 min with concentration efficiencies of 87% and 96%, respectively. Fold changes between concentrated and original samples from qPCR and RT-qPCR results were found to be respectively 11.34-22.27 for E. coli with original concentrations from 104 to 106 cell·mL-1, and 8.20-13.81 for MS2 with original concentrations from 104 to 106 PFU·mL-1. Furthermore, SAP microspheres can be reused for 20 times without performance loss, significantly decreasing the cost of our concentration system.

Electrochemical cell lysis of gram-positive and gram-negative bacteria: DNA extraction from environmental water samples.

Cell lysis is an essential step for the nucleic acid-based surveillance of bacteriological water quality. Recently, electrochemical cell lysis (ECL), which is based on the local generation of hydroxide at a cathode surface, has been reported to be a rapid and reagent-free method for cell lysis. Herein, we describe the development of a milliliter-output ECL device and its performance characterization with respect to the DNA extraction efficiency for gram-negative bacteria (Escherichia coli and Salmonella Typhi) and gram-positive bacteria (Enterococcus durans and Bacillus subtilis). Both gram-negative and gram-positive bacteria were successfully lysed within a short but optimal duration of 1 min at a low voltage of ∼5 V. The ECL method described herein, is demonstrated to be applicable to various environmental water sample types, including pond water, treated wastewater, and untreated wastewater with DNA extraction efficiencies similar to a commercial DNA extraction kit. The ECL system outperformed homogeneous chemical lysis in terms of reaction times and DNA extraction efficiencies, due in part to the high pH generated at the cathode surface, which was predicted by simulations of the hydroxide transport in the cathodic chamber. Our work indicates that the ECL method for DNA extraction is rapid, simplified and low-cost with no need for complex instrumentation. It has demonstrable potential as a prelude to PCR analyses of waterborne bacteria in the field, especially for the gram-negative ones.

Improving thermal and electrical stability of silver nanowire network electrodes through integrating graphene oxide intermediate layers.

Silver nanowire (Ag NW)-based flexible and transparent electrodes are a promising candidate for various electronic and optoelectronic applications. However, thermal and electrical instabilities of Ag NW networks during operation and post treatments need to be improved for practical applications. In this work, Ag NW/Graphene Oxide (GO) hybrid films with a multilayer structure were developed, in which transparent GO sheets were inserted between Ag NWs. For the pristine Ag NW networks, contacted NWs exhibited poorer thermal stability than individual NWs as faster Ag diffusion between NWs led to the breakage of the junctions at working temperatures, hence leading to the overall device failure. In contrast, the GO intermediate layers hindered the Ag diffusion between NWs in the Ag NW/Graphene Oxide hybrid films and maintained the junction structure, giving rise to enhanced thermal stability compared to the pristine networks and the GO-covered samples. For electrical tests, unlike the network degradation under annealing treatments, a local deterioration perpendicular to the current flow was directly observed after electrical breakdown, which was attributed to high local temperature under large applied voltage. The electrical failure of the devices was related to the network structure and defects. Furthermore, the pristine devices showed notable variation of failure voltage, which in the hybrid devices is more uniform and improved in general.

Asymmetric Membrane for Digital Detection of Single Bacteria in Milliliters of Complex Water Samples.

In this work, we introduce an asymmetric membrane as a simple and robust nanofluidic platform for digital detection of single pathogenic bacteria directly in 10 mL of unprocessed environmental water samples. The asymmetric membrane, consisting of uniform micropores on one side and a high density of vertically aligned nanochannels on the other side, was prepared within 1 min by a facile method. The single membrane covers all the processing steps from sample concentration, purification, and partition to final digital loop-mediated isothermal amplification (LAMP). By simple filtration, bacteria were enriched and partitioned inside the micropores, while inhibitors typically found in the environmental samples ( i.e., proteins, heavy metals, and organics) were washed away through the nanochannels. Meanwhile, large particles, indigenous plankton, and positively charged pollutants in the samples were excluded by using a sacrificial membrane stacked on top. After initial filtration, modified LAMP reagents, including NaF and lysozyme, were loaded onto the membrane. Each pore in the asymmetric membrane functioned as an individual nanoreactor for selective, rapid, and efficient isothermal amplification of single bacteria, generating a bright fluorescence for direct counting. Even though high levels of inhibitors were present, absolute quantification of Escherichia coli and Salmonella directly in an unprocessed environmental sample (seawater and pond water) was achieved within 1 h, with sensitivity down to single cell and a dynamic range of 0.3-10000 cells/mL. The simple and low-cost analysis platform described herein has an enormous potential for the detection of pathogens, exosomes, stem cells, and viruses as well as single-cell heterogeneity analysis in environmental, food, and clinical research.

The PD-1 rs36084323 A > G polymorphism decrease cancer risk in Asian: A meta-analysis.

The rs36084323 A > G polymorphism in programmed cell death-1(PD-1) gene has been reported to be associated with cancer risk. However, the results of previous studies were inconsistent. Therefore, we performed a meta-analysis to identify the potential association, by searching the PubMed, EMBASE, Cochrane Library, and the Chinese CNKI, WANFANG and CBM databases. Data were extracted and odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the strength of the association. A total of 10 relevant studies involving 4445 cancer cases and 5126 controls were recruited. Overall, the results indicated that the PD-1 rs36084323 A > G polymorphism was not statistically associated with cancer risk. However, stratified analysis revealed that there was a statistically reduced cancer risk in Asians(G vs. A, OR = 0.89, 95%CI:0.81-0.97, P = 0.008, I2 = 48.8%; GG vs. AA, OR = 0.79, 95% CI:0.66-0.94, P = 0.008, I2 = 48.7%; GG/AG vs. AA, OR = 0.87, 95%CI:0.76-0.98, P = 0.017, I2 = 34.9%; GG vs. AG/AA, OR = 0.85, 95%CI:0.75-0.97, P = 0.027, I2 = 40%) and in the patients with EOC(AG vs. AA, OR = 0.69, 95%CI:0.54-0.90, P = 0.005, I2 = 0%; GG/AG vs. AA, OR = 0.67, 95%CI:0.52-0.85, P = 0.001, I2 = 0). Meta-regression showed that ethnicity (P = 0.029) but not cancer types (P = 0.792), source of controls (P = 0.207) or ample size (P = 0.585) were the sources of heterogeneity. This meta-analysis demonstrates the PD-1 rs36084323 A > G polymorphism is associated with decreased cancer risk in Asian, and suggests it could potentially serve as a biomarker to screen high-risk individuals. Large-scale and well-designed case-control studies are needed to enrich the evidence of this result.

Detection of volatile organic compounds in exhaled breath to screen lung cancer: a systematic review.

To evaluate the clinical value of volatile organic compounds (VOCs) in exhaled breath for lung cancer (LC) screening, a systematic review was performed. Systematic search for studies about exhaled VOCs for LC screening was conducted according to PRISMA. Thirty eight studies with 4873 participants met the criteria for inclusion in this systematic review. Generally speaking, the results suggest that exhaled VOCs have potential to screen LC and more studies are needed in the future.

Propidium monoazide pretreatment on a 3D-printed microfluidic device for efficient PCR determination of live versus dead'microbial cells.

Waterborne microbial pathogen detection via nucleic acid analysis on portable microfluidic devices is a growing area of research, development, and application. Traditional polymerase chain reaction (PCR)-based nucleic acid analysis detects total extracted DNA, but cannot differentiate live and dead cells. A propidium monoazide (PMA) pretreatment step before PCR can effectively exclude DNA from nonviable cells, as PMA can selectively diffuse through compromised cell membranes and intercalate with DNA to form DNA-PMA complex upon light exposure. The complex strongly inhibits the amplification of the bound DNA in PCR, and thus, only cells with intact cell membranes are detected. Herein, this study reports the development of a microfluidic device to carry out PMA pretreatment 'on-chip'. Chip design was guided by computer simu-lations, and prototypes were fabricated using a high-resolution 3D printer. The optimized design utilizes split and recombine mixers for initial PMA-sample mixing and a serpentine flow channel containing her-ringbone structures for dark and light incubation. On-chip PMA pretreatment to differentiate live and dead bacterial cells in buffer and natural pond water samples was successfully demonstrated.