Role of leukocyte parameters in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention with high thrombus burden.

Objective: Leukocyte parameters are associated with cardiovascular diseases. The aim of the present study was to investigate the role of leukocyte parameters in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) with high thrombus burden (HTB). Methods: A total of 102 consecutive STEMI patients with HTB who underwent PPCI within 12 h from the onset of symptoms between June 2020 and September 2021 were enrolled in this study. In addition, 101 age- and sex-matched STEMI patients with low thrombus burden (LTB) who underwent PPCI within 12 h from the onset of symptoms were enrolled as controls. Leukocyte parameters, such as neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and monocyte to lymphocyte ratio (MLR), were calculated at the time of admission. Results: The value of NLR and MLR were significantly higher in the HTB group than in the LTB group (6.24 ± 4.87 vs. 4.65 ± 3.47, p = 0.008; 0.40 ± 0.27 vs. 0.33 ± 0.20, p = 0.038). A cutoff value of >5.38 for NLR had a sensitivity and specificity of 53.9% and 74.3%, respectively, and MLR >0.29 had a sensitivity and specificity of 60.8% and 55.4%, respectively, for determining the STEMI patients with HTB [area under the receiver operating characteristic curve (AUC): 0.603, 95% confidence interval (CI): 0.524-0.681, p = 0.012; AUC: 0.578, 95% CI: 0.499-0.656, p = 0.046]. There was no significant difference of all-cause mortality rate and major adverse cardiac events (MACEs) between the STEMI patients with HTB or with LTB (3.92% in HTB group vs. 2.97% in LTB group, p = 0.712; 10.78% in HTB group vs. 8.91% in LTB group, p = 0.215). Compared with the HTB patients in the low NLR group, C-reactive protein, baseline troponin I, baseline brain natriuretic peptide, and leukocyte parameters, such as white blood cell, neutrophil, lymphocyte, NLR, PLR, and MLR, were also significantly higher in the high NLR group in STEMI patients who underwent PPCI with HTB (18.94 ± 19.06 vs. 35.23 ± 52.83, p = 0.037; 10.99 ± 18.07 vs. 21.37 ± 19.64, p = 0.007; 199.39 ± 323.67 vs. 430.72 ± 683.59, p = 0.028; 11.55 ± 3.56 vs. 9.31 ± 2.54, p = 0.001; 9.77 ± 3.17 vs. 5.79 ± 1.97, p = 0.000; 1.16 ± 0.44 vs. 2.69 ± 1.23, p = 0.000; 9.37 ± 4.60 vs 1.31 ± 2.58, p = 0.000; 200.88 ± 89.90 vs. 97.47 ± 50.99, p = 0.000; 0.52 ± 0.29 vs. 0.26 ± 0.14, p = 0.000, respectively). MACEs and heart failure in the high NLR group were significantly higher than that in the low NLR group of STEMI patients who underwent PPCI with HTB (20.45% vs. 4.25%, p = 0.041; 10.91% vs. 2.13%, p = 0.038). Conclusion: The value of NLR and MLR were higher in STEMI patients who underwent PPCI with HTB. In STEMI patients who underwent PPCI with HTB, a raised NLR could effectively predict the occurrence of MACEs and heart failure.

Modified whitehead hemorrhoidectomy versus partial hemorrhoidectomy for fourth-degree circular mixed hemorrhoids: A retrospective analysis.

Background: Grade IV circular hemorrhoids are difficult to treat. We aim to describe the modified whitehead hemorrhoidectomy procedure and to assess the effectiveness and safety of this procedure for grade IV circular hemorrhoid patients. Methods: Patients with grade Ⅳ circular hemorrhoids who underwent modified Whitehead hemorrhoidectomy and partial hemorrhoidectomy for fourth-degree circular mixed hemorrhoids were retrospectively reviewed. Clinical data were extracted from the database at our institution, and long-term postoperative complications were assessed through repeated outpatient examinations and telephonic communication. Results: A total of 205 patients were included in this study. The mean operative time was 59.2 ± 13.8 min. The average hospital stay was 4.6 ± 1.0 days. For postoperative complications, 66 (32.2%) patients had urinary retention, 10 (4.9%) patients had a sense of incomplete rectal emptying, 5 (2.4%) patients had anal incontinence, and 6 (2.9%) patients had wound infection. For long-term postoperative complications, 3 (1.5%) patients experienced mild to moderate anal stricture, 2 (1%) patients experienced mucosal ectropion, they all had smooth recoveries, and none of them needed secondary surgery. None of these patients had a hemorrhoid recurrence. A total of 205 patients who received modified Whitehead hemorrhoidectomy and 161 who received partial hemorrhoidectomy were included. There were no residual hemorrhoids in patients who received modified Whitehead hemorrhoidectomy, and none had hemorrhoid recurrence. Fifty-eight patients who received partial hemorrhoidectomy had hemorrhoidal residues, and 19 patients experienced hemorrhoid recurrence. After modified Whitehead hemorrhoidectomy, 3 patients developed anal stenosis, and 2 had mucosal ectropion. Four patients developed anal stricture after partial hemorrhoidectomy, and none had mucosal ectropion. They all had smooth recoveries, and none of them needed a secondary surgery. For the mean duration of surgery, postoperative bleeding, postoperative pain, wound infection, sense of incomplete rectal emptying, anal incontinence, and urinary retention, no statistically significant differences were found between the two groups. Conclusions: Compared with partial hemorrhoidectomy, modified whitehead hemorrhoidectomy is an effective and safe surgical procedure and does not significantly increase the risk of anal stenosis and mucosal ectropion for grade IV circular hemorrhoid patients. Prospective randomized controlled trials are needed to verify our results.

Application of AMR in evaluating microvascular dysfunction after ST-elevation myocardial infarction.

BACKGROUND: A guidewire-free angiography-derived microcirculatory resistance (AMR) derived from Quantitative flow ratio (QFR) exhibits good diagnostic accuracy for assessing coronary microvascular dysfunction (CMD), but there are no relevant studies supporting the specific application of AMR in patients with ST-elevation myocardial infarction (STEMI). The study aims to evaluate CMD in patients with STEMI using the AMR index. METHODS: This study included patients with STEMI who underwent percutaneous coronary intervention (PCI) from June 1, 2020 to September 28, 2021. All patients were divided into two groups: the CMD (n = 215) and non-CMD (n = 291) groups. After matching, there were 382 patients in both groups.1-year follow-up major adverse cardiac events (MACEs) were evaluated. RESULTS: After matching, the primary endpoint was achieved in 41 patients (10.7%), with 27 and 14 patients in the CMD and non-CMD groups, respectively (HR 1.954 [95% CI 1.025-3.726]; 14.1% versus 7.3%, p = .042). Subgroup analysis revealed that 18 patients (4.7%) were readmitted for heart failure, with 15 and 3 in the CMD and non-CMD groups, respectively (HR 5.082 [95% CI 1.471-17.554]; 7.9% versus 1.6%, p = .010). Post-PCI AMR ≥ 250 was significantly associated with a higher risk of the primary endpoint and was its independent predictor (HR 2.265 [95% CI 1.136-4.515], p = .020). CONCLUSION: The retrospective use of AMR with a cutoff value of ≥250 after PCI in patients with STEMI can predict a significant difference in the 1-year MACE rates when compared with a propensity score-matched group with normal AMR.

Droplet manipulation on an adjustable closed-open digital microfluidic system utilizing asymmetric EWOD.

The closed-open digital microfluidic (DMF) system offers a versatile and powerful platform for various applications by combining the advantages of both closed and open structures. The current closed-open DMF system faces challenges in scaling up due to electrode structural differences between closed and open regions. Here we developed an adjustable closed-open DMF platform by utilizing the modified slippery liquid-infused porous surfaces (SLIPS) with asymmetric electrowetting on dielectric (AEWOD) as a hydrophobic dielectric layer. The consistent electrode structures of the bottom printed circuit board (PCB) electrode array on both the closed and open regions, and the utilization of a transparent acrylic with floating potential as the top plate allow a low-cost and easily scalable closed-open DMF system to be achieved. The impacts of applied voltage, parallel plate spacing, electrode switching interval, and electrode driving strategies on various droplet manipulations were investigated. The results show that the optimal plate spacings range from 340-510 µm within the closed region. Meanwhile, we also studied the influence of the thickness, geometry, and position of the top plate on the droplet movement at the closed-open boundary. Through force analysis and experimentation, it is found that a thin top plate and a bevel of ∼4° can effectively facilitate the movement of droplets at the boundary. Finally, we successfully achieved protein staining experiments on this platform and developed a customized smartphone application for the accurate detection of protein concentration. This innovative closed-open DMF system provides new possibilities for future applications in real-time biological sample processing and detection.

An unexpected role of neutrophils in clearing apoptotic hepatocytes in vivo.

Billions of apoptotic cells are removed daily in a human adult by professional phagocytes (e.g. macrophages) and neighboring nonprofessional phagocytes (e.g. stromal cells). Despite being a type of professional phagocyte, neutrophils are thought to be excluded from apoptotic sites to avoid tissue inflammation. Here, we report a fundamental and unexpected role of neutrophils as the predominant phagocyte responsible for the clearance of apoptotic hepatic cells in the steady state. In contrast to the engulfment of dead cells by macrophages, neutrophils burrowed directly into apoptotic hepatocytes, a process we term perforocytosis, and ingested the effete cells from the inside. The depletion of neutrophils caused defective removal of apoptotic bodies, induced tissue injury in the mouse liver, and led to the generation of autoantibodies. Human autoimmune liver disease showed similar defects in the neutrophil-mediated clearance of apoptotic hepatic cells. Hence, neutrophils possess a specialized immunologically silent mechanism for the clearance of apoptotic hepatocytes through perforocytosis, and defects in this key housekeeping function of neutrophils contribute to the genesis of autoimmune liver disease.

Every day, the immune cells clears the remains of billions of old and damaged cells that have undergone a controlled form of death. Removing them quickly helps to prevent inflammation or the development of autoimmune diseases. While immune cells called neutrophils are generally tasked with removing invading bacteria, macrophages are thought to be responsible for clearing dead cells. However, in healthy tissue, the process occurs so efficiently that it can be difficult to confirm which cells are responsible. To take a closer look, Cao et al. focused on the liver by staining human samples to identify both immune and dead cells. Unexpectedly, there were large numbers of neutrophils visible inside dead liver cells. Further experiments in mice revealed that after entering the dead cells, neutrophils engulfed the contents and digested the dead cell from the inside out. This was a surprising finding because not only are neutrophils not usually associated with dead cells, but immune cells usually engulf cells and bacteria from the outside rather than burrowing inside them. The importance of this neutrophil behaviour was shown when Cao et al. studied samples from patients with an autoimmune disease where immune cells attack the liver. In this case, very few dead liver cells contained neutrophils, and the neutrophils themselves did not seem capable of removing the dead cells, leading to inflammation. This suggests that defective neutrophil function could be a key contributor to this autoimmune disease. The findings identify a new role for neutrophils in maintaining healthy functioning of the liver and reveal a new target in the treatment of autoimmune diseases. In the future, Cao et al. plan to explore whether compounds that enhance clearance of dead cells by neutrophils can be used to treat autoimmune liver disease in mouse models of the disease.

The Effect of Three Different Cuff/Arm Circumference Ratios Ranging over 80% on Cuff Blood Pressure Measurements.

We aimed to explore whether the cuff/arm (C/A) circumference ratio within the suggested range (> 80%) affects the accuracy of mercury cuff blood pressure (BP) measurement (cuff BP) using intrabrachial BP (IABP) as a reference.A total of 253 patients aged 62.42 ± 9.70 years were included. After coronary angiography, the catheter in the right arm was gradually withdrawn toward the cubital fossa, and the IABP was continuously recorded. The cuff BP of the right arm was measured based on the artery blood flow using a special method similar to the traditional mercury method. The cuff was replaced using another C/A ratio after one minute, and the test was performed again. We used three different cuffs for each participant to meet the C/A ratios of 80%-84%, 85%-89%, and 90%-100%. We calculated the percentage deviation degree (DD) between the cuff BP and IABP values: DD = difference/IABP × 100%. The agreement between the values was evaluated using the Bland-Altman method.The IABP values were 138.52 ± 16.89/79.67 ± 9.81 mmHg. The DD of the systolic BP (SBP), with a ratio of 80%-84% (3.06%), was the smallest. The DD of the diastolic BP (DBP) was lowest at a ratio of 85%-89% (2.47%). Men and women had the lowest DD of the SBP at a C/A ratio of 80%-84% and the lowest DD of the DBP at a C/A ratio of 85%-89%. Regardless of whether the participants had coronary heart disease, the DD of the SBP at a C/A ratio of 80%-84% was the lowest, and the DD of the DBP at a C/A ratio of 85%-89% was the lowest.Even in the suggested range of > 80%, when the C/A ratio was 80%-84%, the difference in the SBP between the cuff and IABP was the lowest, but when the C/A ratio was 85%-89%, the difference in the DBP was the lowest.

Endosomal trafficking of two-pore K+ efflux channel TWIK2 to plasmalemma mediates NLRP3 inflammasome activation and inflammatory injury.

Potassium efflux via the two-pore K+ channel TWIK2 is a requisite step for the activation of NLRP3 inflammasome, however, it remains unclear how K+ efflux is activated in response to select cues. Here, we report that during homeostasis, TWIK2 resides in endosomal compartments. TWIK2 is transported by endosomal fusion to the plasmalemma in response to increased extracellular ATP resulting in the extrusion of K+. We showed that ATP-induced endosomal TWIK2 plasmalemma translocation is regulated by Rab11a. Deleting Rab11a or ATP-ligated purinergic receptor P2X7 each prevented endosomal fusion with the plasmalemma and K+ efflux as well as NLRP3 inflammasome activation in macrophages. Adoptive transfer of Rab11a-depleted macrophages into mouse lungs prevented NLRP3 inflammasome activation and inflammatory lung injury. We conclude that Rab11a-mediated endosomal trafficking in macrophages thus regulates TWIK2 localization and activity at the cell surface and the downstream activation of the NLRP3 inflammasome. Results show that endosomal trafficking of TWIK2 to the plasmalemma is a potential therapeutic target in acute or chronic inflammatory states.

An integrated dual-layer microfluidic platform for multiple respiratory viruses screening.

Currently, the coronavirus disease 2019 (COVID-19) caused by the outbreak of a novel coronavirus (SARS-CoV-2) is spreading rapidly worldwide. Due to the high incidence of influenza coinciding with SARS-CoV-2, rapid detection is crucial to prevent spreading. Here, we present an integrated dual-layer microfluidic platform for specific and highly sensitive SARS-CoV-2, influenza viruses A (FluA) H1N1, H3N2, and influenza virus B (FluB) simultaneous detection. The platform includes a dual microchip (Dµchip) and a portable detection device for real-time fluorescence detection, temperature control and online communication. The Reverse Transcription Loop-mediated Isothermal Amplification (RT-LAMP) and Cas12a cleavage were performed on the Dµchip. The limit of detection (LoD) of the Dµchip assay was 10 copies for SARS-CoV-2, FluA H1N1, H3N2, and FluB RNAs. The Dµchip assay yielded no cross-reactivity against other coronaviruses, so it was suitable for the screening of multiple viruses. Moreover, the positive percentage agreement (PPA) and negative percentage agreement (NPA) of the assay were 97.9% and 100%, respectively, in 75 clinical samples compared to data from RT-PCR-based assays. Furthermore, the assay allowed the detection SARS-CoV-2 and influenza viruses in spiked samples. Overall, the present platform would provide a rapid method for the screening of multiple viruses in hospital emergency, community and primary care settings and facilitate the remote diagnosis and outbreak control of the COVID-19.

Association of living alone and living alone time with hypertension among Chinese men aged 80 years and older: a cohort study.

Objective: There is little evidence of the influence of living alone on hypertension risk among men 80 years or older. Additionally, the influence of living alone duration on hypertension risk lacks thorough investigation. Hence, this cohort study examines living alone and its duration's link to hypertension risk in this specific group. Methods: We included 2009 older men aged ≥80 years without hypertension from the Chinese Longitudinal Healthy Longevity Survey in the 2008 wave. Follow-up was conducted in the 2011 wave. Multivariable Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) to assess hypertension risk related to living alone and living alone time. Results: We included 2,009 older men, with a mean age of 90.7 years (standard deviation: 6.8). Over a median follow-up of 2.9 (1.3-3.0) years, 573 participants (28.5%) developed hypertension. Living alone was significantly associated with a higher hypertension risk than living with family (HR: 1.42; 95% CI 1.11-1.80). When compared to living with family, the hypertension risk was increased in the first quartile of living alone time (0-6.1 years) (HR: 1.76; 95% CI 1.16-2.66), the second quartile (6.1-10.6 years) (HR: 1.56; 95% CI 1.07-2.29), and the third quartile (10.6-19.3 years) (HR: 1.66; 95% CI 1.08-2.55). Surprisingly, no significant association was found in the fourth quartile (≥19.3 years) with hypertension risk. Stratified and Interaction analyses indicated no significant interaction effects between subgroups. Sensitivity analyses yielded consistent results. Conclusion: Living alone was independently associated with an increased risk of hypertension in older men. The highest risk was found in those with the least time alone. These findings imply that social isolation and lack of companionship could be pivotal in hypertension development. Furthermore, the study highlights the need to consider living alone duration when assessing its impact on health outcomes.

Recent advances in PCR-free nucleic acid detection for SARS-COV-2.

As the outbreak of Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory disease coronavirus 2 (SARS-COV-2), fast, accurate, and economic detection of viral infection has become crucial for stopping the spread. Polymerase chain reaction (PCR) of viral nucleic acids has been the gold standard method for SARS-COV-2 detection, which, however, generally requires sophisticated facilities and laboratory space, and is time consuming. This review presents recent advances in PCR-free nucleic acid detection methods for SARS-CoV-2, including emerging methods of isothermal amplification, nucleic acid enzymes, electrochemistry and CRISPR.

Pyroptotic Patterns in Blood Leukocytes Predict Disease Severity and Outcome in COVID-19 Patients.

The global coronavirus disease 2019 (COVID-19) pandemic has lasted for over 2 years now and has already caused millions of deaths. In COVID-19, leukocyte pyroptosis has been previously associated with both beneficial and detrimental effects, so its role in the development of this disease remains controversial. Using transcriptomic data (GSE157103) of blood leukocytes from 126 acute respiratory distress syndrome patients (ARDS) with or without COVID-19, we found that COVID-19 patients present with enhanced leukocyte pyroptosis. Based on unsupervised clustering, we divided 100 COVID-19 patients into two clusters (PYRcluster1 and PYRcluster2) according to the expression of 35 pyroptosis-related genes. The results revealed distinct pyroptotic patterns associated with different leukocytes in these PYRclusters. PYRcluster1 patients were in a hyperinflammatory state and had a worse prognosis than PYRcluster2 patients. The hyperinflammation of PYRcluster1 was validated by the results of gene set enrichment analysis (GSEA) of proteomic data (MSV000085703). These differences in pyroptosis between the two PYRclusters were confirmed by the PYRscore. To improve the clinical treatment of COVID-19 patients, we used least absolute shrinkage and selection operator (LASSO) regression to construct a prognostic model based on differentially expressed genes between PYRclusters (PYRsafescore), which can be applied as an effective prognosis tool. Lastly, we explored the upstream transcription factors of different pyroptotic patterns, thereby identifying 112 compounds with potential therapeutic value in public databases.

Combined Consideration of Tumor-Associated Immune Cell Density and Immune Checkpoint Expression in the Peritumoral Microenvironment for Prognostic Stratification of Non-Small-Cell Lung Cancer Patients.

Given the complexity and highly heterogeneous nature of the microenvironment and its effects on antitumor immunity and cancer immune evasion, the prognostic value of a single immune marker is limited. Here, we show how the integration of immune checkpoint molecule expression and tumor-associated immune cell distribution patterns can influence prognosis prediction in non-small-cell lung cancer (NSCLC) patients. We analyzed tissue microarray (TMA) data derived from multiplex immunohistochemistry results and measured the densities of tumor-infiltrating CD8+ and FOXP3+ immune cells and tumor cells (PanCK+), as well as the densities of programmed cell death 1 (PD-1)+ and programmed cell death ligand 1 (PD-L1)+ cells in the peritumor and intratumor subregions. We found a higher density of infiltrating CD8+ and FOXP3+ immune cells in the peritumoral compartment than in the intratumoral compartment. In addition, unsupervised hierarchical clustering analysis of these markers revealed that the combination of high CD8/FOXP3 expression, low PD-1 and PD-L1 immune checkpoint expression, and lack of epidermal growth factor receptor (EGFR) mutation could be a favorable predictive marker. On the other hand, based on the clustering analysis, low CD8/FOXP3 and immune checkpoint (PD-1 and PD-L1) expression might be a marker for patients who are likely to respond to strategies targeting regulatory T (Treg) cells. Furthermore, an immune risk score model was established based on multivariate Cox regression, and the risk score was determined to be an independent prognostic factor for NSCLC patients. These results indicate that the immune context is heterogeneous because of the complex interactions of different components and that using multiple factors in combination might be promising for predicting the prognosis of and stratifying NSCLC patients.

A versatile integrated tube for rapid and visual SARS-CoV-2 detection.

The coronavirus disease 2019 (COVID-19) caused by novel severe acute respiratory coronavirus 2 (SARS-CoV-2) has been rapidly spreading worldwide. Rapid and widespread testing is essential to promote early intervention and curb the ongoing COVID-19 pandemic. Current gold standard reverse transcription-polymerase chain reaction (RT-PCR) for detecting SARS-CoV-2 is restricted to professional laboratories and well-trained personnel, thus, limiting its widespread use in resource-limited conditions. To overcome these challenges, we developed a rapid and convenient assay using a versatile integrated tube for the rapid and visual detection of SARS-CoV-2. The reaction conditions of the method were optimized using SARS-CoV-2 RNA standards and the sensitivity and specificity were further determined. Finally, it was verified on clinical specimens. The assay was completed within 40 min, and the result was visible by the naked eye. The limits of detection (LODs) for the target ORF1ab and N genes were 50 copies/µl. No cross-reactivity was observed with the RNA standard samples of four respiratory viruses or clinical samples of common respiratory viral infections. Ninety SARS-CoV-2 positive and 30 SARS-CoV-2 negative patient specimens were analyzed. We compared these results to both prior and concurrent RT-PCR evaluations. As a result, the overall sensitivity and specificity for detection SARS-CoV-2 were 94.5 and 100.0%, respectively. Conclusion: The integrated tube assay has the potential to provide a simple, specific, sensitive, one-pot, and single-step assay for SARS-CoV-2.

Remediation of ABCG5-Linked Macrothrombocytopenia With Ezetimibe Therapy.

To investigate refractory hypercholesterolemia, a female patient and relatives were subjected to whole-genome sequencing. The proband was found to have compound heterozygous substitutions p. Arg446Gln and c.1118+3G>T in ABCG5, one of two genes causing sitosterolemia. When tracing these variants in the full pedigree, all maternally related heterozygotes for the intronic ABCG5 variant exhibited large platelets (over 30 fl), which segregated in an autosomal dominant manner, consistent with macrothrombocytopenia, or large platelet syndrome which may be associated with a bleeding tendency. In vitro cell-line and in vivo rat model experiments supported a pathogenic role for the variant and the macrothrombocytopenia was recapitulated in heterozygous rats and human cell lines exhibiting that single variant. Ezetimibe treatment successfully ameliorated all the symptoms of the proband with sitosterolemia and resolved the macrothrombocytopenia of the treated heterozygote relatives. Subsequently, in follow up these observations, platelet size, and size distribution were measured in 1,180 individuals; 30 were found to be clinically abnormal, three of which carried a single known pathogenic ABCG5 variant (p.Arg446Ter) and two individuals carried novel ABCG5 variants of uncertain significance. In this study, we discovered that identification of large platelets and therefore a possible macrothrombocytopenia diagnosis could easily be inadvertently missed in clinical practice due to variable instrument settings. These findings suggest that ABCG5 heterozygosity may cause macrothrombocytopenia, that Ezetimibe treatment may resolve macrothrombocytopenia in such individuals, and that increased attention to platelet size on complete blood counts can aid in the identification of candidates for ABCG5 genetic testing who might benefit from Ezetimibe treatment.

Overexpression of PLXDC2 in Stromal Cell-Associated M2 Macrophages Is Related to EMT and the Progression of Gastric Cancer.

The tumor microenvironment (TME) comprises distinct cell types, including stromal types such as fibroblast cells and macrophage cells, which have recently become a critical factor in tumor development and progression. Here, we identified the TME-related gene, plexin domain containing 2 (PLXDC2), in a high-stromal-score population. And we revealed that this gene was related to poor survival and advanced (tumor-node-metastasis) stage in gastric cancer (GC) patients from The Cancer Genome Atlas database. An integrated gene profile and functional analysis of the proportions of tumor-infiltrating immune cells revealed that the expression of the M2 macrophages cell marker CD163 was positively correlated with PLXDC2 expression. In addition, the M2 macrophages gene signature and high PLXDC2 expression were associated with the inflammatory signaling pathway and the epithelial-to-mesenchymal transition (EMT)-related gene signature. Single-cell study of GC identified PLXDC2 was enriched specifically in fibroblasts and monocytes/macrophages populations, which supported its important role in the stroma. Furthermore, according to a tissue microarray immunohistochemistry analysis, the expression of PLXDC2 elevated in human GC stromal specimens compared to tumor tissue specimens. Moreover, PLXDC2 overexpression in the stromal compartment was associated with CD163-positive regulatory M2 macrophages, and its functions were related to the pathogenesis of GC. Multiplexed immunohistochemistry verified PLXDC2's correlation with EMT markers. Our data suggested that PLXDC2 was expressed in stromal cells and that its crosstalk with tumor-associated macrophages could contribute to cancer biology by inducing the EMT process.

A novel synthesis of graphene quantum dots via thermal treatment of crude graphite oxide in a dry and alkaline condition, and their application in uranyl detection.

In this article, a novel method to synthesize graphene quantum dots was developed via thermal treatment of crude graphite oxide (GO) in a dry and alkaline condition to cut the crude GO sheets into small graphene quantum dots (named as aGQDs). The aGQDs are nano-scale reduced graphene oxide pieces with the sizes around 5-10 nm. The aGQDs could disperse in water for their richment of oxygen-containing groups. The fluorescence properties were carefully investigated. The aGQDS aqueous solution shows a bright yellow-green fluorescence under the UV illumination. Besides, the uranyl ions show a strong fluorescence quenching effect on the a aGQD aqueous solution even at a low concentration (~10-7 M) compared with other common ions in natural water-body, which makes that these aGQDs could be applied as a chemosensor for detection of uranyl ions with good sensitivity and selectivity.

Platinum Single Atoms Supported on Nanoarray-Structured Nitrogen-Doped Graphite Foil with Enhanced Catalytic Performance for Hydrogen Evolution Reaction.

Platinum-based single-atom catalysts (SACs) are among the most promising candidates for the practical applications of electrochemical hydrogen evolution reaction (HER), but their catalytic efficiency remains to be further enhanced. Herein, a well-designed nanoarray-structured nitrogen-doped graphite foil (NNGF) substrate is introduced to support Pt SACs in Pt-N4 construction (Pt1/NNGF) for HER. Within NNGF, the constructed nanoarray-structured surficial layer for supporting Pt SACs could enhance the exposure of active sites to the electrolyte and improve the reaction and diffusion kinetics; meanwhile, the retained graphite structures in bulk NNGF provide not only the required electrical conductivity but also the mechanical stability and flexibility. Because of such double-layer structures of NNGF, stable Pt-N4 construction, and binder-free advantages, the Pt1/NNGF electrode exhibits a low overpotential of 0.023 V at 10 mA cm-2 and a small Tafel slope of 29.1 mV dec-1 as well as an excellent long-term durability.

Plasmon catalytic PATP coupling reaction on Ag-NPs/graphite studied via in situ electrochemical surface-enhanced Raman spectroscopy.

The p-aminothiophenol (PATP) coupling reaction on plasmon substrates such as Ag and Au nanoparticles has received extensive attention since the catalytic effect of the surface plasmon was found. Currently, in situ kinetic studies of this reaction are rare, especially those focusing on the specific role of the hot electron-hole carriers. Here, in situ electrochemical surface-enhanced Raman spectroscopy (SERS) is developed to study the plasmon catalytic reaction of PATP in a controlled aqueous environment involving the factors of O2, electron and hole carriers, and solution pH. Ag nanoparticles supported on graphite serve as a SERS substrate, which could separate hot electron-hole pairs effectively and is beneficial to study the effects of hot carriers on plasmon-driven reactions. In situ electrochemical SERS measurements reveal two reaction paths for the PATP coupling reaction. One is that plasmon-induced hot holes activate the dehydrogenation of PATP and then the radical coupling reaction to form p,p'-dimercaptoazobenzene (DMAB) under O2-free conditions. Another is likely to be that the surface Ag2O/AgOH, which is generated from Ag and 1O2/O2-, catalyzes the oxidation of PATP and then the coupling process under O2-rich conditions. Benefitting from the potential/atmosphere controlled measurements in situ, the intermediate species of PATP(NH)/PATP(N) are observed with vibrational bands at around 1056, 1202, 1253, 1395, 1514 and 1540 cm-1.