Survival and infectivity of second-stage root-knot nematode Meloidogyne incognita juveniles depend on lysosome-mediated lipolysis.

Adaptation to nutrient deprivation depends on the activation of metabolic programs to use reserves of energy. When outside a host plant, second-stage juveniles (J2) of the root-knot nematode (Meloidogyne spp.), an important group of pests responsible for severe losses in the production of crops (e.g., rice, wheat, and tomato), are unable to acquire food. Although lipid hydrolysis has been observed in J2 nematodes, its role in fitness and the underlying mechanisms remain unknown. Using RNA-seq analysis, here, we demonstrated that in the absence of host plants, the pathway for the biosynthesis of polyunsaturated fatty acids was upregulated, thereby increasing the production of arachidonic acid in middle-stage J2 Meloidogyne incognita worms. We also found that arachidonic acid upregulated the expression of the transcription factor hlh-30b, which in turn induced lysosomal biogenesis. Lysosomes promoted lipid hydrolysis via a lysosomal lipase, LIPL-1. Furthermore, our data demonstrated that blockage of lysosomal lipolysis reduced both lifespan and locomotion of J2 worms. Strikingly, disturbance of lysosomal lipolysis resulted in a decline in infectivity of these juveniles on tomato roots. Our findings not only reveal the molecular mechanism of lipolysis in J2 worms but also suggest potential novel strategies for the management of root-knot nematode pests.

Rapid PFOS mineralization with peroxydisulfate activation process mediated by N modified Fe-based catalyst.

As the cheap and efficient catalysts, the iron-based catalysts have been considered as one of the most promising catalysts for peroxydisulfate (PDS) activation and the development of high-performance iron-based catalysts are attracting growing attentions. In this work, a magnetic Fe-based catalysts (Fe/NC-1000) was obtained by using Fe modified ZIF-8 as the precursor and used to activate the PDS for the degradation of perfluorooctane sulphonate (PFOS). Morphology and structure analysis showed that the resulted Fe/NC-1000 catalyst was displayed porous spheres (40-60 nm) and mainly composed of Fe0, FeNx and carbon. When Fe/NC-1000 was employed to activate the PDS (0.1 g/L of catalyst dosage, 0.5 g/L of PDS dosage and at initial pH of 4.6), the Fe/NC-1000/PDS system exhibited excellent efficiency (97.9 ± 0.1) % for PFOS (10 mg/L) degradation within 30 min. The quenching tests and EPR results revealed that the Fe/NC-1000/PDS system degraded PFOS primarily through singlet oxygen (1O2) evolution and electron-transfer process. Besides, based on the degradation byproducts determined by LC-MS-MS, the PFOS first occurred de-sulfonation to form PFOA, and then the resulted PFOA underwent stepwise defluorination in the Fe/NC-1000/PDS system. Density Functional Theory (DFT) calculations and electrochemistry tests strongly confirmed that Fe/NC-1000 exhibited high electron transfer efficiency, resulting in promoted performance on activating PDS. Importantly, the results of Ecological Structure-Activity Relationship (ECOSAR) analysis showed that the intermediates were lowly toxic during the PFOS degradation, manifesting a green process for PFOS removal. This study would provide more understandings for the persulfate activation process mediated by Fe-based catalysts for Perfluorinated alkyl substances (PFAS) elimination.

Efficient adsorption of diclofenac sodium in water by a novel functionalized cellulose aerogel.

In this work, a novel cellulose aerogel (CNC-PVAm/rGO) was fabricated using cellulose nanocrystalline (CNC) modified with polyvinylamine (PVAm) and reduced graphene oxide (rGO). The resultant CNC-PVAm/rGO was then applied for the adsorption of diclofenac sodium (DCF), a typical non-steroidal anti-inflammatory drug. Characterization using ultra-high-resolution field emission scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and the Brunauer-Emmett-Teller surface area revealed that the obtained CNC-PVAm/rGO displayed an evident 3D porous structure, which had an ultralight weight, good recovery, abundant surface functional groups (e.g., -NH2 and -OH), and rGO nanosheets. In addition, the material presented a stable crystal structure and large specific surface area (105.73 m2 g-1). During the adsorption of DCF, the CNC-PVAm/rGO aerogel showed a rather excellent adsorption performance, with a maximum adsorption capacity (qmax) of 605.87 mg g-1, which was approximately 53 times larger than that of the bare CNC aerogel (11.45 mg g-1). The adsorption performance of CNC-PVAm/rGO was also better than that of other reported adsorbents. The adsorption of DCF to CNC-PVAm/rGO obeyed the Langmuir isotherm and pseudo-second-order kinetic models, and underwent a spontaneous exothermic process. Moreover, DCF was easily desorbed from CNC-PVAm/rGO with sodium hydroxide solution (0.1 mol L-1), and the absorbent could be reused four times. The introduction of PVAm and rGO to the CNC-PVAm/rGO aerogel also greatly enhanced electrostatic interactions, π-π interactions, and hydrophobic effects. These enhancements significantly promoted the hydrogen bonding interactions between the DCF molecules and CNC-PVAm/rGO, thus resulting in a large improvement in the adsorption performance of the aerogel.

Hepatitis B e Antigen Inhibits NF-κB Activity by Interrupting K63-Linked Ubiquitination of NEMO.

Viruses have adopted diverse strategies to suppress antiviral responses. Hepatitis B virus (HBV), a virus that is prevalent worldwide, manipulates the host's innate immune system to evade scavenging. It is reported that the hepatitis B e antigen (HBeAg) can interfere with NF-κB activity, which then leads to high viral loads, while HBV with the G1896A mutation remains infectious without the production of HBeAg but can induce more severe proinflammatory response and liver damage. The aim of current work was to study the molecular mechanism by which HBeAg suppresses interleukin-1ß (IL-1ß)-stimulated NF-κB activity, which leads to the suppression of the innate immune responses to HBV infection. Our study revealed that HBeAg could interact with NEMO, a regulatory subunit associated with IκB kinase, which regulates the activation of NF-κB. HBeAg suppressed the IL-1ß-induced tumor necrosis factor (TNF)-associated factor 6 (TRAF6)-dependent K63-linked ubiquitination of NEMO, thereby downregulating NF-κB activity and promoting virus replication. We further demonstrated the inhibitory effect of HBeAg on the NF-κB signaling pathway using primary human hepatocytes, HBV-infected HepG2-NTCP cells, and clinical liver samples. Our study reveals a molecular mechanism whereby HBeAg suppresses IL-1ß-induced NF-κB activation by decreasing the TRAF6-dependent K63-linked ubiquitination of NEMO, which may thereby enhance HBV replication and promote a persistent infection.IMPORTANCE The role of HBeAg in inflammatory responses during the infection of hepatitis B virus (HBV) is not fully understood, and several previous reports with regard to the NF-κB pathway are controversial. In this study, we showed that HBeAg could suppress both Toll-like receptor 2 (TLR2)- and IL-1ß-induced activation of NF-κB in cells and clinical samples, and we further revealed novel molecular mechanisms. We found that HBeAg can associate with NEMO, the regulatory subunit for IκB kinase (IKK) that controls the NF-κB signaling pathway, and thereby inhibits TRAF6-mediated K63-linked ubiquitination of NEMO, resulting in downregulation of NF-κB activity and promotion of virus replication. In contrast, the HBeAg-negative HBV mutant can induce higher levels of NF-κB activity. These results are important for understanding the HBV-induced pathogenesis of chronic hepatitis and indicate that different clinical measures should be considered to treat HBeAg-positive and HBeAg-negative infections. Our findings represent a conceptual advance in HBV-related suppression of NF-κB signaling.

Characteristics and prognosis of acute type A aortic dissection with negative D-dimer result.

BACKGROUND: Evidence regarding the characteristics and prognosis in acute type A aortic dissection (AAD) patients with negative D-dimer result is limited. We aimed to investigate the characteristics and prognosis in AAD patients with negative D-dimer result. METHODS AND RESULTS: 370 AAD patients within 24 h of symptom onset were enrolled in a hospital in China from January 2014 to December 2018. Nine (2.43%) and 361 (97.57%) exhibited negative and positive D-dimer results, respectively. The average age of nine negative D-dimer result participants was 47.67 ± 10.95 years old, and about seven (77.78%) of them were male. The negative group showed a significantly lower blood pressure, white blood cell, hemoglobin, activated partial thromboplastin, ejection fraction and symptom with pain than the positive group. Multivariate analysis showed white blood cell (×109/L) (P = 0.008; odds ratio, 0.566) and symptom with pain (P < 0.001; odds ratio, 0.013) were significantly related to a negative result. The result of the fully-adjusted model showed negative D-dimer result was negatively associated with in-hospital mortality compared with positive group in AAD patients after adjusting confounders (OR = 0.34, 95%CI 0.01 to 10.82). CONCLUSIONS: Negative D-dimer result is strongly influenced by white blood cell and symptom with pain. Negative D-dimer result was negatively associated with in-hospital mortality compared with positive group in AAD patients.

Hepatitis B e antigen and its precursors promote the progress of hepatocellular carcinoma by interacting with NUMB and decreasing p53 activity.

UNLABELLED: Hepatitis B viral infection is one of the leading causes of hepatocellular carcinoma (HCC) worldwide. Although several viral factors have been identified that may increase the risk for HCC development, the molecular mechanisms leading to the transformation of normal hepatocytes into cancer cells remain elusive. In this study, we demonstrated that the intracellular hepatitis B e antigen (HBeAg) and its precore precursors, but not their homologous core protein, could associate with NUMB and thereby impair the stability and transcriptional activity of tumor suppressor p53. HBeAg and its precursors could disrupt p53-NUMB and HDM2-NUMB interactions and tricomplex p53-HDM2-NUMB formation, inhibit the acetylation and translocation of p53 from cytosol to the nucleus, promote HDM2-mediated ubiquitination and degradation of p53, and suppress p53-dependent apoptosis. A xenograft tumorigenicity assay showed that expression of HBeAg and its precursors promoted carcinogenesis in a mouse model. Immunohistochemical analysis of the bioptic liver samples of HCC patients revealed that HBeAg positivity was associated with reduced transcriptional activity of p53. Taken together, the results suggest a role of intracellular HBeAg and its precursors in HCC development. CONCLUSION: HBeAg and its precursors promote HDM2-mediated degradation and impair transcriptional activity of p53 by interacting with NUMB, consequently contributing to HCC development. (Hepatology 2016;64:390-404).

Application of multispectral imaging in quantitative immunohistochemistry study of breast cancer: a comparative study.

Multispectral imaging (MSI) based on imaging and spectroscopy, as relatively novel to the field of histopathology, has been used in biomedical multidisciplinary researches. We analyzed and compared the utility of multispectral (MS) versus conventional red-green-blue (RGB) images for immunohistochemistry (IHC) staining to explore the advantages of MSI in clinical-pathological diagnosis. The MS images acquired of IHC-stained membranous marker human epidermal growth factor receptor 2 (HER2), cytoplasmic marker cytokeratin5/6 (CK5/6), and nuclear marker estrogen receptor (ER) have higher resolution, stronger contrast, and more accurate segmentation than the RGB images. The total signal optical density (OD) values for each biomarker were higher in MS images than in RGB images (all P < 0.05). Moreover, receiver operator characteristic (ROC) analysis revealed that a greater area under the curve (AUC), higher sensitivity, and specificity in evaluation of HER2 gene were achieved by MS images (AUC = 0.91, 89.1 %, 83.2 %) than RGB images (AUC = 0.87, 84.5, and 81.8 %). There was no significant difference between quantitative results of RGB images and clinico-pathological characteristics (P > 0.05). However, by quantifying MS images, the total signal OD values of HER2 positive expression were correlated with lymph node status and histological grades (P = 0.02 and 0.04). Additionally, the consistency test results indicated the inter-observer agreement was more robust in MS images for HER2 (inter-class correlation coefficient (ICC) = 0.95, r s = 0.94), CK5/6 (ICC = 0.90, r s = 0.88), and ER (ICC = 0.94, r s = 0.94) (all P < 0.001) than that in RGB images for HER2 (ICC = 0.91, r s = 0.89), CK5/6 (ICC = 0.85, r s = 0.84), and ER (ICC = 0.90, r s = 0.89) (all P < 0.001). Our results suggest that the application of MS images in quantitative IHC analysis could obtain higher accuracy, reliability, and more information of protein expression in relation to clinico-pathological characteristics versus conventional RGB images. It may become an optimal IHC digital imaging system used in quantitative pathology.

Methods Comparison and Bias Estimation of Three Distinct Biochemistry Analytical Systems in One Clinical Laboratory Using Patient Samples.

BACKGROUND: In China, one laboratory usually owns more than one diagnostic device or reagent kit measuring the same analyte and this situation causes great troubles for quality control and traceability. To determine if the different devices yield equivalent results, the correlation coefficients and predicted bias between three distinct bio-chemistry analyzers in our lab were evaluated. METHODS: 40 analytes were detected and used to evaluate method performance and comparability of results between different analyzers. The Vitros5600 and Hitachi7170 analyzers were separately compared with the Cobas 8000 analyzer according to Clinical and Laboratory Standards Institute (CLSI) guideline (EP9-A2). Within-day and between-day imprecision of the three analytical systems were calculated in accordance with CLSI guidelines EP15-A2. RESULTS: Comparing the Hitachi7170 with Cobas8000 analyzer, except for calcium, magnesium, chloride ion (CL-), and carbon dioxide, the other 36 analytes were closely correlated (R2 > 0.95), while 4 of the 36 analytes' predicted bias exceeded the acceptable criteria. As for the Vitros5600 and Cobas8000, except for albumin, sodium ion (NA+), magnesium, and chloride (CL), the other 13 analytes were closely correlated (R2 > 0.95), while 5 of the 13 analytes' predicted bias exceeded the acceptable criteria. CONCLUSIONS: Significant differences for several analytes between distinct analyzers were found; for some analytes the predicted bias between dry chemical analyzer and conventional wet chemical analyzer can reach 30%, which is worthy of our concern. When one analyte was detected on more than one device, a strict method comparison study should be performed regularly. Reference intervals should be validated and transferred from the Cobas 8000 to Vitros5600 when the bias cannot be adjusted.

Impact of neoadjuvant chemotherapy on lymphocytes and co-inhibitory B7-H4 molecule in gastric cancer: low B7-H4 expression associates with favorable prognosis.

Little is known on the immune response after neoadjuvant chemotherapy (NACT) in gastric cancer (GC). The present study aimed to investigate the effects of NACT on tumor cells and tumor-infiltrating lymphocytes (TILs) in patients with GC. Expressions of CD4+ and CD8+ TILs and identified co-inhibitory B7-H4 molecule were examined by immunohistochemical staining in GC tissues of 56 patients who received NACT (NACT group) and 46 patients who did not receive NACT (nNACT group). These markers, clinicopathological features, and overall survival (OS) time between both groups were compared. Results showed that the clinicopathological features of patients were not significantly associated with NACT (P > 0.05), but the rate of low expression of B7-H4 (78.6 vs. 47.8 %, P = 0.005) and rate of high expression of CD4+ TILs (58.9 vs. 39.1 %, P = 0.048) and CD8+ TILs (92.9 vs. 56.5 %, P < 0.001) were both significantly higher in NACT group than that in nNACT group. Further, Kaplan-Meier analysis indicated that there was no significant difference in OS time between the groups. However, in NACT group, those with low B7-H4 expression had significantly longer OS (P = 0.031). The study findings suggest that low expression of B7-H4 could serve as a candidate biomarker for predicting response to NACT and could provide favorable prognostic information in GC.

Prognostic significance of USP10 as a tumor-associated marker in gastric carcinoma.

Ubiquitin-specific protease 10 (USP10), a novel deubiquitinating enzyme, had been associated with growth of tumor cell. However, the role of USP10 in gastric cancer carcinogenesis had not been elucidated yet. The aim of this study was to investigate the expression level of USP10 in gastric carcinoma (GC) tissues and cell lines, then to evaluate the clinical significance of USP10 in GC patients. USP10, E-cadherin, Ki67 and p53 expressions were detected in 365 GC and 40 non-cancerous mucosa tissues by immunohistochemistry. Western blot for USP10 was performed on additional fresh GC tissues and GC cell lines. The expression level of USP10 in GC tissues was proved lower than that in non-cancerous mucosa tissues (p < 0.05). It was also lower in GC cell lines (AGS, BGC-823 and MKN45 cells) than that in gastric epithelial immortalized cell line (GES-1). Clinicopathological analysis showed that USP10 expression was negatively correlated with gastric wall invasion (p = 0.009), nodal metastasis (p = 0.002), and TNM stage (p = 0.000). In contrast, a positively correlation between the expression of USP10 and E-cadherin was found (p < 0.05), but there was no relationship proved between Ki67, p53 and USP10 (p > 0.05). On the Kaplan-Meier survival curves, we found poor prognosis in GC patients was associated with negative USP10 expression (p < 0.05). Moreover, USP10 expression was an independent prognostic factor for the overall survival in multivariate analysis. Our findings suggested that USP10 was an independent predictor of prognosis of GC patients.

High expression of transform growth factor beta 1 in gastric cancer confers worse outcome: results of a cohort study on 184 patients.

BACKGROUND/AIMS: Transform growth factors beta (TGFbeta) plays different roles at different stages of tumor development. TGFbeta1 is one isoform of TGFbeta, with complex secretion mechanism and bidirectional functions. This study was to investigate TGFbeta1 expression and its clinical significance in different clinicopathological subgroups of gastric cancer (GC) patients. METHODOLOGY: Tumor and peritumoral tissues from 184 GC patients were constructed into three tumor tissue microarrays. The expression of TGFbeta1 was analyzed by immunohistochemistry methods. RESULTS: TGFbeta1 was mainly expressed in the cytoplasm and membrane of GC cells. Low TGFbeta1 expression was observed in 82 (44.6%) tumor and 28 (68.3%) peritumoral tissues, and high expression was observed in 102 (55.4%) tumor and 13 (31.7%) peritumoral tissues. TGFbeta1 expression was significantly higher in tumor than peritumoral tissues (chi2 = 7.554, P = 0.006). The high expression of TGFbeta1 was related to worse overall survival (OS) (P = 0.040). TGFbeta1 expression was higher in the old and intestinal type GC than in the young (P = 0.017) and in diffuse type GC (P = 0.015), respectively. Patients with high TGFbeta1 expression had a worse survival in young people, female, diffuse type GC, poor differentiation, and lymph nodes metastasis. Multivariate Cox proportional hazards analysis showed that age, pathological grading, serosal invasion and TGFbeta1 expression were independent risk factors. CONCLUSIONS: High TGFbeta1 expression may indicate poor prognosis of GC patients and warrant more active treatment against TGFbeta1.

Long term follow up and retrospective study on 533 gastric cancer cases.

BACKGROUND: Gastric cancer (GC) is the third leading cause of cancer death in China and the outcome of GC patients is poor. The aim of the research is to study the prognostic factors of gastric cancer patients who had curative intent or palliative resection, completed clinical database and follow-up. METHODS: This retrospective study analyzed 533 GC patients from three tertiary referral teaching hospitals from January 2004 to December 2010 who had curative intent or palliative resection, complete clinical database and follow-up information. The GC-specific overall survival (OS) status was determined by the Kaplan-Meier method, and univariate analysis was conducted to identify possible factors for survival. Multivariate analysis using the Cox proportional hazard model and a forward regression procedure was conducted to define independent prognostic factors. RESULTS: By the last follow-up, the median follow-up time of 533 GC patients was 38.6 mo (range 6.9-100.9 mo), and the median GC-specific OS was 25.3 mo (95% CI: 23.1-27.4 mo). The estimated 1-, 2-, 3- and 5-year GC-specific OS rates were 78.4%, 61.4%, 53.3% and 48.4%, respectively. Univariate analysis identified the following prognostic factors: hospital, age, gender, cancer site, surgery type, resection type, other organ resection, HIPEC, LN status, tumor invasion, distant metastases, TNM stage, postoperative SAE, systemic chemotherapy and IP chemotherapy. In multivariate analysis, seven factors were identified as independent prognostic factors for long term survival, including resection type, HIPEC, LN status, tumor invasion, distant metastases, postoperative SAE and systemic chemotherapy. CONCLUSIONS: Resection type, HIPEC, postoperative SAE and systemic chemotherapy are four independent prognostic factors that could be intervened for GC patients for improving survival.

Neoadjuvant chemotherapy with FOLFOX4 regimen to treat advanced gastric cancer improves survival without increasing adverse events: a retrospective cohort study from a Chinese center.

BACKGROUND/AIM: To evaluate the clinical efficacy of FOLFOX4 (5-fluomumcil/leucovorin combined and oxaliplatin) neoadjuvant chemotherapy for advanced gastric cancer (AGC). PATIENTS AND METHODS: Fifty-eight AGC patients were enrolled in this retrospective cohort study, 23 in the neoadjuvant group and 35 in the adjuvant group. R0 resection, survival, and adverse events were compared. RESULTS: The two groups were well-matched, with no significant differences in R0 resection rate (82.6% versus 82.0%) and number of lymph nodes dissection (16 (0-49) versus 13 (3-40)) between the two groups (P > 0.05). The number of lymph node metastases in the neoadjuvant group (3 (0-14)) was significantly fewer than that in the adjuvant group (6 (0-27)) (P = 0.04). The neoadjuvant group had significantly better median overall survival (29.0 versus 22.0 months) and 3-year survival rate (73.9% versus 40.0%) than the adjuvant group (P = 0.013). The positive expression rate of Ki-67 in the neoadjuvant group (40.0%, 8/20) was lower than that in the adjuvant group (74.2%, 23/31; P = 0.015). CONCLUSION: The FOLFOX4 neoadjuvant chemotherapy could improve survival without increasing adverse events in patients with AGC.

Racial and ethnic disparities in bystander resuscitation for out-of-hospital cardiac arrests.

INTRODUCTION: Bystander-provided cardiopulmonary resuscitation (CRP) influences the survival rates of out-of-hospital cardiac arrests (OHCAs). Disparities on bystander resuscitation measures between Black, Hispanic, Asians and Non-Hispanic White OHCAs is unclear. Examining racial and ethnic differences in bystander resuscitations is essential to better target interventions. METHODS: 15,542 witnessed OHCAs were identified between April 1, 2011, and June 30, 2015 using the Resuscitation Outcomes Consortium Epidemiologic Registry 3, a multi-center, controlled trial about OHCAs in the United States and Canada. Multivariable logistic regression model was used to analyze the differences in bystander resuscitation (bystander CRP [B-CPR], CPR plus ventilation, automated external defibrillators/defibrillator application [B-AED/D], or delivery of shocks) and clinical outcomes (death at the scene or en route, return of spontaneous circulation upon first arrival at the emergency department [ROSC-ED], survival until ED discharge [S-ED], survival until hospital discharge [S-HOS], and favorable neurological outcome at discharge) between Black, Hispanic, or Asian victims and Non-Hispanic White victims. RESULTS: Compared to OHCA victims in Non-Hispanic Whites, Black, Hispanic, and Asians were less likely to receive B-CPR (adjusted OR: 0.79; 95 % CI: 0.63-0.99), and B-AED/D (adjusted OR: 0.80; 95 % CI: 0.65-0.98) in public locations. And, Black, Hispanic, and Asian OHCAs were less likely to receive bystander resuscitation in street/highway locations and public buildings, and less likely to have better clinical outcomes, including ROSC-ED, S-ED and S-HOS. CONCLUSION: Black, Hispanic and Asian victims with witnessed OHCAs are less likely to receive bystander resuscitation and more likely to get worse outcomes than Non-Hispanic White victims.

Association between prehospital time and in-hospital outcomes in out-of-hospital cardiac arrests according to resuscitation outcomes consortium epidemiologic registry.

INTRODUCTION: For out-of-hospital cardiac arrests (OHCAs), time is of the essence. While the relationship between EMS response time (ERT) and OHCA outcomes is well studied, a more comprehensive assessment of the effects of other intervention time is needed, which is essential to guide clinical practice. OBJECTIVES: Evaluating how a longer total pre-hospital time (TPT), ERT, advance life support response time (ART) and EMS cardiopulmonary resuscitation time (ECT) increase the mortality rates, unfavorable neurological outcomes, and severe complications at discharge of OHCAs. METHODS: 31,926 OHCAs from the USA and Canada were identified in Resuscitation Outcomes Consortium Epidemiologic Registry. Twelve adjusted models were used to analyze the relationship between the prehospital time (TPT, ERT, ART and ECT) and three outcomes (in hospital mortality, unfavorable neurological outcomes, and severe complications for surviving OHCAs). RESULTS: Every 10-min increase in TPT was associated with a 0.14-fold increase in the risk of death (adjusted odds ratio [OR] = 1.14, 95 % confidence interval [CI] = 1.10-1.17) and a 0.13-fold increase of adverse neurological outcomes (OR = 1.13, CI =1.08-1.18). The risk of patient mortality markedly increased with every 5 min increase in ERT (OR = 1.36, CI = 1.26-1.47), ART (OR =1.10, CI = 1.06-1.15), and ECT (OR = 1.46, CI = 1.37-1.56). Adverse neurological outcome was associated with ERT and ECT, and severe complications with ERT and ART. CONCLUSION: Prolonged prehospital time, particularly ERT and ECT, are closely associated with in-hospital mortality, unfavorable neurological functions, and severe complications at discharge in OHCAs.

Glycemic variability evaluated by HbA1c rather than fasting plasma glucose is associated with adverse cardiovascular events.

Background: Although studies have shown that glycemic variability is positively associated with an increased risk of cardiovascular disease, few studies have compared hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) variability with adverse cardiovascular events in patients with type 2 diabetes mellitus (T2DM). Methods: This was a post hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study. Cox proportional hazards models were used to explore the relationship between HbA1c or FPG variability and the incidence of major adverse cardiovascular events (MACEs). Results: In total, 9,547 patients with T2DM were enrolled in this study. During the median 4.6 ± 1.5 years follow-up period, 907 patients developed MACEs. The risk of MACEs increased in the HbA1c variability group in each higher quartile of HbA1c variability (P < 0.01). Compared with those in the first quartile of HbA1c variability, patients in the fourth quartile had a hazard ratio of 1.37 (Model 2, 95% confidence interval: 1.13-1.67) for MACEs. Higher FPG variability was not associated with a higher risk of MACEs in patients with T2DM (P for trend=0.28). A U-shaped relationship was observed between HbA1c and FPG variability, and MACEs. Glucose control therapy modified the relationship between HbA1c and MACEs; participants with higher HbA1c variability receiving intensive glucose control were more likely to develop MACEs (P for interaction <0.01). Conclusion: In adults with T2DM, the relationship between glycemic variability evaluated using HbA1c and FPG was U-shaped, and an increase in HbA1c variability rather than FPG variability was significantly associated with MACEs. The relationship between HbA1c variability and MACEs was affected by the glucose control strategy, and a higher HbA1c variability was more strongly associated with MACEs in patients receiving an intensive glucose control strategy.

The Macrophage migration inhibitory factor is a vital player in Pan-Cancer by functioning as a M0 Macrophage biomarker.

BACKGROUND: The role of the macrophage migration inhibitory factor (MIF) has recently attracted considerable attention in cancer research; nonetheless, the insights provided by current investigations remain constrained. Our main objective was to investigate its role and the latent mechanisms within the pan-cancer realm. METHODS: We used comprehensive pan-cancer bulk sequencing data and online network tools to investigate the association between MIF expression and patient prognosis, genomic instability, cancer cell stemness, DNA damage repair, and immune infiltration. Furthermore, we validated the relationship between MIF expression and M0 macrophages using single-cell datasets, the SpatialDB database, and fluorescence staining. Additionally, we assessed the therapeutic response using the ROC plotter tool. RESULTS: We observed the upregulation of MIF expression across numerous cancer types. Notably, elevated MIF levels were associated with a decline in genomic stability. We found a significant correlation between increased MIF expression and increased expression of mismatch repair genes, stemness features, and homologous recombination genes across diverse malignancies. Subsequently, through an analysis using ESTIMATE and cytokine results, we revealed the involvement of MIF in immune suppression. Then, we validated MIF as a hallmark of the M0 macrophages involved in tumor immunity. Our study suggests an association with other immune-inhibitory cellular populations and restraint of CD8 + T cells. In addition, we conducted a comparative analysis of MIF expression before and after treatment in three distinct sets of therapy responders and non-responders. Intriguingly, we identified notable disparities in MIF expression patterns in bladder urothelial carcinoma and ovarian cancer following particular therapeutic interventions. CONCLUSION: Comprehensive pan-cancer analysis revealed notable enrichment of MIF within M0 macrophages, exerting a profound influence on tumor-associated immunosuppression and the intricate machinery of DNA repair.

Gold Nanoparticles Bioproduced in Cyanobacteria in the Initial Phase Opened an Avenue for the Discovery of Corresponding Cerium Nanoparticles.

The production of isolated metallic nanoparticles with multifunctionalized properties, such as size and shape, is crucial for biomedical, photocatalytic, and energy storage or remediation applications. This study investigates the initial particle formations of gold nanoparticles (AuNPs) bioproduced in the cyanobacteria Anabaena sp. using high-resolution transmission electron microscopy images for digital image analysis. The developed method enabled the discovery of cerium nanoparticles (CeNPs), which were biosynthesized in the cyanobacteria Calothrix desertica. The particle size distributions for AuNPs and CeNPs were analyzed. After 10 h, the average equivalent circular diameter for AuNPs was 4.8 nm, while for CeNPs, it was approximately 5.2 nm after 25 h. The initial shape of AuNPs was sub-round to round, while the shape of CeNPs was more roundish due to their amorphous structure and formation restricted to heterocysts. The local PSDs indicate that the maturation of AuNPs begins in the middle of vegetative cells and near the cell membrane, compared to the other regions of the cell.

Porous covalent organic framework nanofibrous membrane for excellent enrichment and ultra-high sensitivity detection of trace organochlorine pesticides in water.

Developing adsorbents with high performance and long service life for effective extracting the trace organochlorine pesticides (OCPs) from real water is attracting numerous attentions. Herein, a self-standing covalent organic framework (COF-TpPa) membrane with fiber morphology was successfully synthesized by using electrospun nanofiber membranes as template and employed as solid-phase microextraction (SPME) coating for ultra-high sensitivity extraction and analysis of trace OCPs in water. The as-synthesized COF-TpPa membrane exhibited a high specific surface area (800.83 m2 g-1), stable nanofibrous structure, and excellent chemical and thermal stability. Based on the COF-TpPa membrane, a new SPME analytical method in conjunction with gas chromatography-mass spectrometry (GC-MS) was established. This proposed method possessed favorable linearity in concentration of 0.05-2000 ng L-1, high sensitivity with enrichment factors ranging from 2175 to 5846, low limits of detection (0.001-0.150 ng L-1), satisfactory precision (RSD < 10 %), and excellent repeatability (>150 cycles), which was better than most of the reported works. Additionally, the density functional theory (DFT) calculations and XPS results demonstrated that the outstanding enrichment performance of the COF-TpPa membrane was owing to synergistic effect of π-π stacking effects, high specific surface area and hydrogen bonding. This work will expect to extend the applications of COF membrane to captures trace organic pollutants in complex environmental water, as well as offer a multiscale interpretation for the design of effective adsorbents.

Efficient dispersive solid phase extraction of trace nitrophenol pollutants in water with triazine porous organic polymer modified nanofiber membrane.

Detecting trace endocrine disruptors in water is crucial for evaluating the water quality. In this work, a innovative modified polyacrylonitrile@cyanuric chloride-triphenylphosphine nanofiber membrane (PAN@CC-TPS) was prepared by in situ growing triazine porous organic polymers on the polyacrylonitrile (PAN) nanofibers, and used in the dispersive solid phase extraction (DSPE) to enrich trace nitrobenzene phenols (NPs) in water. The resluted PAN@CC-TPS nanofiber membrane consisted of numerous PAN nanofibers cover with CC-TPS solid spheres (∼2.50 µm) and owned abundant functional groups, excellent enrichment performance and good stability. In addition, the method based on PAN@CC-TPS displayed outstanding capacity in detecting the trace nitrobenzene phenols, with 0.50-1.00 µg/L of the quantification, 0.10-0.80 µg/L of the detection limit, 85.35-113.55 % of the recovery efficiency, and 98.08-103.02 of the enrichment factor, which was comparable to most materials. Meanwhile, when PAN@CC-TPS was adopted in the real water samples (sea water and river water), the high enrichment factors and recovery percentages strongly confirmed the feasibility of PAN@CC-TPS for enriching and detecting the trace NPs. Besides, the related mechanism of extracting NPs on PAN@CC-TPS mainly involved the synergistic effect of hydrogen bonding, π-π stacking and hydrophobic effect.