Identification of PANoptosis-related subtypes, construction of a prognosis signature, and tumor microenvironment landscape of hepatocellular carcinoma using bioinformatic analysis and experimental verification.

Background: Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide. PANoptosis is a recently unveiled programmed cell death pathway, Nonetheless, the precise implications of PANoptosis within the context of HCC remain incompletely elucidated. Methods: We conducted a comprehensive bioinformatics analysis to evaluate both the expression and mutation patterns of PANoptosis-related genes (PRGs). We categorized HCC into two clusters and identified differentially expressed PANoptosis-related genes (DEPRGs). Next, a PANoptosis risk model was constructed using LASSO and multivariate Cox regression analyses. The relationship between PRGs, risk genes, the risk model, and the immune microenvironment was studies. In addition, drug sensitivity between high- and low-risk groups was examined. The expression profiles of these four risk genes were elucidate by qRT-PCR or immunohistochemical (IHC). Furthermore, the effect of CTSC knock down on HCC cell behavior was verified using in vitro experiments. Results: We constructed a prognostic signature of four DEPRGs (CTSC, CDCA8, G6PD, and CXCL9). Receiver operating characteristic curve analyses underscored the superior prognostic capacity of this signature in assessing the outcomes of HCC patients. Subsequently, patients were stratified based on their risk scores, which revealed that the low-risk group had better prognosis than those in the high-risk group. High-risk group displayed a lower Stromal Score, Immune Score, ESTIMATE score, and higher cancer stem cell content, tumor mutation burden (TMB) values. Furthermore, a correlation was noted between the risk model and the sensitivity to 56 chemotherapeutic agents, as well as immunotherapy efficacy, in patient with. These findings provide valuable guidance for personalized clinical treatment strategies. The qRT-PCR analysis revealed that upregulated expression of CTSC, CDCA8, and G6PD, whereas downregulated expression of CXCL9 in HCC compared with adjacent tumor tissue and normal liver cell lines. The knockdown of CTSC significantly reduced both HCC cell proliferation and migration. Conclusion: Our study underscores the promise of PANoptosis-based molecular clustering and prognostic signatures in predicting patient survival and discerning the intricacies of the tumor microenvironment within the context of HCC. These insights hold the potential to advance our comprehension of the therapeutic contribution of PANoptosis plays in HCC and pave the way for generating more efficacious treatment strategies.

Elucidating the Mechanism of Action of the Gram-Negative-Pathogen-Selective Cyclic Antimicrobial Lipopeptide Brevicidine.

Due to the accelerated appearance of antimicrobial-resistant (AMR) pathogens in clinical infections, new first-in-class antibiotics, operating via novel modes of action, are desperately needed. Brevicidine, a bacterial nonribosomally produced cyclic lipopeptide, has shown potent and selective antimicrobial activity against Gram-negative pathogens. However, before our investigations, little was known about how brevicidine exerts its potent bactericidal effect against Gram-negative pathogens. In this study, we find that brevicidine has potent antimicrobial activity against AMR Enterobacteriaceae pathogens, with MIC values ranging between 0.5 µM (0.8 mg/L) and 2 µM (3.0 mg/L). In addition, brevicidine showed potent antibiofilm activity against the Enterobacteriaceae pathogens, with the same 100% inhibition and 100% eradication concentration of 4 µM (6.1 mg/L). Further mechanistic studies showed that brevicidine exerts its potent bactericidal activity by interacting with lipopolysaccharide in the outer membrane, targeting phosphatidylglycerol and cardiolipin in the inner membrane, and dissipating the proton motive force of bacteria. This results in metabolic perturbation, including the inhibition of ATP synthesis; the inhibition of the dehydrogenation of NADH; the accumulation of reactive oxygen species in bacteria; and the inhibition of protein synthesis. Finally, brevicidine showed a good therapeutic effect in a mouse peritonitis-sepsis model. Our findings pave the way for further research on the clinical applications of brevicidine to combat prevalent infections caused by AMR Gram-negative pathogens worldwide.

A dual-optical sensor for mancozeb by UCNP@PVP@MnO2 nanozyme.

In this work, a fluorescence/colorimetric dual-mode detection method based on MnO2 nanoflower-decorated upconversion nanoparticles: NaYF4:Yb/Er@polyvinylpyrrolidone@MnO2 (UCNP@PVP@MnO2) was proposed to detect the presence of mancozeb (MB). In this detection system, the MnO2 nanoflowers in the nanocomplex of UCNP@PVP@MnO2 would quench the fluorescence of the UCNP. With the addition of H2O2 and 3,3',5,5'-tetramethylbenzidine (TMB), the reaction between MnO2 and H2O2 resulted in the dissolution of MnO2 and the dissolution of the MnO2 layer contributed to the fluorescence recovery of UCNP. Simultaneously, MnO2 oxidized the colorless TMB to a blue product oxidized 3,3',5,5'-tetramethylbenzidine (oxTMB). The blue solution was able to quench the recovered fluorescence of UCNP due to the fluorescence inter filter effect (IFE) between the UCNP and blue oxTMB. Finally, with the addition of MB, the oxTMB was reduced to TMB by MB and the color of the solution became lighter while the fluorescence intensity of the solution increased. The detection method had a good linear range of 5-120 µM and 0.5-60 µM for fluorescence and colorimetric detection, respectively, and the limits of detection (LOD) were 2.34 and 0.245 µM, respectively.

The silencing of lnc-NONHSAT071210 suppresses the proliferation, fibrosis, migration, and invasion of TGFß1-treated lung epithelial cells.

Background: Pulmonary fibrosis, which is a frequent manifestation of connective tissue disease (CTD), is a leading cause of morbidity and mortality. However, the role of long non-coding ribonucleic acids (lncRNAs) in CTD-associated pulmonary fibrosis requires clarification. This study sought to examine the effects of lnc-NONHSAT071210 on the phenotypes of transforming growth factor ß1 (TGFß1)-treated lung epithelial cells. Methods: The GeneChip was used to identify differentially expressed lncRNAs in CTD-associated pulmonary fibrosis patients. After lnc-NONHSAT071210 was knocked down in the TGFß1-challenged lung epithelial cells, cell viability, cell cycle, migration, and invasion were estimated by Cell Counting Kit-8 assays, a flow cytometry analysis, wound-healing assays, and transwell assays, respectively. The expression and levels of the fibrosis-associated factors were examined by enzyme-linked immunosorbent assays, RT-qPCR, and western blots. Results: The expression of the top 7 most significantly upregulated lncRNAs in the CTD-associated pulmonary fibrosis patients was depicted in a heat map and examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The results showed that the expression of lnc-NONHSAT071210 was significantly increased in the tissues of the CTD-associated pulmonary fibrosis patients (P<0.001). The silencing of Lnc-NONHSAT071210 suppressed proliferation, migration, and invasion in the TGFß1-exposed alveolar epithelial cells (P<0.001). Conclusions: Thus, lnc-NONHSAT071210 expression was increased in the tissues of the CTD-associated pulmonary fibrosis patients and TGFß1-treated lung epithelial cells, and TGFß1-induced lung epithelial cell injury was alleviated by impeding the expression of lnc-NONHSAT071210.

Incidence trends of acute viral hepatitis caused by four viral etiologies between 1990 and 2019 at the global, regional and national levels.

BACKGROUND: Hepatitis is a major public health challenge and a leading cause of death worldwide. We aimed to study the cause-specific incidence and temporal trends of acute viral hepatitis (AVH). METHODS: Data on AVH etiologies were available from the Global Burden of Disease study 2019. Estimated annual percentage change (EAPC) was used to quantify temporal trend in AVH age-standardized incidence rates (ASIRs) by region, sex and aetiology. RESULTS: From 1990 to 2019, the global incidence of AVH increased by 8.02%, from 244 350 063 in 1990 to 263 951 645 in 2019, with an average decreasing ASIR of 0.52% (95% CI -0.58% to -0.45%) annually. The ASIR of AVH due to hepatitis B virus (HBV) decreased, while those of hepatitis A (HAV), hepatitis C (HCV) and hepatitis E (HEV) remained stable, with EAPCs (95% CI) of -1.47 (-1.58 to -1.36), 0 (-0.09 to 0.09), -0.35 (-0.83 to -0.13), and -0.16 (-0.41 to 0.09) respectively. Although the number of new AVH cases increased in the low sociodemographic index (SDI), low-middle SDI regions, the ASIRs decreased in all five SDI regions. Globally, HAV and HBV are the leading causes of acute hepatitis. The EAPC is significantly associated with a baseline ASIR of less than 5500 per 100 000 population (ρ = -0.44), and with the 2019 human development index (HDI) (ρ = 0.16) for AVH. CONCLUSIONS: Although the ASIR of AVH showed a generally decreasing trend, the burden of AVH remains a major public health challenge globally. The findings may be helpful for policymakers in establishing appropriate policies to reduce the viral hepatitis burden.

Effect Evaluation of Echocardiography on Right Ventricular Function in Patients after the Recovering from Coronavirus Disease 2019.

This research was aimed at exploring the changes in right ventricular function in patients after the recovery of coronavirus disease 2019 (COVID-19) under echocardiography and providing a reference for the rehabilitation and treatment of COVID-19 patients. Three echocardiographic follow-up examinations were performed on 40 recovered COVID-19 patients and 40 healthy people. Right ventricular function between patients after COVID-19 rehabilitation and healthy people was compared. The mean values of right ventricular fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE), right ventricular ejection fraction (RVEF), right myocardial performance index (RMPI), and tricuspid annular plane systolic speed (S') were compared between patients after COVID-19 rehabilitation and healthy subjects. The technical parameters of two-dimensional speckle tracking were compared. The results showed that the differences in RVFAC, TAPSE, RVEF, and RMPI between COVID-19 patients and healthy controls were not significant during the three follow-up periods (P > 0.05). At the first follow-up, the S' was 12.78 cm/s in COVID-19 patients and 13.18 cm/s in healthy subjects. At the second follow-up, the S' was 11.98 cm/s in COVID-19 patients and 12.77 cm/s in healthy subjects. At the third follow-up, the S' was 12.79 cm/s in COVID-19 patients and 13.12 cm/s in healthy subjects. There was no significant difference between the two groups (P > 0.05). In addition, there was no significant difference in right ventricular function between COVID-19 patients and healthy controls, and there was no significant difference in cardiovascular symptoms (P > 0.05). In summary, COVID-19 had no substantial effect on right ventricular function and better recovery in patients.

A Transvenous Endovascular Approach in Straight Sinus Has Minor Impacts on Chordae Willisii.

Cerebral dural sinuses contain different types of chordae willisii (CW). The transvenous endovascular approach, which has become an optimal method for the treatment of cerebrovascular diseases, such as malformation, fistula, and chronic intracranial hypertension, due to sinus thromboses, frequently uses retrograde navigation through dural sinuses. Whether or how much the endoscopic procedure damages the chordae willisii is often not well-assessed. In our study, an overall number of 38 cadaveric heads were analyzed for the distribution and features of the chordae willisii in the straight sinus. We used an endoscope on these samples mimicking a mechanical thrombectomy procedure performed in the straight sinus. Both endoscopic gross observation and light microscopic histological examination were used to assess the damages to the chordae willisii by the procedure. We found that the valve-like lamellae and longitudinal lamellae structures were mainly found in the posterior part of straight sinus whereas trabeculae were present in both anterior and posterior portions. We treated a group of samples with a stent and another with a balloon. The stent-treated group had a significantly higher rate of Grade 1 damage comparing with the balloon-treated group (p = 0.02). The incidence of damage to the surface of chordae willisii was also higher in the stent-treated group (p = 0.00). Neither the use of stent nor of balloon increased the rate of damage to chordae willisii during repeated experiments. These findings indicated that stent or balloon navigation through the straight sinus can cause minor damages to the chordae willisii and frequent uses of retrograde navigation through the straight sinus do not appear to increase the rates of damage to chordae willisii.

The burden of primary liver cancer caused by specific etiologies from 1990 to 2019 at the global, regional, and national levels.

BACKGROUND: Liver cancer is one of the most common cancers worldwide. We aimed to report the burden of liver cancer at the global, regional, and national levels in 204 countries from 1990 to 2019, stratified by etiology, sex, age, and sociodemographic index (SDI). METHODS: Data of mortality, incidence, and disability-adjusted life years (DALYs) of liver cancer and its etiology were available from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2019. The trends in the liver cancer burden were assessed by the annual percentage change. All estimates are presented as numbers and age-standardized rates (ASRs) per 100,000 population, with uncertainty intervals (UIs). RESULTS: Globally, 484,577 (95% UI 444,091-525,798) mortalities, 534,364 (486,550-588,639) incident cases, and 12,528,422 (11,400,671-13,687,675) disability-adjusted life years (DALYs) due to liver cancer occurred in 2019. The ASRs were 5.95 (5.44-6.44), 6.51 (5.95-7.16), and 151.08 (137.53-164.8) per 100,000 population for the mortalities, incidences, and DALYs, respectively. From 1990 to 2019, the numbers increased, whereas the ASRs decreased. Hepatitis B and Hepatitis C are the major causes of liver cancer mortality. The liver cancer mortality in 2019 increased with age, peaking at 65-69 and 70-74 age group in males and females, respectively, and the number was higher in males than in females. Generally, there were nonlinear associations between the ASR and SDIs values at the regional and national levels. China had the highest numbers of mortalities, incident cases, and DALYs, whereas Mongolia has the highest ASR in 2019. CONCLUSION: Liver cancer remains a major public health issue worldwide, but etiological and geographical variations exist. It is necessary to increase awareness of the population regarding liver cancer, its etiologies and the importance of early detection, and diagnosis and treatment.

Application of a novel artificial neural network model in flood forecasting.

In this paper, a novel ANN flood forecasting model is proposed. The ANN model is combined with traditional hydrological concepts and methods, taking the initial Antecedent Precipitation Index (API), rainfall, upstream inflow and initial flow at the forecast river section as input of model, and flood flow forecast of the next time steps as output of the model. The distributed rainfall is realized as the input of the model. The simulation is processed by dividing the watershed into several rainfall-runoff processing units. Two hidden layers are used in the ANN, and the topology of ANN is optimized by connecting the hidden layer neurons only with the input which has physical conceptual causes. The topological structure of the proposed ANN model and its information transmission process are more consistent with the physical conception of rainfall-runoff, and the weight parameters of the model are reduced. The arithmetic moving-average algorithm is added to the output of the model to simulate the pondage action of the watershed. Satisfactory results have been achieved in the Mozitan and Xianghongdian reservoirs in the upper reaches of Pi river in Huaihe Basin, and the Fengman reservoir in the upper reach of Second Songhua river in Songhua basin in China.

Impacts on Thrombus and Chordae Willisii During Mechanical Thrombectomy in the Superior Sagittal Sinus.

The anatomical structures of the superior sagittal sinus (SSS) are usually damaged during mechanical thrombectomy (MT), and MT procedure could lead to new thrombosis in the sinuses. However, the mechanism remains unclear. We aimed to investigate the risks of embolism and assess the damage to chordae willisii (CW)-associated MT using a stent passing across the thrombus. A contrast-enhanced in vitro model was used to mimick MT in the SSS. The thrombus was removed with a stent. The emboli generated during the procedure were collected and measured. The residual thrombus area after the MT was measured by J Image software. The damage of CW was evaluated by an endoscope. Three procedural experiments were carried out on each cadaveric sample. The average numbers of visible emboli particles in experiments 1, 2, and 3 were 11.17 ± 2.17, 9.00 ± 2.07, and 5.00 ± 2.96, respectively. The number of large size particles produced by experiment 1 was significantly higher than that of the other experiments. The thrombus area measured after experiment 3 was larger than that of experiments 1 and 2. The number of minor damage cases to CW was 55 (90.16%), and there were six serious damage cases (9.84%). The use of stent resulted in no significant increase in damage to CW after the three experimental procedures. A large amount of thrombi particles was produced during MT, and multiple MT procedures on the same sample can increase residual thrombus area. Moreover, the stent caused minor damages to the CW in SSS.

Traveling-Wave Convection with Periodic Source Defects in Binary Fluid Mixtures with Strong Soret Effect.

This paper studied the Rayleigh-Bénard convection in binary fluid mixtures with a strong Soret effect (separation ratio ψ = - 0.6 ) in a rectangular container heated uniformly from below. We used a high-accuracy compact finite difference method to solve the hydrodynamic equations used to describe the Rayleigh-Bénard convection. A stable traveling-wave convective state with periodic source defects (PSD-TW) is obtained and its properties are discussed in detail. Our numerical results show that the novel PSD-TW state is maintained by the Eckhaus instability and the difference between the creation and annihilation frequencies of convective rolls at the left and right boundaries of the container. In the range of Rayleigh number in which the PSD-TW state is stable, the period of defect occurrence increases first and then decreases with increasing Rayleigh number. At the upper bound of this range, the system transitions from PSD-TW state to another type of traveling-wave state with aperiodic and more dislocated defects. Moreover, we consider the problem with the Prandtl number P r ranging from 0.1 to 20 and the Lewis number L e from 0.001 to 1, and discuss the stabilities of the PSD-TW states and present the results as phase diagrams.

High order fast neutron multiplicity measurement equations based on liquid scintillation detector.

Fast neutron multiplicity counting (FNMC) analysis method is a new nondestructive analysis method for nuclear materials. It uses a fast neutron detector array to detect the neutrons emitted by the sample. The quality of plutonium in the sample is obtained by recording the neutron coincidence counting of fast neutron multiplicity. At present, the first three multiplets widely studied including singlets, doublets and triplets can no longer meet the needs of the research. In this paper, The derivation process of fast neutron multiplicity measurement equation for liquid scintillation detector is studied in detail based on the basic principle, neutron counting method, by using the methods of the factorial moments, probability generating functions and parameter estimation method, and considering the influence of scattering crosstalk. Finally, the fast neutron multiplicity measurement equation including singlets, doublets, triplets, quadruplets and pentuplets are established according to the parameter estimation method and the two kinds of solution methods of this equation are given. The work in this paper lays a theoretical and analytical foundation for the research of fast neutron multiplicity measurement system based on liquid scintillation detector.

Observation of the effect of bone marrow mesenchymal stem cell transplantation by different interventions on cirrhotic rats.

Bone marrow mesenchymal stem cells (BMSCs) transplantation has attracted attention for the treatment of liver cirrhosis and end-stage liver diseases. Therefore, in this study, we evaluated the effect of different methods of BMSCs transplantation in the treatment of liver cirrhosis in rats. Seventy-two male Sprague-Dawley rats were divided into 7 groups: 10 were used to extract BMSCs, 10 were used as normal group, and the remaining 52 rats were randomly divided into five groups for testing: control group, BMSCs group, BMSCs+granulocyte colony-stimulating factor (G-CSF) group, and BMSCs+Jisheng Shenqi decoction (JSSQ) group. After the end of the intervention course, liver tissue sections of rats were subjected to hematoxylin and eosin (H&E) and Masson staining, and pathological grades were scored. Liver function [aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB)] and hepatic fibrosis markers [hyaluronidase (HA), laminin (LN), type III procollagen (PCIII), type IV collagen (CIV)] were measured. BMSCs+JSSQ group had the best effect of reducing ALT and increasing ALB after intervention therapy (P<0.05). The reducing pathological scores and LN, PCIII, CIV of BMSCs+G-CSF group and BMSCs+JSSQ group after intervention therapy were significant, but there was no significant difference between the two groups (P>0.05). The effect of JSSQ on improving stem cell transplantation in rats with liver cirrhosis was confirmed. JSSQ combined with BMSCs could significantly improve liver function and liver pathology scores of rats with liver cirrhosis.

Metabolomic study of natrin-induced apoptosis in SMMC-7721 hepatocellular carcinoma cells by ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry.

Natrin, a new member of the cysteine-rich secretory protein (CRISP) family purified from the snake venom of Naja naja atra, has been demonstrated to have anticancer activity. However, the underlying molecular mechanisms need further elucidation. In this study, MTT was used to evaluate cell viability. Apoptotic cells were analyzed by employing a transmission electron microscope (TEM). Metabolomic study of the metabolic perturbations caused by natrin-induced apoptosis in differentiated SMMC-7721 cells was performed for the first time by using integrative ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF MS). To investigate the possible mechanism in the mitochondrial pathway of natrin-induced apoptosis, we measured apoptosis-related mRNA changes using real-time fluorescent quantitative PCR (FQ-PCR). Cell proliferation was significantly inhibited after treatment with natrin in a dose-dependent manner. Principal component analysis (PCA) and partial least squares-discriminate analysis (PLS-DA) clearly demonstrated that metabolic profiles were affected by natrin. The results of multivariate statistical analysis showed that a total of 13 metabolites were characterized as potential biomarkers highly implicated in natrin-induced apoptosis, which corresponded to fluctuations of five pathways, including sphingolipid metabolism, fatty acid biosynthesis, fatty acid metabolism, glycerophospholipid metabolism and glycosphingolipid biosynthesis. Furthermore, natrin-induced apoptosis showed an increase in the Bax/Bcl-2 ratio in the mitochondrial pathway compared with controls. This study illustrated that rapid and holistic cell metabolomics combining molecular biological approaches might be a powerful tool for evaluating the underlying mechanisms of natrin-induced apoptosis, which would help to deepen specific insights into the anti-hepatoma mechanisms of natrin and facilitate the clinical application of natrin in the future.

Identification of a novel PDGFRA point mutation at p.P6L as a potential molecular target of imatinib in an eosinophilia patient showing genetic heterogeneity.

Eosinophilia is a severe disease with increased eosinophil count. The transcript of FIP1L1-PDGFRA fusion gene is a genetic biomarker of clonal eosinophilia screened routinely by reverse transcript PCR (RT-PCR) during diagnosis. Another significant genetic biomarker is the PDGFRA gene alone as some of its mutations are targets of imatinib. In this study, we identified a patient who had typical symptoms of Eosinophilia but had no response to the first-line treatment of hormonotherapy. This patient also showed bone rupture and eosinophil bone infiltration, which are extremely rare among all known eosinophilia patients. We identified the FIP1L1-PDGFRA fusion gene via RT-PCR and Sanger sequencing. Using next generation sequencing (NGS), we detected point mutations in PDGFRA, MYOM2, and ASXL3. The patient then received imatinib therapy, leading to the complete disappearance of FIP1L1-PDGFRA fusion gene and mutated MYOM2. The level of PDGFRA point mutation was also decreased from pre-treatment: 57.86% down to 42.99% at 6 months and to 38.80% at one-year after treatment. The level of ASXL3 mutations did not change significantly. To the best of our knowledge, this is the first case in which the point mutation of PDGFRA has been identified at p.P6L in exon 2, likely making it sensitive to imatinib and thus should be further studied as a potential new molecular target of imatinib therapy.

Observation of the effect of bone marrow mesenchymal stem cell transplantation by different interventions on cirrhotic rats

Bone marrow mesenchymal stem cells (BMSCs) transplantation has attracted attention for the treatment of liver cirrhosis and end-stage liver diseases. Therefore, in this study, we evaluated the effect of different methods of BMSCs transplantation in the treatment of liver cirrhosis in rats. Seventy-two male Sprague-Dawley rats were divided into 7 groups: 10 were used to extract BMSCs, 10 were used as normal group, and the remaining 52 rats were randomly divided into five groups for testing: control group, BMSCs group, BMSCs+granulocyte colony-stimulating factor (G-CSF) group, and BMSCs+Jisheng Shenqi decoction (JSSQ) group. After the end of the intervention course, liver tissue sections of rats were subjected to hematoxylin and eosin (H&E) and Masson staining, and pathological grades were scored. Liver function [aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB)] and hepatic fibrosis markers [hyaluronidase (HA), laminin (LN), type III procollagen (PCIII), type IV collagen (CIV)] were measured. BMSCs+JSSQ group had the best effect of reducing ALT and increasing ALB after intervention therapy (P<0.05). The reducing pathological scores and LN, PCIII, CIV of BMSCs+G-CSF group and BMSCs+JSSQ group after intervention therapy were significant, but there was no significant difference between the two groups (P>0.05). The effect of JSSQ on improving stem cell transplantation in rats with liver cirrhosis was confirmed. JSSQ combined with BMSCs could significantly improve liver function and liver pathology scores of rats with liver cirrhosis.

CA153 in Breast Secretions as a Potential Molecular Marker for Diagnosing Breast Cancer: A Meta Analysis.

PURPOSE: Many studies have reported that carbohydrate antigen 153 (CA153) in breast secretions (BS) can discriminate breast cancer (BC) patients from healthy individuals, indicating CA153 in BS as a potential index for BC. This meta-analysis aimed to evaluate the actual diagnostic value of CA153 in BS. METHODS: Related papers were obtained from Pubmed, Embase, Scopus, Ovid, Sciverse, the Cochrane library, Chinese Biomedical literature Database (CBM), Technology of Chongqing (VIP), Wan Fang Data, and Chinese National Knowledge Infrastructure (CNKI). Pooled sensitivity, specificity, and diagnostic odds ratio (DOR) of CA153 in BS for BC diagnosis were analyzed with the random effect model. SROC and the area under the curve (AUC) were applied to assess overall diagnostic efficiency. RESULTS: This meta-analysis included five studies with a total of 329 BC patients and 381 healthy subjects. For CA153 in BS, the summary sensitivity, specificity, and DOR to diagnose BC were 0.63 (95% confidence interval (CI): 0.57∼0.68), 0.82 (95% CI: 0.78∼0.86), and 9.18 (95% CI: 4.22∼19.95), respectively. Furthermore, the AUC of BS CA153 in the diagnosis of BC was 0.8614. CONCLUSIONS: CA153 in BS is a valuable molecular marker in diagnosing BC and should be applied in standard clinical practices of BC screening upon confirmation of our findings in a larger prospective study.

Cloning of a big defensin gene and its response to Vibrio parahaemolyticus challenge in the noble scallop Chlamys nobilis (Bivalve: Pectinidae).

The noble scallop Chlamys nobilis has been an important marine cultured bivalve in the Southern Sea of China for decades. However, large-scale mortality events often occurred during the scallop' cultivation. As one of AMPs (antimicrobial peptides), big defensin is an important component of the innate immunity against pathogenic microorganisms in invertebrates. In order to investigate whether the big defensin can play a role in the immune defense against pathogenic microorganisms in noble scallop, a big defensin gene from the hemocytes of Chlamys nobilis (CnBD) was cloned, and the mRNA level was measured after an acute Vibrio parahaemolyticus challenge of 36 h. The CnBD cDNA contains an open reading frame (ORF) of 381 bp encoding a peptide of 126 amino acids residues. The deduce amino acid sequence of CnBD shows a high similarity with that from Argopecten irradians and displays common features of big defensin, indicating that CnBD is a new member of the big defensin family. Compared with the control group, the relative mRNA level of CnBD was significantly up-regulated at 3, 24 and 36 h. The present result indicated that CnBD played an immune role against bacterial infection in noble scallop.

CEA in breast ductal secretions as a promising biomarker for the diagnosis of breast cancer: a systematic review and meta-analysis.

PURPOSE: Other studies have shown that levels of carcinoembryonic antigen (CEA) in breast ductal secretions (BDS) differ significantly between breast cancer (BC) patients and healthy individuals, providing direct evidence for CEA in BDS as a promising biomarker for BC. This meta-analysis was designed to assess the potential diagnostic value of CEA in BDS. METHODS: Relevant articles were retrieved from Embase, Pubmed, and the Cochrane Library. Sensitivity, specificity, and diagnostic odds ratio (DOR) of CEA in BDS for diagnosing BC were pooled using random effects models. SROC and the area under the curve (AUC) were used to estimate overall diagnostic performance. RESULTS: This meta-analysis comprised five studies with a total of 340 BC patients and 448 healthy controls. For CEA in BDS, the pooled sensitivity, specificity, and DOR to diagnose BC were 58 % [95 % confidence interval (CI): 52-63 %], 87 % (95 % CI: 84-90 %), and 7.07 (95 % CI: 3.10-16.12), respectively. Moreover, the AUC of CEA in the diagnosis of BC was 0.8570. CONCLUSIONS: CEA in BDS is a promising biomarker in the diagnosis of BC and should be evaluated as a standard screening tool upon verification of our results in a larger study population.

Dual-doping to suppress cracking in spinel LiMn2O4: a joint theoretical and experimental study.

Electrochemical cycling stabilities were compared for undoped and Al/Co dual-doped spinel LiMn2O4 synthesized by solid state reactions. We observed the suppression of particle fracture in Al/Co dual-doped LiMn2O4 during charge/discharge cycling and its distinguishable particle morphology with respect to the undoped material. Systematic first-principles calculations were performed on undoped, Al or Co single-doped, and Al/Co dual-doped LiMn2O4 to investigate their structural differences at the atomistic level. We reveal that while Jahn-Teller distortion associated with the Mn(3+)O6 octahedron is the origin of the lattice strain, the networking -i.e. the distribution of mixed valence Mn ions - is much more important to release the lattice strain, and thus to alleviating particle cracking. The calculations showed that the lattice mismatching between Li(+) intercalation and deintercalation of LiMn2O4 can be significantly reduced by dual-doping, and therefore also the volumetric shrinkage during delithiation. This may account for the near disappearance of cracks on the surface of Al/Co-LiMn2O4 after 350 cycles, while some obvious cracks have developed in undoped LiMn2O4 at similar particle size even after 50 cycles. Correspondingly, Al/Co dual-doped LiMn2O4 showed a good cycling stability with a capacity retention of 84.1% after 350 cycles at a rate of 1C, 8% higher than the undoped phase.