Cohort-Individual Cooperative Learning for Multimodal Cancer Survival Analysis.

Recently, we have witnessed impressive achievements in cancer survival analysis by integrating multimodal data, e.g., pathology images and genomic profiles. However, the heterogeneity and high dimensionality of these modalities pose significant challenges for extracting discriminative representations while maintaining good generalization. In this paper, we propose a Cohortindividual Cooperative Learning (CCL) framework to advance cancer survival analysis by collaborating knowledge decomposition and cohort guidance. Specifically, first, we propose a Multimodal Knowledge Decomposition (MKD) module to explicitly decompose multimodal knowledge into four distinct components: redundancy, synergy and uniqueness of the two modalities. Such a comprehensive decomposition can enlighten the models to perceive easily overlooked yet important information, facilitating an effective multimodal fusion. Second, we propose a Cohort Guidance Modeling (CGM) to mitigate the risk of overfitting task-irrelevant information. It can promote a more comprehensive and robust understanding of the underlying multimodal data, while avoiding the pitfalls of overfitting and enhancing the generalization ability of the model. By cooperating the knowledge decomposition and cohort guidance methods, we develop a robust multimodal survival analysis model with enhanced discrimination and generalization abilities. Extensive experimental results on five cancer datasets demonstrate the effectiveness of our model in integrating multimodal data for survival analysis. The code will be publicly available soon.

Mathematical Modeling of Tumor Growth in Preclinical Mouse Models with Applications in Biomarker Discovery and Drug Mechanism Studies.

Oncology drug efficacy is evaluated in mouse models by continuously monitoring tumor volumes, which can be mathematically described by growth kinetic models. Although past studies have investigated various growth models, their reliance on small datasets raises concerns about whether their findings are truly representative of tumor growth in diverse mouse models under different vehicle or drug treatments. In this study, we systematically evaluated six parametric models (exponential, exponential quadratic, monomolecular, logistic, Gompertz, and von Bertalanffy) and the semiparametric generalized additive model (GAM) on fitting tumor volume data from more than 30,000 mice in 930 experiments conducted in patient-derived xenografts, cell line-derived xenografts, and syngeneic models. We found that the exponential quadratic model is the best parametric model and can adequately model 87% studies, higher than other models including von Bertalanffy (82%) and Gompertz (80%) models; the latter is often considered the standard growth model. At the mouse group level, 7.5% of growth data could not be fit by any parametric model and were fitted by GAM. We show that endpoint gain integrated in time, a GAM-derived efficacy metric, is equivalent to exponential growth rate, a metric we previously proposed and conveniently calculated by simple algebra. Using five studies on paclitaxel, anti-PD1 antibody, cetuximab, irinotecan, and sorafenib, we showed that exponential and exponential quadratic models achieve similar performance in uncovering drug mechanism and biomarkers. We also compared exponential growth rate-based association analysis and exponential modeling approach in biomarker discovery and found that they complement each other. Modeling methods herein are implemented in an open-source R package freely available at https://github.com/hjzhou988/TuGroMix. SIGNIFICANCE: We present a general strategy for mathematically modeling tumor growth in mouse models using data from 30,000 mice and show that modeling and nonmodeling approaches are complementary in biomarker discovery and drug mechanism studies.

Synthesis of self-supported NiCoFe(OH)x via fenton-like effect corrosion for highly efficient water oxidation.

Efficientandinexpensiveoxygenevolutionreaction(OER)catalysts are essential for the electrochemical splitting of water into hydrogen fuel. Herein, we have successfully synthesized NiCoFe(OH)x nanosheets on Ni-Fe foam (NFF) by exploiting the Fenton-like effect of Co2+ and S2O82- to corrode the NFF foam. The as-prepared NiCoFe(OH)x/NFF exhibits the porous structure with the interconnected nanosheets that are firmly bonded to the conductive substrate of NFF, thereby enhancing ions and charge transfer kinetics. The unique structure and composition of NiCoFe(OH)x/NFF result in the low overpotentials of 200 and 262 mV at current densities of 10 and 100 mA cm-2, respectively, as well as a low Tafel slope of 53.25 mV dec-1. In addition, NiCoFe(OH)x/NFF displays low overpotentials of 267 and 294 mV at a high current density of 100 mA cm-2 in simulated and real seawater, respectively. Furthermore, the assembled NiCoFe(OH)x//Pt/C water electrolysis cell has achieved a current density of 10 mA cm-2 at a low voltage of 1.49 V, and displayed the good stability with slight attenuation for 110 h. The high OER performance of NiCoFe(OH)x is attributed to the co-catalytic effect of the three metal ions and the interconnected porous nanosheet structure.

Facile synthesis of amorphous/crystalline Ni-Fe thiophenedicarboxylate coordination polymer nanobelts for efficient water oxidation.

The oxygen evolution reaction (OER) is a complex four-electron transfer process that poses a significant challenge to the efficient production of hydrogen through water splitting. However, developing non-noble metal electrocatalyst with excellent OER performance is still a big challenge. Herein, we propose a new strategy for the in-situ growth of two-dimensional amorphous/crystalline thiophene-based Ni-Fe metal-organic frameworks (MOFs) using Ni-Fe foam (NFF) as metal source and current collector, and thiophene-2,5-dicarboxylic acid (TDC) as corrosion agent and ligand. TDC was ionized at high temperature to produce H+ ions that etch NFF to release Ni2+ and Fe2+ ions, which were coordinated with TDC to in situ synthesize two-dimensional Ni-Fe thiophenedicarboxylate coordination polymer (NiFe-TDC) nanobelts on NFF. The unique structure and synergistic effect of Ni and Fe ions of NiFe-TDC0.05 result in the excellent OER performance with an overpotential of 224 and 256 mV at current densities of 10 and 100 mA cm-2, respectively, and it can run stably for 100 h at a current density of 100 mA cm-2, indicating the outstanding stability. Furthermore, NiFe-TDC0.05 remains the excellent OER performance with an extremely low potential of 196 and 271 mV at current densities of 10 and 100 mA cm-2 in seawater with 1 mol L-1 (M) KOH, respectively. The assembled NiFe-TDC0.05 || Pt/C water electrolysis cell achieves a current density of 100 mA cm-2 at a low voltage of 1.78 V. The work provides a new method to prepare two dimensional MOFs for efficient water oxidation.

Multiomics identifies metabolic subtypes based on fatty acid degradation allocating personalized treatment in hepatocellular carcinoma.

BACKGROUND AND AIMS: Molecular classification is a promising tool for prognosis prediction and optimizing precision therapy for HCC. Here, we aimed to develop a molecular classification of HCC based on the fatty acid degradation (FAD) pathway, fully characterize it, and evaluate its ability in guiding personalized therapy. APPROACH AND RESULTS: We performed RNA sequencing (RNA-seq), PCR-array, lipidomics, metabolomics, and proteomics analysis of 41 patients with HCC, in which 17 patients received anti-programmed cell death-1 (PD-1) therapy. Single-cell RNA sequencing (scRNA-seq) was performed to explore the tumor microenvironment. Nearly, 60 publicly available multiomics data sets were analyzed. The associations between FAD subtypes and response to sorafenib, transarterial chemoembolization (TACE), immune checkpoint inhibitor (ICI) were assessed in patient cohorts, patient-derived xenograft (PDX), and spontaneous mouse model ls. A novel molecular classification named F subtype (F1, F2, and F3) was identified based on the FAD pathway, distinguished by clinical, mutational, epigenetic, metabolic, and immunological characteristics. F1 subtypes exhibited high infiltration with immunosuppressive microenvironment. Subtype-specific therapeutic strategies were identified, in which F1 subtypes with the lowest FAD activities represent responders to compounds YM-155 and Alisertib, sorafenib, anti-PD1, anti-PD-L1, and atezolizumab plus bevacizumab (T + A) treatment, while F3 subtypes with the highest FAD activities are responders to TACE. F2 subtypes, the intermediate status between F1 and F3, are potential responders to T + A combinations. We provide preliminary evidence that the FAD subtypes can be diagnosed based on liquid biopsies. CONCLUSIONS: We identified 3 FAD subtypes with unique clinical and biological characteristics, which could optimize individual cancer patient therapy and help clinical decision-making.

Development and application of a universal extraction-free reagent based on an algal glycolipid.

In this study, we independently developed a universal nasopharyngeal swab extraction-free reagent based on a trehalose lipid for the rapid detection of pathogen nucleic acids in respiratory infectious diseases. By comparing the isothermal amplification results of a 2019-nCoV pseudovirus solution treated with different components of the extraction-free reagent, we determined the optimal composition of the extraction-free reagent to be a mixed solution of 10 mmol L-1 tris-HCl containing 0.05 mmol L-1 EDTA (TE solution), 5% glycine betaine, 0.5% Triton X-100, and 1.5% trehalose lipid. The results showed that the extraction-free reagent could cleave DNA viruses, RNA viruses, and bacteria to release nucleic acids and did not affect the subsequent nucleic acid amplification. Its efficiency was consistent with that of magnetic bead extraction. Real-time fluorescence quantitative PCR was used to analyze the stability and repeatability of the detection results of the samples treated with the extraction-free reagent and the sensitivity of the extraction-free reagent. The results showed that the extraction-free kit could stably store the pathogen nucleic acid for at least 24 hours, the detection repeatability was satisfactory, and there was no incompatibility with the detection limits of various manufacturers' nucleic acid detection reagents. In conclusion, the established nucleic acid extraction-free method can effectively lyse respiratory infectious disease pathogens to release nucleic acids (DNA and RNA) at room temperature and can directly amplify nucleic acids without extraction steps. This method takes a short time and has high efficiency. The released nucleic acid met the requirements of molecular biological detection methods such as real-time fluorescence quantitative PCR (qPCR), reverse transcription-polymerase chain reaction (RT-PCR), and isothermal nucleic acid amplification (INAA).

Evaluation of a platform-switched Morse taper connection for all-on-four or six treatment in edentulous or terminal dentition treatment: A retrospective study with 1-8 years of follow-up.

BACKGROUND: The survival rate, marginal bone loss and soft tissue health of the Ankylos implants and the balanced base abutments in all-on-four or six implant restoration of edentulous or terminal dentition patients has not been reported in the clinical research. PURPOSE: This retrospective study aimed to evaluate the Ankylos implants and the balanced base abutments in all-on-four or six implant restoration of edentulous or terminal dentition patients after 1-8 years of follow-up. MATERIALS AND METHODS: A retrospective study was conducted based on the medical records of 33 patients who received all-on-four or six treatments from April 2014 to May 2020. Four radiographic examinations [immediate postoperative (T0), definitive restorations (T1), 1-3 years after prosthetic restorations (T2), and more than 3 years after prosthetic restorations (T3)] were obtained to evaluate vertical bone height (VBH). We also calculated the survival rate and examined the condition of soft tissue with this implant system in edentulous or terminal dentition patients. Three-level linear model analyses were used to explore potential risk factors for VBH changes on the mesial and distal sides. The generalized linear model was used to analyze the influencing factors of BOP and plaque. RESULTS: A total of 218 implants were included in this study. The cumulative survival rate of the implants was 97.25% before the definitive prosthesis, 96.33% within 3 years of follow-up and 95.32% after more than 3 years of follow-up. The mean ± standard deviation (SD) bone losses of the VBH were 0.27 ± 0.05 mm (T1-T3) on the mesial side and 0.49 ± 0.06 mm (T1-T3) on the distal side. During 1-8 years of follow-up, the height and angle of the abutment (p < 0.001), the mandible implant site (p < 0.001), the length of the implant (p = 0.014 < 0.05) and age (p = 0.029 < 0.05) showed statistically significant effects on vertical mesial bone height (VMBH) and vertical distal bone height (VDBH). The risk of BOP among participants who brushed three times a day was lower than those who brushed less than three times. The plaque risk of short abutment height was higher than the long abutment. CONCLUSION: The current study showed that the Ankylos implants with the balanced base abutments in all-on-four or six implants treatment is a viable and predictable option with a high survival rate and low marginal bone loss in edentulous or terminal dentition patients. VBH around the implants was strongly associated with the mandible implant site, abutment height and angle, the length of the implant and age. Moreover, teeth-brushing times and abutment height significantly affect soft tissue health.

Advances in the application of molecular diagnostic techniques for the detection of infectious disease pathogens (Review).

Infectious diseases are a major global cause of morbidity and mortality, seriously affecting public health and socioeconomic stability. Since infectious diseases can be caused by a wide variety of pathogens with similar clinical manifestations and symptoms that are difficult to accurately distinguish, selecting the appropriate diagnostic techniques for the rapid identification of pathogens is crucial for clinical disease diagnosis and public health management. However, traditional diagnostic techniques have low detection rates, long detection times and limited automation, which means that they do not meet the requirements for rapid diagnosis. Recent years have seen continuous developments in molecular detection technology, which has a higher sensitivity and specificity, shorter detection time and increased automation, and performs an important role in the early and rapid detection of infectious disease pathogens. The present study summarizes recent progress in molecular diagnostic technologies such as PCR, isothermal amplification, gene chips and high­throughput sequencing for the detection of infectious disease pathogens, and compares the technical principles, advantages and disadvantages, applicability and costs of these diagnostic techniques.

Establishment and Evaluation of Recombinant Expression of HCV Transmembrane Protein (p7) and Detection of Anti-p7 Antibody in Serum of HCV-Infected Patients by Chemiluminescence.

OBJECTIVE: Our aim was to establish a chemiluminescence method for detecting anti-transmembrane protein (p7) antibody in the serum of patients with hepatitis C virus (HCV) infection. METHODS: The p7 gene was amplified by polymerase chain reaction using the plasmid PUC-p7 containing the p7 nucleic acid sequence of the HCV 1b genotype as the template, and recombinant plasmid pGEX-KG-p7 was constructed. After p7 fusion, the protein was induced and expressed in the prokaryote, extracted, and purified; the anti-p7 antibody detection kit was prepared, and its efficacy was evaluated. RESULTS: The plasmid pGEX-KG-p7 was constructed correctly, and p7 fusion protein was obtained. The methodological indexes of the kit, the precision test, blank limit and detection limit, etc, met the requirements. The positive rate of serum anti-p7 antibody in 45 patients with HCV infection was 20%. CONCLUSIONS: The kit can be used in screening diagnosis, condition monitoring, prognosis, and disease mechanism and epidemiological study of HCV infection. The p7 protein has immune response in HCV-infected patients.

Temporal profile of angiogenesis and expression of extracellular matrix-related genes in rat brains following experimental intracerebral hemorrhage.

BACKGROUND: Angiogenesis is essential for the repair process after intracerebral hemorrhage (ICH). METHODS: Given the importance of the extracellular matrix (ECM) in angiogenesis, we analysed the temporal profile of angiogenesis in rat brains on days 4, 7, and 21 after ICH. To this end, we compared the expression of ECM-related genes between ICH-induced and sham-operated groups using a complementary DNA (cDNA) array. We further measured protein expression using western blot and immunohistochemistry assays. Fluorescein isothiocyanate (FITC)-dextran was injected into the tail vein to examine the angioarchitecture in the perihematomal region. RESULTS: Among the 88 ECM-related genes, we identified 42, 50, and 38 genes that were significantly upregulated on days 4, 7, and 21 after ICH, respectively (P < 0.05). Particularly, collagens, integrins, and matrix metalloproteinases (MMPs) were significantly increased on day 4 post-ICH and continued to increase at the other time points. Western blot and immunohistochemistry analyses showed a comparable trend in the upregulation of MMPs. Compared to the sham group, FITC-dextran labelling demonstrated decreased perfusion and increased vascular permeability in the perihematomal region in the ICH group. Doxycycline, an MMP inhibitor, significantly reduced angiogenesis (P < 0.05). CONCLUSIONS: The results of this study indicate that MMPs are involved in modulating angiogenesis following ICH.

Traditional Chinese Medicine Enema Therapy in a Patient With a Confirmed Negative SARS-CoV-2 Test in the Respiratory Tract but Positive in the Intestinal Tract: A Case Report.

We report the case of a 43-year-old man who was infected with SARS-CoV-2 in February 2020 and actively cooperated with treatment in the hospital. During the course of treatment, we found that the respiratory SARS-CoV-2 nucleic acid became negative, but remained positive in the intestinal tract. As a result, we adjusted the treatment plan to include traditional Chinese medicine enema treatment. The patient had negative intestinal SARS-CoV-2 nucleic acid test within 4 days, and the subsequent repeated review of intestinal SARS-CoV-2 nucleic acid was negative, and the virus was undetectable. It is suggested that traditional Chinese medicine enema treatment may be helpful to remove the SARS-CoV-2 in the intestines of patients with COVID-19 infection, and may support the treatment of patients with respiratory SARS-CoV-2 nucleic acid negative and positive in the intestinal tract.

Neighborhood active aging infrastructure and cognitive function: A mixed-methods study of older Americans.

Physical exercise benefits cognitive functioning and can protect against neurodegeneration. Neighborhood environments may be pivotal to physically active aging, and thus help shape older adults' cognitive function. This mixed-methods study investigated where older adults exercised outside the home, and whether availability of these neighborhood sites was associated with cognitive function. We thematically analyzed qualitative data from semi-structured interviews in 2015 with 125 older adults (mean age = 71) in the Minneapolis (MN) metropolitan area. Results identified nearby public parks, fitness/sports amenities, and walkable destinations as motivators for recreational exercise and active transit among participants. These findings informed quantitative analysis of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a national sample of older Black and white Americans (n = 21,151; mean age at assessment = 67; data collected 2006-2017). We used generalized additive multilevel models to examine whether neighborhood features that qualitative participants identified as encouraging physical activity were associated with elevated levels of cognitive function. Results indicated that residing in neighborhoods with greater availability of local parks, access to recreational amenities, and business density was associated with higher levels of cognitive function. We found no evidence to suggest a significant association between availability of these neighborhood resources and rate of cognitive decline. This study identifies specific neighborhood active aging infrastructure that may support cognitive function among older adults aging in place.

Contour-Aware Loss: Boundary-Aware Learning for Salient Object Segmentation.

We present a learning model that makes full use of boundary information for salient object segmentation. Specifically, we come up with a novel loss function, i.e., Contour Loss, which leverages object contours to guide models to perceive salient object boundaries. Such a boundary-aware network can learn boundary-wise distinctions between salient objects and background, hence effectively facilitating the salient object segmentation. Yet the Contour Loss emphasizes the boundaries to capture the contextual details in the local range. We further propose the hierarchical global attention module (HGAM), which forces the model hierarchically to attend to global contexts, thus captures the global visual saliency. Comprehensive experiments on six benchmark datasets show that our method achieves superior performance over state-of-the-art ones. Moreover, our model has a real-time speed of 26 fps on a TITAN X GPU.

Electroacupuncture ameliorates cerebral ischemia/reperfusion injury by suppressing autophagy via the SIRT1-FOXO1 signaling pathway.

Cerebral ischemia/reperfusion (CIR) injury occurs when blood flow is restored in the brain, causing secondary damage to the ischemic tissues. Previous studies have shown that electroacupuncture (EA) treatment contributes to brain protection against CIR injury through modulating autophagy. Studies indicated that SIRT1-FOXO1 plays a crucial role in regulating autophagy. Here we investigated the mechanisms underlying the neuroprotective effect of EA and its role in modulating autophagy via the SIRT1-FOXO1 signaling pathway in rats with CIR injury. EA pretreatment at "Baihui", "Quchi" and "Zusanli" acupoints (2/15Hz, 1mA, 30 min/day) was performed for 5 days before the rats were subjected to middle cerebral artery occlusion, and the results indicated that EA pretreatment substantially reduced the Longa score and infarct volume, increased the dendritic spine density and lessened autophagosomes in the peri-ischemic cortex of rats. Additionally, EA pretreatment also reduced the ratio of LC3-II/LC3-I, the levels of Ac-FOXO1 and Atg7, and the interaction of Ac-FOXO1 and Atg7, but increased the levels of p62, SIRT1, and FOXO1. The above effects were abrogated by the SIRT1 inhibitor EX527. Thus, we presume that EA pretreatment elicits a neuroprotective effect against CIR injury, potentially by suppressing autophagy via activating the SIRT1-FOXO1 signaling pathway.

Protection of the Geum japonicum Thunb. var. chinense extracts against oxygen-glucose deprivation and re-oxygenation induced astrocytes injury via BDNF/PI3K/Akt/CREB pathway.

Geum japonicum Tunb. var. chinense (GJ) is a traditional Chinese medicine usually used for the alleviation of dizziness and headache. Previous studies have reported that the GJ extracts could alleviate cerebral I/R injury by reducing apoptosis in vivo. To further elucidate the positive role and underlying mechanism of the GJ extracts in cerebral I/R injury, the current study investigated the effects of the GJ extracts on oxygen-glucose deprivation and re-oxygenation (OGD/R)-induced astrocytes injury in light of BDNF/PI3K/Akt/CREB signaling pathway with seropharmacological method. In the present study, the LC-MS profiling of the GJ extracts, obtain by reflux extraction, led to the identification of three possible active components were 5-desgalloylstachyurin, tellimagrandin II (TG II) and 3,4,5-Trihydroxybenzaldehyde (THBA). Drug-containing serum was collected from rats given different doses of the GJ extracts (0, 1.75 g/kg, 7 g/kg). Data indicated that the GJ extracts could increase the cell viability and decrease apoptosis and the expression of glial fibrillary acidic protein (GFAP) in OGD/R-induced astrocytes. In addition, the detection of apoptosis-related factors showed that the GJ extracts could obviously increase the expression of Bcl-2 and reduce the expression of Bax, Caspase-3 and cleaved-Caspase-3. Furthermore, the GJ extracts markedly increased the expression of BDNF, TrkB, PI3K, p-Akt and p-CREB. All these effects of the GJ extracts could be significantly reversed by LY294002, an inhibitor of PI3K. These data indicated that the GJ extracts could protect astrocytes against OGD/R-induced injury by inhibiting astrocytes reactivity and apoptosis, owing to the activation of the BDNF/PI3K/Akt/CREB pathway. The results support the application of the GJ extracts in the treatment of ischemic stroke and other ischemic encephalopathy.

Thrombin-induced miRNA-24-1-5p upregulation promotes angiogenesis by targeting prolyl hydroxylase domain 1 in intracerebral hemorrhagic rats.

OBJECTIVE: Thrombin is a unique factor that triggers post-intracerebral hemorrhage (ICH) angiogenesis by increasing hypoxia-inducible factor-1α (HIF-1α) at the protein level. However, HIF-1α mRNA remains unchanged. MicroRNAs (miRNAs) mediate posttranscriptional regulation by suppressing protein translation from mRNAs. This study aimed to determine if miRNAs might be involved in thrombin-induced angiogenesis after ICH by targeting HIF-1α or its upstream prolyl hydroxylase domains (PHDs). METHODS: The study was divided into two parts. In part 1, rats received an injection of thrombin into the right globus pallidus. An miRNA array combined with miRNA target prediction, luciferase activity assay, and miRNA mimic/inhibitor transfection were used to identify candidate miRNAs and target genes. Part 2 included experiments 1 and 2. In experiment 1, rats were randomly divided into the sham group, ICH group, and ICH+hirudin-treated (thrombin inhibitor) group. In experiment 2, the rats were randomly divided into the sham group, ICH group, ICH+antagomir group, ICH+antagomir-control group, and ICH+vehicle group. Western blotting and quantitative real-time polymerase chain reaction were used to determine the expression of protein and miRNA, respectively. The coexpression of miR-24-1-5p (abbreviated to miR-24) and von Willebrand factor was detected by in situ hybridization and immunohistochemical analysis. The angiogenesis was evaluated by double-labeling immunofluorescence. Neurological function was evaluated by body weight, modified Neurological Severity Scores, and corner turn and foot-fault tests. RESULTS: In part 1, it was shown that miR-24, which is predicted to target PHD1, was upregulated (fold-change of 1.83) after thrombin infusion, and that the miR-24 mimic transfection decreased luciferase activity and downregulated PHD1 expression (p < 0.05). miR-24 inhibitor transfection increased PHD1 expression (p < 0.05). In part 2, it was shown that miR-24 was expressed in endothelial cells. The HIF-1α protein level and proliferating cell nuclear antigen-positive (PCNA+) nuclei in vessels were increased, while the PHD1 protein level was decreased after ICH, and these effects were reversed by hirudin (p < 0.05). The antagomiR-24-treated rats exhibited a markedly lower body weight and significantly poorer recovery from neurological deficit compared with those in ICH groups (p < 0.05). AntagomiR-24 intervention also led to lower miR-24 expression, a higher PHD1 protein level, and fewer PCNA+ nuclei in vessels compared with those in ICH groups (p < 0.05). CONCLUSIONS: The present study suggests that thrombin reduces HIF-1α degradation and initiates angiogenesis by increasing miR-24, which targets PHD1 after ICH.

Clinical characteristics and association analysis of persistent low-level HBsAg expression in a physical examination population with HBV infection.

Certain patients with hepatitis B virus (HBV) infection present with persistently low levels of serum hepatitis B surface antigen (HBsAg) and have been indicated to have low rates of HBV nucleic acid replication. To explore the serological and molecular epidemiological characteristics of HBV population with low-level HBsAg in the present study, associated serum markers and virologic genotype detection were performed accordingly. Determination of HBV markers was performed using a chemiluminescence immunoassay from which 2,544 out of 45,256 adults who underwent routine health examination were tested positive for HBsAg. HBV DNA was detected by real-time fluorescent quantitative PCR. The patients were divided into low-level and high-level groups, according to their HBsAg levels (cut-off value, 10 IU/ml). The prevalence and levels of HBsAg positivity and HBV DNA in patients with HBV infection were analyzed by age, sex, serological pattern and clinical type. The fibrosis status of patients with low-level HBsAg was assessed by determining the aspartate aminotransferase-to-platelet ratio (APRI), and sequencing was employed to determine serotypes and genotypes. HBV-infected patients with low-level HBsAg (<10 IU/ml) accounted for 15.41% of the 2,544 HBsAg-positive patients, and the prevalence of HBsAg positivity exhibited a tendency to increase with age. The male-to-female ratio was ~1.9:1, and the average age was 54.98±16.28 years among HBV-infected patients with low-level HBsAg. The major serological pattern and clinical types were HBsAg/antibody against hepatitis Be antigen (anti-HBe)/antibody against hepatitis B core antigen (anti-HBc)-positive (94.90%) and chronic asymptomatic (ASC) (97.95%), respectively. HBV DNA exhibited a low-level of replication and the prevalence of HBV DNA positivity assessed by the routine method and by the enrichment method was 27.74% (97/392) and 45.92% (180/392), respectively. No significant differences among the age groups were identified in the different HBsAg level groups (P>0.05). The prevalence of HBV DNA positivity was associated with HBsAg only in patients with serological pattern HBV-M2 (HBsAg/anti-HBe/anti-HBc-positive) in the low-level HBsAg group (odds ratio: 1.30; 95% CI: 1.15-1.47; P<0.05). The APRI had no association with age, HBsAg, HBV DNA level or liver function index in ASC patients in the low-level HBsAg group (P>0.05). The prevalence of the serotype adw and genotype B was 85.53 and 89.47%, respectively. Further improvement in the systematic study of populations with low-level HBsAg has important clinical and epidemiological significance for improving the detection of HBV serological markers, elucidating the mechanisms leading to low-level HBsAg, overcoming immune tolerance to eliminate HBV infection and preventing HBV transmission.

Leukemia Inhibitory Factor Decreases Neurogenesis and Angiogenesis in a Rat Model of Intracerebral Hemorrhage.

Neurogenesis and angiogenesis can improve the neurologic function after intracerebral hemorrhage (ICH). Leukemia inhibitory factor (LIF) plays an important role in neurogenesis and angiogenesis. In this study, a rat model of autologous blood-induced ICH was used to evaluate the effect of LIF on the neurogenesis and angiogenesis following ICH. After ICH, LIF-positive neurons and dilated vessels were detected in the peri-hematomal region. It was found that LIF levels increased significantly and peaked 14 days after ICH induction. Double immunofluorescence confirmed that LIF was expressed in neurons and endothelial cells. ICH also led to increases of doublecortin (DCX)- and von Willebrand factor (vWF)-positive cells as well as proliferation of cell nuclear antigen (PCNA)+/DCX+ and PCNA+/vWF+ nuclei. All these ICH-induced increases were significantly attenuated by exogenous LIF infusion. These data suggested that LIF was a negative regulator of neurogenesis and angiogenesis after ICH.

Simultaneous Electrochemical Deposition of Cobalt Complex and Poly(pyrrole) Thin Films for Supercapacitor Electrodes.

Supercapacitors are beneficial as energy storage devices and can obtain high capacitance values greater than conventional capacitors and high power densities compared to batteries. However, in order to improve upon the overall cost, energy density, and charge-discharge rates, the electrode material of supercapacitors needs to be fine-tuned with an inexpensive, high conducting source. We prepared a Co(III) complex and polypyrrole (PPy) composite thin films (CoN4-PPy) that was electrochemically deposited on the surface of a glassy carbon working electrode. Cyclic voltammetry studies indicate the superior performance of CoN4-PPy in charge storage in acidic electrolyte compared to alkaline and organic solutions. The CoN4-PPy material generated the highest amount of specific capacitance (up to 721.9 F/g) followed by Co salt and PPy (Co-PPy) material and PPy alone. Cyclic performance studies showed the excellent electrochemical stability of the CoN4-PPy film in the acidic medium. Simply electrochemically depositing an inexpensive Co(III) complex with a high electrically conducting polymer of PPy delivered a superior electrode material for supercapacitor applications. Therefore, the results indicate that novel thin films derived from Co(III) metal complex and PPy can store a large amount of energy and maintain high stability over many cycles, revealing its excellent potential in supercapacitor devices.