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.

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.

An Intersectional Study of LncRNAs and mRNAs Reveals the Potential Therapeutic Targets of Buyang Huanwu Decoction in Experimental Intracerebral Hemorrhage.

BACKGROUND/AIMS: Both experimental and clinical studies have revealed satisfactory effects of the traditional Chinese formula Buyang Huanwu decoction (BYHWD) in improving post-intracerebral hemorrhage (ICH) neurological deficiencies. However, the multifaceted mechanisms of BYHWD in ICH treatment are not comprehensively understood. The present study explored various therapeutic targets of BYHWD by using lncRNA and mRNA transcriptomics. METHODS: LncRNA and mRNA microarrays were used to identify differentially expressed genes. ICH-induced upregulated genes (ICH vs sham) and BYHWD-induced downregulated genes (BYHWD vs ICH) were first identified. The intersection between these 2 sets was determined to identify ICH-induced highly expressed genes that were reversed by BYHWD. Then, the genes downregulated after ICH and the genes upregulated after BYHWD treatment were used to generate another set of intersections. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were subsequently performed to determine relative biological functions and signaling transduction pathways according to genes within the intersections. Quantitative real-time PCR was used to validate changes in gene expression observed using the microarray. Finally, a lncRNA-mRNA co-expression network was established to identify links among the genes within the intersections. RESULTS: A total of 18 differentially expressed lncRNAs and 33 differentially expressed mRNAs were identified using 2 lncRNA arrays (ICH vs sham and BYHWD vs ICH). The altered genes were enriched in the hemoglobin complex, oxygen transport and oxygen transporter and were closely associated with pyruvate metabolism. The co-expression network consisted of 53 nodes and 595 connections (308 positive interactions and 287 negative interactions). CONCLUSION: The hemoglobin complex, oxygen transport, oxygen transporter activity and pyruvate metabolism are possible therapeutic targets of BYHWD in ICH treatment. The present study provides the basis and direction for future investigations to explore the mechanisms by which BYHWD protects against long-term neurological deficiencies after ICH.

A Trichromatic and White-Light-Emitting MOF Composite for Multi-Dimensional and Multi-Response Ratiometric Luminescent Sensing.

Present here is a new dual ratiometric luminescent probe D which is a trichromatic and white-light-emitting metal-organic framework (MOF) composite facilely obtained by incorporating red/green-emitting complex modules into a blue-emitting MOF. Probe D exhibits remarkable capabilities of sensing different volatile organic solvents (VOSs) via 2D code recognition of the two VOS-dependent MOF ligand-to-module ratios of the emission-peak intensities. For specific VOSs, the resultant luminescent color changes from the starting white color are sharp enough to be visible to the naked eye. Remarkably, D can differentiate solution-phase nitroaromatics and metal ions by recording the evolution of the two ratios during titration processes, enabling an unusual 3D code recognition using the titrant amount as the third dimension for the first time. D also can be used to detect dinoseb, Fe3+ and Al3+ ions quantitatively by analysis of the ratios with detection limits as low as 0.050, 0.41, and 0.12 ppm, respectively. Clearly, such a self-referencing trichromatic probe can maximize the output information and significantly enhance the detection selectivity and sensitivity via multi-dimensional sensing, and has great potentials for practical applications.

Clinical Characteristics and Correlation Analysis of Subjects with Chronic Hepatitis B Virus (HBV) Infection and Sustained Low Levels of Hepatitis B Surface Antigen (HBsAg).

BACKGROUND The aim of this study was to investigate the clinical characteristics of individuals with chronic hepatitis B virus (HBV) infection with persistent low levels of hepatitis B surface antigen (HBsAg) and to undertake a correlation analysis of the clinical characteristics. MATERIAL AND METHODS The study included 1,204 subjects with chronic HBV infection. Serum HBsAg, HBV envelope antigen (HBeAg), and HBV core antigen (HBcAg) levels were measured using the chemiluminescent microparticle immunoassay (CMIA) and the neutralization test. HBV DNA was measured using real-time fluorescence quantitative polymerase chain reaction (RT-FQ-PCR). RESULTS There were 1,023 subjects in the high-level HBsAg group (HBsAg level ≥10 IU/mL) and 181 subjects in the low-level HBsAg group (HBsAg level <10 IU/mL). In the low-level HBsAg group, the main serological pattern (93.37%) was HBsAg and HBeAg and HBcAg-positive (HBV-M2), and the asymptomatic carrier (ASC) status was 98.34%. The low-level HBsAg group had a lower HBV DNA-positive rate compared with the high-level HBsAg group (40.33% vs. 75.07%), with a normal distribution across all age groups (P>0.05). The low-level HBsAg group included an older age group. A low-level of HBsAg was positively correlated with a low level of replication of HBV DNA (r=0.452). CONCLUSIONS The findings of this study showed that individuals with chronic HBV infection and sustained low-levels of HBsAg were an older population and had a lower level of replicating HBV DNA when compared with individuals with high levels of HBsAg, and the majority (93.7%) were also HBsAg and HBeAg and HBcAg-positive.

Hyperbaric oxygen for experimental intracerebral haemorrhage: Systematic review and stratified meta-analysis.

OBJECTIVE: Hyperbaric oxygen (HBO) is widely used in treating various neurological diseases. However, HBO for treatment of intracerebral haemorrhage (ICH) remains controversial, in either animal or clinical studies. Therefore, we conducted this systematic review and meta-analysis on studies describing the efficacy of HBO in animal models of ICH. METHODS: Studies were identified by searching mainstream databases through November 2015. The efficacy of HBO in animal models of ICH was assessed by changes in the brain water content (BWC), neurobehavioural outcome (NO) or both. Subgroup analyses were performed according to different design characteristics. RESULTS: In total 15 studies met our inclusion criteria. HBO can reduce the BWC (-0.982, 95% CI, -1.148 to -0.817; P < 0.01; 57 comparisons), and improve NO (-0.767, 95% CI, -1.376 to -0.159; P < 0.01; eight comparisons). HBO was most effective in reducing BWC when given 72 h after ICH for a 4- to 5-day consecutive treatment at the chamber pressure of 3.0 atmosphere absolute. Efficacy was higher with phenobarbital anaesthesia, the blood infusion model and in rabbits. CONCLUSION: Although HBO was found to be effective in experimental ICH, additional confirmation is needed due to possible publication bias, poor study quality and the limited number of studies conducting clinical trials.

1-D "Platinum Wire" Stacking Structure Built of Platinum(II) Diimine Bis(σ-acetylide) Units with Luminescence in the NIR Region.

A square-planar platinum(II) complex, Pt(DiBrbpy)(C≡CC6H4Et-4)2 (1) (DiBrbpy = 4,4-dibromo-2,2'-bipyridine), and crystals of its three solvated forms, namely, 1·DMSO, 1·1/2(CH3CN), and 1·1/8(CH2Cl2), were developed and characterized. 1·DMSO and 1·1/2(CH3CN) contain quasi-dimeric and dimeric structures with luminescence in the visible range, whereas 1·1/8(CH2Cl2) exhibits NIR luminescence at 1022 nm due to its intrinsic 1-D "platinum wire" stacking structure with strong Pt-Pt interactions. 1·1/8(CH2Cl2) represents the first compound based on platinum(II) diimine bis(σ-acetylide) molecular units with the NIR luminescence beyond 1000 nm. 1 selectively responds to DMSO and CH3CN by changing its color and luminescence property and the three solvated forms can be reversibly converted to each other upon exposure to corresponding solvent vapors. Their desolvated forms, namely 1a, 1b, and 1c, obtained after heating 1·DMSO, 1·1/2(CH3CN), and 1·1/8(CH2Cl2), respectively, can also be restored to the original solvated forms upon exposure to corresponding solvent vapors. 1a and 1b emit NIR luminescence peaked at 998 and 1018 nm respectively, suggesting indirect synthetic methods as powerful alternatives to achieve NIR luminescence with long wavelength. In contrast, 1c exhibits a red luminescence with a broad unstructured emission band centered at 667 nm. All the responses to organic solvent vapors and heating are due to the structural transformations which result in the conversion of the lowest energy excited states between 3MLCT/3LLCT and 3MMLCT in solid-state as supported by time-dependent density functional theory (TD-DFT) calculations.

Buyang huanwu decoction promotes angiogenesis via vascular endothelial growth factor receptor-2 activation through the PI3K/Akt pathway in a mouse model of intracerebral hemorrhage.

BACKGROUND: Intracerebral hemorrhage (ICH) is a fatal subtype of stroke that lacks effective treatments. Angiogenesis following ICH is an important response mediating brain recovery and repair. Phosphorylation of vascular endothelial growth factor receptor 2 (pVEGFR2) via PI3K/Akt signaling plays a key role in mediating cellular processes involved in repair, such as mitogenesis, angiogenesis, and vascular permeability. This study aimed to investigate the potential effects of Buyang Huanwu Decoction (BYHWD), a traditional Chinese medicine formula, on angiogenesis by VEGFR2 activation through the phosphatidylinositol 3 kinase (PI3K)/Akt signaling pathway in a mouse model of ICH. METHODS: Adult male Kunming mice (n = 50) were randomly assigned into sham and ICH-operated groups and treated with one of the followings SU5416 (VEGFR2 inhibitor), BYHWT and BYHWT + SU5416. ICH was induced in mice by injecting collagenase (type VII) into the right globus pallidus of the mouse brain. BYHWD (4.36 g/kg) was administrated in mice by intragastric infusion. Neurological function was evaluated in mice by a modified Neurological Severity Scores (mNSS) as well as corner turn and foot-fault tests. Angiogenesis was examined by intraperitoneal injection of 5-bromodeoxyuridine (BrdU) in mice to quantify new brain vessel growth. SU5416 treatment and assessment of VEGFR2 phosphorylation as well as alterations in PI3K/Akt signaling were performed to determine whether the effect of BYHWD on angiogenesis was partly mediated by phosphorylation of VEGFR2 via the PI3K/Akt signaling pathway. RESULTS: We show that BYHWD treated mice exhibited (i) significantly better recovery from neurological dysfunction, (ii) increased BrdU(+) nuclei in vWF(+) dilated brain vessels and (iii) higher VEGFR2 phosphorylation immunoreactivity in brain microvessels (P <0.05), (iv) higher expression of PI3K and pAkt at the protein level (P <0.05) when compared to untreated ICH mice. These beneficial effects were reversed by SU5416 (P <0.05). CONCLUSIONS: BYHWD promoted neurological recovery and angiogenesis after ICH in mice by enhancing VEGFR2 phosphorylation through the PI3K/Akt signaling pathway.

Electroacupuncture improves recovery after hemorrhagic brain injury by inducing the expression of angiopoietin-1 and -2 in rats.

BACKGROUND: Angiopoietin (Ang) is one of the major effectors of angiogenesis, playing a critical role in neurovascular remodeling after stroke. Acupuncture has been widely used for treating stroke in China for a long time. Recently, we have demonstrated that electroacupuncture (EA) can accelerate intracerebral hemorrhage (ICH)-induced angiogenesis in rats. In the present study, we investigated the effect of EA on the expression of Ang-1 and Ang-2 in the brain after ICH. METHODS: ICH was induced by stereotactic injection of collagenase type VII into the right globus pallidus. Adult male Sprague-Dawley rats were randomized into the following four groups: sham-operation (SHAM), stroke-no electroacupuncture (SNE), stroke-EA at the Zusanli acupoint (SEZ), and stroke-EA at a nonacupoint (SEN). EA was applied to the bilateral Zusanli (ST36) acupoint in the SEZ group and a nonacupoint in the SEN group. The expression of Ang-1 and Ang-2 was evaluated by immunohistochemistry and quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Some Ang-1 and Ang-2 immunoreactive microvessels with a dilated outline were detected in the perihematomal tissues after ICH, and the vessels extended into the clot from the surrounding area since day 7. The expression of Ang-1 increased notably as long as 2 weeks after ICH, while Ang-2 immunoreactivity declined at about 7 days following a striking upregulation at 3 days. EA at the Zusanli (ST36) acupoint upregulated the expression of Ang-1 and Ang-2 at both the protein and mRNA levels. However, EA at a nonacupoint had little effect on the expression of Ang-1 and Ang-2. CONCLUSIONS: Our data suggest that EA at the Zusanli (ST36) acupoint exerts neuroprotective effects on hemorrhagic stroke by upregulation of Ang-1 and Ang-2.

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.

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.

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.

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.

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.

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.

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).

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.

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.