Bridging Flocculation of a Sterically Stabilized Cationic Latex as a Biosensor for the Detection of Microbial DNA after Amplification via PCR.

There is a high demand for rapid, sensitive, and accurate detection methods for pathogens. This paper demonstrates a method of detecting the presence of amplified DNA from a range of pathogens associated with serious infections including Gram-negative bacteria, Gram-positive bacteria, and viruses. DNA is amplified using a polymerase chain reaction (PCR) and consequently detected using a sterically stabilized, cationic polymer latex. The DNA induces flocculation of this cationic latex, which consequently leads to rapid sedimentation and a visible change from a milky-white dispersion to one with a transparent supernatant, presenting a clear visible change, indicating the presence of amplified DNA. Specifically, a number of different pathogens were amplified using conventional or qPCR, including Staphylococcus aureus, Escherichia coli, and Herpes Simplex Virus (HSV-2). This method was demonstrated to detect the presence of bacteria in suspension concentrations greater than 380 CFU mL-1 and diagnose the presence of specific genomes through primer selection, as exemplified using methicillin resistant and methicillin susceptible Staphylococcus aureus. The versatility of this methodology was further demonstrated by showing that false positive results do not occur when a PCR of fungal DNA from C. albicans is conducted using bacterial universal primers.

From ZnF2 to ZnF2(H2O)4: Partial Substitution Achieves Structural Transformation and Nonlinear Optical Activity while Keeping Short Ultraviolet Cutoff Edge.

Exploring nonlinear optical (NLO) materials with short ultraviolet cutoff edges are significant for developing an all-solid-state laser. Here, a noncentrosymmetric zinc fluoride hydrate, ZnF2(H2O)4, was synthesized by a hydrothermal method. It crystallizes in the polar space group of Pca21. The compound consists of the central Zn2+ combined with F- and coordination water to form the [ZnF2(H2O)4] octahedra, and each octahedron is isolated from each other to form a 0-dimensional structure. As an acentric compound, ZnF2(H2O)4 shows a phase-matchable second-harmonic-generation (SHG) activity with an intensity about 0.5 times that of KH2PO4. More attractively, it also shows a short ultraviolet cutoff edge below 200 nm, which is rare in reported halide hydrate systems. Interestingly, from ZnF2 to ZnF2(H2O)4, the partial substitution of the coordinated F atoms by H2O molecules leads to the structural transformation from centric to acentric with SHG activity off to on. Structural analyses, NLO activity, and theoretical calculations are presented in this work.

Management of experimental trabeculectomy filtering blebs via crosslinking of the scleral flap inhibited vascularization.

PURPOSE: The aim of this study was to evaluate whether UVA-light-activated riboflavin-induced collagen crosslinking (UVA-CXL) can maintain the function of filtering blebs after trabeculectomy (TRAB) in rabbits. METHODS: Thirty-six healthy rabbits were randomized to one of the following groups with 12 rabbits in each group: Trabeculectomy group (TRAB group), trabeculectomy combined with CXL group (CXL group), and trabeculectomy combined with MMC group (MMC group). Six rabbits of each group were performed with intraocular pressure (IOP), optical coherence tomography (OCT), and OCT angiography (OCTA). Bleb structure was observed via hematoxylin & eosin (H&E) and Masson staining. Immunohistochemistry, proteomic study, western blot, and tensile test were performed between CXL group and the control. In vitro, cell viability was evaluated by CCK-8 and Calcein/PI staining. TRPV4 and VEGF-a expression levels were measured by Q-PCR. Ca2+ concentration was observed with Fluo-4 AM. RESULTS: The IOP and bleb median survival day were significantly modified in CXL (5.92 ± 0.32 mmHg and 15.5 days) than TRAB group (7.50 ± 0.43 mmHg and 9 days). The bleb area and height increased. CXL inhibited vascularization, and vascularization peaked at postoperative day (POD) 14 and then decreased gradually. In proteomic analyses, Z disc, actin filament binding, and sarcomere organization were significantly enriched. CXL inhibited scleral stress‒strain in tensile tests. Compared with TRAB group, TRPV4 expression was significantly increased, but VEGF-a and TGF-ß1 levels were reduced in the CXL group in western blot. Meanwhile, TRPV4 expression colocalized with CD31. In vitro, CXL inhibited HUVECs cell viability. After CXL, expression level of TRPV4 was increased and calcium influx was activated, but VEGF-a was decreased in HUVECs. CONCLUSIONS: This study demonstrates that intraoperative UV-RF CXL can significantly improve the success rate of TRAB via inhibiting filtering bleb vascularization. CXL increased sclera stiffness, in turn, induced TRPV4 activation, thus contributing to vascular endothelial cells suppression.

Mining Real-World Big Data to Characterize Adverse Drug Reaction Quantitatively: Mixed Methods Study.

BACKGROUND: Adverse drug reactions (ADRs), which are the phenotypic manifestations of clinical drug toxicity in humans, are a major concern in precision clinical medicine. A comprehensive evaluation of ADRs is helpful for unbiased supervision of marketed drugs and for discovering new drugs with high success rates. OBJECTIVE: In current practice, drug safety evaluation is often oversimplified to the occurrence or nonoccurrence of ADRs. Given the limitations of current qualitative methods, there is an urgent need for a quantitative evaluation model to improve pharmacovigilance and the accurate assessment of drug safety. METHODS: In this study, we developed a mathematical model, namely the Adverse Drug Reaction Classification System (ADReCS) severity-grading model, for the quantitative characterization of ADR severity, a crucial feature for evaluating the impact of ADRs on human health. The model was constructed by mining millions of real-world historical adverse drug event reports. A new parameter called Severity_score was introduced to measure the severity of ADRs, and upper and lower score boundaries were determined for 5 severity grades. RESULTS: The ADReCS severity-grading model exhibited excellent consistency (99.22%) with the expert-grading system, the Common Terminology Criteria for Adverse Events. Hence, we graded the severity of 6277 standard ADRs for 129,407 drug-ADR pairs. Moreover, we calculated the occurrence rates of 6272 distinct ADRs for 127,763 drug-ADR pairs in large patient populations by mining real-world medication prescriptions. With the quantitative features, we demonstrated example applications in systematically elucidating ADR mechanisms and thereby discovered a list of drugs with improper dosages. CONCLUSIONS: In summary, this study represents the first comprehensive determination of both ADR severity grades and ADR frequencies. This endeavor establishes a strong foundation for future artificial intelligence applications in discovering new drugs with high efficacy and low toxicity. It also heralds a paradigm shift in clinical toxicity research, moving from qualitative description to quantitative evaluation.

Na2 CeF6 : A Highly Laser Damage-Tolerant Double Perovskite Type Ce(IV) Fluoride Exhibiting Strong Second-Harmonic Generation Effect.

Perovskite structure compounds are significant candidates for designing new optical function materials due to their structural variability. Here, an inorganic tetravalent cerium fluoride, Na2 CeF6 , is derived from the perovskite structure through double-site cation co-substitution. Na2 CeF6 crystalizes in the non-centrosymmetric space group P 6 ¯ 2 m ${P}^{\bar{6}}2m$ . Edge-sharing connected NaF9 and CeF9 polyhedra build the whole 3D structure of Na2 CeF6 . Importantly, it represents the first Ce(IV) fluoride nonlinear optical (NLO) crystal and can produce a strong and phase-matchable second-harmonic generation (SHG) effect of ≈2.1 times that of KH2 PO4 (KDP), making it the strongest among non-lone pair electron metal fluoride system. Further, it exhibits a high laser-induced damage threshold (LIDT) of 74.65-76.25 MW cm-2 , which is over 20 times that of AgGaS2 . It also exhibits a wide transparent region (0.5-14.3 µm). This work provides a facile route for exploring high-performance halide NLO materials.

TcpC inhibits toll-like receptor signaling pathway by serving as an E3 ubiquitin ligase that promotes degradation of myeloid differentiation factor 88.

TcpC is a virulence factor of uropathogenic E. coli (UPEC). It was found that TIR domain of TcpC impedes TLR signaling by direct association with MyD88. It has been a long-standing question whether bacterial pathogens have evolved a mechanism to manipulate MyD88 degradation by ubiquitin-proteasome pathway. Here, we show that TcpC is a MyD88-targeted E3 ubiquitin ligase. Kidney macrophages from mice with pyelonephritis induced by TcpC-secreting UPEC showed significantly decreased MyD88 protein levels. Recombinant TcpC (rTcpC) dose-dependently inhibited protein but not mRNA levels of MyD88 in macrophages. Moreover, rTcpC significantly promoted MyD88 ubiquitination and accumulation in proteasomes in macrophages. Cys12 and Trp106 in TcpC are crucial amino acids in maintaining its E3 activity. Therefore, TcpC blocks TLR signaling pathway by degradation of MyD88 through ubiquitin-proteasome system. Our findings provide not only a novel biochemical mechanism underlying TcpC-medicated immune evasion, but also the first example that bacterial pathogens inhibit MyD88-mediated signaling pathway by virulence factors that function as E3 ubiquitin ligase.

PE (0:0/14:0), an endogenous metabolite of the gut microbiota, exerts protective effects against sepsis-induced intestinal injury by modulating the AHR/CYP1A1 pathway.

Sepsis is known to cause damage to the intestinal mucosa, leading to bacterial translocation, and exacerbation of both local and remote organ impairments. In the present study, fecal samples were collected from both septic and healthy individuals. Analysis through 16s rRNA sequencing of the fecal microbiota revealed that sepsis disrupts the balance of the gut microbial community. Recent research has highlighted the association of lipid metabolism with disease. By analyzing the fecal metabolome, four lipid metabolites that showed significant differences between the two groups were identified: PE (O-16:0/0:0), PE (17:0/0:0), PE (0:0/14:0), and PE (12:0/20:5 (5Z, 8Z, 11Z, 14Z, 17Z)). Notably, the serum levels of PE (0:0/14:0) were higher in the healthy group. Subsequent in vitro and in vivo experiments demonstrated the protective effects of this compound against sepsis-induced intestinal barrier damage. Label-free proteomic analysis showed significant differences in the expression levels of the aryl hydrocarbon receptor (AHR), a protein implicated in sepsis pathogenesis, between the LPS-Caco-2 and LPS-Caco-2 + PE (0:0/14:0) groups. Further analysis, with the help of Discovery Studio 3.5 software and co-immunoprecipitation assays, confirmed the direct interaction between AHR and PE (0:0/14:0). In the cecal ligation and puncture (CLP) model, treatment with PE (0:0 /14:0) was found to up-regulate the expression of tight junction proteins through the AHR/Cytochrome P450, family 1, subfamily A, and polypeptide 1 (CYP1A1) pathway. This highlights the potential therapeutic use of PE (0:0/14:0) in addressing sepsis-induced intestinal barrier damage.

3D printable, thermo-responsive, self-healing, graphene oxide containing self-assembled hydrogels formed from block copolymer wormlike micelles.

Graphene oxide (GO) containing block copolymer nanocomposite hydrogels formed from poly(glycerol monomethacrylate-block-hydroxypropyl methacrylate) (PGMA-PHPMA) wormlike micelles were prepared by either mixing GO and copolymer at low temperature or via in situ reversible addition-fragmentation chain-transfer (RAFT) polymerisation-induced self-assembly (PISA) of HPMA in the presence of a PGMA macromolecular chain-transfer agent and GO flakes. Hydrogels containing 15-25% w/w copolymer and 0 and 8% w/w GO, based on copolymer, were investigated and the maximum gel strength measured was ∼33 kPa for a 25% w/w copolymer gel prepared by in situ polymerisation and containing 2% w/w GO based on copolymer. This gel strength represents a fifteen-fold increase over the same copolymer gel without the addition of GO. The nanocomposite gels were found to recover efficiently after the application of high shear, with up to 98% healing efficiency within seconds. These gels are also 3D printable, self-healing, adhesive and temperature responsive on cooling and re-heating. The observed properties were both GO and copolymer concentration dependent, and tensile testing demonstrated that the nanocomposite gels had higher moduli, elongation at break and toughness than gels prepared without GO.

Dihydroartemisinin inhibits melanoma migration and metastasis by affecting angiogenesis.

Tumor angiogenesis is critical for tumor metastasis by providing oxygen, nutrients, and metastatic pathways. As a potential anti-angiogenic agent, Dihydroartemisinin (DHA) can effectively inhibit tumor metastasis. However, the mechanism how it regulates angiogenesis to affect tumor metastasis has not been fully clarified. To investigate the mechanisms of how DHA regulates melanoma progression. In this study, bioinformatics methods were used to analyze the correlation between angiogenesis and melanoma metastasis. Then, B16F10, A375, HUVECs and mouse metastasis models were adapted to clarify the inhibition of DHA in melanoma. GESA analysis revealed melanoma metastasis significantly positive correlated with angiogenesis. Meanwhile, DHA significantly decreased melanoma nodules and lung wet weight in metastatic tumor mice, and inhibited the expression of the angiogenic marker CD31 in vitro and in vivo. Similarly, DHA inhibited the expression of the angiogenic signal molecule VEGFR2 in A375 and B16F10 cells, and significantly suppressed the formation of their tubular structures. DHA-treated supernatants significantly inhibited the tubule-forming ability as well as lateral and longitudinal migration ability of HUVECs compared with untreated melanoma cell supernatants. Screening yielded the angiogenic pathways HIF-1α/VEGF, PI3K/ATK/mTOR associated with melanoma metastasis, and DHA may inhibit tumor metastasis by inhibiting these angiogenic pathways in melanoma cells to inhibit tumor metastasis. Further non-targeted metabolomics analysis revealed that DHA-treated model mice produced differential metabolites that were also associated with angiogenic pathways. DHA inhibits melanoma invasion and metastasis by mediating angiogenesis. These results have important implications for the potential use of DHA in treatment of melanoma.

Chinese Expert Consensus on the Use of Biologics in Patients with Chronic Rhinosinusitis (2022, Zhuhai).

BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. SUMMARY: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. KEY MESSAGES: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.

Development of a Macrophage-Related Risk Model for Metastatic Melanoma.

As a metastasis-prone malignancy, the metastatic form and location of melanoma seriously affect its prognosis. Although effective surgical methods and targeted drugs are available to enable the treatment of carcinoma in situ, for metastatic tumors, the diagnosis, prognosis assessment and development of immunotherapy are still pending. This study aims to integrate multiple bioinformatics approaches to identify immune-related molecular targets viable for the treatment and prognostic assessment of metastatic melanoma, thus providing new strategies for its use as an immunotherapy. Immunoinfiltration analysis revealed that M1-type macrophages have significant infiltration differences in melanoma development and metastasis. In total, 349 genes differentially expressed in M1-type macrophages and M2-type macrophages were extracted from the MSigDB database. Then we derived an intersection of these genes and 1111 melanoma metastasis-related genes from the GEO database, and 31 intersected genes identified as melanoma macrophage immunomarkers (MMIMs) were obtained. Based on MMIMs, a risk model was constructed using the Lasso algorithm and regression analysis, which contained 10 genes (NMI, SNTB2, SLC1A4, PDE4B, CLEC2B, IFI27, COL1A2, MAF, LAMP3 and CCDC69). Patients with high+ risk scores calculated via the model have low levels of infiltration by CD8+ T cells and macrophages, which implies a poor prognosis for patients with metastatic cancer. DCA decision and nomogram curves verify the high sensitivity and specificity of this model for metastatic cancer patients. In addition, 28 miRNAs, 90 transcription factors and 29 potential drugs were predicted by targeting the 10 MMIMs derived from this model. Overall, we developed and validated immune-related prognostic models, which accurately reflected the prognostic and immune infiltration characteristics of patients with melanoma metastasis. The 10 MMIMs may also be prospective targets for immunotherapy.

[Mendelian randomization of diabetes and prostate cancer risk in East Asian population].

OBJECTIVE: Mendelian randomization (MR) was used to explore the causal relationship between diabetes (type 1 and type 2) and prostate cancer (PCa) in East Asian population. METHODS: Mendelian randomization is a causal inference method based on genetic variation, which uses the influence of randomly assigned genotypes in nature on phenotype to infer the impact of biological factors on diseases. This study used genetic variation genes related to inflammatory biomarkers as instrumental variables to improve inference, and patient data was obtained from the GWAS database's aggregated association results. In the individual sample, we estimated the correlation between instrumental variables (SNPs) and type 1 and type 2 diabetes, and screened out strongly related SNPs, and excluded SNPs related to prostate cancer. After screening, further sensitivity analysis and visualization of research results were carried out to test the blood glucose level and the causal relationship between diabetes and prostate cancer. RESULTS: Our MR analysis found that there was a negative causal relationship between the risk of prostate cancer and type 2 diabetes.The ratio of type 2 diabetes to prostate cancer causal relationship (OR)=1.0039, 95% confidence interval (CI)=(1.0008, 1.0071), P=0.013, while type 1 diabetes had fewer SNPs screened, Failed to conduct relevant follow-up analysis. CONCLUSIONS: Under Mendel's randomization hypothesis, our research results show that in the East East Asian population, the gene predicted type 2 diabetes and the occurrence of prostate cancer have a negative causal relationship, while the causal relationship between type 1 diabetes and prostate cancer is unknown due to the limited number of instrumental variables.

Oxygen Free Radical Scavenger PtPd@PDA as a Dual-Mode Quencher of Electrochemiluminescence Immunosensor for the Detection of AFB1.

Here, a dual-mode quenched electrochemiluminescence (ECL) immunosensor based on PtPd@PDA was proposed. Among them, nitrogen-doped hydrazide conjugated carbon dots (NHCDs), as an ECL emitter and a donor of resonance energy transfer, were quenched by PtPd@PDA (receptor). At the same time, PDA in PtPd@PDA, as an oxygen radical scavenger, completed the further quenching of the ECL signal by consuming O2•- generated by the decomposition of co-reactant H2O2. The dual-mode quenching from the above two channels was achieved. In addition, compared with the traditional carbon quantum dots, NHCDs as ECL emitters had lower excitation potential. Moreover, a large number of amino groups provided by aminated MWCNTs could capture more antibodies while connecting with NHCDs. Under the optimum experimental conditions, taking aflatoxin B1 as the target, the proposed sensor with good specificity, stability, and reproducibility had good linearity when the concentration of AFB1 was 0.01-100 ng/mL, with the detection limit of 2.63 pg/mL (S/N = 3). This strategy provided more possibilities for the application of dopamine metal nanocomposites in electrochemiluminescence analysis and offered a new approach to detect AFB1.

The interleukin-enhanced binding factor 3-mediated inhibition of nitric oxide production via phosphoinositide 3-kinase/protein kinase B pathway contributes to central cardiovascular regulation in the rostral ventrolateral medulla in hypertension.

Hypertension is characterized by sympathetic hyperactivity, which is related to the overexcitation of the presympathetic neurons in the rostral ventrolateral medulla (RVLM). Nitric oxide (NO) has been reported to be a vital neuromodulator involved in central cardiovascular regulation. However, the mechanism of interleukin-enhanced binding factor 3 (ILF3) participating in blood pressure (BP) regulation is still unclear. Therefore, this study aims to clarify the role of ILF3 within the rostral ventrolateral medulla (RVLM) in regulating NO in hypertension. It was found that the expression level of ILF3 was significantly increased in the RVLM of spontaneously hypertensive rats (SHR) compared with Wistar-Kyoto (WKY) rats through microarray gene expression analysis, Western blot, and immunofluorescence. Overexpression of ILF3 by injecting constructed adenovirus into the RVLM increased the BP and renal sympathetic nerve activity (RSNA) of the WKY rats, significantly decreasing NO production and neuronal nitric oxide synthase (nNOS) expression. Knockdown of ILF3 in the RVLM of SHR significantly reduced BP but increased NO production and the neuronal nitric oxide synthase (nNOS) expression. Furthermore, it was found that the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway was activated via Western blotting in the RVLM after overexpression of ILF3, whereas it was attenuated after knockdown of ILF3 in SHR. In addition, inhibition of PI3K by intracisternal infusion of the PI-103 attenuated the increase in Akt phosphorylation and decrease in nNOS expression and NO production caused by overexpressing ILF3, which ultimately blunted high BP induced by overexpressing ILF3. Taken together, this current study suggests that ILF3 participates in high BP via reducing NO production in the RVLM through PI3K/Akt pathway.

Physical Adsorption of Graphene Oxide onto Polymer Latexes and Characterization of the Resulting Nanocomposite Particles.

Polymer/graphene oxide (GO) nanocomposite particles were prepared via heteroflocculation between 140-220 nm cationic latex nanoparticles and anionic GO nanosheets in either acidic or basic conditions. It is demonstrated that nanocomposite particles can be formed using either poly(2-vinylpyridine)-b-poly(benzyl methacrylate) (P2VP-PBzMA) block copolymer nanoparticles prepared by reversible-addition chain-transfer (RAFT)-mediated polymerization-induced self-assembly (PISA), or poly(ethylene glycol)methacrylate (PEGMA)-stabilized P2VP latexes prepared by traditional emulsion polymerization. These two latexes are different morphologically as the P2VP-PBzMA block copolymer latexes have P2VP steric stabilizer chains in their corona, whereas the PEGMA-stabilized P2VP particles have a P2VP core and a nonionic steric stabilizer. Nevertheless, both the P2VP-PBzMA and PEGMA-stabilized P2VP latexes are cationic at low pH. Thus, the addition of GO to these latexes causes flocculation to occur immediately due to the opposite charges between the anionic GO nanosheets and cationic latexes. Control heteroflocculation experiments were conducted using anionic sterically stabilized poly(potassium 3-sulfopropyl methacrylate)-b-poly(benzyl methacrylate) (PKSPMA-PBzMA) and nonionic poly(benzyl methacrylate) (PBzMA) nanoparticles to demonstrate that polymer/GO nanocomposite particles were not formed. The degree of flocculation and the strength of electrostatic interaction between the cationic polymer latexes and GO were assessed using disc centrifuge photosedimentometry (DCP), transmission electron microscopy (TEM), and UV-visible spectrophotometry. These studies suggest that the optimal conditions for the formation of polymer/GO nanocomposite particles were GO contents between 10% and 20% w/w relative to latex, with the latexes containing P2VP in their corona having a stronger electrostatic attraction to the GO sheets.

Preparation and characterisation of graphene oxide containing block copolymer worm gels.

This paper reports a generic method for preparing reinforced nanocomposite worm-gels. Aqueous poly(glycerol monomethacrylate)-b-poly(2-hydroxypropyl methacrylate) (PGMA-PHPMA) and methanolic poly(glycerol monomethacrylate)-b-poly(benzyl methacrylate) (PGMA-PBzMA) worm gels were prepared by RAFT-mediated polymerisation-induced self-assembly (PISA). The former system undergoes a reversible worm-to-sphere degelation transition upon cooling to 5 °C whilst the latter system undergoes the same transition on heating to 56 °C. This transition allows these copolymer dispersions to be readily mixed with graphene oxide (GO) whilst in a low viscosity state and form nanocomposite gels on returning to room temperature via a sphere-to-worm transition. Various quantities of GO were added to the studied copolymer dispersions at a fixed copolymer content of 15% w/w. A general trend was observed whereby relatively small quantities of GO caused the gel strength of the nanocomposite gel to be higher than that of the pristine worm-gel, as determined by oscillatory rheology. Additional quantities of GO resulted in gel weakening or prevented gel-reformation altogether. For instance, 15% w/w PGMA52-PHPMA130 worm gels had a storage modulus (G') of approximately 1.5 kPa. The addition of 1.5% w/w GO based on the copolymer caused G' to increase to approximately 4.0 kPa but >1.5% w/w GO resulted in gel strengths <1.0 kPa. A combination of aqueous electrophoresis and transmission electron microscopy measurements were used to investigate the mechanism of nanocomposite gel formation. It was observed that the PGMA-based copolymers readily absorb onto the surface of GO. Thus, the role of GO is both to strengthen the worm-gels when an optimal concentration of GO is used, but also prevent worm-reformation if too much copolymer becomes absorbed on the surface of the sheets.

Contrast-enhanced CT findings-based model to predict MVI in patients with hepatocellular carcinoma.

BACKGROUND: Microvascular invasion (MVI) is important in early recurrence and leads to poor overall survival (OS) in hepatocellular carcinoma (HCC). A number of studies have reported independent risk factors for MVI. In this retrospective study, we designed to develop a preoperative model for predicting the presence of MVI in HCC patients to help surgeons in their surgical decision-making and improve patient management. PATIENTS AND METHODS: We developed a predictive model based on a nomogram in a training cohort of 225 HCC patients. We analyzed patients' clinical information, laboratory examinations, and imaging features from contrast-enhanced CT. Mann-Whitney U test and multiple logistic regression analysis were used to confirm independent risk factors and develop the predictive model. Internal and external validation was performed on 75 and 77 HCC patients, respectively. Moreover, the diagnostic performance of our model was evaluated using receiver operating characteristic (ROC) curves. RESULTS: In the training cohort, maximum tumor diameter (> 50 mm), tumor margin, direct bilirubin (> 2.7 µmol/L), and AFP (> 360.7 ng/mL) were confirmed as independent risk factors for MVI. In the internal and external validation cohort, the developed nomogram model demonstrated good diagnostic ability for MVI with an area under the curve (AUC) of 0.723 and 0.829, respectively. CONCLUSION: Based on routine clinical examinations, which may be helpful for clinical decision-making, we have developed a nomogram model that can successfully assess the risk of MVI in HCC patients preoperatively. When predicting HCC patients with a high risk of MVI, the surgeons may perform an anatomical or wide-margin hepatectomy on the patient.

Can C1 lateral mass and C3 pedicle screw fixation be used as an option for atlantoaxial reduction and stabilization in Klippel-Feil patients? A study of its morphological feasibility, technical nuances, and clinical efficiency.

In Klippel-Feil patients with atlantoaxial dislocation, narrow C2 pedicles are often encountered preventing pedicle screw placement. Alternative techniques, including translaminar screws, pars screws, and inferior process screws could not achieve 3-column rigid fixation, and have shown inferior biomechanical stability. The present study aimed to evaluate the feasibility, safety, and efficacy of C3 pedicle screws (C3PSs) as an option for atlantoaxial stabilization in Klippel-Feil patients, and to introduce a freehand technique, the "medial sliding technique," for safe and accurate C3PS insertion. Thirty-seven Klippel-Feil patients with congenital C2-3 fusion who have received atlantoaxial fixation were reviewed. Preoperative CT and CT angiography were acquired to evaluate the feasibility of C3PS placement. C1 lateral mass and C3PS constructs were used for atlantoaxial stabilization. The "medial sliding technique" was introduced to facilitate C3PS insertion. Clinical outcomes and complications were evaluated, and screw accuracy was graded on postoperative CT scans. Morphological measurements showed that more than 80% C3 pedicles could accommodate a 3.5-mm screw. Fifty-eight C3PSs were placed in 33/37 patients using the medial sliding technique. Overall, 96.7% screws were considered safe and there was no related neurovascular complications; 27/33 patients exhibited neurological improvement and 30/33 patients had a solid bone fusion at an average 19.3-month follow-up. Therefore, the C3PS was a feasible option for atlantoaxial fixation in Klippel-Feil patients. The clinically efficiency of C3PS was satisfied with high fusion rates and low complications. The medial sliding technique we used could facilitate safe and accurate placement of C3PSs in Klippel-Feil patients with fused C2-3 vertebra.

Ratiometric electrochemical immunoassay for procalcitonin based on dual signal probes: Ag NPs and Nile blue A.

In order to determine procalcitonin, a sandwich-type ratiometic electrochemical immunosensor was developed by differential pulse voltammetry (DPV). Due to high chemical stability and good biocompatibility, graphitic carbon nitride (g-C3N4) could be used as feasible supporter to carry silver nanoparticles (Ag NPs) with an obvious oxidative peak (measured typically at + 0.3 V vs. SCE). Ag NPs loaded onto g-C3N4 were not only beneficial to prevent the agglomeration of Ag NPs, but also favorable to improve the electron transfer velocity of g-C3N4. Moreover, the g-C3N4-Ag NPs as the matrix could immobilize primary antibody by Ag-N bond. Nile blue A (NBA), an excellent redox probe based on the redox reaction with two-electrons, provides a current signal at - 0.38 V (vs. SCE). Zr-based metal organic framework (UiO-67), an ideal framework material with large specific surface area and high porosity, could absorb the substantial water-soluble NBA by electrostatic adsorption. The UiO-67 modified by NBA (NBA-UiO-67) owned admirable biocompatibility and was a qualifying marker to load the secondary antibody. For the immunosensor, the current ratio of NBA to Ag NPs (INBA/IAg NPs) was increased as the concentrations of PCT increased. Under the optimum conditions, the linear range of the immunosensor was 0.005 to 50 ng/mL; the detection limit was 1.67 pg/mL (S/N = 3), which reflected the excellent analytical performance of the sensor. The proposed immunosensor strategy is a simple and dependable platform, with great application potential in biometric analysis.

Identification of Novel Hub Genes Associated with Psoriasis Using Integrated Bioinformatics Analysis.

Psoriasis is a chronic, prolonged, and recurrent inflammatory skin disease and the current therapeutics can only alleviate the symptoms rather than cure it completely. Therefore, we aimed to identify the molecular signatures and specific biomarkers of psoriasis to provide novel clues for psoriasis and targeted therapy. In the present study, the Gene Expression Omnibus (GEO) database was used to retrieve three microarray datasets (GSE166388, GSE50790 and GSE42632) and to explore the differentially expressed genes (DEGs) in psoriasis using the Affy package in R software. The gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment were utilized to determine the common DEGs and their capabilities. The STRING database was used to develop DEG-encoded proteins and a protein-protein interaction network (PPI) and the Cytohubba plugin to classify hub genes. Using the NetworkAnalyst platform, we detected transcription factors (TFs), microRNAs and drug candidates interacting with hub genes. In addition, the expression levels of hub genes in HaCaT cells were detected by western blot. We screened the up- and downregulated DEGs from the transcriptome microarrays of corresponding psoriasis patients. Functional enrichment of DEGs in psoriasis was mainly associated with positive regulation of leukocyte cell-cell adhesion and T cell activation, cytokine binding, cytokine activity and the Wnt signaling pathway. Through further data processing, we obtained 57 intersecting genes in the three datasets and probed them in STRING to determine the interaction of their expressed proteins and we obtained the critical 10 hub genes in the Cytohubba plugin, including TOP2A, CDKN3, MCM10, PBK, HMMR, CEP55, ASPM, KIAA0101, ESC02, and IL-1ß. Using these hub genes as targets, we obtained 35 TFs and 213 miRNAs that may regulate these genes and 33 potential therapeutic agents for psoriasis. Furthermore, the expression levels of TOP2A, MCM10, PBK, ASPM, KIAA0101 and IL-1ß were observably increased in HaCaT cells. In conclusion, we identified potential biomarkers, risk factors and drugs for psoriasis.