Utility of enteral nutrition via percutaneous transhepatic cholangiography drainage catheterization in late-stage malignant obstructive jaundice.

Objective: The purpose of this study was to explore the clinical benefits of establishing an enteral nutrition (EN) pathway via percutaneous transhepatic cholangiography drainage (PTCD) catheterization in patients with late-stage malignant obstructive jaundice (MOJ).Methods: We selected 30 patients diagnosed as having late-stage MOJ with malnutrition. A dual-lumen biliary-enteral nutrition tube was placed via PTCD along with a biliary stent implantation. Postoperative EN was provided, and we observed the time taken for tube placement, its success rate, complications, and therapeutic efficacy.Results: Tube placement was successful in all 30 patients with an average procedural time of 5.7 ± 1.4 min with no tube placement complications. Compared to preoperative measures, there was a significant improvement in postoperative jaundice reduction and nutritional indicators one month after the procedure (p < 0.05). Post-placement complications included tube perileakage in 5 cases, entero-biliary reflux in 4 cases, tube blockage in 6 cases, tube displacement in 4 cases, accidental tube removal in 3 cases, and tube replacement due to degradation in 8 cases, with tube retention time ranging from 42 to 314 days, averaging 124.7 ± 37.5 days. All patients achieved the parameters for effective home-based enteral nutrition with a noticeable improvement in their quality of life.Conclusion: In this study, we found that the technique of establishing an EN pathway via PTCD catheterization was minimally invasive, safe, and effective; the tube was easy to maintain; and patient compliance was high. It is, thus, suitable for long-term tube retention in patients with late-stage MOJ.

Manganese-Enriched Zinc Peroxide Functional Nanoparticles for Potentiating Cancer Immunotherapy.

Immunotherapies have shown high clinical success, however, the therapeutical efficacy is largely restrained by insufficient immune activation and an immunosuppressive microenvironment. Herein, we report tumor microenvironment (TME)-responsive manganese-enriched zinc peroxide nanoparticles (MONPs) for synergistic cancer immunotherapy by inducing the immunogenic death (ICD) of cancer cells and activating the stimulator of the interferon gene (STING) pathway. MONPs especially disassociate upon exposure to acidic tumor tissue and in situ generate •OH for the ICD effect. Moreover, Mn2+ activated the STING and synergistically induced the secretion of type I interferon and inflammatory cytokines for specific T cell responses. Meanwhile, MONPs relieved the immunosuppression of TME through decreasing Tregs and polarizing M2 macrophages to the M1 type to unleash a cascade adaptive immune response. In combination with the anti-PD-1 antibody, MONPs showed superior efficacy in inhibiting tumor growth and preventing lung metastasis. Our study demonstrates the feasibility of functional nanoparticles to amplify STING innate stimulation, showing a prominent strategy for cancer immunotherapy.

Harnessing Nanomaterials for Cancer Sonodynamic Immunotherapy.

Immunotherapy has made remarkable strides in cancer therapy over the past decade. However, such emerging therapy still suffers from the low response rates and immune-related adverse events. Various strategies have been developed to overcome these serious challenges. Therein, sonodynamic therapy (SDT), as a non-invasive treatment, has received ever-increasing attention especially in the treatment of deep-seated tumors. Significantly, SDT can effectively induce immunogenic cell death to trigger systemic anti-tumor immune response, termed sonodynamic immunotherapy. The rapid development of nanotechnology has revolutionized SDT effects with robust immune response induction. As a result, more and more innovative nanosonosensitizers and synergistic treatment modalities are established with superior efficacy and safe profile. In this review, the recent advances in cancer sonodynamic immunotherapy are summarized with a particular emphasis on how nanotechnology can be explored to harness SDT for amplifying anti-tumor immune response. Moreover, the current challenges in this field and the prospects for its clinical translation are also presented. It is anticipated that this review can provide rational guidance and facilitate the development of nanomaterials-assisted sonodynamic immunotherapy, helping to pave the way for next-generation cancer therapy and eventually achieve a durable response in patients.

[Design and application of a new type of biliary-intestinal nutrient tube].

The establishment of a nutritional pathway is the premise and basis of nutritional therapy for patients with malignant tumor. The nasogastric tube, nasoenteric tube, and percutaneous endoscopic gastric/jejunostomy are commonly used clinical pathways for enteral nutrition (EN) therapy. However, these EN pathways are often difficult to establish in patients with malignant obstructive jaundice (MOJ) with pyloric or duodenum primary obstruction. For this reason, a new type biliary-intestinal nutrient tube placed through percutaneous transhepatic cholangiography drainage (PTCD) pathway was designed by the medical staff of hepatobiliary surgery department of Yinchuan First People's Hospital, and National Utility Model Patent of China were obtained (ZL 2020 2 0283951.5, ZL 2020 2 0288938.9). The new biliary-intestinal nutrient tube has two types: double-lumen tube and single-lumen tube, which consists of tube head, tube body, tail ring and developing ring. The double lumen tube realizes bile internal drainage and EN simultaneously through the double lumen structure of the tube body. The single-lumen tube is used for nutrient infusion after bile duct metal stent implantation, which is not limited by the type of nutrient solution. The tail ring of the two types of nutrient tube is placed in the upper jejunum to reduce retrograde infection and unexpected extubation. Compared with the prior art, the utility model has the advantages of simple structure, reasonable design, safe and effective placement through PTCD pathway, and opens up a new EN path for MOJ patients.

AFM-IR probing the influence of polarization on the expression of proteins within single macrophages.

Macrophages are essential in innate immunity and are involved in a variety of biological functions. Due to high plasticity, macrophages are polarized in different phenotypes depending on different microenvironments to perform specific functions. Although many studies have focused on macrophage polarization, few have explored the polarization characteristics of macrophages at the subcellular level, even at nanoscale resolution. Here, we utilize AFM-based infrared spectroscopy (AFM-IR) to investigate the influence of an inducer on the expressed proteins of M1/M2 macrophages (induced by LPS and IL-13, respectively). The results from AFM-IR combined with principal component analysis revealed that the characteristic proteins within M1 contain about 35% antiparallel ß-sheets (due to the high expression of TNF-α), while the proteins within M2 are made up of approximately 38.8% α-helices. The corresponding nanoscale chemical mapping demonstrates a remarkably heterogeneous distribution of expressed proteins inside single macrophages. Beside the biochemical properties, the biomechanical properties of macrophages were found to be softened in response to the polarization process.

Simulation of a bidisperse magnetorheological fluid using the combination of a two-component lattice Boltzmann method and a discrete element approach.

In this study, a two-component lattice Boltzmann method (TLBM) in combination with a discrete element approach (DEA) based on a representative volume element (RVE) with respect to a bidisperse magnetorheological fluid (MRF) was performed to simulate the behavior and microstructure formation of magnetic particles in a carrier liquid. The bidisperse MRF reported herein is a suspension dispersed by soft micron carbonyl iron (CI) particles and Fe3O4 nanoparticles dual-coated with gelatin and multi-walled carbon nanotubes (MWCNTs) in the carrier liquid. In the TLBM of two-component liquid and particle simulation, the inter-particle interactions were completely ignored; on the other hand, the DEA was just employed for calculating the dynamic behavior of particles. Therefore, due to the explicit nature of the combination of TLBM and DEA, it is a more efficient and accurate strategy for the simulation and calculation of complex MRF systems. Moreover, the immersed boundary method (IBM) was used to describe the interactions between the magnetic particles and the carrier liquid. The RVE of the bidisperse MRF was selected to eliminate specific operational conditions and reduce the calculation costs. New numerical results were obtained for the motion velocities, microstructure evolution and kinetic energy of bidisperse magnetic particles (BMPs) under the effect of a magnetic field; when the mass fraction of the nanoparticles was 0.1, the bidisperse MRF exhibited an improved response time in terms of the particle motion and microstructure formation. In addition, the effects of the Reynolds (Re) and Hartmann (Ha) numbers on the fluid-particle interaction and flow velocity were illustrated.

The Constitutive Expression of a Chrysanthemum ERF Transcription Factor Influences Flowering Time in Arabidopsis thaliana.

AP2/ERF transcription factors (TFs) represent valuable targets for the genetic manipulation of crop plants, as they participate in the control of metabolism, growth and development, as well as in the plants' response to environmental stimuli. Here, an ERF TF encoded by the chrysanthemum (Chrysanthemum morifolium) genome, designated CmERF110, was cloned and functionally characterized. The predicted CmERF110 polypeptide included a conserved DNA-binding AP2/ERF domain. A transient expression experiment revealed that the protein was deposited in the nucleus, and a transactivation experiment in yeast suggested that it had no transcriptional activity. The gene was transcribed in the chrysanthemum root, stem and leaf, with its transcript level following a circadian rhythm under both long and short days. The effect of constitutively expressing the gene in Arabidopsis thaliana was to accelerate flowering. Transcriptional profiling implied that its effect on floral initiation operated through the photoperiod pathway.

Bidisperse Magnetic Particles Coated with Gelatin and Graphite Oxide: Magnetorheology, Dispersion Stability, and the Nanoparticle-Enhancing Effect.

The magnetorheology and dispersion stability of bidisperse magnetic particles (BMP)-based magnetorheological (MR) fluids were improved by applying a novel functional coating composed of gelatin and graphite oxide (GO) to the surfaces of the micron-sized carbonyl iron (CI) and nanoparticles Fe3O4. Gelatin acted as a grafting agent to reduce the aggregation and sedimentation of CI particles and prevent nanoparticles Fe3O4 from oxidation. In addition, a dense GO network on the surface of gelatin-coated BMP was synthesized by self-assembly to possess a better MR performance and redispersibility. The rheological properties of MR fluids containing dual-coated BMP were measured by a rotational rheometer under the presence of magnetic field and their dispersion stability was examined through sedimentation tests. The results showed that CI@Fe3O4@Gelatin@GO (CI@Fe3O4@G@GO) particles possessed enhanced MR properties and dispersion stability. In addition, the nanoparticle-enhancing effects on the dispersion stability of BMP-based MR fluids were investigated using Monte Carlo simulations.

Free Vibration Analysis of Moderately Thick Orthotropic Functionally Graded Plates with General Boundary Restraints.

In this paper, a modified Fourier series method is presented for the free vibration of moderately thick orthotropic functionally graded plates with general boundary restraints based on the first-order shear deformation theory. Regardless of boundary restraints, displacements and rotations of each plate are described as an improved form of double Fourier cosine series and several closed-form auxiliary functions to eliminate all the boundary discontinuities and jumps. Exact solutions are obtained by the energy functions of the plates based on Rayleigh-Ritz method. The convergence and reliability of the current method and the corresponding theoretical formulations are verified by comparing the present results with those available in the literature, and numerous new results for orthotropic functionally graded (OFG) plates with general boundary restraints are presented. In addition, the effects of gradient index, volume fraction and geometric parameters on frequencies with general boundary restraints are illustrated.

The Effects of Fungicide, Soil Fumigant, Bio-Organic Fertilizer and Their Combined Application on Chrysanthemum Fusarium Wilt Controlling, Soil Enzyme Activities and Microbial Properties.

Sustained monoculture often leads to a decline in soil quality, in particular to the build-up of pathogen populations, a problem that is conventionally addressed by the use of either fungicide and/or soil fumigation. This practice is no longer considered to be either environmentally sustainable or safe. While the application of organic fertilizer is seen as a means of combating declining soil fertility, it has also been suggested as providing some control over certain soil-borne plant pathogens. Here, a greenhouse comparison was made of the Fusarium wilt control efficacy of various treatments given to a soil in which chrysanthemum had been produced continuously for many years. The treatments comprised the fungicide carbendazim (MBC), the soil fumigant dazomet (DAZ), the incorporation of a Paenibacillus polymyxa SQR21 (P. polymyxa SQR21, fungal antagonist) enhanced bio-organic fertilizer (BOF), and applications of BOF combined with either MBC or DAZ. Data suggest that all the treatments evaluated show good control over Fusarium wilt. The MBC and DAZ treatments were effective in suppressing the disease, but led to significant decrease in urease activity and no enhancement of catalase activity in the rhizosphere soils. BOF including treatments showed significant enhancement in soil enzyme activities and microbial communities compared to the MBC and DAZ, evidenced by differences in bacterial/fungi (B/F) ratios, Shannon-Wiener indexes and urease, catalase and sucrase activities in the rhizosphere soil of chrysanthemum. Of all the treatments evaluated, DAZ/BOF application not only greatly suppressed Fusarium wilt and enhanced soil enzyme activities and microbial communities but also promoted the quality of chrysanthemum obviously. Our findings suggest that combined BOF with DAZ could more effectively control Fusarium wilt disease of chrysanthemum.

Magnetoelectric Coupling in Well-Ordered Epitaxial BiFeO3/CoFe2O4/SrRuO3 Heterostructured Nanodot Array.

Multiferroic magnetoelectric (ME) composites exhibit sizable ME coupling at room temperature, promising applications in a wide range of novel devices. For high density integrated devices, it is indispensable to achieve a well-ordered nanostructured array with reasonable ME coupling. For this purpose, we explored the well-ordered array of isolated epitaxial BiFeO3/CoFe2O4/SrRuO3 heterostructured nanodots fabricated by nanoporous anodic alumina (AAO) template method. The arrayed heterostructured nanodots demonstrate well-established epitaxial structures and coexistence of piezoelectric and ferromagnetic properties, as revealed by transmission electron microscopy (TEM) and peizoeresponse/magnetic force microscopy (PFM/MFM). It was found that the heterostructured nanodots yield apparent ME coupling, likely due to the effective transfer of interface couplings along with the substantial release of substrate clamping. A noticeable change in piezoelectric response of the nanodots can be triggered by magnetic field, indicating a substantial enhancement of ME coupling. Moreover, an electric field induced magnetization switching in these nanodots can be observed, showing a large reverse ME effect. These results offer good opportunities of the nanodots for applications in high-density ME devices, e.g., high density recording (>100 Gbit/in.(2)) or logic devices.

[Effects of bio-organic fertilizer and fungicide application on continuous cropping obstacles of cut chrysanthemum].

Abstract: Fusarium wilt is a soil borne disease caused by plant continuous cropping in monoculture Chrysanthemum morifolium 'Youxiang' monoculture not only declines plant quality and yield but also decreases soil enzymes and soil microbial diversity over successive cultivation. In this article, the effects of fungicide (Carbendazim MBC), antifungal enhanced bio-organic fertilizer (BOF), and their combined application on the quality and soil enzymes activities of Chrysanthemum morifolium 'Youxiang' in continuous cropping systems were investigated. The results showed that both bioorganic fertilizer (BOF) and fungicide (MBC) single application could effectively prevent the occurrence of Fusarium wilt disease of cut chrysanthemum. Bio-organic fertilizer application was more effective on root activity, soil enzymes activities and quality (shoot height, stem diameter, leaf SPAD value, ray floret number, shoot fresh mass) improvement of cut chrysanthemum, while fungicide single application was responsible for soil enzymatic activities suppression to some extent. The combined application treatment (MBC+BOF) showed the best effects on quality improvement and soil enzyme activities promotion.

Magnetoelectric quasi-(0-3) nanocomposite heterostructures.

Magnetoelectric composite thin films hold substantial promise for applications in novel multifunctional devices. However, there are presently shortcomings for both the extensively studied bilayer epitaxial (2-2) and vertically architectured nanocomposite (1-3) film systems, restricting their applications. Here we design a novel growth strategy to fabricate an architectured nanocomposite heterostructure with magnetic quasiparticles (0) embedded in a ferroelectric film matrix (3) by alternately growing (2-2) and (1-3) layers within the film. The new heteroepitaxial films not only overcome the clamping effect from substrate, but also significantly suppress the leakage current paths through the ferromagnetic phase. We demonstrate, by focusing on switching characteristics of the piezoresponse, that the heterostructure shows magnetic field dependence of piezoelectricity due to the improved coupling enabled by good connectivity amongst the piezoelectric and magnetostrictive phases. This new architectured magnetoelectric heterostructures may open a new avenue for applications of magnetoelectric films in micro-devices.

Anatomy of vertical heteroepitaxial interfaces reveals the memristive mechanism in Nb2O5-NaNbO3 thin films.

Dynamic oxygen vacancies play a significant role in memristive switching materials and memristors can be realized via well controlled doping. Based on this idea we deposite Nb2O5-NaNbO3 nanocomposite thin films on SrRuO3-buffered LaAlO3 substrates. Through the spontaneous phase separation and self-assembly growth, two phases form clear vertical heteroepitaxial nanostructures. The interfaces between niobium oxide and sodium niobate full of ion vacancies form the conductive channels. Alternative I-V behavior attributed to dynamic ion migration reveals the memristive switching mechanism under the external bias. We believe that this phenomenon has a great potential in future device applications.

Converging evidence implicates the abnormal microRNA system in schizophrenia.

BACKGROUND: Previous findings are inconsistent; yet, converging evidence suggests an association between schizophrenia (SZ) and the impairment of posttranscriptional regulation of brain development through microRNA (miRNA) systems. METHODS: This study aims to (1) compare the overall frequency of 121 rare variants (RVs) in 59 genes associated with the miRNA system in genome-wide association studies (GWAS)-derived data including 768 SZ cases and 1348 healthy controls and validated in an independent GWAS data including 1802 SZ cases and 1447 controls; (2) profile genome-wide miRNA expression in blood collected from 15 early-onset SZ (EOS) cases and 15 healthy controls; and (3) construct a miRNA-messenger RNA (mRNA) regulatory network using our previous genome-wide mRNA expression data generated from a separate sample of 18 EOS cases and 12 healthy controls. RESULTS: Our findings indicate that: (1) In genes associated with the control of miRNAs, there are approximately 50% more RVs in SZ cases than in controls (P ≤ 2.62E-10); (2) The observed lower miRNA activity in EOS patients compared with the healthy controls suggests that miRNAs are abnormally downregulated; (3) There exists a predicted regulatory network among some downregulated miRNAs and some upregulated mRNAs. CONCLUSIONS: Collectively, results from all 3 lines of evidence, suggest that the genetically based dysregulation of miRNA systems undermines miRNAs' inhibitory effects, resulting in the abnormal upregulation of genome transcription in the development of SZ.

Two-dimensional quasi-freestanding molecular crystals for high-performance organic field-effect transistors.

Two-dimensional atomic crystals are extensively studied in recent years due to their exciting physics and device applications. However, a molecular counterpart, with scalable processability and competitive device performance, is still challenging. Here, we demonstrate that high-quality few-layer dioctylbenzothienobenzothiophene molecular crystals can be grown on graphene or boron nitride substrate via van der Waals epitaxy, with precisely controlled thickness down to monolayer, large-area single crystal, low process temperature and patterning capability. The crystalline layers are atomically smooth and effectively decoupled from the substrate due to weak van der Waals interactions, affording a pristine interface for high-performance organic transistors. As a result, monolayer dioctylbenzothienobenzothiophene molecular crystal field-effect transistors on boron nitride show record-high carrier mobility up to 10 cm(2) V(-1) s(-1) and aggressively scaled saturation voltage ~1 V. Our work unveils an exciting new class of two-dimensional molecular materials for electronic and optoelectronic applications.

Cognitive biases toward Internet game-related pictures and executive deficits in individuals with an Internet game addiction.

BACKGROUND: The cue-related go/no-go switching task provides an experimental approach to study individual's flexibility in changing situations. Because Internet addiction disorder (IAD) belongs to the compulsive-impulsive spectrum of disorders, it should present cognitive bias and executive functioning deficit characteristics of some of these types of disorders. Until now, no studies have been reported on cognitive bias and executive function involving mental flexibility and response inhibition in IAD. METHODOLOGY/PRINCIPAL FINDINGS: A total of 46 subjects who met the criteria of the modified Young's Diagnostic Questionnaire for Internet addiction (YDQ) were recruited as an Internet game addiction (IGA) group, along with 46 healthy control individuals. All participants performed the Internet game-shifting task. Using hit rate, RT, d' and C as the dependent measures, a three-way ANOVA (group × target × condition) was performed. For hit rate, a significant effect of group, type of target and condition were found. The group-target interaction effect was significant. For RT, significant effects were revealed for group and type of target. The group-target interaction effect was significant. Comparisons of the means revealed that the slowing down of IGA relative to NIA was more pronounced when the target stimuli were neutral as opposed to Internet game-related pictures. In addition, the group-condition interaction effect was significant. For d', significant effects of group, type of target and condition were found. The group-target interaction effect was significant. For C, the type of target produced a significant effect. There was a positive correlation between the length of the addiction (number of years) and the severity of the cognitive bias. CONCLUSIONS: IGA present cognitive biases towards information related to Internet gaming. These biases, as well as poor executive functioning skills (lower mental flexibility and response inhibition), might be responsible for Internet game addiction. The assessment of cognitive biases in IGA might provide a methodology for evaluation of therapeutic effects.

Effect of tryptophan hydroxylase-2 rs7305115 SNP on suicide attempts risk in major depression.

BACKGROUND: Suicide and major depressive disorders (MDD) are strongly associated, and genetic factors are responsible for at least part of the variability in suicide risk. We investigated whether variation at the tryptophan hydroxylase-2 (TPH2) gene rs7305115 SNP may predispose to suicide attempts in MDD. METHODS: We genotyped TPH2 gene rs7305115 SNP in 215 MDD patients with suicide and matched MDD patients without suicide. Differences in behavioral and personality traits according to genotypic variation were investigated by logistic regression analysis. RESULTS: There were no significant differences between MDD patients with suicide and controls in genotypic (AG and GG) frequencies for rs7305115 SNP, but the distribution of AA genotype differed significantly (14.4% vs. 29.3%, p < 0.001). The G-allele frequency was significantly higher in cases than control group (58.1% vs.45.6%, p < 0.001), but the A-allele carrier indicated a decreased trend in MDD with suicide behaviors than control group (41.9% vs.54.4%, p < 0.001). The multivariate logistic regression analysis indicated that TPH2 rs7305115 AA (OR 0.33, 95% CI 0.22-0.99), family history of suicide (OR 2.98, 95% CI 1.17-5.04), negative life events half year ago (OR 6.64, 95% CI 2.48-11.04) and hopelessness (OR 7.68, 95% CI 5.79-13.74) were significantly associated with the suicide behaviors in MDD patients. CONCLUSIONS: The study suggested that hopelessness, negative life events and family history of suicide were risk factors of attempted suicide in MDD while the TPH2 rs7305115A remained a significant protective predictor of suicide attempts.

Tyrosine hydroxylase, interleukin-1beta and tumor necrosis factor-alpha are overexpressed in peripheral blood mononuclear cells from schizophrenia patients as determined by semi-quantitative analysis.

The aim of this study is to profile the peripheral biomarkers (tyrosine hydroxylase, TH; interleukin-1beta, IL-1beta; and tumor necrosis factor-alpha, TNF-alpha) for schizophrenia and explore their relations with clinical symptoms. Thirty-nine patients with schizophrenia were evaluated using the Positive and Negative Syndrome Scale (PANSS), and 25 siblings and 30 normal healthy subjects were used as controls. The mRNA expression levels of TH, IL-1beta and TNF-alpha in peripheral blood mononuclear cells, as determined with semi-quantitative reverse transcription-polymerase chain reaction, were all significantly increased in both patients (3-fold) and siblings (2-fold) as compared with normal control. Both IL-1beta and TNF-alpha were significantly correlated with scores on the general psychopathology subscale of the PANSS. A significant positive correlation between IL-1beta and TH expression was found in both sibling and normal controls, but not in patients, while a positive correlation between IL-1beta and TNF-alpha was significant in all the groups. These results suggest that TH, IL-1beta and TNF-alpha are overexpressed in the peripheral blood mononuclear cells of schizophrenia patients, perhaps due to the hereditary factors. IL-1beta and TNF-alpha may influence the symptoms of schizophrenia in the cognition dysfunction and anxiety/depression domains of the PANSS.