Spatial heterogeneity and management challenges of ecosystem service trade-offs: a case study in Guangdong Province, China.

Ecosystem services (ESs) play a crucial connecting role between human well-being and natural ecosystems. Investigating ESs and their interrelationships can aid in the rational distribution of resources and benefits and inform planning decisions that align with the principles of ecological civilization. Nonetheless, our current understanding of these relationships remains limited; thus, further theoretical exploration is required. This study employs the InVEST model to assess the key ESs in Guangdong Province for 2000 and 2018 and applies the multi-scale geographically weighted regression (MGWR) method to identify the primary drivers of ES changes and capture trends in spatial variations. The results showed that (1) from 2000 to 2018, the total carbon storage (CS) and habitat quality (HQ) decreased while the water yield (WY) and net primary productivity (NPP) increased. These ESs also showed spatial differences, with higher values observed in the hilly and mountainous areas of the north compared with the coastal and plain areas of the south. (2) Although the spatial distribution of ES trade-off strength varied, the overall pattern remained consistent from 2000 to 2018. The pairwise trade-off strength of CS-WY and WY-HQ decreased significantly in the northern region of Guangdong due to low rainfall, while that of CS-HQ decreased significantly in the Pearl River delta as a result of urbanization. Cultivated and forested land displayed higher and lower levels of NPP and WY, respectively, with forested land exhibiting greater trade-off strength than the other land use types. (3) Evident spatial heterogeneity was observed in the properties and intensity of the correlations between driving factors and changes in ES trade-offs. Natural factors were the primary determinants of trade-offs among ESs. However, at a regional scale, the landscape index and socioeconomic factors tended to represent stronger drivers. Based on these findings, we suggest that ecological management should be adjusted based on the geographic scale. This study offers a valuable approach to understanding the relationship between ES trade-offs and their drivers in geographic space and serves as a reference for the sustainable provisioning of ESs both locally and globally.

Association of the dietary inflammation index (DII) with the prevalence of chronic kidney disease in patients with type-2 diabetes mellitus.

Chronic kidney disease (CKD) is a major complication of diabetes mellitus (DM). Inflammation is an essential component in the process of CKD progression in patients with DM. Diet is a significant determinant of systemic inflammation levels. However, the association between the dietary inflammatory index (DII) and CKD in individuals with DM remains largely unknown; therefore, the aim of this study was to explore whether the DII is linked to the prevalence of CKD in patients with DM. The research method was as follows: first, data from the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2018 were obtained. There were 7,974 participants in our study. These individuals were then classified into three groups according to DII tertiles (T1-T3), with each group consisting of 2,658 participants. Logistic regression analysis was employed to examine whether there was a connection between the DII and CKD. We observed a significant association between the DII and the prevalence of CKD in individuals with DM. After full adjustment for age, sex, ethnicity, smoking, drinking, body mass index (BMI), triglyceride (TG), total cholesterol (TC), metabolic equivalents (METs), energy intake, hypoglycemic medications, hypertension, and cardiovascular disease (CVD), the group with a higher DII had a greater frequency of CKD (T2 group: OR: 1.40; 95% CI: 1.10-1.76; p = 0.006; T3 group: OR: 1.67; 95% CI: 1.29-2.17; p < 0.001). The implementation of an anti-inflammatory diet could serve as an intervention strategy for patients with DM to prevent the onset of CKD.

An Amphiphilic PEGylated Peptide Dendron-Gemcitabine Prodrug-Based Nanoagent for Cancer Therapy.

An amphiphilic peptide dendrimer conjugated with gemcitabine (GEM), PEGylated dendron-Gly-Phe-Leu-Gly-GEM (PEGylated dendron-GFLG-GEM), is developed as a nano-prodrug for breast cancer therapy. The self-assembled behavior is observed under a transmission electron microscopy and dynamic light scattering. The negatively charged surface and hydrodynamic size of the amphiphilic nanosized prodrug supported that the prodrug can maintain the stability of GEM during circulation and accumulate in the tumor tissue. Drug release assays are conducted to monitor the release of GEM from this nanodrug delivery system in response to the tumor microenvironment, and these assays confirm that GEM released from the nanocarrier is identical to free GEM. The GEM prodrug can prevent proliferation of tumor cells. The therapeutic effect against breast cancer is systematically investigated using an in vivo animal model. Immunohistochemical results are aligned with the significantly enhanced anticancer efficacy of GEM released from the prodrug. This self-assembled amphiphilic drug delivery nanocarrier may broaden the application for GEM and other anticancer agents for breast cancer chemotherapy.

Hotair mediates tumorigenesis through recruiting EZH2 in colorectal cancer.

Long noncoding RNAs (lncRNA)  have been demonstrated to extensively participate in a wide spectrum of biological activities ranging from embryogenesis and cancer progression. HOX transcript antisense RNA (Hotair), an lncRNA located in the HOXC locus, has been reported to play an important role in carcinogenesis. As a well-known oncogene, it potentiates cancer metastasis and tumor progression. And it also serves as a biomarker for poor prognosis and tumor recurrence. In this study, Hotair was found to be upregulated in colorectal cancer (CRC) cells and clinical specimens. Further investigation showed that knockdown of Hotair dramatically suppressed cell proliferation and colony formation, suggesting that Hotair may stimulate tumorigenesis of CRC. The enhancer of zeste homolog 2 (EZH2), a regulator of epigenetic modification, was upregulated in CRC cells and clinical samples. And the silence of EZH2 significantly suppressed cell viability and colony formation. Furthermore, the RNA immunoprecipitation assay revealed that Hotair directly bound EZH2 in CRC cells. In conclusion, Hotair mediated tumorigenesis via recruiting EZH2, which might shed light on the development of a novel therapeutic approach for patients with CRC.

Quantitative magnetic resonance imaging in patellar tendon-lateral femoral condyle friction syndrome: relationship with subtle patellofemoral instability.

OBJECTIVE: To investigate the correlation of patellar tendon-lateral femoral condyle friction syndrome (PTLFCFS) with subtle patellofemoral instability to explore its pathogenesis. MATERIALS AND METHODS: One hundred knees of 80 patients with PTLFCFS were analyzed retrospectively by retrieving magnetic resonance imaging (MRI) data over a 3-year period from our database. Seven quantitative parameters for evaluating patellofemoral stability were measured on MR images, including the Insall-Salvati ratio, tibial tuberosity-trochlear groove (TT-TG) distance, trochlear groove depth, medial trochlear/lateral trochlear length (MT/LT) ratio, medial trochlear/lateral trochlear height (MH/LH) ratio, lateral patellofemoral angle (LPA), and lateral trochlear inclination (LTI) angle. These patellofemoral parameters of the PTLFCFS group and the normal control group were compared (n = 88), and receiving-operator characteristic (ROC) curve analysis was conducted to determine the specificity and sensitivity of these parameters. RESULTS: The trochlear depth, MT/LT, LPA, and LTI angle were significantly lower (p < 0.001) and the Insall-Salvati ratio was significantly higher (p < 0.001) in the PTLFCFS group. However, the TT-TG distance and MH/LH ratio showed no significant difference (p = 0.231 and 0.073 respectively). The area under the ROC curve of the Insall-Salvati ratio, trochlear depth, MT/LT, LPA, and LTI angle were 0.925, 0.784, 0.8, 0.731, and 0.675 respectively. The efficiency of the Insall-Salvati ratio was the highest among those five parameters. CONCLUSION: This study verified the presence of subtle patellofemoral instability by measuring various patellofemoral parameters in patients with PTLFCFS. It confirmed that PTLFCFS is associated with subtle patellofemoral instability and could largely explain the pathogenesis of PTLFCFS.

Effects of dietary supplementation with epidermal growth factor-expressing Saccharomyces cerevisiae on duodenal development in weaned piglets.

The aim of the present study was to assess the effects of dietary supplementation with epidermal growth factor (EGF)-expressing Saccharomyces cerevisiae on duodenal development in weaned piglets. In total, forty piglets weaned at 21-26 d of age were assigned to one of the five groups that were provided basic diet (control group) or diet supplemented with S. cerevisiae expressing either empty-vector (INVSc1(EV) group), tagged EGF (T-EGF) (INVSc1-TE(-) group), extracellular EGF (EE-EGF) (INVSc1-EE(+) group) or intracellular EGF (IE-EGF) (INVSc1-IE(+) group). All treatments were delivered as 60·00 µg/kg body weight EGF/d. On 0, 7, 14 and 21 d, eight piglets per treatment were sacrificed to analyse the morphology, activities and mRNA expressions of digestive enzymes, as well as Ig levels (IgA, IgM, IgG) in duodenal mucosa. The results showed significant improvement on 7, 14 and 21 d, with respect to average daily gain (P<0·05), mucosa morphology (villus height and crypt depth) (P<0·05), Ig levels (P<0·01), activities and mRNA expressions of digestive enzymes (creatine kinase, alkaline phosphatase, lactate dehydrogenase and sucrase) (P<0·05) and the mRNA expression of EGF-receptor (P<0·01) in NVSc1-TE(-), INVSc1-EE(+) and INVSc1-IE(+) groups compared with control and INVSc1(EV) groups. In addition, a trend was observed in which the INVSc1-IE(+) group showed an improvement in Ig levels (0·05

The Potential of Poly[N-(2-hydroxypropyl)methacrylamide] via Reversible Addition-Fragmentation Chain Transfer Polymerization as Safe Nanocarrier.

N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers have been presented as nanoscale drug/gene delivery systems and imaging probes, and the well-defined HPMA copolymers prepared via reversible addition-fragmentation chain transfer (RAFT) polymerization promote their to clinical trials, as the significant enhanced anticancer efficacy. The biosafety is another issue associated with the carriers. In this study, we prepared the linear and branched HPMA copolymers labeled with Cy5.5 via RAFT polymerization and click chemistry, and their potential biosafety was studied. The linear copolymer was prepared via RAFT polymerization mediated by the ends-functionalized peptide chain transfer agent (peptide2CTA), resulting in well-defined and block linear HPMA copolymer with molecular weight (MW) of 98 kDa. Additionally, the branched HPMA copolymer was also prepared via RAFT polymerization. Followed by Cy5.5 labeling, the two copolymers showed negative zeta potential and their accumulation into tumor was studied by in vivo optical fluorescence imaging in the nude mice with breast tumors. The biosafety studies on in vitro cytotoxicity and hemocompatibility studies, including hemolysis tests, plasma coagulation and thromboelastography assay were carried out well, demonstrating that the linear HPMA copolymer-Cy5.5 with MW around 100 kDa and biodegradable moiety in the main chain might be utilized as safe nanoscale carrier.

[Nuclear magnetic resonance-based metabonomics for sedative and hypnotic effect of Banxia Houpo decoction].

Insomnia was a common disease, which might be correlated with γ-aminobutyric acid A (GABAA) receptor mechanism, cytokine regulatory mechanism, excitatory amino acid mechanism and hydroxytryptamine (5-HT) receptor mechanism, but the correlations between these independent mechanisms and pathological characterization were still unclear. To further explore the effect of Banxia Houpo decoction on known or unknown biological pathways during treatment of insomnia, the metabonomics method based on ¹H-NMR was developed for detecting the significant changes in metabolomics after the administration with Banxia Houpo decoction in pentobarbital sodium-induced rat sleeping experiment. Serum and urine samples were analyzed by ¹H-NMR. Principal component analysis (PCA) was carried out for endogenous small molecule metabolites in urine and serum. H-NMR spectroscopies and relevant metabolites were found and identified by Simca-p 17.0 (Umet-rics, Umea, Sweden) and Chenomx NMR Suite 7.1 (Chenomx, Inc., Edmonton, Alberta, Canada) software. The result suggests that Banxia Houpo decoction group and indiplon group had significant differences. The load diagram showed the biggest variation metabolites and intergroup significant differences among 10 metabolic substances. According to the experiment, Banxia Houpo decoction group and indiplon group can prolonge the sleeping time of pentobarbital sodium-induced sprague-dawley rats, with a synergistic effect. The significant changes of these biomarkers indicated that the Banxia Houpo decoction could aid sleep by adjusting the content of glutamine, creatine phosphate, 2-oxoglutarate, and reducing the activity of brain nerves.

Comparison of the biological activities of Saccharomyces cerevisiae-expressed intracellular EGF, extracellular EGF, and tagged EGF in early-weaned pigs.

Epidermal growth factor (EGF) ameliorates stress and prevents incomplete gastrointestinal development in early-weaned piglets in commercial swine farming. This study aimed to further analyze the biological activities of intracellularly expressed EGF (IE-EGF), extracellularly expressed EGF (EE-EGF), and tagged EGF (T-EGF) from Saccharomyces cerevisiae in early-weaned pigs. In this study, we assigned 24 pigs to each of 5 groups that were provided a basic diet (the control group) or a diet supplemented with empty vector-expressing S. cerevisiae [the INVSc1(EV) group], T-EGF-expressing S. cerevisiae [the INVSc1-TE(-) group], EE-EGF-expressing S. cerevisiae [the INVSc1-EE(+) group], or IE-EGF-expressing S. cerevisiae [the INVSc1-IE(+) group]. All treatments were delivered at a dose of 60 µg EGF/kg body weight (BW) everyday. All the piglets were sacrificed after 21 day to determine their physio-biochemical indexes, immune functions, and intestinal development. In the piglet experiments, recombinant S. cerevisiae survived throughout the intestinal tract. The BW and intestinal development (e.g., mean villous height, crypt depth, villous height:crypt depth ratio (IVR), and total protein, DNA, and RNA contents) of the piglets were significantly enhanced in the INVSc1-IE(+) group compared with the animals in the INVSc1-EE(+) and INVSc1-TE(-) groups (P < 0.05). In addition, increased proliferating cell nuclear antigen (PCNA) staining was observed in the piglets that received the INVSc1-IE(+) treatment (approximately 80 %) compared with those that received the INVSc1-TE(-) (approximately 70 %) and INVSc1-EE(+) treatments (approximately 70 %). The levels of lactate dehydrogenase (LDH), creatine kinase (CK), alkaline phosphatase (ALP), immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin G (IgG) were also significantly increased in the INVSc1-IE(+) group compared with the INVSc1-EE(+) and INVSc1-TE(-) groups (P < 0.05). Furthermore, the proliferation of piglet enterocytes was also significantly stimulated by both IE-EGF and EE-EGF compared with T-EGF in vitro (P < 0.05). Our data further demonstrate the previously reported hypothesis that IE-EGF is more suitable than EE-EGF or T-EGF for applications in early-weaned pigs.

Analysis of the biological activities of Saccharomyces cerevisiae expressing intracellular EGF, extracellular EGF, and tagged EGF in early-weaned rats.

A growing number of studies suggest that epidermal growth factor (EGF) plays an important role in early-weaned animals. The objective of this experiment was to compare the biological activity of intracellularly expressed EGF (IE-EGF), extracellularly expressed EGF (EE-EGF), and tagged EGF (T-EGF) from Saccharomyces cerevisiae (S. cerevisiae) both in vivo and in vitro. Strains of S. cerevisiae expressing IE-EGF, EE-EGF, and T-EGF were designated INVSc1-IE(+), INVSc1-EE(+), and INVSc1-TE(-), respectively. The production performance, intestinal development, physio-biochemical indexes, and immunological function of early-weaned rats were measured in vivo to evaluate the biological activity of IE-EGF, EE-EGF, and T-EGF. In addition, the proliferation of rat enterocyte was also measured in vitro. In the in vivo experiment, the recombinant S. cerevisiae was shown to survive throughout the intestinal tract. The production performance (e.g., body weight) and intestinal development (e.g., mean villous height, crypt depth, total protein, DNA, and RNA) of the rats were significantly enhanced in the INVSc1-IE(+) group compared with the INVSc1-EE(+) and INVSc1-TE(-) groups (P < 0.05). However, the levels of lactate dehydrogenase (LDH), immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin G (IgG) showed no difference in the INVSc1-IE(+) group compared to the INVSc1-EE(+) and INVSc1-TE(-) groups (P > 0.05), with the only significant difference being found for creatine kinase (CK) (P < 0.05). In the in vitro experiment, the proliferation of enterocyte was significantly stimulated by both IE-EGF and EE-EGF compared with T-EGF (P < 0.05). Herein, IE-EGF is more suitable for application to early-weaned animals compared with EE-EGF and T-EGF.

Disruption of Ttll5/stamp gene (tubulin tyrosine ligase-like protein 5/SRC-1 and TIF2-associated modulatory protein gene) in male mice causes sperm malformation and infertility.

TTLL5/STAMP (tubulin tyrosine ligase-like family member 5) has multiple activities in cells. TTLL5 is one of 13 TTLLs, has polyglutamylation activity, augments the activity of p160 coactivators (SRC-1 and TIF2) in glucocorticoid receptor-regulated gene induction and repression, and displays steroid-independent growth activity with several cell types. To examine TTLL5/STAMP functions in whole animals, mice were prepared with an internal deletion that eliminated several activities of the Stamp gene. This mutation causes both reduced levels of STAMP mRNA and C-terminal truncation of STAMP protein. Homozygous targeted mutant (Stamp(tm/tm)) mice appear normal except for marked decreases in male fertility associated with defects in progressive sperm motility. Abnormal axonemal structures with loss of tubulin doublets occur in most Stamp(tm/tm) sperm tails in conjunction with substantial reduction in α-tubulin polyglutamylation, which closely correlates with the reduction in mutant STAMP mRNA. The axonemes in other structures appear unaffected. There is no obvious change in the organs for sperm development of WT versus Stamp(tm/tm) males despite the levels of WT STAMP mRNA in testes being 20-fold higher than in any other organ examined. This defect in male fertility is unrelated to other Ttll genes or 24 genes previously identified as important for sperm function. Thus, STAMP appears to participate in a unique, tissue-selective TTLL-mediated pathway for α-tubulin polyglutamylation that is required for sperm maturation and motility and may be relevant for male fertility.

Identification of location and kinetically defined mechanism of cofactors and reporter genes in the cascade of steroid-regulated transactivation.

A currently obscure area of steroid hormone action is where the component factors, including receptor and reporter gene, act. The DNA binding of factors can be precisely defined, but the location and timing of factor binding and action are usually not equivalent. These questions are addressed for several factors (e.g. glucocorticoid receptor (GR), reporter, TIF2, NCoR, NELF-A, sSMRT, and STAMP) using our recently developed competition assay. This assay reveals both the kinetically defined mechanism of factor action and where the above factors act relative to both each other and the equilibrium equivalent to the rate-limiting step, which we call the concentration limiting step (CLS). The utility of this competition assay would be greatly increased if the position of the CLS is invariant and if the factor acting at the CLS is known. Here we report that the exogenous GREtkLUC reporter acts at the CLS as an accelerator for gene induction by GRs in U2OS cells. This mechanism of reporter function at the CLS persists with different reporters, factors, receptors, and cell types. We, therefore, propose that the reporter gene always acts at the CLS during gene induction and constitutes a landmark around which one can order the actions of all other factors. Current data suggest that how and where GR and the short form of SMRT act is also constant. These results validate a novel and rational methodology for identifying distally acting factors that would be attractive targets for pharmaceutical intervention in the treatment of diseases involving GR-regulated genes.

Binding of the N-terminal region of coactivator TIF2 to the intrinsically disordered AF1 domain of the glucocorticoid receptor is accompanied by conformational reorganizations.

Control of gene transcription by glucocorticoid receptors (GRs) is important for many physiological processes. Like other steroid hormone receptors, the regulation of target genes by GR is mediated by two transactivation domains: activation function 1 (AF1) in the N-terminal domain and AF2 in the C-terminal ligand-binding domain (LBD). Full receptor activity requires both AF1 and -2 plus assorted coregulatory proteins. Crystal structures of the ligand-bound LBD have provided insight regarding how AF2 interacts with specific coactivators. However, despite its being the major activation domain of GRs, knowledge of AF1 structure/function has languished. This is mainly because of the highly disorganized structure of the GR N-terminal domain. This lack of AF1 structure is shared by all members of the steroid/nuclear receptor superfamily for which it has been examined and AF1 is thought to allow productive interactions with assorted cofactors via protein-induced changes in secondary/tertiary structures. To date, there are no reports of a classical coactivator altering the secondary/tertiary structure of the GR AF1 domain. Earlier, we reported an N-terminal fragment of the p160 coactivator TIF2, called TIF2.0, that binds the GR N-terminal domain and alters GR transcriptional activity. We therefore proposed that TIF2.0 binding to AF1 changes both its conformation and transcriptional activity. We now report that TIF2.0 interacts with the GR AF1 domain to increase the amount of α-helical structure in the complex. Furthermore, TIF2 coactivator activity is observed in the absence of the GR LBD in a manner that requires the AF1 domain. This contrasts with previous models where TIF2 receptor interaction domains binding to GR LBD somehow alter AF1 conformation. Our results establish for the first time that coactivators can modify the structure of the AF1 domain directly via the binding of a second region of the coactivator and suggest a molecular explanation for how coactivators increase the transcriptional activity of GR-agonist complexes.

Automatic classification of ligneous leaf diseases via hierarchical vision transformer and transfer learning.

Background: Identification of leaf diseases plays an important role in the growing process of different types of plants. Current studies focusing on the detection and categorization of leaf diseases have achieved promising outcomes. However, there is still a need to enhance the performance of leaf disease categorization for practical applications within the field of Precision Agriculture. Methods: To bridge this gap, this study presents a novel approach to classifying leaf diseases in ligneous plants by offering an improved vision transformer model. The proposed approach involves utilizing a multi-head attention module to effectively capture contextual information about the images and their classes. In addition, the multi-layer perceptron module has also been employed. To train the proposed deep model, a public dataset of leaf disease is exploited, which consists of 22 distinct kinds of images depicting ligneous leaf diseases. Furthermore, the strategy of transfer learning is employed to decrease the training duration of the proposed model. Results: The experimental findings indicate that the presented approach for classifying ligneous leaf diseases can achieve an accuracy of 85.0% above. Discussion: In summary, the proposed methodology has the potential to serve as a beneficial algorithm for automated detection of leaf diseases in ligneous plants.

RNF43 mutation as a predictor of immunotherapeutic efficacy in colorectal cancer.

RNF43 is a tumor suppressor for various cancers and is considered to drive carcinogenesis when mutated. However, the correlation between RNF43 mutation and colorectal cancer (CRC) immunotherapy remains unreported. We evaluated the role of RNF43 using publicly available data from the Cancer Genome Atlas (TCGA) and Memorial Sloan Kettering Cancer Center (MSKCC). In addition, further analysis was performed on an internal validation cohort (hcohort). The mutant profiles of RNF43 were analyzed in 873 Chinese CRC patients. The relationship between clinical pathologic features and RNF43 were analyzed using the two-sided chi-squared test or the Fisher exact test. Clinicopathologic characteristics were associated with overall survival using Cox regression and the Kaplan-Meier method. We found that RNF43 mutation was significantly associated with high TMB and high MSI score (all p-values < 0.05) in the MSKCC cohort. Additionally, RNF43 mutation was found to be enriched in MSI instability. Kaplan-Meier survival analysis revealed that patients with RNF43 mutation had better OS compared to RNF43 wild-type (not reached vs. 13 months, HR, 0.12; 95% CI 0.03 to 0.49; P = 0.0034). However, no association was observed between RNF43 and OS in the TCGA cohort (HR, 1.83; 95% CI 0.66 to 5.07; P = 0.2479). Our CRC hcohort confirmed the significance of RNF43 mutation in predicting better clinical outcomes, including ORR (45% vs. 21%, P = 0.0468). RNF43 mutation correlated with a high tumor mutation burden (P < 0.001). The mutation frequency of RNF43 in CRC patients was 8.4% (73/873); RNF43 G659Vfs*41 was found to be the most frequent mutation site. In patients with RNF43 mutations, TP53, KRAS, and TGFBR2 were genes with a high frequency of mutations. Compared with RNF43 wild-type patients, those with RNF43 mutations had a higher TMB score and a greater proportion of MSI-H, but no difference in PD-L1 expression. Moreover, the content of immune-related B cells, CD8+ T cells, neutrophils, and dendritic cells was higher in the RNF43 mutant group than in the wild-type group. Our results suggest that RNF43 mutation may correlate with better OS in CRC patients receiving PD-1/PD-L1 inhibitors. The exact mechanisms underlying RNF43 require further investigation.

Enhanced Organic Thin-Film Transistor Stability by Preventing MoO3 Diffusion with Metal/MoO3/Organic Multilayered Interface Source-Drain Contact.

The source-drain electrode with a MoO3 interfacial modification layer (IML) is considered the most promising method to solve electrical contact issues impeding organic thin-film transistors (OTFTs) from commercialization. However, this method raises many concerns because MoO3 might diffuse into organic materials, which causes device instability. In this work, we observed a significant device stability degradation by damaging on/off switching performance caused by MoO3 diffusion. To prevent the MoO3 diffusion, a source-drain electrode with a multilayered interface contact (MIC) consisting of a top-down stack of metal, MoO3 IML, and organic buffer layer (OBL) is proposed. In the MIC device, the MoO3 IML serves well for its intended functions of reducing contact resistance and suppressing minority carrier injection to the OTFT channel. The inclusion of OBL to the MIC helps block MoO3 diffusion and thereby leads to better device stability and an increased on/off ratio. Through combinations with several organic compounds as a buffer layer, the MoO3 diffusion related electrical behaviors of OTFTs are systematically studied. Key parameters related to MoO3 diffusion such as the Fick coefficient and bias-stress stability such as carrier trapping time are extracted from numerical device analysis. Finally, we summarize a general rule of material selection for making robust source-drain contact.

Prevention of Nanoscale Fines in Open-Hole Horizontal Coalbed Methane Wells During the Drainage Process.

Because coal is quite weak compared with conventional sandstone, shear failure downhole will produce a large amount of nanoscale coal fines during the drainage process. Since the size of pores in coal is on the nanoscale range, these fines will sometimes cause serious damage problems downhole. The origin of coal fines cannot be explained by conventional sand prediction theory, which was previously designed for conventional sandstone. During the drainage process, the in situ stress change in coal was caused by the combination of the poroelastic effect, methane desorption and compression around the borehole. To prevent nanoscale coal fines, the critical pressure drawdown can be predicted by the comprehensive stress model. A special test was also designed to determine the key model parameters, making the model easy to use. It was proven that the induced stress due to methane desorption can exaggerate the shear failure, which is different from conventional sand prediction theory. Based on the stress model, the safe window of bottom hole pressure was applied for open-hole horizontal wells to prevent the origin of nanoscale coal fines.

A Method for Evaluating the Methane Content of the Nanoscale Pores in Deep Coalbeds.

Since the sampling depth is large in deep coalbed methane wells, during the lifting process of coalbed cores, the core surface pressure drops nonlinearly with time, which is contradictory to the premise of the conventional United States Bureau of Mines (USBM) method and the Smith-Williams method. In this paper, a desorption-diffusion model was established to quantitatively characterize the actual escape process of methane gas from nanoscale pores in coal cores in both the wellbore and desorption tank by considering the nonlinear relationship between the core surface pressure and time. Based on the optimization method, the measured volume of the desorbed gas in the desorption tank was fitted, and then, the amount of lost gas in the wellbore was inferred. The calculation result of the USBM method was smaller than that of the method used in this paper. In the calculation model of lost gas volume proposed in this paper, the lost gas time was corrected, and the non-uniform decreasing characteristics of the core surface pressure were considered. Therefore, the lost gas obtained by this model was more accurate than that obtained by the conventional method.

Virus-Mimicking Liposomal System Based on Dendritic Lipopeptides for Efficient Prevention Ischemia/Reperfusion Injury in the Mouse Liver.

Hepatic ischemia-reperfusion injury (IRI) is a pathophysiological and huge challenge during liver surgical procedures. Herein, virus-mimicking liposomal system based on dendritic lipopeptides for efficient prevention of IRI is reported. These virus-mimicking liposomes not only have virus-like nanostructures and components, but also possess virus-like infections to liver tissue, liver cells, and organelles. The distinguished features for prevention of IRI of viral mimics are as follows: (i) viral envelope-like structure to help avoid the host immune system; (ii) well-defined nanostructure and surface to improve the accumulated efficiency in liver tissue; (iii) viral capsids mimic to enhance liver cell uptake and achieve mitochondrial targeting. This type of virus-mimicking design makes prevention of IRI by drug-loading greatly exceed the control groups with high biocompatibility and facile manufacturing.

Reduction-sensitive polymeric micelles as amplifying oxidative stress vehicles for enhanced antitumor therapy.

Chemotherapy-photodynamic therapy (PDT)-based combination therapy is a currently frequently used means in cancer treatment that photosensitizer was able to generate reactive oxygen species (ROS) for improving chemotherapy, owing to the high oxidative stress of the tumor microenvironment (TME). Whereas, cancer cells were accustomed to oxidative stress by overexpression of antioxidant such as glutathione (GSH), which would consume the damage of ROS, as well as it could result in ineffective treatment. Herein, amplification of oxidative stress preferentially in tumor cells by consuming GSH or generating ROS is a reasonable treatment strategy to develop anticancer drugs. To achieve excellent therapeutic effects, we designed a GSH-scavenging and ROS-generating polymeric micelle mPEG-S-S-PCL-Por (MSLP) for amplifying oxidative stress and enhanced anticancer therapy. The amphiphilic polymer of methoxy poly(ethylene glycol) (mPEG)-S-S-poly(ε-caprolactone) (PCL)-Protoporphyrin (Por) was self-assembled into polymeric micelles with the anticancer drug doxorubicin (DOX) for treatment and tracking via FRET. Spherical DOX/MSLP micelles with the average size of 88.76 ±â€¯3.52 nm was procured with negatively charged surface, reduction sensitivity and high drug loading content (17.47 ±â€¯1.53 %). The intracellular ROS detection showed that the MSLP could deplete glutathione and regenerate additional ROS. The cellular uptake of DOX/MSLP micelles was grabbed real-time monitoring by the Fluorescence resonance energy transfer (FRET) effect between DOX and MSLP. The reduction-sensitive polymeric micelles MSLP as amplifying oxidative stress vehicles combined chemotherapy and PDT exhibited significant antitumor activity both in vitro (IC50 = 0.041 µg/mL) and much better antitumor efficacy than that of mPEG-PCL-Por (MLP) micelles in vivo.