Effects of dietary energy levels on microorganisms and short-chain fatty acids of rumen and tight junction proteins in Honghe Yellow cattle.

This study was conducted to investigate the effects of dietary energy levels on microorganisms and short-chain fatty acids (SCFAs) of rumen and the expression of tight junction proteins in Honghe Yellow cattle. A total of fifteen male Honghe Yellow cattle were randomly divided into three treatments (five replicates per treatment), consisting of formulated energy concentrations of 5.90 MJ/kg (high-energy diet, group H), 5.60 MJ/kg (medium-energy diet, group M) and 5.30 MJ/kg (low-energy diet, group L). The results showed that compared with group H, the expression of Claudin-1 in rumen epithelium of groups M and L was increased, but the expression of ZO-1 was decreased (p < 0.05). Moreover, compared with group H, group M down-regulated the expression of Occludin and Claudin-1 in the brain (p < 0.05). For rumen bacteria, the dominant phyla included Bacteroidetes and Firmicutes, the abundance of Actinobacteriota in groups M and L was significantly increased compared with group H (p < 0.05). At the genus level, the relative abundance of Corynebacterium, Eubacterium_nodatum_group and Neisseraceae in groups M and L was significantly decreased compared with group H (p < 0.05). For rumen fungi, the dominant phyla included Basidiomycota, Ascomycota and Neocariastigomycota, the relative abundance of Ascomycetes was significantly higher than that of groups M and L compared with group H (p < 0.05). At the genus level, the relative abundance of Neocelimastigaceae and Myceliophthora in groups M and L was significantly reduced compared with group H (p < 0.05). Furthermore, the expression of Claudin-1 in rumen epithelium was significantly positively correlated with Actinobacteriota, Corynebacterium and Neisseriaceae. The expression of ZO-1 in the spinal cord was significantly positively correlated with Myceliophthora. The expression of Occludin in brain was positively correlated with valerate content (p < 0.05). In summary, dietary energy levels affected the rumen microbiota of Honghe Yellow cattle. The expression of Claudin-1 in rumen epithelium and the total SCFAs concentration were increased with decreasing dietary energy levels, but the expression of Claudin-1 in brain and ZO-1 in the spinal cord were reduced with decreasing dietary energy levels. Meanwhile, the rumen microbiota and SCFAs were significantly correlated with the expression of TJP.

Crystal engineering of bimetallic cobalt-based metal-organic framework nanosheets for high-performance aqueous rechargeable cobalt-zinc batteries.

Aqueous rechargeable Zn-based batteries (ARZBs) have attracted increasing attention as favorable candidates for energy storage systems due to their high security, environmental friendliness, and abundance of electrode materials. At present, the most widely reported materials used in cobalt-zinc (Co-Zn) batteries are cobalt-based oxides and their derivatives, however, they still exhibit low actual capacities and unsatisfactory cycle lives. Metal-organic frameworks (MOFs), as a new class of porous materials with high specific surface area and adjustable pore size, have attracted considerable attention in the field of energy storage. Currently, pristine MOFs have currently few applications in Co-Zn batteries, and their performance is not ideal. Herein, we report a series of two-dimensional (2D) bimetallic CoM-MOF (M = Ni, Mn, Mg and Cu) nanosheets based on trimesic acid (H3BTC) ligand as cathodes for alkaline Co-Zn batteries via a simple one-pot hydrothermal synthesis. Among the synthesized MOFs, the CoNi-MOF nanosheets have the best performance, exhibiting a high reversible capacity of 344 mA h g-1 and demonstrating a good cycling life with 90 % capacity retention at 20 A g-1 after 1500 cycles. The energy storage mechanism is studied through a series of ex-situ characterizations. This study is of great importance in advancing the application of 2D pristine MOFs for high-performance Co-Zn batteries.

Asymmetric Synthesis of CIDD-0072424 via an Enantioselective Nitro-Mannich Reaction: A Central Nervous System Penetrant, Selective Small Molecule Inhibitor of Protein Kinase C Epsilon.

CIDD-0072424 is a novel small molecule developed in silico with remarkable activity for the inhibition of protein kinase C (PKC)-epsilon to treat alcohol use disorder. We developed a concise synthesis of (S)-2 that is highly enantioselective, scalable, and amenable for 3-point structure-activity relationship (SAR) studies for compound optimization. The highly enantioselective nitro-Mannich reaction was achieved through a dual-reagent catalysis system. The overall utility and the efficiency of the enantioselective route provided a scalable synthesis of both PKCε inhibitors 1 and 2.

Bilayered nanostructured V2O5 nH2O xerogel constructed 2D nano-papers for efficient aqueous zinc/magnesium ion storage.

Aqueous zinc ion batteries (AZIBs) and aqueous magnesium ion batteries (AMIBs) offer powerful alternatives for large-scale energy storage because of their high safety and low cost. Consequently, the design of high-performance cathode materials is essential. In this paper, we present a simple strategy that combines oxygen defect (Od) engineering with a 2D-on-2D homogeneous nanopape-like bilayer V2O5 nH2O xerogel (BL-HVOd NPS). This strategy employs Od to improve Zn2+/Mg2+insertion/extraction kinetics and reduce irreversible processes for high-performance AZIBs/AMIBs. And interlayer water molecules serve as an effective spacer to stabilize the expanded interlayer gap in BL-HVOd NPS, thereby providing extended diffusion channels for Zn2+/Mg2+ during insertion/extraction. The interlayer water molecules help shield the electrostatic interaction between Zn2+/Mg2+ and BL-HVOd NPS lattice, which improves diffusion kinetics during repeated. In addition, electrochemical characterization results indicate that the BL-HVOd NPS can effectively the surface adsorption and internal diffusion of Zn2+/Mg2+. More importantly, the successfully prepared unique 2D-on-2D homogenous nanopaper structure enhances electrolyte/electrode contact and reduces the migration/diffusion path of electrons/Zn2+ and Mg2+, thus greatly improving rate performance. As a result, the BL-HVOd NPS as AZIBs/AMIBs electrodes offer better reversible capacity of 361.8 and 162.8 mA h g-1 (at 0.2 A g-1), while displaying impressively long cycle lifes. This method provides a way to prepare advanced xerogel cathode materials for AZIBs and AMIBs.

Emerging Doped Metal-Organic Frameworks: Recent Progress in Synthesis, Applications, and First-Principles Calculations.

Metal-organic frameworks (MOFs) are crystalline porous materials with a long-range ordered structure and excellent specific surface area and have found a wide range of applications in diverse fields, such as catalysis, energy storage, sensing, and biomedicine. However, their poor electrical conductivity and chemical stability, low capacity, and weak adhesion to substrates have greatly limited their performance. Doping has emerged as a unique strategy to mitigate the issues. In this review, the concept, classification, and characterization methods of doped MOFs are first introduced, and recent progress in the synthesis and applications of doped MOFs, as well as the rapid advancements and applications of first-principles calculations based on the density functional theory (DFT) in unraveling the mechanistic origin of the enhanced performance are summarized. Finally, a perspective is included to highlight the key challenges in doping MOF materials and an outlook is provided on future research directions.

Liver injury due to endothelin receptor antagonists: a real-world study based on post-marketing drug monitoring data.

BACKGROUND: Liver injury is the hallmark adverse reaction of endothelin receptor antagonist (ERA). Since the first drug, bosentan has been widely used in clinical practice, hepatotoxicity has been accompanied by the history of ERA. The new ERA has been proven to have a lower liver risk but the current research findings are inconsistent. ERA-based targeted drug combinations are commonly used in the treatment of pulmonary arterial hypertension, where the risk of liver injury is difficult to estimate. OBJECTIVES: This study aimed to compare the correlation between ERA and different ERA combination regimens with liver injury in the real world. DESIGN: This is a retrospective study using data from the Adverse Event Reporting System (Food and Drug Administration AERS, FAERS). METHODS: The study used proportional imbalance and Bayesian analysis to mine FAERS data from January 2004 to December 2022 to determine the association of three ERAs with liver injury and to further mine the risk of liver injury due to the combination of ERAs with other targeted drugs. In addition, we analyzed the onset time, mortality, and hospitalization rate of liver injury caused by different ERA combination regimens. RESULTS: We screened out 3581 ERA-related liver injury events, of which bosentan (59.82%) had the largest number of cases. The patients with liver injury were mainly female (60.63%), and the age was concentrated between 61 and 75 years (26.75%). According to different signal mining methods, reporting odds ratio (ROR; 3.38, 95% confidence interval = 3.23-3.53), proportional reporting ratio (PRR; 3.22, χ2 = 37.84), Bayesian confidence propagation neural network (BCPNN; 1.68, 95% confidence interval = 1.61), multi-item gamma Poisson shrinker (MGPS; 3.21, 95% confidence interval = 3.09), bosentan had the strongest association with liver injury compared to ambrisentan and macitentan. Furthermore, bosentan + sildenafil [ROR (2.52, 95% confidence interval = 2.23-2.84), PRR (2.44, χ2 = 15.92), BCPNN (1.29, 95% confidence interval = 1.14), MGPS (2.44, 95% confidence interval = 2.21)], bosentan + epoprostenol [ROR (5.39, 95% confidence interval = 4.29-6.77), PRR (4.94, χ2 = 65.18), BCPNN (2.30, 95% confidence interval = 1.83), MGPS (4.94, 95% confidence interval = 4.08)], bosentan + iloprost [ROR (2.70, 95% confidence interval = 2.11-3.45), PRR (2.61, χ2 = 31.03), BCPNN (1.38, 95% confidence interval = 1.08), MGPS (2.61, 95% confidence interval = 2.12)] had a higher risk of liver injury caused by the three ERA combination regimens. The median time to onset of hepatotoxicity associated with all ERA combination regimens was 259 days (interquartile range: 58-716.5 days). Finally, the hospitalization rate for patients experiencing hepatotoxicity with ERA combination regimens was 47.86% and the mortality rate was 12.67%. CONCLUSION: By mining the FAERS, we analyzed and compared the risk of liver injury related to different ERA and ERA combination regimens, and the onset time and adverse reaction outcomes of all ERA combination regimens. According to the results of the study, bosentan had the highest risk of liver injury and the combination regimens bosentan + sildenafil, bosentan + epoprostenol, and bosentan + iloprost had a stronger risk of liver injury. From the early stages of treatment, we need to regularly monitor the liver function of patients, especially for females and the elderly, and discontinue the suspected drug as soon as the liver injury occurs.

Specific tissue engineering for temporomandibular joint disc perforation.

BACKGROUND: The temporomandibular joint (TMJ) disc is a critical fibrocartilaginous structure with limited regenerative capacity in the oral system. Perforation of the TMJ disc can lead to osteoarthritis and ankylosis of the TMJ because of the lack of disc protection. Clinical treatments for TMJ disc perforation, such as discectomy, hyaluronic acid injection, endoscopic surgery and high position arthroplasty of TMJ, are questionable with regard to long-term outcomes, and only three fourths of TMJ disc perforations are repairable by surgery, even in the short-term. Tissue engineering offers the potential for cure of repairable TMJ disc perforations and regeneration of unrepairable ones. OBJECTIVES: This review discusses the classification of TMJ disc perforation and defines typical TMJ disc perforation. Advancements in the engineering-based repair of TMJ disc perforation by stem cell therapy, construction of a disc-like scaffold and functionalization by offering bioactive stimuli are also summarized in the review, and the barriers developing engineering technologies need to overcome to be popularized are discussed.

Emerging Pristine MOF-Based Heterostructured Nanoarchitectures: Advances in Structure Evolution, Controlled Synthesis, and Future Perspectives.

Metal-organic frameworks (MOFs) can be customized through modular assembly to achieve a wide range of potential applications, based on their desired functionality. However, most of the initially reported MOFs are limited to microporous systems and are not sufficiently stable, which restricts their popularization. Heterogeneity is introduced into a simple MOF framework to create MOF-based heterostructures with fascinating properties and interesting functions. Heterogeneity can be introduced into the MOFs via postsynthetic/ligand exchange. Although the ligand exchange has shown potential, it is difficult to precisely control the degree of exchange or position. Among the various synthesis strategies, hierarchical assembly is particularly attractive for constructing MOF-based heterostructures, as it can achieve precise regulation of MOF-based heterostructured nanostructures. The hierarchical assembly significantly expands the compositional diversity of MOF-based heterostructures, which has high elasticity for lattice matching during the epitaxial growth of MOFs. This review focuses on the synthetic evolution mechanism of hierarchical assemblies of MOF-based nanoarchitectures. Subsequently, the precise control of pore structure, pore size, and morphology of MOF-based nanoarchitectures by hierarchical assembly is emphasized. Finally, possible solutions to address the challenges associated with heterogeneous interfaces are presented, and potential opportunities for innovative applications are proposed.

A Survey on Label-Efficient Deep Image Segmentation: Bridging the Gap Between Weak Supervision and Dense Prediction.

The rapid development of deep learning has made a great progress in image segmentation, one of the fundamental tasks of computer vision. However, the current segmentation algorithms mostly rely on the availability of pixel-level annotations, which are often expensive, tedious, and laborious. To alleviate this burden, the past years have witnessed an increasing attention in building label-efficient, deep-learning-based image segmentation algorithms. This paper offers a comprehensive review on label-efficient image segmentation methods. To this end, we first develop a taxonomy to organize these methods according to the supervision provided by different types of weak labels (including no supervision, inexact supervision, incomplete supervision and inaccurate supervision) and supplemented by the types of segmentation problems (including semantic segmentation, instance segmentation and panoptic segmentation). Next, we summarize the existing label-efficient image segmentation methods from a unified perspective that discusses an important question: how to bridge the gap between weak supervision and dense prediction - the current methods are mostly based on heuristic priors, such as cross-pixel similarity, cross-label constraint, cross-view consistency, and cross-image relation. Finally, we share our opinions about the future research directions for label-efficient deep image segmentation.

Selective and brain-penetrant lanosterol synthase inhibitors target glioma stem-like cells by inducing 24(S),25-epoxycholesterol production.

Glioblastoma (GBM) is an aggressive adult brain cancer with few treatment options due in part to the challenges of identifying brain-penetrant drugs. Here, we investigated the mechanism of MM0299, a tetracyclic dicarboximide with anti-glioblastoma activity. MM0299 inhibits lanosterol synthase (LSS) and diverts sterol flux away from cholesterol into a "shunt" pathway that culminates in 24(S),25-epoxycholesterol (EPC). EPC synthesis following MM0299 treatment is both necessary and sufficient to block the growth of mouse and human glioma stem-like cells by depleting cellular cholesterol. MM0299 exhibits superior selectivity for LSS over other sterol biosynthetic enzymes. Critical for its application in the brain, we report an MM0299 derivative that is orally bioavailable, brain-penetrant, and induces the production of EPC in orthotopic GBM tumors but not normal mouse brain. These studies have implications for the development of an LSS inhibitor to treat GBM or other neurologic indications.

Emerging 2D Copper-Based Materials for Energy Storage and Conversion: A Review and Perspective.

2D materials have shown great potential as electrode materials that determine the performance of a range of electrochemical energy technologies. Among these, 2D copper-based materials, such as Cu-O, Cu-S, Cu-Se, Cu-N, and Cu-P, have attracted tremendous research interest, because of the combination of remarkable properties, such as low cost, excellent chemical stability, facile fabrication, and significant electrochemical properties. Herein, the recent advances in the emerging 2D copper-based materials are summarized. A brief summary of the crystal structures and synthetic methods is started, and innovative strategies for improving electrochemical performances of 2D copper-based materials are described in detail through defect engineering, heterostructure construction, and surface functionalization. Furthermore, their state-of-the-art applications in electrochemical energy storage including supercapacitors (SCs), alkali (Li, Na, and K)-ion batteries, multivalent metal (Mg and Al)-ion batteries, and hybrid Mg/Li-ion batteries are described. In addition, the electrocatalysis applications of 2D copper-based materials in metal-air batteries, water-splitting, and CO2 reduction reaction (CO2 RR) are also discussed. This review also discusses the charge storage mechanisms of 2D copper-based materials by various advanced characterization techniques. The review with a perspective of the current challenges and research outlook of such 2D copper-based materials for high-performance energy storage and conversion applications is concluded.

Fe, Co-codoped layered double hydroxide nanosheet arrays derived from zeolitic imidazolate frameworks for high-performance aqueous hybrid supercapacitors and Zn-Ni batteries.

In the past decade, layered double hydroxides (LDHs) have attracted great attention in the field of energy storage owing to their excellent two-dimensional (2D) hydrotalcite-like structure, highly reversible redox kinetics, and adjustable composition. At the same time, nanomaterials constructed by ultrathin nanosheets have enhanced conductivity, rich electrochemical active sites and fast charge transfer channels, showing better electrochemical properties. Herein, we designed three-dimensional (3D) NiFeCo LDH vertical nanosheet arrays (denoted NiFeCo-LDH NA) assembled by the tight interconnection of 2D nanosheets using a Ni-coordinated zeolitic imidazolate framework (Ni-ZIF-L) as a sacrificial template via facile ion exchange and etching reaction processes under hydrothermal conditions. The appropriate doping ratio of iron and cobalt ions is regulated. Electrochemical tests show that the NiFeCo LDH NA-based electrode shows a high specific capacity of 1495C g-1 at 1 A g-1 and has great cycling stability (89% capacitance retention over 10,000 cycles). The assembled hybrid supercapacitor (NiFeCo LDH NA//AC) achieves a fine energy density of 34.4 W h kg-1 at a power density of 935.5 W kg-1 with good cycling stability of over a 96% retention rate (compared with the initial capacitance) and outstanding coulombic efficiency (nearly 99%) after 15,000 cycles. The constructed aqueous Zn-Ni battery (NiFeCo LDH NA//Zn) exhibits a remarkable specific capacity of 272 mA h g-1 at 3 A g-1 with a high energy density of 464.7 W h kg-1 and retains 81% of the initial specific capacity after 2000 cycles at 20 A g-1. This work not only proves that ternary LDHs can be used as good energy storage materials but also provides a new way to prepare nanomaterials with specific morphology.

Application of Fluorescence In Situ Hybridization (FISH) in Oral Microbial Detection.

Varieties of microorganisms reside in the oral cavity contributing to the occurrence and development of microbes associated with oral diseases; however, the distribution and in situ abundance in the biofilm are still unclear. In order to promote the understanding of the ecosystem of oral microbiota and the diagnosis of oral diseases, it is necessary to monitor and compare the oral microorganisms from different niches of the oral cavity in situ. The fluorescence in situ hybridization (FISH) has proven to be a powerful tool for representing the status of oral microorganisms in the oral cavity. FISH is one of the most routinely used cytochemical techniques for genetic detection, identification, and localization by a fluorescently labeled nucleic acid probe, which can hybridize with targeted nucleic acid sequences. It has the advantages of rapidity, safety, high sensitivity, and specificity. FISH allows the identification and quantification of different oral microorganisms simultaneously. It can also visualize microorganisms by combining with other molecular biology technologies to represent the distribution of each microbial community in the oral biofilm. In this review, we summarized and discussed the development of FISH technology and the application of FISH in oral disease diagnosis and oral ecosystem research, highlighted its advantages in oral microbiology, listed the existing problems, and provided suggestions for future development..

A water-soluble fluorescent probe for monitoring mitochondrial GSH fluctuations during oxidative stress.

In this research, we constructed a styrylpyridine derivative-based fluorescent probe MITO-PQDNs to monitor mitochondrial glutathione (GSH). The probe MITO-PQDNs could react rapidly (20 min) with GSH in PBS buffer and exhibited a strong fluorescence signal (586 nm) as well as a significant Stokes shift (200 nm). Moreover, MITO-PQDNs could quantitatively detect GSH with high sensitivity (LOD = 253 nM). Meanwhile, MITO-PQDNs possessed favorable biocompatibility and could detect both endogenous and exogenous GSH in MCF-7 cells. Above all, MITO-PQDNs enabled the detection of fluctuations in mitochondrial GSH concentrations during oxidative stress.

Metal-organic frameworks and their derivatives for metal-ion (Li, Na, K and Zn) hybrid capacitors.

Metal-ion hybrid capacitors (MIHCs) hold particular promise for next-generation energy storage technologies, which bridge the gap between the high energy density of conventional batteries and the high power density and long lifespan of supercapacitors (SCs). However, the achieved electrochemical performance of available MIHCs is still far from practical requirements. This is primarily attributed to the mismatch in capacity and reaction kinetics between the cathode and anode. In this regard, metal-organic frameworks (MOFs) and their derivatives offer great opportunities for high-performance MIHCs due to their high specific surface area, high porosity, topological diversity, and designable functional sites. In this review, instead of simply enumerating, we critically summarize the recent progress of MOFs and their derivatives in MIHCs (Li, Na, K, and Zn), while emphasizing the relationship between the structure/composition and electrochemical performance. In addition, existing issues and some representative design strategies are highlighted to inspire breaking through existing limitations. Finally, a brief conclusion and outlook are presented, along with current challenges and future opportunities for MOFs and their derivatives in MIHCs.

Exploring 2D Energy Storage Materials: Advances in Structure, Synthesis, Optimization Strategies, and Applications for Monovalent and Multivalent Metal-Ion Hybrid Capacitors.

The design and development of advanced energy storage devices with good energy/power densities and remarkable cycle life has long been a research hotspot. Metal-ion hybrid capacitors (MHCs) are considered as emerging and highly prospective candidates deriving from the integrated merits of metal-ion batteries with high energy density and supercapacitors with excellent power output and cycling stability. The realization of high-performance MHCs needs to conquer the inevitable imbalance in reaction kinetics between anode and cathode with different energy storage mechanisms. Featured by large specific surface area, short ion diffusion distance, ameliorated in-plane charge transport kinetics, and tunable surface and/or interlayer structures, 2D nanomaterials provide a promising platform for manufacturing battery-type electrodes with improved rate capability and capacitor-type electrodes with high capacity. In this article, the fundamental science of 2D nanomaterials and MHCs is first presented in detail, and then the performance optimization strategies from electrodes and electrolytes of MHCs are summarized. Next, the most recent progress in the application of 2D nanomaterials in monovalent and multivalent MHCs is dealt with. Furthermore, the energy storage mechanism of 2D electrode materials is deeply explored by advanced characterization techniques. Finally, the opportunities and challenges of 2D nanomaterials-based MHCs are prospected.

A NIR fluorescence probe for monitoring Cys upregulation induced by balsam pear polysaccharide and imaging in zebrafish.

In this work, we introduced the acrylate recognition group into dicyanoisophorone derivative DCI-C-OH to construct the NIR fluorescent probe DCI-C-Cys with a large Stokes shift (240 nm). DCI-C-Cys could specifically respond to Cys, resulting in a 22-fold increase in fluorescence intensity at 702 nm. Meanwhile, the probe has the advantages of good water solubility, high sensitivity (93 nM), and excellent biocompatibility. Moreover, DCI-C-Cys successfully monitored endogenous and exogenous Cys in HepG2 cells and zebrafish. Most importantly, we found that balsam pear polysaccharide could lead to the increase of intracellular Cys levels, which might be conducive to the further study of the antioxidant mechanism of balsam pear polysaccharide.

The uncertainty of boundary can improve the classification accuracy of BI-RADS 4A ultrasound image.

PURPOSE: The Breast Imaging-Reporting and Data System (BI-RADS) for ultrasound imaging provides a widely used reporting schema for breast imaging. Previous studies have shown that in ultrasound imaging, 90% of BI-RADS 4A tumors are benign lesions after biopsies. Unnecessary biopsy procedures can be avoided by accurate classification of BI-RADS 4A tumors. However, the classification task is challenging and has not been fully investigated by existing studies. For benign and malignant tumors of BI-RADS 4A, the appearances of intra-class tumors are highly variable, the characteristics of inter-class tumors is overall-similar. Discriminative features need to be found to improve classification accuracy of BI-RADS 4A tumors. METHODS: In this study, we designed the network using the clinical features of BI-RADS 4A tumors to improve the discrimination ability of network. The boundary information is embedded into the input of the network using the uncertainty. A fine-grained data augmentation method is used to find discriminative features in tumor information embedded with boundary information. Two mathematical methods, voting-based and variance-based, are used to define the uncertainty of boundary, and the differences of these two definitions are compared in a classification network. RESULTS: The dataset we used to evaluate our method had 1155 2D grayscale images. Each image represented a unique BI-RADS 4A tumor. Among them, 248 tumors were proven to be malignant by biopsy, and the remaining 907 were benign. A weakly supervised data augmentation network (WS-DAN) was used as the backbone classification network, which showed competitive performance in finding discriminative features. Using the auxiliary input of the uncertain boundaries defined by the voting method, the area under the curve (AUC) value of our method was 0.8347 (sensitivity = 0.7774, specificity = 0.7459). The AUC value of the variance-based uncertainty was 0.7789. The voting-based uncertainty was higher than the baseline (AUC = 0.803), which only inputs the original image. Compared with the classic classification network, our method had a significant effect improvement (p < 0.01). CONCLUSIONS: Using the uncertain boundaries defined by the voting methods as auxiliary information, we obtained a better performance in the classification of BI-RADS 4A ultrasound images, while variance-based uncertain boundaries had no effect on improving classification performance. Additionally, fine-grained network helped find discriminative features comparing with the commonly used classification networks.

The Effect of Temperature and Moisture on Colonization of Apple Fruit and Branches by Botryosphaeria dothidea.

Botryosphaeria dothidea causes severe disease of apple trees in China. The process of conidium germination, colonization, and infection of apple fruit and branches was examined on 'Fuji' apple and the effect of temperature, surface wetness and relative humidity (RH), and host surface washates on these processes was studied in controlled environments. Initial germ tube development and hyphal growth resulted in the colonization of the host surface without forming an infection structure. Hyphae expanded radially across the host surface and, after entering lenticels, developed into a dense mycelium mass or differentiated pseudoparenchyma. Hyphae from the bottom of the pseudoparenchyma either directly penetrated the lenticel surface intercellularly through the cell layer, or formed an undifferentiated hypha that invaded the lenticel through cracks formed during the lenticel development. Conidial germination and hyphal colonization occurred at 10 to 40°C, with an optimum of approximately 28°C. Conidial germination required an RH > 95% or surface wetness but, for hyphal colonization, an RH > 90% was sufficient. Conidia germinated and formed germ tubes within 1 h under optimum conditions. However, the pathogen required a longer period at RH > 90% or surface wetness for hyphae to colonize and form pseudoparenchyma or dense mycelia on the host surface. Hyphal colonization is a crucial stage for infection of apple tissues by B. dothidea.

Cytotoxic effect of carbohydrate derivatives of digitoxigenin involves modulation of plasma membrane Ca2+ -ATPase.

Cardiac glycosides, such as digoxin and digitoxin, are compounds that interact with Na+ /K+ -ATPase to induce anti-neoplastic effects; however, these cardiac glycosides have narrow therapeutic index. Thus, semi-synthetic analogs of digitoxin with modifications in the sugar moiety has been shown to be an interesting approach to obtain more selective and more effective analogs than the parent natural product. Therefore, the aim of this study was to assess the cytotoxic potential of novel digitoxigenin derivatives, digitoxigenin-α-L-rhamno-pyranoside (1) and digitoxigenin-α-L-amiceto-pyranoside (2), in cervical carcinoma cells (HeLa) and human diploid lung fibroblasts (Wi-26-VA4). In addition, we studied the anticancer mechanisms of action of these compounds by comparing its cytotoxic effects with the potential to modulate the activity of three P-type ATPases; Na+ /K+ -ATPase, sarco/endoplasmic reticulum Ca2+ -ATPase (SERCA), and plasma membrane Ca2+ -ATPase (PMCA). Briefly, the results showed that compounds 1 and 2 were more cytotoxic and selectivity for HeLa tumor cells than the nontumor cells Wi-26-VA4. While the anticancer cytotoxicity in HeLa cells involves the modulation of Na+ /K+ -ATPase, PMCA and SERCA, the modulation of these P-type ATPases was completely absent in Wi-26-VA4 cells, which suggest the importance of their role in the cytotoxic effect of compounds 1 and 2 in HeLa cells. Furthermore, the compound 2 inhibited directly erythrocyte ghosts PMCA and both compounds were more cytotoxic than digitoxin in HeLa cells. These results provide a better understanding of the mode of action of the synthetic cardiac glycosides and highlights 1 and 2 as potential anticancer agents.