Mitochondrial activity related genes of mast cells identify poor prognosis and metastasis of ovarian cancer.

The pro-tumorigenic or anti-tumorigenic role of tumor infiltrating mast cells (TIMs) in tumors depends not only on the type of cancer and the degree of tumor progression, but also on their location in the tumor bulk. In our investigation, we employed immunohistochemistry to reveal that the mast cells (MCs) in the tumor stroma are positively correlated with metastasis of ovarian cancer (OC), but not in the tumor parenchyma. To delve deeper into the influence of different culture matrix stiffness on MCs' biological functions within the tumor parenchymal and stromal regions, we conducted a transcriptome analysis of the mouse MC line (P815) cultured in two-dimensional (2D) or three-dimensional (3D) culture system. Further research has found that the softer 3D extracellular matrix stiffness could improve the mitochondrial activity of MCs to promote proliferation by increasing the expression levels of mitochondrial activity-related genes, namely Pet100, atp5md, and Cox7a2. Furthermore, employing LASSO regression analysis, we identified that Pet100 and Cox7a2 were closely associated with the prognosis of OC patients. These two genes were subsequently employed to construct a risk score model, which revealed that the high-risk group model as one of the prognostic factors for OC patients. Additionally, the XCell algorithm analysis showed that the high-risk group displayed a broader spectrum of immune cell infiltrations. Our research revealed that TIMs in the tumor stroma could promote the metastasis of OC, and mitochondrial activity-related proteins Pet100/Cox7a2 can serve as biomarkers for prognostic evaluation of OC.

Cell sheet formation enhances the therapeutic effects of adipose-derived stromal vascular fraction on urethral stricture.

Urethral stricture (US) is a common disease in urology, lacking effective treatment options. Although injecting a stem cells suspension into the affected area has shown therapeutic benefits, challenges such as low retention rate and limited efficacy hinder the clinical application of stem cells. This study evaluates the therapeutic impact and the mechanism of adipose-derived vascular fraction (SVF) combined with cell sheet engineering technique on urethral fibrosis in a rat model of US. The results showed that SVF-cell sheets exhibit positive expression of α-SMA, CD31, CD34, Stro-1, and eNOS. In vivo study showed less collagen deposition, low urethral fibrosis, and minimal tissue alteration in the group receiving cell sheet transplantation. Furthermore, the formation of a three-dimensional (3D) tissue-like structure by the cell sheets enhances the paracrine effect of SVF, facilitates the infiltration of M2 macrophages, and suppresses the TGF-ß/Smad2 pathway through HGF secretion, thereby exerting antifibrotic effects. Small animal in vivo imaging demonstrates improved retention of SVF cells at the damaged urethra site with cell sheet application. Our results suggest that SVF combined with cell sheet technology more efficiently inhibits the early stages of urethral fibrosis.

Technical Risk Stratification Nomogram Model for 90-Day Mortality Prediction in Patients With Acute Basilar Artery Occlusion Undergoing Endovascular Thrombectomy: A Multicenter Cohort Study.

BACKGROUND: This study aimed to establish and validate a nomogram model for predicting 90-day mortality in patients with acute basilar artery occlusion receiving endovascular thrombectomy. METHODS AND RESULTS: A total of 242 patients with basilar artery occlusion undergoing endovascular thrombectomy were enrolled in our study, in which 172 patients from 3 stroke centers were assigned to the training cohort, and 70 patients from another center were assigned to the validation cohort. Univariate and multivariate logistic regression analyses were adopted to screen prognostic predictors, and those with significance were subjected to establish a nomogram model in the training cohort. The discriminative accuracy, calibration, and clinical usefulness of the nomogram model was verified in the internal and external cohorts. Six variables, including age, baseline National Institutes of Health Stroke Scale score, Posterior Circulation-Alberta Stroke Program Early CT (Computed Tomography) score, Basilar Artery on Computed Tomography Angiography score, recanalization failure, and symptomatic intracranial hemorrhage, were identified as independent predictors of 90-day mortality of patients with basilar artery occlusion and were subjected to develop a nomogram model. The nomogram model exhibited good discrimination, calibration, and clinical usefulness in both the internal and the external cohorts. Additionally, patients were divided into low-, moderate-, and high-risk groups based on the risk-stratified nomogram model. CONCLUSIONS: Our study proposed a novel nomogram model that could effectively predict 90-day mortality of patients with basilar artery occlusion after endovascular thrombectomy and stratify patients with high, moderate, or low risk, which has a potential to facilitate prognostic judgment and clinical management of stroke.

Boosting knowledge diversity, accuracy, and stability via tri-enhanced distillation for domain continual medical image segmentation.

Domain continual medical image segmentation plays a crucial role in clinical settings. This approach enables segmentation models to continually learn from a sequential data stream across multiple domains. However, it faces the challenge of catastrophic forgetting. Existing methods based on knowledge distillation show potential to address this challenge via a three-stage process: distillation, transfer, and fusion. Yet, each stage presents its unique issues that, collectively, amplify the problem of catastrophic forgetting. To address these issues at each stage, we propose a tri-enhanced distillation framework. (1) Stochastic Knowledge Augmentation reduces redundancy in knowledge, thereby increasing both the diversity and volume of knowledge derived from the old network. (2) Adaptive Knowledge Transfer selectively captures critical information from the old knowledge, facilitating a more accurate knowledge transfer. (3) Global Uncertainty-Guided Fusion introduces a global uncertainty view of the dataset to fuse the old and new knowledge with reduced bias, promoting a more stable knowledge fusion. Our experimental results not only validate the feasibility of our approach, but also demonstrate its superior performance compared to state-of-the-art methods. We suggest that our innovative tri-enhanced distillation framework may establish a robust benchmark for domain continual medical image segmentation.

In Situ Exfoliation Growth Strategy Realizing Controlled Synthesis of 3D to 2D MOF Materials as High-Performance Electrochemical Biosensors.

Two-dimensional (2D) metal-organic framework (MOF) nanosheets with large surface area, ultrathin thickness, and highly accessible active sites have attracted great research attention. Developing efficient approaches to realize the controllable synthesis of well-defined 2D MOFs with a specific composition and morphology is critical. However, it is still a significant challenge to construct thin and uniform 2D MOF nanosheets and resolve the reagglomeration as well as poor stability of target 2D MOF products. Here, an "in situ exfoliation growth" strategy is proposed, where a one-step synthetic process can realize the successful fabrication of PBA/MIL-53(NiFe)/NF nanosheets on the surface of nickel foam (NF) via in situ conversion and exfoliation growth strategies. The PBA/MIL-53(NiFe)/NF nanosheets combine the individual advantages of MOFs, Prussian blue analogues (PBAs), and 2D materials. As expected, the resulting PBA/MIL-53(NiFe)/NF as a glucose electrode exhibits an extremely high sensitivity of 25.74 mA mM-1 cm-2 in a very wide concentration range of 180 nM to 4.8 µM. The present exciting work provides a simple and effective strategy for the construction of high-performance nonenzymatic glucose electrochemical biosensors.

A general approach to stereospecific Pd-catalyzed cross-coupling reactions of benzylic stereocenters.

We have developed a general process for the formation of enantioenriched benzylic stereocenters via stereospecific Pd-catalyzed cross-coupling reactions of enantioenriched benzylic tricyclohexyltin nucleophiles. This process proceeds with excellent stereospecificity for a remarkably broad scope of electrophilic coupling partners including aryl and heteroaryl halides and triflates, acid chlorides, thioesters, chloroformates, and carbamoyl chlorides. Thus, enantioenriched 1,1-diarylalkanes as well as formal products of asymmetric enolate arylation are readily accessed using this approach. We additionally provide the first demonstration of a Sn-selective cross-coupling reaction using a vicinal alkylborylstannane nucleophile. In these reactions, the presence of cyclohexyl spectator ligands on tin is essential to ensure selective transfer of the secondary benzylic unit from tin to palladium.

Trajectory-Aware Adaptive Imaging Clue Analysis for Guidewire Artifact Removal in Intravascular Optical Coherence Tomography.

Guidewire Artifact Removal (GAR) involves restoring missing imaging signals in areas of IntraVascular Optical Coherence Tomography (IVOCT) videos affected by guidewire artifacts. GAR helps overcome imaging defects and minimizes the impact of missing signals on the diagnosis of CardioVascular Diseases (CVDs). To restore the actual vascular and lesion information within the artifact area, we propose a reliable Trajectory-aware Adaptive imaging Clue analysis Network (TAC-Net) that includes two innovative designs: (i) Adaptive clue aggregation, which considers both texture-focused original (ORI) videos and structure-focused relative total variation (RTV) videos, and suppresses texture-structure imbalance with an active weight-adaptation mechanism; (ii) Trajectory-aware Transformer, which uses a novel attention calculation to perceive the attention distribution of artifact trajectories and avoid the interference of irregular and non-uniform artifacts. We provide a detailed formulation for the procedure and evaluation of the GAR task and conduct comprehensive quantitative and qualitative experiments. The experimental results demonstrate that TAC-Net reliably restores the texture and structure of guidewire artifact areas as expected by experienced physicians (e.g., SSIM: 97.23%). We also discuss the value and potential of the GAR task for clinical applications and computer-aided diagnosis of CVDs.

Transcriptome and anatomical studies reveal alterations in leaf thickness under long-term drought stress in tobacco.

Drought is one of the foremost environmental factors that limit the growth of plants. Leaf thickness (LT) is an important quantitative trait in plant physiology. The experiment was carried out in a growth room and the plants were divided into two groups such as well-watered and drought-stressed. This work investigated leaf growth in terms of leaf surface growth and expansion rate, leaf stomata traits, LT, anticlinal growth, and leaf cell layers. The results showed that the leaf area and leaf surface expansion rate were decreased by drought stress (DS). Similarly, LT, anticlinal expansion rate, palisade and spongy tissue thickness, and their related expansion rates were also decreased at different days' time points (DTP) of DS. However, a steady increase was observed in the aforementioned parameters after 12 DTP of DS. The stomatal density increased while stomata size decreased at 3 DTP and 12 DTP (low leaf water potential and relative leaf water content at these time points) and vice versa at 24 DTP compared with the well-watered plants indicating adaptations in these traits in response to DS, and thus the leaf water status played a role in the regulation of leaf stomata traits. The cell length decreased in the upper epidermis, palisade and spongy tissues by DS up to 12 DTP led to lower LT while an increase was observed after 12 DTP that resulted in higher LT. The increase in the LT was supported by the upregulation of starch and sucrose metabolism, glycerolipid metabolism, protein processing in endoplasmic reticulum pathways at 18 DTP along with the differentially expressed genes induced that were related to cell wall remodeling (cellulose, expansin, xyloglucans) and cell expansion (auxin response factors and aquaporin). The results explain the response of leaf thickness to drought stress and show alterations in LT and leaf stomatal traits. This study might serve as a valuable source of gene information for functional studies and provide a theoretical basis to understand leaf growth in terms of leaf anatomy and leaf stomatal traits under drought stress.

Application of 2,4-Epibrassinolide Improves Drought Tolerance in Tobacco through Physiological and Biochemical Mechanisms.

Drought stress is a major abiotic stress that hinders plant growth and development. Brassinosteroids (BR), including 2,4-epibrassinolide (EBR), play important roles in plant growth, development, and responses to abiotic stresses, including drought stress. This work investigates exogenous EBR application roles in improving drought tolerance in tobacco. Tobacco plants were divided into three groups: WW (well-watered), DS (drought stress), and DSB (drought stress + 0.05 mM EBR). The results revealed that DS decreased the leaf thickness (LT), whereas EBR application upregulated genes related to cell expansion, which were induced by the BR (DWF4, HERK2, and BZR1) and IAA (ARF9, ARF6, PIN1, SAUR19, and ABP1) signaling pathway. This promoted LT by 28%, increasing plant adaptation. Furthermore, EBR application improved SOD (22%), POD (11%), and CAT (5%) enzyme activities and their related genes expression (FeSOD, POD, and CAT) along with a higher accumulation of osmoregulatory substances such as proline (29%) and soluble sugars (14%) under DS and conferred drought tolerance. Finally, EBR application augmented the auxin (IAA) (21%) and brassinolide (131%) contents and upregulated genes related to drought tolerance induced by the BR (BRL3 and BZR2) and IAA (YUCCA6, SAUR32, and IAA26) signaling pathways. These results suggest that it could play an important role in improving mechanisms of drought tolerance in tobacco.

Vanadium-Based Trimetallic Metal-Organic-Framework Family as Extremely High-Performing and Ultrastable Electrocatalysts for Water Splitting.

This is the first time that the pore-space-partition (PSP) strategy is being successfully applied in the electrochemical field for water splitting, realizing the highly efficient construction of a series of ultrastable pristine MOF electrocatalysts. On integrating the vanadium-based trimetallic building cluster (M2V), the target M2V-MOFs exhibit excellent electrocatalytic activity for HER, OER, and water splitting. In particular, ultralow overpotentials of 314 and 198 mV for Fe2V-MOF as OER and HER electrocatalysts, respectively, can drive a current density of 10 mA cm-2. The fabricated Fe2V-MOF||Pt/C two-electrode configuration for the overall water splitting yields a current density of 10 mA cm-2 at only 1.6 V vs RHE, which is superior to that of the commercial IrO2||Pt/C couple. Notably, high structural and chemical stabilities still can be observed in alkaline condition. This work opens up an exciting pathway to design efficient and stable electrocatalysts based on pristine MOF by integrating the PSP strategy and multimetallic centers.

Molecular Regulation Based on Functional Trimetallic Metal-Organic Frameworks for Efficient Oxygen Evolution Reaction.

Metal-organic frameworks (MOFs) as classic crystalline porous materials have attracted great interest in the catalytic field. However, how to realize molecular regulation of the MOF structure to achieve a remarkable oxygen evolution reaction (OER) electrocatalyst is still a challenge. Herein, we designed several series of special MOF materials to explore the relationship between the structure and properties as well as the related reactive mechanism. First, various metal centers, including Fe, Co, Ni, Zn, and Mg, were utilized to construct the first series of trimetallic MOF materials, namely, M3-MOF-BDC, where BDC = 1,4-benzenedicarboxylic acid, also known as terephthalic acid. Among of them, Fe3-MOF-BDC shows the best OER performance and only needs an overpotential of 312 mV at 10 mA cm-2. Then, functional BDC-X ligands (X = NH2, OH, NO2, DH) with various characteristic groups were selected to construct a new series, namely, Fe3-MOF-BDC-X, to further improve its OER electrocatalytic performance. As expected, Fe3-MOF-BDC-NH2 exhibited a greatly enhanced OER performance with ultralow Tafel slopes of 45 mV dec-1 and overpotentials of 280 mV at 10 mA cm-2 when the BDC-NH2 ligand was adopted, even superior to commercial IrO2 (323 mV) and most of the reported pristine MOFs as OER electrodes. Much higher structural stability was proven. The detailed structure-property relationship and mechanism are discussed. In a word, this work provides a very important theoretical basis for the design and exploration of new MOF electrocatalysts.

Diazepam ameliorated myocardial ischemia-reperfusion injury via inhibition of C-C chemokine receptor type 2/tumor necrosis factor-alpha/interleukins and Bcl-2-associated X protein/caspase-3 pathways in experimental rats.

Myocardial ischemia-reperfusion injury (IRI) is one of the most leading concerns for public health globally. Diazepam, a local anesthetic, has been reported for its cardioprotective potential. The present investigation aimed to evaluate the possible mechanism of action of diazepam against left anterior descending ligation-induced myocardial IRI in experimental rats. IRI was induced in healthy male rats by ligating coronary artery for 30 min and then reperfused for 60 min. The animals were pre-treated with either vehicle or diltiazem (10 mg/kg) or diazepam (1, 2.5, and 5 mg/kg) for 14 days. Compared to the IRI group, diazepam (2.5 and 5 mg/kg) markedly (P<0.05) attenuated IRI-induced alterations in cardiac function and oxido-nitrosative stress. In addition, diazepam prominently (P<0.05) improved cardiac Na+K+ATPase, Ca2+ATPase levels and hypoxia-inducible factor-1 alpha (HIF-1α) mRNA expression. It also significantly (P<0.05) down-regulated cardiac mRNA expressions of cardiac troponin I (cTn-I), C-C chemokine receptor type 2 (CCR2), tumor necrosis factor-alpha (TNF-α), interleukins (IL)-1ß, and IL-6. In western blot analysis, IRI-induced myocardial apoptosis was reduced by diazepam treatment reflected by a marked (P<0.05) decreased in Bcl-2-associated X protein (Bax) and Caspase-3 protein expression. Diazepam also efficiently (P<0.05) improved IRI-induced histological aberration in cardiac tissue. In conclusion, diazepam exerts cardioprotective effect by inhibiting inflammatory release (CCR2, TNF-α, and ILs), oxido-nitrosative stress, and apoptosis (Bax and Caspase-3) pathway during myocardial IRI in experimental rats.

Exogenous application of brassinosteroids regulates tobacco leaf size and expansion via modulation of endogenous hormones content and gene expression.

Brassinosteroids (BR) play diverse roles in the regulation of plant growth and development. BR promotes plant growth by triggering cell division and expansion. However, the effect of exogenous BR application on the leaf size and expansion of tobacco is unknown. Tobacco seedlings are treated with different concentrations of exogenous 2,4-epibrassinolide (EBL) [control (CK, 0 mol L-1), T1 (0.5 × 10-7 mol L-1), and T2 (0.5 × 10-4 mol L-1)]. The results show that T1 has 17.29% and T2 has 25.99% more leaf area than control. The epidermal cell area is increased by 24.40% and 17.13% while the number of epidermal cells is 7.06% and 21.06% higher in T1 and T2, respectively, relative to control. So the exogenous EBL application improves the leaf area by increasing cell numbers and cell area. The endogenous BR (7.5 times and 68.4 times), auxin (IAA) (4.03% and 25.29%), and gibberellin (GA3) contents (84.42% and 91.76%) are higher in T1 and T2, respectively, in comparison with control. Additionally, NtBRI1, NtBIN2, and NtBES1 are upregulated showing that the brassinosteroid signaling pathway is activated. Furthermore, the expression of the key biosynthesis-related genes of BR (NtDWF4), IAA (NtYUCCA6), and GA3 (NtGA3ox-2) are all upregulated under EBL application. Finally, the exogenous EBL application also upregulated the expression of cell growth-related genes (NtCYCD3;1, NtARGOS, NtGRF5, NtGRF8, and NtXTH). The results reveal that the EBL application increases the leaf size and expansion by promoting the cell expansion and division through higher BR, IAA, and GA3 contents along with the upregulation of cell growth-related genes. The results of the study provide a scientific basis for the effect of EBL on tobacco leaf growth at morphological, anatomical, biochemical, and molecular levels. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12298-021-00971-x.

Circular drought-hardening confers drought tolerance via modulation of the antioxidant defense system, osmoregulation, and gene expression in tobacco.

Drought stress hinders the growth and development of crop plants and ultimately its productivity. It is expected that drought stress will be frequent and intense in the future due to drastic changes in the global climate. It is necessary to make crop plants more resilient to drought stress through various techniques; drought-hardening is one of them. Defining various metabolic strategies used by tobacco plants to confer drought tolerance will be important for maintaining plant physiological functions, but studies addressing this topic are limited. This study was designed to elucidate the drought tolerance and adaptation strategies used by tobacco plants via the application of different circular drought-hardening cycles (control: no drought-hardening, T1: one cycle of drought hardening, T2: two cycles of drought-hardening, and T3: three cycles of drought-hardening) to two tobacco varieties namely Honghuadajinyuan (H) and Yun Yan-100 (Y). The results revealed that drought-hardening decreased the fresh and dry biomass of the tobacco plants. The decrease was more pronounced in the T3 treatment for both H (23 and 29%, respectively) and Y (26 and 31%, respectively) under drought stress. The MDA contents, especially in T1 and T2 in both varieties, were statistically similar compared with control under drought stress. Similarly, higher POD, APX, and GR activities were observed, especially in T3, and elevated amounts of AsA and GSH were also observed among the different circular drought-hardening treatments under drought stress. Thus circular drought-hardening mitigated the oxidative damage by increasing the antioxidant enzyme activities and elevated the content of antioxidant substances, a key metabolic strategy under drought stress. Similarly, another important plant metabolic strategy is the osmotic adjustment. Different circular drought-hardening treatments improved the accumulation of proline and soluble sugars contents which contributed to osmoregulation. Finally, at the molecular level, circular drought-hardening improved the transcript levels of antioxidant enzyme-related genes (CAT, APX1, and GR2), proline and polyamines biosynthesis-related genes (P5CS1 and ADC2), and ABA signaling (SnRK2), and transcription factors (AREB1 and WRKY6) in response to drought stress. As a result, circular drought-hardening (T2 and T3 treatments) promoted tolerance to water stress via affecting the anti-oxidative capacity, osmotic adjustment, and regulation of gene expression in tobacco.

The Effects of the Alkaloid Tambjamine J on Mice Implanted with Sarcoma 180 Tumor Cells.

The tambjamines are a small group of bipyrrolic alkaloids that, collectively, display a significant range of biological activities including antitumor, antimicrobial and immunosuppressive properties. The key objective of the present study was to undertake preclinical assessments of tambjamine J (T-J) so as to determine its in vivo antitumor effects. To that end, sarcoma 180 cells were transplanted in mice and the impacts of the title compound then evaluated using a range of protocols including hematological, biochemical, histopathological, genotoxic and clastogenic assays. As a result it was established that this alkaloid has a significant therapeutic window and effectively reduces tumor growth (by 40 % and 79 % at doses of 10 and 20 mg/kg/day, respectively). In this regard it displays similar antitumor activity to the anticancer agent cyclophosphamide and alters animal weight in an analogous manner.

Drought-hardening improves drought tolerance in Nicotiana tabacum at physiological, biochemical, and molecular levels.

BACKGROUND: Drought stress is the most harmful one among other abiotic stresses with negative impacts on crop growth and development. Drought-hardening is a feasible and widely used method in tobacco seedlings cultivation. It has gained extensive interests due to its role in improving drought tolerance. This research aimed to investigate the role of drought-hardening and to unravel the multiple mechanisms underlying tobacco drought tolerance and adaptation. RESULTS: This study was designed in which various drought-hardening treatments (CK (no drought-hardening), T1 (drought-hardening for 24 h), T2 (drought-hardening for 48 h), and T3 (drought-hardening for 72 h)) were applied to two tobacco varieties namely HongHuaDaJinYuan (H) and Yun Yan-100 (Y). The findings presented a complete framework of drought-hardening effect at physiological, biochemical, and gene expression levels of the two tobacco varieties under drought stress. The results showed that T2 and T3 significantly reduced the growth of the two varieties under drought stress. Similarly, among the various drought-hardening treatments, T3 improved both the enzymatic (POD, CAT, APX) and non-enzymatic (AsA) defense systems along with the elevated levels of proline and soluble sugar to mitigate the negative effects of oxidative damage and bringing osmoregulation in tobacco plants. Finally, the various drought-hardening treatments (T1, T2, and T3) showed differential regulation of genes expressed in the two varieties, while, particularly T3 drought-hardening treatment-induced drought tolerance via the expression of various stress-responsive genes by triggering the biosynthesis pathways of proline (P5CS1), polyamines (ADC2), ABA-dependent (SnRK2, AREB1), and independent pathways (DREB2B), and antioxidant defense-related genes (CAT, APX1, GR2) in response to drought stress. CONCLUSIONS: Drought-hardening made significant contributions to drought tolerance and adaptation in two tobacco variety seedlings by reducing its growth and, on the other hand, by activating various defense mechanisms at biochemical and molecular levels. The findings of the study pointed out that drought-hardening is a fruitful strategy for conferring drought tolerance and adaptations in tobacco. It will be served as a useful method in the future to understand the drought tolerance and adaptation mechanisms of other plant species. Drought-hardening improved drought tolerance and adaptation of the two tobacco varieties. T1 indicates drought-hardening for 24 h, T2 indicates drought-hardening for 48 h, T3 indicates drought-hardening for 72 h.

MOF-Derived Bimetallic CoFe-PBA Composites as Highly Selective and Sensitive Electrochemical Sensors for Hydrogen Peroxide and Nonenzymatic Glucose in Human Serum.

The fabrication of two-dimensional (2D) metal-organic frameworks (MOFs) and Prussian blue analogues (PBAs) combines the advantages of 2D materials, MOFs and PBAs, resolving the poor electronic conductivity and slow diffusion of MOF materials for electrochemical applications. In this work, 2D leaflike zeolitic imidazolate frameworks (Co-ZIF and Fe-ZIF) as sacrificial templates are in situ converted into PBAs, realizing the successful fabrication of PBA/ZIF nanocomposites on nickel foam (NF), namely, CoCo-PBA/Co-ZIF/NF, FeFe-PBA/Fe-ZIF/NF, CoFe-PBA/Co-ZIF/NF, and Fe/CoCo-PBA/Co-ZIF/NF. Such fabrication can effectively reduce transfer resistance and greatly enhance electron- and mass-transfer efficiency due to the electrochemically active PBA particles and NF substrate. These fabricated electrodes as multifunctional sensors achieve highly selective and sensitive glucose and H2O2 biosensing with a very wide detective linear range, extremely low limit of detection (LOD), and good stability. Among them, CoFe-PBA/Co-ZIF/NF exhibits the best sensing performance with a very wide linear range from 1.4 µM to 1.5 mM, a high sensitivity of 5270 µA mM-1 cm-2, a low LOD of 0.02 µM (S/N = 3), and remarkable stability and selectivity toward glucose. What is more, it can realize excellent detection of glucose in human serum, demonstrating its practical applications. Furthermore, this material as a multifunctional electrochemical sensor also manifests superior detection performance against hydrogen peroxide with a wide linear range of 0.2-6.0 mM, a high sensitivity of 196 µA mM-1 cm-2, and a low limit of detection of 1.08 nM (S/N = 3). The sensing mechanism for enhanced performance for glucose and H2O2 is discussed and proved by experiments in detail.

Antitumor Potential of the Isoflavonoids (+)- and (-)-2,3,9-Trimethoxypterocarpan: Mechanism-of-Action Studies.

Synthetically derived samples of (+)-(6aS,11aS)-2,3,9-trimethoxypterocarpan [(+)-1] and its enantiomer [(-)-1], both of which are examples of naturally occurring isoflavonoids, were evaluated, together with the corresponding racemate, as cytotoxic agents against the HL-60, HCT-116, OVCAR-8, and SF-295 tumor cell lines. As a result it was established that compound (+)-1 was particularly active with OVCAR-8 cells being the most sensitive and responding in a dose-dependent manner. A study of cell viability and drug-induced morphological changes revealed the compound causes cell death through a mechanism characteristic of apoptosis. Finally, a computational study of the interactions of compound (+)-1 and (S)-monastrol, an established, synthetically derived, potent, and cell-permeant inhibitor of mitosis, with the kinesin-type protein Eg5 revealed that both bind to this receptor in a similar manner. Significantly, compound (+)-1 binds with greater affinity, an effect attributed to the presence of the associated methoxy groups.

A General Approach to Stereospecific Cross-Coupling Reactions of Nitrogen-Containing Stereocenters.

A novel strategy employing cyclohexyl spectator ligands in Stille cross-coupling reactions has been developed as a general solution to the long-standing challenge of conducting stereospecific cross-coupling reactions at nitrogen-containing stereocenters. This method enables direct access to enantioenriched products that are difficult (or impossible) to obtain via alternative preparative methods. Selective and predictable transfer of a single secondary alkyl unit can be achieved under reaction conditions that exploit subtle electronic differences between activated and unactivated alkyl units. Through this approach, enantioenriched α-stannylated nitrogen-containing stereocenters undergo Pd-catalyzed arylation and acylation reactions with exceptionally high stereofidelity in all instances investigated. We demonstrate this process by using α-stannylated pyrrolidine, azetidine, and open-chain (benzylic and non-benzylic) nucleophiles in stereospecific reactions. This process will facilitate rapid and reliable access to enantioenriched compounds possessing nitrogen-substituted stereocenters, which constitute ubiquitous structural motifs in biologically active compounds emerging from the drug-discovery process.