Search

The long-lived latently infected cells persist in spite of prolonged highly active anti-retroviral therapy and present a major barrier to a cure of human immunodeficiency virus type 1 (HIV-1) infection. Elimination of this reservoir requires reactivation of the latent virus. None of the current agents can safely and effectively reactivate latent HIV-1 reservoirs. Dilazep, a nucleoside transport inhibitor, is used to treat ischemic dysfunction. However, little is known about the effect of dilazep in inducing HIV expression in latently infected cells. Using the Jurkat T cell model of HIV-1 latency, we found that dilazep effectively reactivates latent HIV-1 gene expression in a dose manner. We observed that dilazep synergistically reactivated latent HIV-1 transcription with valproic acid. We also found that dilazep activates viral latency without inducing cell surface activation markers CD25 and CD69 activation. In summary, dilazep, alone or in combination with VPA, could be useful in future eradication strategies. [ABSTRACT FROM AUTHOR]

Mechanical excavation in hard or very hard rocks is still challenging in rock engineering. One plausible solution is to reduce rock strength prior to mechanical excavation to increase excavation and cost-efficiency. The present study utilizes a 6 kW microwave to irradiate rock specimens and evaluates the variation in rock strength and indentation hardness. Since the contact between the drill bits of roadheaders and the rock surface is a dynamic impact process, dynamic tests are conducted and compared with the quasi-static results. The experimental results demonstrate that short microwave irradiation (30 s) can produce substantial damage to the rock. The reduction of uniaxial compressive strength, Brazilian tensile strength, and indentation hardness under quasi-static loading can be about 39%, 43%, and 44%, respectively, and 33%, 26%, and 50%, respectively, under dynamic loading. In addition, it is found that the tensile strength is the most sensitive to microwave, while the crack density is the least sensitive. More importantly, this reduction is not linear and not monotonic to the irradiation time. The fast reduction of rock strength and indentation hardness after microwave irradiation implies the reduction in the drill-bit wear and increase in the excavation rate, and vigorously demonstrates the great potential of microwave-assisted mechanical excavation of hard or very hard rocks. Highlights: The dynamic indentation test is used to simulate the impact between drill bits and rock surfaces. Short microwave irradiation (30 s) can largely reduce the diorite strength and indentation hardness. The reduction is not linear and not monotonic to the irradiation time, regardless of loading rates. Different physical properties have different sensitivities to the microwave. Experimental results demonstrate the great potential of the microwave technique in hard rock excavation. [ABSTRACT FROM AUTHOR]

In this paper, effect of the coupling matrix with a weight parameter on synchronization pattern in a globally coupled network is investigated. On the basis of matrix theory, the threshold values of the coupling strength and the weight parameter for cluster synchronization have been obtained by utilizing the attractiveness criteria of the invariant synchronization manifold. It shows that cluster synchronization bifurcation comes forth, which concept is first put forward. That is to say, via changing the weight parameter and the coupling strength, the purpose of controlling the number of clusters is achieved, which provides a new idea for control the number of clusters in a network. Numerical simulations are given to demonstrate the theoretical results. In addition, the theoretical results and the numerical simulations also show that full synchronization may not be realized even if the network is globally coupled when there are some negative couplings. [ABSTRACT FROM AUTHOR]

In this paper, the dynamical behavior of a linear Hamiltonian system under two kinds of impulsive control is discussed by means of both theoretical and numerical ways. The existence and stability of the periodic solution are investigated. Moreover, the conditions of existence for a Neimark-Sacker bifurcation are derived by using a discrete map. Numerical results for phase portraits, periodic solutions, and bifurcation diagrams are in good agreement with the theoretical analysis. [ABSTRACT FROM AUTHOR]

Under the assumption that the incidence rate of the infection and the removal rate of the infective by cytotoxic T lymphocytes are nonlinear, we study the global dynamics of a HIV infection model with the response of the immune system using characteristic equation, the Fluctuation lemma, and the direct Lyapunov method. The existence of a threshold parameter, i.e., the basic reproduction number or basic reproductive ratio is established and the global stability of the equilibria is discussed. [ABSTRACT FROM AUTHOR]

Abstract: The dynamical behavior of a stage structure population model with birth pulses and impulsive pest management strategy is discussed analytically and numerically. It is assumed that birth pulse and impulsive pest management strategy act with the same period, but not simultaneously. The existence and stability of the positive 2T-period solution are investigated. By using center manifold theorem and bifurcation theorem, the conditions of existence for flip bifurcation are derived. Moreover, some detailed numerical results for phase portraits, periodic solutions, bifurcation diagram, and chaotic attractors, which are illustrated with two examples, are in good agreement with the theoretical analysis. [Copyright &y& Elsevier]

The thermal damage induced by microwave treatment in rocks has not been well explored, especially when using the dielectric-loaded converging waveguide antennas (DLCWAs). In this paper, the effects of microwave power level, heating time and working distance on the temperature increase, ultrasonic wave velocity reduction, and more importantly, the fracturing characteristics and the damage zone, are comprehensively investigated using a 6 kW microwave source and a customized DLCWA. A novel method is also proposed to adjust the P-wave velocity (V p) reduction across the thickness of the specimens and to determine the equivalent damage zone. The results show that the temperature and high temperature area, crack number, length and density, and the V p reduction rate as well as the damage zone all increase as either the power level or the heating time increases and decrease as the working distance increases. The damage zone can be divided into the crushed zone, fracture zone and discrete fragment zone based on the crack characteristics and the crack generation mechanisms. The method proposed is demonstrated to be reliable in predicting the damage zone induced by microwave heating. • Used a dielectric loaded converging waveguide antenna to fracture a biotite diorite. • Investigated the effects of microwave power level, heating time and working distance on thermal fracturing. • Proposed a novel method to estimate the P-wave velocity distribution across the total thickness. • Determined the equivalent thermal damage zone based on the spatial P-wave velocity reduction. [ABSTRACT FROM AUTHOR]

To contain the spread of the virus at ports, many countries have implemented quarantine policies for vessels from abroad during COVID-19. In response, vessels chose to skip the port to save time or undergo a 14-day quarantine to ensure critical supplies, both of which significantly affected the performance of the port network. However, due to the combined effect of many factors, data analysis techniques can hardly identify the impact of quarantine policies on the outcomes. Therefore, to enable both networkwide performance assessment and detailed evaluation for individual vessels and ports under such an unprecedented policy, a microscopic simulation model for the global port network (GPN) is desired. The proposed simulation method is based on real-world vessel movement data from Automatic Identification Systems (AIS) combined with a port database. It is found that the effect of the quarantine policy on a particular port consists of two parts, i.e. the direct impact caused by vessels' port skipping and the indirect impact caused by network interaction, which is further determined by the location of, and the policy implemented by the port. Furthermore, the ability of the global port network to maintain its performance under different levels of pandemic situations and different rates for vessels to skip the ports requiring quarantine is investigated. Interestingly, in most cases, a moderate port skipping rate (mostly between 20% and 50%) could help improve network performance. The results and presented simulation method can assist policymakers in coping with COVID-19 and potential global catastrophes. [ABSTRACT FROM AUTHOR]

Partial component consensus means that some components of all state variables in a multi-agent system tend to be convergence as time tends to be infinite. It is a dynamics behavior that is weaker than identical consensus. In this paper, partial component consensus of nonlinear multi-agent systems via intermittent pinning control is investigated for the first time, and the intermittent signal can be aperiodic. With the help of permutation matrix method, the corresponding error system is reduced to a new error system. Then, partial component consensus in the multi-agent system is converted into the stability of the new error system with respect to partial variables. Based on matrix theory, graph theory and stability theory of partial variables, some sufficient conditions to guarantee exponential partial component consensus are derived. Finally, numerical simulations are shown to demonstrate correctness of the theoretical results. • Partial component consensus dependence on exponential partial variable stability is discussed for the first time. • The internal communication network between agents is a directed graph. • Aperiodically and periodically intermittent pinning control are taken into account, respectively. • Some novel criteria for partial component consensus via intermittent pinning control protocols are derived. [ABSTRACT FROM AUTHOR]

Sulfonamide is present in many important drugs, due to its unique chemical and biological properties. In contrast, naturally occurring sulfonamides are rare, and their biosynthetic knowledge are scarce. Here we identify the biosynthetic gene cluster of sulfonamide antibiotics, altemicidin, SB-203207, and SB-203208, from Streptomyces sp. NCIMB40513. The heterologous gene expression and biochemical analyses reveal unique aminoacyl transfer reactions, including the tRNA synthetase-like enzyme SbzA-catalyzed L-isoleucine transfer and the GNAT enzyme SbzC-catalyzed β-methylphenylalanine transfer. Furthermore, we elucidate the biogenesis of 2-sulfamoylacetic acid from L-cysteine, by the collaboration of the cupin dioxygenase SbzM and the aldehyde dehydrogenase SbzJ. Remarkably, SbzM catalyzes the two-step oxidation and decarboxylation of L-cysteine, and the subsequent intramolecular amino group rearrangement leads to N-S bond formation. This detailed analysis of the aminoacyl sulfonamide antibiotics biosynthetic machineries paves the way toward investigations of sulfonamide biosynthesis and its engineering. Sulfonamide is in many important drugs yet is rare in nature and little is known about the synthesis of sulfonamide containing antibiotics. Here, the authors report on a detailed analysis of the biosynthesis machineries of the aminoacyl sulfonamide antibiotics. [ABSTRACT FROM AUTHOR]

Lipid-lowering is one of the most effective methods of prevention and treatment for cardiovascular diseases. However, most clinical lipid-lowering drugs have adverse effects and cannot achieve the desired efficacy in some complex hyperlipidemia patients, so it is of great significance to develop safe and effective novel lipid-lowering drugs. In the course of our project aimed at discovering the chemical novelty and bioactive natural products of marine-derived actinomycetes, we found that the organic crude extracts (OCEs) of Nocardiopsis sp. ZHD001 exhibited strong in vivo efficacies in reducing weight gain, lowering LDL-C, TC, and TG levels, and improving HDL-C levels in high-fat-diet-fed mice models. Chemical investigations of the active OCEs led to identifying two new sphydrofuran-derived compounds (1–2) and one known 2-methyl-4-(1-glycerol)-furan (3). Their structures were elucidated by the analysis of HRESIMS, 1D and 2D NMR spectroscopic data, and ECD calculations. Among these compounds, compound 1 represents a novel rearranged sphydrofuran-derived derivative. Bioactivity evaluations of these pure compounds showed that all the compounds exhibited significant lipid-lowering activity with lower cytotoxicity in vitro compared to simvastatin. Our results demonstrate that sphydrofuran-derived derivatives might be promising candidates for lipid-lowering drugs. [ABSTRACT FROM AUTHOR]

Flavanones have a wide range of pharmacological activities. Previously, we showed that CYP105D7, a cytochrome P450, from Streptomyces avermitilis can catalyze hydroxylation of diclofenac at the C4′ position. Here, we demonstrated that CYP105D7 also catalyzes hydroxylation of two flavanones, naringenin and pinocembrin. Naringenin was hydroxylated at the 3′-position in a regiospecific manner to yield eriodictyol. Spectroscopic analyses showed that CYP105D7 binds to naringenin and pinocembrin in a weakly cooperative manner with an affinity of 103 μM and 52 μM, and a Hill coefficient of 1.25 and 1.47, respectively. A possible binding model of naringenin was investigated by molecular-docking analyses. The substrate-binding pocket of CYP105D7 is sufficiently wide to accommodate two naringenin molecules simultaneously, and the C3′ atom of the proximal molecule is in the appropriate location for aromatic hydroxylation. [ABSTRACT FROM AUTHOR]

Water and KCl solutions were exposed to four different magnetic fields for 20 min respectively. Influences of magnetic field on microscopic structures and macroscopic properties of water and KCl solutions were studied by FTIR and the continuous spectrum techniques of linearly polarized light in ultraviolet, visible and near-infrared areas. Simultaneously, these quantities were determined for unmagnetized samples, as references. It was found that in the UV–vis area, the transmittance of all samples presented different phenomena when the incident light with different polarized, it resulted from the orientation of water molecules affected by the static magnetic field and the spiral motion of ions in the magnetic field. The IR spectrum showed that KCl had a significant structure-breaking effect when the intensity of the magnetic field increased and the absorption in the spectrum of KCl was a reflection of the perturbations that water bore in the presence of K + and Cl − ions. [ABSTRACT FROM AUTHOR]

Successive lag synchronization (SLS) is a novel and important synchronization pattern, whose control problem has been deeply investigated in the past several years. However, the impact of noise perturbation on the control of SLS is still unclear. To this end, this paper focuses on the intermittent pinning control of SLS on a dynamical network with noise perturbation. In order to push the SLS to a desired trajectory, we design an intermittent pinning control scheme that is active only on controlled intervals and a small proportion of nodes. By applying the stability theory of stochastic differential equation, we obtain sufficient conditions under which the network can realize the SLS with exponential stability in mean square. According to these conditions, we can determine which nodes should be controlled or not, the minimum control ratio and the impact of noise perturbation on the SLS. An interesting finding is that performing the control on at least half of each subinterval can ensure the stochastic stability of SLS, which is independent of any network parameters. The effectiveness of proposed intermittent pinning control scheme is verified by the network of coupled Chua's circuits. [ABSTRACT FROM AUTHOR]

In this paper, we present a new microfluidic microwave sensor loaded with a star-slotted patch for detecting the quality of edible oil. The relative dielectric permittivity and the quality of edible oil will change after being heated at a high temperature. Therefore, the quality of edible oil can be detected by measuring the relative dielectric permittivity of edible oil. The sensor is used to determine the edible oil with different dielectric permittivity by measuring the resonance frequency offset of the input reflection coefficient, which operates at 2.68 GHz. This sensor is designed based on a resonant approach to provide the best sensing accuracy and is implemented using a substrate integrated waveguide structure combined with a pentagonal slot antenna operating at 2.3~2.9 GHz. It can detect greasy liquids with the real part of the complex permittivity ranging from two to three. [ABSTRACT FROM AUTHOR]

Partial component consensus is a phenomenon that some components of agents reach identity, but the others components are not the same. In this paper, the partial component consensus problem of second-order and third-order nonlinear multi-agent systems has been investigated. Some concepts and results of partial component consensus are given through partial component stability theory and pinning control protocol. Numerical simulations are finally given to verify the theoretical results. • Investigating the partial component consensus problems in second-order and third-order nonlinear leader-following systems. • Deriving some sufficient conditions of partial component consensus for high-order multi-agent systems. • Illustrating the effectiveness of the results through second-order and third-order systems. [ABSTRACT FROM AUTHOR]

The morphology of hydraulic fracture is affected by many factors. In previous studies, due to the heterogeneity of rock samples and the limitations of sample size, influence degree of various factors on fracture deflection angle has not been well distinguished in laboratory experiments. Based on the boundary element method, we established a mathematical model to study the factors controlling the morphology of hydraulic fracture. Simulation results show that with increasing injection pressure, the radius of the fracture curvature increases. When the difference between the injection pressure and the maximum principal stress is 5 times the ground stress difference, the influence of in situ stress on hydraulic fracture deflection can be ignored. Hydraulic fracture deflection angle was relatively larger when considering the viscosity of the fracturing fluid. When stress difference is too small or the injection pressure is too big, the deflection angle of fracture is easy to fluctuate during initial propagation. Too large Young's modulus and too small Poisson's ratio will inhibit the fracture deflection and cause a narrower width of fracture. The effect of Poisson's ratio on fracture aperture is less than 1 mm. When perforation angle is perpendicular to maximum horizontal principal stress, the fracture width first increases rapidly and then gradually decreases from heel to tip. The influence degree of each factor on fracture deflection is ranked: stress difference of in-situ stress is the biggest, followed by injection pressure and perforation angle. This study is of great significance for the control of hydraulic fracture morphology and the further improvement of fracturing effect. [ABSTRACT FROM AUTHOR]

[Display omitted] • A strong association was found between pathological response and long-term survival outcomes after neoadjuvant immunotherapy at patient level. • Using pathological response as surrogate is still questionable for patients applying neoadjuvant immunotherapy. • Relationship above applied to most solid tumors. • Other potential surrogate outcomes like downstaging of the primary tumor or lymph node are waited for further research. Complete pathological response (pCR) and major pathological response (MPR) have been proven to have a close association with improved event-free survival (EFS) and overall survival (OS) for patients accepting chemotherapy or chemoradiotherapy. However, further study focusing on neoadjuvant immunotherapy is limited. Here we provided an updated and comprehensive evaluation of the association between pathological response and long-term survival outcomes at patient level and trial level for neoadjuvant immunotherapy. We systematically searched and assessed studies in PubMed, Embase, the Cochrane Library and relevant conference abstracts from inception to June 1, 2023. Studies reported EFS/OS results by pCR/MPR status were eligible. Forty-three studies comprising a total of 4100 patients were eligible for the analysis, which included 39 studies for the patient-level analysis and 5 randomized controlled trials for the trial-level analysis. Our results highlighted that pCR was associated with improved EFS (HR, 0.48 [95 % CI, 0.39–0.60]) and OS (HR, 0.55 [95 % CI, 0.41–0.74]). The magnitude of HRs by MPR status were similar to the results by pCR status (EFS HR, 0.31 [95 % CI, 0.18–0.53]) and OS HR, 0.43 [95 % CI, 0.19–0.96]). However, no association between pCR and EFS at trial level was found (P = 0.8, R2 = 0). Our meta-analysis demonstrates a strong association between pathological response and long-term survival outcomes at patient level across studies applying neoadjuvant immunotherapy in most solid tumors but we fail to validate the relationship at trial level. Therefore, an accepted surrogate endpoint applied to both patient and trial levels are waited for further search. [ABSTRACT FROM AUTHOR]

Abstract: Keap1–Nrf2 pathway has emerged as a regulator for the endogenous antioxidant response, which is critical in defending cells against carcinogenesis. Herein, we demonstrated that depleting the cellular level of glutathione (GSH) by a novel electrophilic agent 2-(pro-1-ynyl)-5-(5,6-dihydroxypenta-1,3-diynyl) thiophene (PYDDT) could activate Keap1–Nrf2 pathway. In above process, it was found that Keap1 was modified by S-glutathionylation, an important post-translational modification of protein cysteines with critical roles in oxidative stress and signal transduction. We concluded from our findings that conjugation with intracellular GSH by PYDDT might lead to Keap1 S-glutathionylation and was a key event involved in its Nrf2 inducing activity. [ABSTRACT FROM AUTHOR]

Digestive system cancers are associated with high morbidity and mortality. Chemotherapy and radiotherapy are the main treatment modalities for these cancers. However, the development of therapy resistance leads to high rates of tumor recurrence and metastasis, resulting in dismal prognosis. Long non-coding RNA (LncRNA) H19, one of the most intriguing non-coding RNAs, has been shown to play a key role in the development and therapy resistance of various digestive system cancers (including hepatocellular carcinoma, colorectal cancer, pancreatic ductal adenocarcinoma, esophageal carcinoma, gastric cancer, and biliary system cancer) by regulating the abnormal expression of genes. In this review, we discuss the potential mechanisms of LncRNA H19 related therapy resistance in the context of digestive system cancers. LncRNA H19 is a potential novel therapeutic target for amelioration of cancer therapy resistance. [ABSTRACT FROM AUTHOR]

Abstract Alokicenones A-H (1–8), eight new tetrahydroanthracenes and one known okicenone (9) were identified from the secondary metabolites of mangrove-derived Streptomyces sp. HN-A101. Their structures were elucidated by HRESIMS and NMR spectroscopic data. The absolute configurations of them were determined by the calculated and experimental ECD curves. Compounds 1–2 and 9 showed moderate cytotoxicity against HCT116 and SW620 cancer cell lines with IC 50 values from 0.63 to 7.73 μ M. In addition, compounds 1 – 3 and 7 – 9 also exhibited inhibitory activities against ROCK2 or BRD4. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

Abstract Thioquinomycins A-D (1–4), four novel naphthothiophenediones were isolated from the rice-based medium of the marine-derived Streptomyces sp. SS17F. Their structures were elucidated by spectroscopic methods and HRESIMS data. The absolute configurations of all the compounds were elucidated by X-ray diffraction analysis, ECD and Mosher's method combined with 19F-NMR. Compounds 1–4 showed moderate cytotoxicity against NCI-H1975 with IC 50 values from 17.5 to 50 μ M. In addition, compounds 1–4 also exhibited inhibitory activities against PKCα and ROCK2 protein kinase. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

Polychlorinated biphenyls (PCBs) and microplastics (MPs) commonly co-exist in various environments. MPs inevitably start aging once they enter environment. In this study, the effect of photo-aged polystyrene MPs on microbial PCB dechlorination was investigated. After a UV aging treatment, the proportion of oxygen-containing groups in MPs increased. Photo-aging promoted the inhibitory effect of MPs on microbial reductive dechlorination of PCBs, mainly attributed to the inhibition of meta-chlorine removal. The inhibitory effects on hydrogenase and adenosine triphosphatase activity by MPs increased with increasing aging degree, which may be attributed to electron transfer chain inhibition. PERMANOVA showed significant differences in microbial community structure between culturing systems with and without MPs (p < 0.05). Co-occurrence network showed a simpler structure and higher proportion of negative correlation in the presence of MPs, especially for biofilms, resulting in increased potential for competition among bacteria. MP addition altered microbial community diversity, structure, interactions, and assembly processes, which was more deterministic in biofilms than in suspension cultures, especially regarding the bins of Dehalococcoides. This study sheds light on the microbial reductive dechlorination metabolisms and mechanisms where PCBs and MPs co-exist and provides theoretical guidance for in situ application of PCB bioremediation technology. [Display omitted] • MPs at a higher aging degree more strongly inhibited microbial PCB dechlorination. • Aged MPs likely inhibited PCB dechlorination by affecting Hase and ATPase activity. • Microbial community structures varied between biofilms and suspension cultures. • Aged PS simplified community networks and increased negative correlations on biofilm. • The assembly process was more deterministic in biofilms than in suspension cultures. [ABSTRACT FROM AUTHOR]

Ten new and 13 known prenylated 2,5-diketopiperazines (2,5-DKPs) were identified from co-culture of Penicillium sp. DT-F29 with Bacillus sp. B31. The constitutions and relative configurations of new compounds were established by 1D and 2D NMR spectroscopic data analysis. The isolated 2,5-DKPs in bioactivity test showed bromodomain-containing protein 4 (BRD4) inhibitory activities, and compound 14 , with IC 50 values of 6.54 μ M, was potential for BRD4 inhibitor discovery. [ABSTRACT FROM AUTHOR]

Breast cancer metastasis is a major challenge in clinical therapy because of the absence of effective treatments. Rho-associated coiled-coil kinase (ROCK), which is essential for cell invasion and migration, has recently been suggested as a potential target for the treatment of cancer metastasis. Herein, we report the structure−activity relationships (SAR) of indolocarbazoles against ROCK2 and reveal the crucial role of the C-3 hydroxyl for ROCK2 inhibition. The most potent unglycosylated aglycone THK01 was demonstrated to bind to and stabilize ROCK2 with potent anti-metastatic effects in breast cancer in vitro and in vivo with no obvious toxicities. Further mechanistic studies revealed that the anti-metastatic effect of THK01 was closely related to the suppression of STAT3Y705 activation. Moreover, THK01 exhibited excellent selectivity over the isoform protein ROCK1 (>100-fold). Taken together, with low toxicity, the ROCK2 inhibitor THK01 potently inhibited breast cancer metastasis through the ROCK2-STAT3 signaling pathway, which offers a new opportunity for the treatment of metastatic breast cancer. [Display omitted] • An extensive SAR study of indolocarbazoles against ROCK2 was established. • The binding modes were verified by molecular docking and the single-point mutated ROCK2. • THK01 significantly suppresses breast cancer metastasis in vitro and in vivo. • THK01 inhibits the activation and nuclear translocation of STAT3. • THK01 is a highly isoform-selective ROCK2 inhibitor. [ABSTRACT FROM AUTHOR]

• The multiple functions of axial oxygen ligand in improving ORR activity were exploited. • The axial oxygen ligand may participate in the catalysis. • The homolateral adsorbate evolution mechanism is preferential for oxygen reduction. • The dynamically wobbly oxygen will modulate the orbital orientation of metal atom. The catalytic activity of single metal atom were effectively enhanced by different coordination environments, and the underlying improvement mechanisms are generally ascribed to the electronic structure modification by in-plane ligands. Herein, taking the recently synthesized MoNO composites modified carbon as representative, we clarified the multiple functions of axial oxygen ligand in improving the oxygen reduction activity. The active Mo atom is protruded from graphene plane due to the interaction with axial oxygen ligand, and during adsorption of oxygenates, the hanging oxygen ligand would wag to leave space and meanwhile tune the orbital orientation of Mo atom, giving rise to an optimal adsorption strength on the side in presence of oxygen ligand. The dynamic oxygen ligand may participate in the catalysis through hydrogenation reaction at the coadsorption stage with oxygen intermediate. The obtained overpotential of 0.35 V on MoN 2 O 1 -pen-gra along homolateral adsorbate evolution mechanism is comparable to recent experiments, approving the reliability of models and mechanism proposed in current study. The present results could provide some new insights into the functions of axial ligands and further guide the rational design of axial coordination to improve the catalytic performance. Graphical Abstract: [Display omitted] [ABSTRACT FROM AUTHOR]

Glycoproteomics is greatly developed in recent years and big data of N -glycoproteome in mammalian tissues and cells were already established. However, the glycoproteomic studies on plant, fungus and bacteria are far left behind. In this study, we comprehensively mapped and quantified the N -glycosylation of Fusarium graminearum by combining stable isotope dimethyl labeling, hydrophilic interaction chromatography (HILIC) and high-resolution mass spectrometry. The N -glycosylation changes in Fusarium graminearum after fungicide treatment were extensively studied. Altogether we identified 927 N -glycopeptides, corresponding to 406 proteins and 774 sites and the glycosylation level was found to be largely down-regulated upon fungicide treatment. With the help of advanced bioinformatics, it was found that the N -glycoproteome changes were highly enriched in cell wall, membrane and extracellular regions. Moreover, the fungal metabolism, protein and glycosylation synthesis, and protease and glycosyl-transferase activity were all closely related with the down-regulated proteins, indicates that fungicide may affect fungal development in these aspects. These results will be useful for future studies on fungal biology. The established system for N -glycoproteome quantification has comparative or better performance compared with previous strategies and will be helpful in N -glycoproteomics of fungus and other species. Significance We developed a robust HILIC-based system for N -glycoproteome quantification in fungus and established the largest quantitative N -glycosylation dataset in fungus, showing the high performance of the new system. The identified N -glycoproteins were proved to be high confident due to the high percentage of proteins in extracellular region and plasma. The quantification results were also accuracy and reproducible in two replicates. By the help of advanced bioinformatic tools, the obtained data was systematically analyzed. It was found that the N -glycosylation level was largely changed in cell wall, membrane and extracellular regions. Moreover, the cell metabolism, protein synthesis, and protease activity were also greatly deceased after fungicide treatment. [ABSTRACT FROM AUTHOR]

Competitive coexistence of different microorganism species is a fundamental ecological process in the evolution and maintenance of biodiversity. This work studied the interactions happened in the competitive coexistence process of actinomycete Streptomyces sp. and Escherichia coli from morphological and secondary metabolites perspective. We found three important interactions occurred in their successful coexistence process: medium pH was elevated, indole alkaloids with dual inhibiting effects were produced, and culture environment was spatially structured. For the weed-like superior competitor E. coli, its massive growth was suppressed by the elevated pH and the newly produced novel bisindole alkaloid hepchrome. For the inferior Streptomyces sp., its mycelium floated to the medium surface for further colonization, and the growth in liquid medium was inhibited by its self-produced alkaloids such as halichrome A, 1,1,1-Tris (3-indolyl) methane, vibrindole A, and hepchrome. The coexistence of E. coli and Streptomyces sp. was thereby achieved through reduction of spatial and energy resource overlapping and suppression of competition. [ABSTRACT FROM AUTHOR]

To estimate global crude oil trade flows, current research either considers only crude oil tankers, or simply applies external information to distinguish between crude and refined product oil cargoes transported by coated product tankers; these limitations often reduce an estimation's accuracy or compromise replicability. Our methodology directly addresses these issues by applying the random forest (RF) ensemble learning technique to Automatic Identification System (AIS) data in order to predict the cargo types of coated product tankers. By leveraging domain knowledge, we construct a set of unique input variables for the RF model, and use its predictions to quantify the global crude oil trade in a more accurate manner. Our estimation shows that coated product tankers were responsible for approximately 8% of global seaborne crude oil trade from 2017–2020. Further, unanticipated variations in the crude oil volume carried by these tankers are consistent with several major historical oil trade disruptions. Our study further extends current applications of AIS data in the domains of operations management and maritime transportation, and facilitates the exploration of the more minute characteristics of oil transportation. The resulting shipping dataset and associated decomposition strategy also enable relevant stakeholders to quickly identify emerging trade flow risks and adapt more effectively. • Predict the cargo types of coated product tankers by random forest method. • Construct a set of unique input variables leveraging domain knowledge. • Use predictions to quantify the global crude oil trade in a more accurate manner. • Estimation shows that coated product tankers responsible for approximately 8% of global seaborne crude oil trade from 2017–2020. [ABSTRACT FROM AUTHOR]

In recent years, the successive lag synchronization (SLS) has been deeply analyzed, however, the control theory of SLS on complex networks with noise perturbation is lacking. To this end, this paper focuses on the pinning control of SLS on a dynamical network with noise perturbation. Both the constant pinning control law and adaptive pinning control law are designed respectively to push the network to achieve the desired SLS. By utilizing the Lyapunov stability theory of stochastic differential equations, several sufficient conditions for the controlled networks to achieve the SLS are obtained. The influences of network structure, noise strength and coupling strength on the realization of SLS are also discussed. We find that the noise can suppress or even destroy the realization of SLS. Meanwhile, we attain the index set of pinned nodes, which can tell us whether a node should be controlled or not. In particular, those nodes with zero in-degree must be controlled to achieve SLS, while those nodes with non-zero in-degree need not to be controlled if the coupling strength is large enough. All theoretical results are verified by numerical simulations. • A dynamical network with noise perturbation is introduced to realize the SLS. • Stochastic stability conditions of SLS on the controlled networks are obtained. • The noise can suppress or even destroy the SLS. • The pinned nodes are determined by solving 1-dimensional inequalities. [ABSTRACT FROM AUTHOR]

Abstract: Affinity chromatography, applied to discover the enzyme inhibitors, needs special column with target protein and its carrier. Selection of stationary phase and mobile phase needs careful considerations due to the characteristics of proteins. In this study, a method immunoprecipitation (IP) coupled with HPLC-DAD–MS was developed to discover the aromatase ligands from Glycyrrhiza uralensis. An SB-C18 column was employed to separate target compounds without special consideration in mobile phase. Twenty-one compounds, including isolated compounds 4, 7, 8, 10, 11, 13, 15, 18–20, 23 and non-isolated compounds A-J, were found to have good affinity to aromatase by LC–MS. Seven of them (7, 15, 18, 19, 23, D, E) were detected to bind with aromatase in MCF-7 cells by IP coupled with HPLC–MS/MS. Bioassays disclosed aromatase inhibitory activities of the isolated compounds mentioned above, verifying the efficiency of IP coupled with HPLC–MS/MS as a method to screen aromatase ligands. [Copyright &y& Elsevier]

Abstract: In the present study, it was demonstrated that the petroleum extract of Andrographis paniculata (AP) had quinone reductase (QR) inducing activity, which might be attributed to the modification of key cysteine residues in Keap1 by Michael addition acceptors (MAAs) in it. To screen MAAs in AP, glutathione (GSH) was employed, and a LC/MS/MS method was implied. Three compounds, andrographoside, andrographolide, 14-deoxy-14,15-dehydroandrographolide were revealed could well conjugated with GSH. Then, andrographolide along with 4 new and 14 known compounds were isolated to conduct QR induction evaluation, and the CD (the concentration required to double the activity of QR) value of andrographolide is 1.43μM. The QR induce activity of andrographolide might be attributed to its targeting multiple cysteine residues in Keap1, therefore, the alkylation of Keap1 by andrographolide was further studied and the result showed that four cysteine residues: Cys77, Cys151, Cys273 and Cys368 were alkylated, which indicated that Keap1 is a potential target for the QR induce activity of andrographolide. [Copyright &y& Elsevier]

Abstract: A LC–MS method, which GSH was used as substrate, was employed to reveal the compounds with NQO1 induction activity from Angelica keiskei. Some compounds, proposed as isobavachalcone, xanthoangelol and 4-hydroxyderricin, have NQO1 induction activity. To make the actual structures and bioactivities of these compounds clear, 23 compounds, including above mentioned compounds and two new compounds 4-hydroxy-3,5,5-trimethyl-4-(1,2,3-trihydroxybutyl)cyclohex-2-enone (18) and (Z)-2-(3-hydroxypent-1-ynyl)-3-(non-1-enyl)oxiran-2-ol (23), were isolated from the 95% ethanol extract of A. keiskei. The bioassay results suggested the compounds had notable NQO1 induction activity. The radical scavenging and α-glucosidase inhibition activities of the isolated compounds were also tested. Compounds (E)-1-(2,4-dihydroxy-3-(3-methylbut-2-enyl)phenyl)-3-(4-hydroxyphenyl)prop-2-en-1-one (1), (E)-1-(3-((E)-3,7-dimethylocta-2,6-dienyl)-2,4-dihydroxyphenyl)-3-(4-hydroxyphenyl)prop-2-en-1-one (2), 1-(3-hydroxy-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[α]phenanthren-17-yl)ethanone (17), 4-hydroxy-3,5,5-trimethyl-4-(1,2,3-trihydroxybutyl)cyclohex-2-enone (18) could scavenge DPPH radical by more than 20%. Compounds (E)-1-(2,4-dihydroxy-3-(3-methylbut-2-enyl)phenyl)-3-(4-hydroxyphenyl)prop-2-en-1-one (1), (E)-1-(3-((E)-3,7-dimethylocta-2,6-dienyl)-2,4-dihydroxyphenyl)-3-(4-hydroxyphenyl)prop-2-en-1-one (2), (E)-1-(2-hydroxy-4-methoxy-3-(3-methylbut-2-enyl)phenyl)-3-(4-hydroxyphenyl)prop-2-en-1-one (3), 7-hydroxy-6-(3-methylbut-2-enyl)-2H-chromen-2-one (5), 10-hydroxy-8,8-dimethyl-2-oxo-9,10-dihydropyrano[6,5-H]chromen-9-yl)-3-methylbut-2-enoate (9), 2-(4-hydroxyphenyl)-7-methoxy-8-(3-methylbut-2-enyl)-2,3-dihydrochromen-4-one (16), (10S,15R,Z)-10,15-dihydroxyheptadeca-8,16-dien-11,13-diynyl acetate (20), (3R,8S,Z)-heptadeca-1,9-dien-4,6-diyne-3,8-diol (21) exhibited excellent α-glucosidase inhibition activity. [Copyright &y& Elsevier]

Abstract: An abietane diterpenoid, triptobenzene Y and six sesquiterpene polyol esters, wilforsinines C–H, together with 14 known compounds, have been isolated from the roots of Tripterygium wilfordii. The structures of the compounds were elucidated on the basis of spectroscopic analyses. The quinone reductase (QR) induction assay indicated that two compounds showed moderate QR-inducing activities at concentrations of 25μM and 50μM, respectively. [Copyright &y& Elsevier]

Abstract: Protein-conjugated PbS nanocrystals with the average sizes of 15, 25, and 35nm have been synthesized by adjusting the concentration of the bovine serum albumin (BSA) solution at room temperature. The obtained BSA-conjugated PbS nanoparticles have been characterized by powder X-ray diffraction, transmission electron microscopy, selected-area electron diffraction, high-resolution transmission electron microscopy, thermal analyses and photoluminescence. The quantum-confined effect of the BSA-conjugated PbS nanoparticles has been confirmed by the UV–vis spectra. The results indicated that the BSA not only induced the nucleation, but inhibited the further growth of PbS nanocrystals. The effect of Pb2+ on BSA and the change of BSA conformation were studied through Fourier transform infrared spectroscopy and circular dichroism spectroscopy. The possible mechanism of BSA-conjugated PbS nanoparticles growth was also discussed. [Copyright &y& Elsevier]

Abstract: In the present study, we examined the potential chemopreventive activity of dichloromethane extract of Eurycorymbus cavaleriei by investigating the change of constitutions after incubation with glutathione (GSH). The major constitutions in the dichloromethane extract of E. cavaleriei were cumarin compounds and their cleavage pattern was examined by LC–MS-MS and the characteristic product ions at m/z 206 and 207 were helpful to determine the substitutions of coumarinolignoid compounds. The mechanism of conjugations of 5′-demethylaquillochin and its isomer with GSH was discussed and validated through analysis of the conjugations of reference compound 6-hydroxy-7-methoxycoumarin with GSH by LC–MS-MS and NMR spectrum. The relative ability to induce the detoxification enzyme, NAD(P)H:quinone oxidoreductase 1 (NQO1) of nine coumarin compounds was tested which also showed 5′-demethylaquillochin exhibited the most potential chemopreventive ability. These observations suggest that 5′-demethylaquillochin and its isomer from the dichloromethane extract of E. cavaleriei have potential as chemopreventive agents through induction of detoxification enzymes. [Copyright &y& Elsevier]

Abstract: Background: Motherwort has been used as medicinal herb for many years in both China and Europe. In particular, Chinese motherwort has been commonly used to treat disorders of mammary gland in Chinese traditional medicine (TCM). Chinese motherwort aqueous extract (MAE) was previously reported to have anti-cancer activity in breast cancer cells with low potency (IC50s in a range of 8–40mg/mL). However, treatment of motherwort ethanol extract in vivo markedly suppressed the development of uterine adenomyosis and mammary cancers in mice. Therefore, anti-cancer activity of Chinese motherwort, especially in a form of ethanol extract, needs to be confirmed further at cellular level. Materials and methods: Aerial part of Chinese motherwort (Leonurus japonicus Houtt) dry powder is extracted with 70% ethanol and the chemical components were characterized with HPLC finger print as well as mass spectrometry. Cytotoxicity of the motherwort aqueous ethanol extract (MAEE) was analyzed with MTT assay on ER negative MDA-MB-231 and ER positive MCF-7 human breast cancer cell lines. Hoechst 33342 staining and flow cytometry were used to verify whether the cell death induced by MAEE is apoptosis in nature. Cell cycle status of MAEE treated cells were analyzed with flow cytometry. Results: Our results showed that MAEE caused cell death in a dose-dependent and time-dependent fashion in both ER positive and negative breast cancer cells. Morphology, Hoechst 33342 staining and flow cytometry evidence all indicated the cell death is not in an apoptotic nature. Furthermore, low concentrations of MAEE caused cell cycle arrest at G2/M phase. Conclusions: These data suggest that Chinese motherwort aqueous ethanol extract may effectively inhibit the proliferation of breast cancer cells through mechanisms of both cytotoxicity and cell cycle arrest. The cellular effects of MAEE are non-apoptotic and ER independent on breast cancer cells. [Copyright &y& Elsevier]

Tumor-associated macrophages (TAMs) in the tumor microenvironment (TME) play an important role in the development of tumors by secreting a variety of cytokines or directly communicating with tumor cells, making TAMs-targeted therapeutic strategies very attractive. It has been reported that oncogene c-Myc is related to every aspect of the oncogenic process of tumor cells and the alternative activation of macrophages. Hence, we constructed a glycolipid nanocarrier containing ROS-responsive peroxalate linkages (CSOPOSA) for ROS-triggered release of drugs and further modified it with Ex 26 (Ex 26-CSOPOSA), a selective sphingosine 1-phosphate receptor 1 (S1PR1) antagonist, to achieve the dual-targeted delivery of the c-Myc inhibitor JQ1 via S1PR1, which is overexpressed on both tumor cells and TAMs, thereby inducing apoptosis of tumor cells, and blocking M2 polarization of macrophages. More strikingly, our studies found that JQ1 could effectively inhibit the migration of tumor cells induced by M2 macrophages-derived exosomes via blocking Caveolin-1 related intercellular exosome exchange through lncRNA H19 and miR-107. The in vivo results revealed that this dual-targeted delivery strategy effectively inhibited tumor growth and metastasis with less systemic toxicity, providing a potential method for effective tumor treatment. [Display omitted] [ABSTRACT FROM AUTHOR]