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•aMCD belongs to HHV-8–negative MCD, which might be a potential early stage of iMCD.•Patients with aMCD do not need immediate treatment but should be closely monitored.

The major impediment to the additional industrialization of water splitting is the high cost of the co-catalyst made of noble metals and the sacrificial reagent. A binary photocatalytic system, consisting of B-doped g-C3N4nanosheets (Cu20@BCN-X) and atomically accurate copper clusters, is designed in this study. The copper clusters serve as co-catalysts for H2evolution and exhibit Pt-like activity, whereas the nanosheets serve as carriers and semiconductor components for O2evolution. Such binary system, created using simple techniques, demonstrates hydrogen bonding interactions that promote synergistic effects and efficient binding and charge transfer across the interface between the two components. Band position manipulation of carbon nitride nanosheets demonstrates a Z-scheme charge transfer mechanism between the nanosheets and copper clusters. This photocatalytic system can accomplish the photocatalytic overall water splitting process (259.9 µmol g−1h−1of H2and 129.4 µmol g−1h−1of O2) without using sacrificial agents or noble metal co-catalysts. This work lays the foundation for the design of overall water splitting catalysts by precisely manipulating the energy levels, and it also paves the way for commercialized photocatalytic catalysts that do not require noble metals or sacrificial chemicals.

Nitrogen-containing compounds, especially those with chiral amine structures, play a pivotal role in the field of organic active pharmaceutical ingredients. Traditional racemate resolution and chemical synthesis methods for the preparation of chiral amines suffer drawbacks such as high cost and environmental pollution. Over the past decades, stereoselective synthesis of nitrogen-containing compounds by biocatalytic methods such as imine reductase (IRED)-mediated transformation has become increasingly prominent. The prominence of imine reductases lies in their capacity to catalyze the reductive amination of aldehydes or ketones with primary or secondary amines, as well as their broader substrate scope. Furthermore, imine reductases exhibit diverse catalytic cycling systems that are unaffected by adverse reaction equilibria. This article focuses on the development of drug molecules or intermediates in biocatalytic synthesis mediated by imine reductase.

Although the diverse impacts of elevated dissolved CO2and warming on organisms within various trophic levels in marine food webs are well documented, we have yet to explore the biological links across different levels of biological organization from primary producers to secondary producers on an evolutionary time scale in a high‐CO2ocean. Here, we cultured a model marine diatom Phaeodactylum tricornutum(primary producer) in predicted future high‐CO2and/or warming conditions for ~ 1250 d with an experimental evolution approach and then fed them to the clam Coelomactra antiquata(secondary producer). We present an in‐depth multi‐omics analysis along the methylome (primary producer)–transcriptome (primary producer)–metabolome (primary producer)–metabolome (secondary producer) continuum. Our results showed that the downregulated terpenoid backbone biosynthesis in the methylome and transcriptome lead to decreased pyruvate levels and upregulation of some pathways (such as phenylalanine metabolism) in the metabolome of the primary producer in the long‐term warming conditions. These changes in metabolomic profile in the primary producer were then transferred to the secondary producer, resulting in changes in abundance of some metabolites, such as decreases in pyruvate, and in pyruvaldhyde (also known as methylglyoxal), and increases in 2‐hydroxylamino‐4,6‐dinitrotoluene. Our study provides a new insight into the molecular mechanisms underlying the trophic transfer from primary to secondary producers in a future high‐CO2ocean and may provide more accurate projections of marine ecosystem services and functions over the next century.

Great hope has been pinned on seaweed cultivation as being a potent way of removing CO2to reduce rates of sea surface warming and acidification. Marine heatwaves and nitrogen pollution in coastal ecosystems are serious current issues that need to be better understood to inform decision making and policy. Here, we investigated the effects of a simulated heatwave and nitrogen pollution on carbon sequestration by an important seaweed crop species and its phycosphere bacteria. Gracilaria lemaneiformiswas grown in ambient and high nitrogen conditions (14 and 200 μM L−1). Photosynthetic rate, seaweed biomass and particulate organic carbon accumulation were significantly increased in “high nitrogen‐no heatwave” conditions. In “ambient nitrogen heatwave” conditions, the expression of genes related to photosynthesis was down regulated and the seaweeds lost more dissolved organic carbon (DOC) to the surrounding water, resulting in more refractory dissolved organic carbon (RDOC). In “high nitrogen heatwave” conditions, photosynthetic gene expression was upregulated; bacterial abundance was also increased that can explain the reduced DOC and RDOC accumulation. The simulated heatwave reduced bacterial diversity while high nitrogen alleviated this effect. These findings suggest that the economically important alga G. lemaneiformismay lose more DOC and RDOC to nearshore waters during marine heatwave events, enhancing carbon sequestration, while nitrogen enrichment has a counteractive effect.

In order to achieve accurate and robust indoor position estimation in a wireless sensor network using particle filtering (PF)-based positioning algorithms, particle impoverishment, a problem that aroused from the traditional replicating-and-replacing resampling operation, must be well addressed. The loss of particle diversity not only degrades positioning accuracy but can also result in filtering divergence. To address this problem, this article proposes an adaptive neighbor-guided particle optimization strategy to substitute the traditional resampling operation. The strategy optimizes the distribution of the posterior particles through three steps: neighbor radius calculation, true neighbor identification, and neighbor-guided attraction. The proposed strategy is then integrated into the PF framework to form a novel positioning algorithm referred to as adaptive neighbor-guided particle optimization-based PF algorithm (ANPOPF). The test results show that the integration of the proposed particle optimization strategy considerably enhances the robustness of the PF algorithm, mitigating the effects of particle impoverishment. With the aid of the strategy, the ANPOPF algorithm achieves higher positioning accuracy compared to several existing positioning algorithms. Moreover, the ANPOPF algorithm owns an affordable computation load for most real-time applications.

Small- and medium-sized enterprises (SMEs) in low-carbon supply chains often face financing obstacles for improving carbon emission reduction (CER) level. Armed with unique advantages beyond offline financing methods, online peer-to-peer (P2P) lending can offer financing service for SMEs to alleviate capital constraints. This article investigates the equilibrium strategies under online P2P lending and effects of such a financing scheme in funding low-carbon supply chains through multi-level Stackelberg game models under two possible scenarios: the manufacturer independently bears CER investment cost and the retailer shares the cost with the manufacturer. In the models, a P2P platform first sets a service rate and charges a commission. Under a carbon cap-and-trade policy, a manufacturer borrows capital through the P2P platform and decides CER level. As the follower, a retailer determines a retail price. We find that the P2P platform's financial decision is a double-edged sword in influencing its own profit through commission and loan size. The cost sharing is alarmingly not always helpful for the supply chain finance system and improvement of CER level. Online P2P lending plays a complementary role to bank credits by bringing more social welfare and greater promotion degree of CER level.

Bosten Lake is a crucial water source in arid northwest China, which has been maintaining the ecological balance of the southern Xinjiang region. It contributes to the sustainable development of the local economy and watershed ecology. Insufficient hydrological data for the basin, however, cause uncertainty in hydrological modeling and makes it difficult to calculate water availability and lake-water storage using conventional methods. Therefore, this article proposed a novel method to retrieve the lake’s water depth from Landsat-8 OLI and ICESat-2 satellite data using neural network (NN) model. Specifically, the Rayleigh-corrected top-of-atmosphere (TOA) reflectance ( $\rho _{\mathrm {rc}}$ ) in the 443–2300 nm range was employed as the input to the NN model for the retrieval of water depth. This avoids the requirement to correct the effects of aerosols. In addition, the water depth retrieved by the NN model was compared with a conventional dual-band ratio model (DBRM). To evaluate the accuracy of the corrected ICESat-2 photon data, the in situ water depths were compared with the corrected ICESat-2 photon data (considering water-level variations at different times), and 20 in situ water depth values near the ICESat-2 track were selected for verification. The results showed that 1) the in situ water depth and the corrected ICESat-2 photon data had the coefficient of determination ( $R^{2}$ ) values of 0.94; 2) NN inversion of bathymetry presented a feasible method of obtaining regional bathymetry, with $R^{2}$ of 0.87, root mean square error (RMSE) being 1.17 m, and mean absolute error (MAE) being 0.26 m. In contrast, DBRM generated the $R^{2}$ , RMSE, and MAE values of 0.74, 1.62, and 0.93 m, respectively; and 3) the water storage in Bosten Lake’s from April to September in 2022 ranged from $6.73\times 10^{9}$ to $7.50\times 10^{9}\,\,\text{m}^{3}$ . The findings can provide a strong scientific basis for the sustainable development and the rational allocation regional water resources.

Interfacial assemblies formed by colloidal complexation are effective in multiphase stabilization, as shown in structured liquids and Pickering emulgels. Herein, we demonstrate a type of biobased colloidal system that spontaneously stabilizes an organic phase in a continuous hydrogel phase. Specifically, a triterpene extracted from bark (betulin, BE) is added to an organic phase containing a coniferous resin (rosin acid, a diterpene). BE is shown to take part in strong noncovalent interactions with the nanochitin dispersed in the aqueous (hydrogel) phase, leading to a complex of high interfacial activity. The viscoelastic response of the system is rationalized by the presence of a superstable structured dual network. When used as a templating material, the emulgel develops into structured liquids and cryogels. The herein introduced all-biobased type of nanoparticle surfactant system forms a gel (“emulsion-filled” with “aggregated droplets”) that features the functional benefits of both betulin and nanochitin.

Fluctuations in outer space's temperature would affect the spacecraft's regular operation. This paper aims to study the temperature influences of the aluminum honeycomb buffer in the tether-net launcher. Firstly, a buffer structure was designed to attenuate the pyroshock generated by the pyrotechnic device. Secondly, the mechanical properties of aluminum honeycomb at different temperatures were obtained through quasi-static compression experiments. Then, the internal ballistic responses of the launcher were gained by the closed bomb tests and the equivalent classical interior ballistic model. Finally, the recoil performance of the launcher with aluminum honeycomb buffer at different temperatures was studied. It is revealed that the aluminum honeycomb crushing force gradually decreases with the temperature increases. The peak pressure, burning rate coefficient and velocity increase while the peak time decreases with the temperature increase for the interior ballistics. For the launcher recoil responses, the average launch recoil decreases if the aluminum honeycomb doesn't enter the dense stage. The impact acceleration, projectile velocity and displacement increase as the temperature increase. The paper spotlights the temperature's influence on the recoil characteristics of the aluminum honeycomb buffer, which provides a new idea for buffering technology of pyrotechnic devices in a complex space environment.

Phosphine-containing porous organic polymers (phosphine-POPs) are a kind of potential catalyst support for alkene hydroformylation. However, the synthesis of phosphine-POPs with strong π-acceptor is still a challenge. Herein, we report the synthesis of phosphine-POPs with different π-acceptor properties [POL-P(Pyr)3, CPOL-BPa&PPh3-15, and CPOL-BP&PPh3-15] and evaluated their performances as ligands to coordinate with Rh(acac)(CO)2for hydroformylation of alkenes. We found that the Rh center with stronger π-acceptor phosphine-POPs showed better catalytic performance. Rh/CPOL-BPa&PPh3-15 with strong π-acceptor bidentate phosphoramidites showed obviously higher activity and regioselectivity (TON = 7.5 × 103, l/b = 26.1) than Rh/CPOL-BP&PPh3-15 (TON = 5.3 × 103, l/b = 5.0) with weaker π-acceptor bidentate phosphonites. Particularly, the TON of the hydroformylation reached 27.7 × 103upon using Rh/POL-P(Pyr)3which possessed tris(1-pyrrolyl)phosphane coordination sites. Overall, our study provides an orientation to design phosphine-POPs for hydroformylation reactions.

Platinum (Pt) catalysts are the most practical electrocatalysts; however, their low abundance and high cost severely limit their large-scale applications. Efficient recovery is a key issue to be resolved before the use of Pt-based electrocatalysts can be broadly extended. Herein, the newly designed polyoxometalate [PtII(NH3)4]2[Mo8O26] (Mo8Pt) acts as an ideal recycling medium for renewable and highly effective Pt electrocatalysts. Starting from Mo8Pt, by a facile reduction reaction, the formed Pt/Mo2C/Mo2N@C-N electrocatalyst shows superior electrocatalytic activity as compared to commercial Pt/C (20%) under both acidic and alkaline conditions. Notably, the reaction of Pt/Mo2C/Mo2N@C-N in H2O2solution can regenerate Mo8Pt for Pt renew-ability. It is also demonstrated that the Pt electrocatalyst can be used for at least five rounds of recycling and regeneration, showing its efficiency and stability as well as its effectiveness. This work highlights a recycling medium strategy to the new generation of renewable Pt-based catalysts.

Treatment with therapy targeting BRAF and MEK (BRAF/MEK) has revolutionized care in melanoma and other cancers; however, therapeutic resistance is common and innovative treatment strategies are needed1,2. Here we studied a group of patients with melanoma who were treated with neoadjuvant BRAF/MEK-targeted therapy (NCT02231775, n= 51) and observed significantly higher rates of major pathological response (MPR; ≤10% viable tumour at resection) and improved recurrence-free survival (RFS) in female versus male patients (MPR, 66% versus 14%, P= 0.001; RFS, 64% versus 32% at 2 years, P= 0.021). The findings were validated in several additional cohorts2–4of patients with unresectable metastatic melanoma who were treated with BRAF- and/or MEK-targeted therapy (n= 664 patients in total), demonstrating improved progression-free survival and overall survival in female versus male patients in several of these studies. Studies in preclinical models demonstrated significantly impaired anti-tumour activity in male versus female mice after BRAF/MEK-targeted therapy (P= 0.006), with significantly higher expression of the androgen receptor in tumours of male and female BRAF/MEK-treated mice versus the control (P= 0.0006 and P= 0.0025). Pharmacological inhibition of androgen receptor signalling improved responses to BRAF/MEK-targeted therapy in male and female mice (P= 0.018 and P= 0.003), whereas induction of androgen receptor signalling (through testosterone administration) was associated with a significantly impaired response to BRAF/MEK-targeted therapy in male and female patients (P= 0.021 and P< 0.0001). Together, these results have important implications for therapy.

The COVID-19 pandemic caused by the SARS-CoV-2 virus remains a global public health crisis. Although widespread vaccination campaigns are underway, their efficacy is reduced owing to emerging variants of concern1,2. Development of host-directed therapeutics and prophylactics could limit such resistance and offer urgently needed protection against variants of concern3,4. Attractive pharmacological targets to impede viral entry include type-II transmembrane serine proteases (TTSPs) such as TMPRSS2; these proteases cleave the viral spike protein to expose the fusion peptide for cell entry, and thus have an essential role in the virus lifecycle5,6. Here we identify and characterize a small-molecule compound, N-0385, which exhibits low nanomolar potency and a selectivity index of higher than 106in inhibiting SARS-CoV-2 infection in human lung cells and in donor-derived colonoids7. In Calu-3 cells it inhibits the entry of the SARS-CoV-2 variants of concern B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma) and B.1.617.2 (Delta). Notably, in the K18-human ACE2 transgenic mouse model of severe COVID-19, we found that N-0385 affords a high level of prophylactic and therapeutic benefit after multiple administrations or even after a single administration. Together, our findings show that TTSP-mediated proteolytic maturation of the spike protein is critical for SARS-CoV-2 infection in vivo, and suggest that N-0385 provides an effective early treatment option against COVID-19 and emerging SARS-CoV-2 variants of concern.

Morphology-controlled electrocatalysts with the ability of CO2adsorption/activation, mass transfer, high stability and porosity are much desired in electrochemical CO2reduction reaction (CO2RR). Here, three kinds of multi-dimensional nanostructures (i.e., hollow sphere, nanosheets and nanofibers) have been successfully produced through the modulation of porphyrin-based covalent organic frameworks (COFs) with various modulators. The obtained nanostructures with high-stability, large surface-area, and single metal sites enable efficient CO2RR into CH4. Notably, they all exhibit higher FECH4(hollow sphere, 68.2%; nanosheet, 64.2% and nanofiber, 71.0%, −0.9 V) than COF-366-Cu (43.0%, −0.9 V) after morphology control. Noteworthy, the FECH4of COF-366-Cu (HS) keeps higher than 52.4% over a wide potential range from −0.9 V to −1.1 V and the achieved FECH4+C2H4(82.8%, −0.9 V) is superior to most of reported COFs and copper-based electrocatalysts. This work paves a new way in the exploration of COF-based multi-dimensional nanostructures applicable in efficient CO2RR to CH4.

Impact velocity (v0), target strength (fc) and target thickness (hc) are important factors affecting opening damage (D¯) of PELE penetration into RC target. In this paper, based on the three influence factors of v0, fcand hc, experimental and numerical simulation studies on PELE penetration into RC target were carried out. The study results show that: (1) Since interaction force (or penetration resistance) between projectile and target is positively correlated with v0and fc, with the increase of v0and fc, deformation mode of jacket is changed from small bending deformation to large bending deformation and then to curling deformation. Therefore, the variation of jacket deformation mode causes opening diameter of RC target to increase first and then to decrease. It is found that the two factors approximately satisfy a quadratic function relationship, respectively. (2) For PELE projectile penetrating RC targets with thickness of 80–400 mm, the opening diameter of six sets of RC targets grows from 240 to 500 mm, and hcwith D¯approximately satisfy a linear relationship. (3) Based on the above study results, the relationship between two dimensionless parameters (I=mv02d13fcand H=hcl) and dimensionless opening diameter (D¯/d1) was determined. Combined with the results of previous research, a dimensionless opening diameter model D¯d1=f1(Q,G,I)f2(H)was established. By tests verified, the test results are all within ±10% error of the theoretical model, which verifies the accuracy of the model.

When a penetrator with enhanced lateral effect (PELE) impacts on a reinforced concrete (RC) target, the target is damaged with a large opening. An understanding of how PELE projectile parameters affect the opening dimension, is essential for effective design of the PELE projectile. In this study, under the condition that the impact velocity and target parameters (strength and thickness) were fixed values, the important influence factors of the PELE (jacket wall thickness B, jacket material strength Y1, filling material strength Y2and angle of monolithic jacket θ) were determined by a dimensional analysis. Tests and simulations of the PELE penetrating the RC target were conducted to analyze the influence of these factors on opening diameter (D¯, an equivalent diameter under relative kinetic energy). Based on the test and simulation results, it is found that the influence of these factors B, Y1and θon the deformation mode of the jacket shows a similar trend: as values of the three factors decrease, the jacket deforms from small bending deformation to large one, and then to curling deformation. This causes the opening diameter to first increase with the decrease of these three factors, and then decreases. It is well known that the bending resistance of the jacket is related to these factors B, Y1and θ. Therefore, a plastic limit bending moment (M0) of the jacket was quoted to characterize the influence of these factors on the bending deformation of the jacket and the opening diameter of the target. The influence factor Y2causes D¯to first increase with the increase of Y2, and then decreases. A formula was developed to predict the opening diameter, whose influence parameters were considered in a dimensionless way. It has been shown that the dimensionless opening diameter D¯/d1is dependent on two dimensionless parameters Q=d13fcM0and G=fcY2, where d1and fcare the outer diameter of the projectile and the compressive strength of the target, respectively.

The sluggish kinetics and unclear mechanism have significantly hindered the development of Li-CO2batteries. Here, a Li-CO2battery cathode catalyst based on a porphyrin-based covalent organic framework (TTCOF-Mn) with single metal sites is reported to reveal intrinsic catalytic sites of aprotic CO2conversion from the molecular level. The battery with TTCOF-Mn exhibits a low overpotential of 1.07 V at 100 mA/g as well as excellent stability at 300 mA/g, which is one of the best Li-CO2battery cathode catalysts to date. The unique features of TTCOF-Mn including uniform single-Mn(II)-sites, fast Li+transfer pathways, and high electron transfer efficiency contribute to effective CO2reduction and Li2CO3decomposition in the Li-CO2system. Density functional theory calculations reveal that different metalloporphyrin sites lead to different reaction pathways. The single-Mn(II) sites in TTCOF-Mn can activate CO2and achieve an efficient four-electron CO2conversion pathway. It is the first example to reveal the catalytic active sites and clear reaction pathways in aprotic Li-CO2batteries.

Polyoxometalates (POMs), possessing multiple-electron redox ability, controllable size, and precise structure, hold much promise to be applied as anode materials in lithium-ion batteries (LIBs). However, the applications of them have been largely limited by the low conductivity and dissolution in an electrolyte. Herein, we report a series of covalently connected MnMo6–2NH2–GO ultrathin nanosheets (as thin as ∼1.1 nm), in which MnMo6–2NH2as the electron sponge is covalently linked to graphene oxide and the covalent bond as the electron bridge is highly adventurous for battery applications. Specifically, MnMo6–2NH2–GO-2 presents a reversible capacity of 1143 mAh g–1(0.1 A g–1) after 100 cycles, and the capacity retention is nearly 100% at 1000 mA g–1over 500 cycles. In addition, it also shows excellent rate capability (301 mAh g–1in 5 A g–1). This work paves a new way in designing POM-based novel electrode materials for high-performance LIBs.

We report on the formation of water-in-water liquid crystal emulsions with permeable colloidal assemblies. Rodlike cellulose nanocrystals (CNC) spontaneously self-assemble into a helical arrangement with the coexistence of nonionic, hydrophilic polyethylene glycol (PEG) and dextran, whereas the two polymer solutions are thermodynamically incompatible. Stable water-in-water emulsions are easily prepared by mixing the respective CNC/polymer solutions, showing micrometric CNC/PEG dispersed droplets and a continuous CNC/dextran phase. With time, the resulting emulsion demixes into an upper, droplet-lean isotropic phase and a bottom, droplet-rich cholesteric phase. Owing to the osmotic pressure gradient between PEG and dextran phases, target transfer of cellulose nanoparticles occurs across the water/water interface to reassemble into a liquid crystal-in-liquid crystal emulsion with global cholesteric organization. The observed structural, optical, and temporal evolution confirm that the colloidal particles in the two immiscible phases experience short-range interactions and form long-range assemblies across the interface.

Motility plays a critical role in algal survival and reproduction, with implications for aquatic ecosystem stability. However, the effect of elevated CO2on marine, brackish and freshwater algal motility is unclear. Here we show, using laboratory microscale and field mesoscale experiments, that three typical phytoplankton species had decreased motility with increased CO2. Polar marine Microglenasp., euryhaline Dunaliella salinaand freshwater Chlamydomonas reinhardtiiwere grown under different CO2concentrations for 5 years. Long-term acclimated Microglenasp. showed substantially decreased photo-responses in all treatments, with a photophobic reaction affecting intracellular calcium concentration. Genes regulating flagellar movement were significantly downregulated (P< 0.05), alongside a significant increase in gene expression for flagellar shedding (P< 0.05). D. salinaand C. reinhardtiishowed similar results, suggesting that motility changes are common across flagellated species. As the flagella structure and bending mechanism are conserved from unicellular organisms to vertebrates, these results suggest that increasing surface water CO2concentrations may affect flagellated cells from algae to fish.

The sinter cooling flue gas expelled from the end of an annular cooler was taken as the heat source of an organic Rankine cycle (ORC) system, and R123, R245fa, R600, R601 and R601a were selected as the working fluids of the ORC system. The effects of evaporation temperature and superheat degree of working fluid, as well as the pinch point temperature difference in the evaporator on the system thermal performance, were analyzed in detail. The results show that the system net output power and exergy efficiency for different working fluids first increase and then decrease with an increase in the evaporation temperature and decrease with an increase in the superheat degree and pinch point temperature difference. The change in pinch point temperature difference has no effect on the system thermal efficiency. For a given operational condition, the system thermal efficiency and exergy efficiency of R123 are the maximum, while the system total irreversible loss of R245fa is the maximum. When the evaporation temperature is greater than 110 °C, the system net output power of R600 is the maximum. The ORC system could obtain the maximum net output power and exergy efficiency through the adjustment of evaporation temperature of working fluid.

Aiming at the evaluation of creep damage at elevated temperature of ferromagnetic materials in engineering application, the hysteresis loop measurement technology was adopted to study the creep damage behaviour of 1Cr5Mo steel. The creep testing at 600°C/90MPa of 1Cr5Mo steel were carried out to prepare specimens with various degrees of creep damage. The variation of magnetic parameter including coercivity (HC) and remanence (Br) with creep damage was analyzed. The microstructure evolution of 1Cr5Mo steel with different degrees of creep damage was observed by optical microscope. The results show that the coercivity and remanence show certain regularity with creep damage at elevated temperature. Moreover, the regularity is repeatable which indicates that the measurement technology based on magnetic parameters can be used for the evaluation of high temperature creep damage.

A totally structure-determined organosilver(I) metal-oganic framework (MOF) of [{Ag18(CF3COO)18(H2O)2}{Ag4(erlotinib)4}]n•7nCH3OH•3nH2O (1) was first synthesized by the self-assembly of erlotinib drug ligand and silver salts in the study. 1formed a NbO-like 3D network, which was built from Ag(I)-erlotinib induced chains and 18-core silver(I) nanoclusters. When 1was dispersed in methanol solution, it formed derivative nanoparticles (1-NPs) with the average size of 3.81 nm. Silver(I) ion is an efficient reactive oxygen species (ROS) evocator, whereas the erlotinib ligand possesses the targeting activity towards tumor cells. Therefore, IC50values of 1-NPs for A549 and MRC-5 cells were respectively 0.97 and 7.28 μM, which were lower than IC50value of erlotinib. It should be noted that the 7.5-fold higher inhibition effect on A549 cells allows 1-NPs to be a potential targeting anticancer drug for curing lung cancer. The study opens a new avenue to design anticancer drugs based on organosilver(I) MOF derivatives that can realize the value-added reactivity by combining clinical drugs with ROS-inductive silver(I) ion.

Harmful cyanobacterial blooms represent an increasing threat to freshwater resources globally. Despite increased research, the physiological basis of how the dominant bloom-forming cyanobacteria, Microcystisspp., proliferate and then maintain high population densities through changing environmental conditions is poorly understood. In this study, we examined the transcriptional profiles of the microbial community in Lake Taihu, China at 9 stations sampled monthly from June to October in 2014. To target Microcystispopulations, we collected metatranscriptomic data and mapped reads to the M. aeruginosaNIES 843 genome. Our results revealed significant temporal gene expression patterns, with many genes separating into either early or late bloom clusters. About one-third of genes observed from M. aeruginosawere differentially expressed between these two clusters. Conductivity and nutrient availability appeared to be the environmental factors most strongly associated with these temporal gene expression shifts. Compared with the early bloom season (June and July), genes involved in N and P transport, energy metabolism, translation, and amino acid biosynthesis were down-regulated during the later season (August to October). In parallel, genes involved in regulatory functions as well as transposases and the production of microcystin and extracellular polysaccharides were up-regulated in the later season. Our observation indicates an eco-physiological shift occurs within the Microcystisspp. transcriptome as cells move from the rapid growth of early summer to bloom maintenance in late summer and autumn.

Basin‐scale current fields are fundamental to determining the environmental characteristics and ecological attributes of large polymictic lakes. However, little is known concerning the effects of different winds on the currents and further on ecological systems of these lakes. Therefore, synchronous meteorological and hydrological data were collected from Lake Taihu (China) during summer 2015. Time series analysis and stress calculations conducted to elucidate the basin‐scale current field revealed frequent occurrence of a bilayer current mode, comprising a wind‐driven surface current and bottom compensation current, under low or medium wind conditions. The main forcings of the lake currents are seasonal winds related to the East Asian monsoon, and the lake‐land thermal contrast wind with 24‐hr periodicity causes marked diurnal fluctuation. Inflows, outflows, the Coriolis force, and bottom frictional stress also make important contributions to the bilayer current mode, and weak temperature stratification can stabilize this mode. However, as wind speed increases, wind‐driven surface currents can develop downward to form uniform currents throughout the water depth, and water temperature stratification is destroyed during typhoon‐affected periods. During such short‐term strong wind events, the current structure mainly adopts a monolayer current mode and the incidence of the bilayer current mode decreases substantially. The monolayer current mode causes a clockwise circulation and a basin‐scale temporary oscillation with ~80‐hr periodicity. The influences of the monsoon and lake‐land thermal contrast wind on lake currents were masked by the pulse‐like strong winds. Both modes can contribute to persistent cyanobacterial blooms in the northwest of Lake Taihu. Large lake currents profoundly influence the lake environmental characteristics and ecological attributes. However, little is known concerning about the current distribution in response to the different wind fields. Therefore, synchronous meteorological and hydrological data were observed in Lake Taihu during the summer of 2015. It was found that a bilayer current mode was frequently observed under condition of low wind speed. This current mode comprised a wind‐driven surface current and bottom opposite compensation current. The main driving forces were the seasonal winds related to the East Asian monsoon and land‐lake thermal contrast wind, inflow‐outflow, the Coriolis force, and bottom frictional stress. A weak temperature stratification can stabilize this mode. However, wind‐driven surface currents could develop downward trends with greater wind speeds to form uniform currents throughout the entire water column and the water temperature stratification was destroyed during typhoon‐affected periods. During the monolayer current period, a clockwise circulation and a basin‐scale temporary oscillation with a periodicity of ~80 hr were observed. Both modes can contribute the persistent cyanobacterial blooms in the northwest region of Lake Taihu. A bilayer current mode generated by the East Asian monsoon and other forcings frequently occurs under low or medium wind conditionsA monolayer current mode driven by typhoon‐induced strong winds causes a clockwise circulation and a basin‐scale temporary oscillationLake‐land thermal contrast wind results in diurnal fluctuation of lake currents

Metabolic reprograming is an emerging hallmark of tumor biology and an actively pursued opportunity in discovery of oncology drugs. Extensive efforts have focused on therapeutic targeting of glycolysis, whereas drugging mitochondrial oxidative phosphorylation (OXPHOS) has remained largely unexplored, partly owing to an incomplete understanding of tumor contexts in which OXPHOS is essential. Here, we report the discovery of IACS-010759, a clinical-grade small-molecule inhibitor of complex I of the mitochondrial electron transport chain. Treatment with IACS-010759 robustly inhibited proliferation and induced apoptosis in models of brain cancer and acute myeloid leukemia (AML) reliant on OXPHOS, likely owing to a combination of energy depletion and reduced aspartate production that leads to impaired nucleotide biosynthesis. In models of brain cancer and AML, tumor growth was potently inhibited in vivo following IACS-010759 treatment at well-tolerated doses. IACS-010759 is currently being evaluated in phase 1 clinical trials in relapsed/refractory AML and solid tumors.

Lung cancer is a devastating disease that remains a top cause of cancer mortality. Despite improvements with targeted and immunotherapies, the majority of patients with lung cancer lack effective therapies, underscoring the need for additional treatment approaches. Genomic studies have identified frequent alterations in components of the SWI/SNF chromatin remodeling complex including SMARCA4and ARID1A. To understand the mechanisms of tumorigenesis driven by mutations in this complex, we developed a genetically engineered mouse model of lung adenocarcinoma by ablating Smarca4in the lung epithelium. We demonstrate that Smarca4acts as a bona fide tumor suppressor and cooperates with p53loss and Krasactivation. Gene expression analyses revealed the signature of enhanced oxidative phosphorylation (OXPHOS) in SMARCA4mutant tumors. We further show that SMARCA4mutant cells have enhanced oxygen consumption and increased respiratory capacity. Importantly, SMARCA4mutant lung cancer cell lines and xenograft tumors have marked sensitivity to inhibition of OXPHOS by a novel small molecule, IACS-010759, that is under clinical development. Mechanistically, we show that SMARCA4-deficient cells have a blunted transcriptional response to energy stress creating a therapeutically exploitable synthetic lethal interaction. These findings provide the mechanistic basis for further development of OXPHOS inhibitors as therapeutics against SWI/SNF mutant tumors. SMARCA4 loss in non-small-cell lung cancer creates a metabolic dependency on oxidative phosphorylation that can be targeted using a new small-molecule inhibitor.

Sustainable performance of heavy structures such as tanks, storage yards and tall buildings often rely on an efficient transfer of vertical and lateral loads to underlying ground. If the foundation soil does not have sufficient strength, the piles may be belled out (under-reamed) at the base, often termed as large-diameter belled piles (LDBPs). In reality the deformation and failure mechanism of LDBPs are significantly different and are influenced by the nature of foundation soil. However, in the absence of appropriate design guidelines, LDBPs are simply treated as conventional straight piles, often ignoring enlarged base. To access effects of enlarged base on load-deformation behavior, full-scale load tests are conducted on several LDBPs. A novel interpreted failure load criterion is proposed for LDBPs. The general applicability of this criterion is verified using the data from nine independent pile load tests retrieved from four different projects across China. Adopting the proposed method, provision of a much effective and economic design for LDBPs is feasible in comparison with the criteria currently prevalent in practice.

A new hot-dip galvanizing method was employed on hot-rolled low carbon steel. The effects of Al contents on microstructure, micro-hardness and corrosion resistance of Zn-Al alloy coatings were systematically investigated. Phase composition, microstructure and element distribution in Zn-Al alloy coatings were analyzed using X-ray diffraction (XRD) and electron probe micro analysis (EPMA), respectively. It is found that Al content (0. 6–6. 0 wt. %) in galvanizing zinc affects surface quality and adhesion between coatings and matrix in the newly developed method. In addition, with increasing Al content, micro-hardness significantly increased due to the increase in Zn-Al eutectoid phases. Potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) also revealed that increase in Al plays a noticeable role in improving the corrosion resistance of Zn-Al alloy coatings.

In eutrophic lakes, heterotrophic bacteria are closely associated with algal detritus and play a crucial role in nutrient cycling. However, the seasonal and spatial dynamics of free‐living (FL) and particle‐attached (PA) bacteria and the environmental factors shaping this relationship remain poorly understood. To address this issue, we explored the spatiotemporal patterns of bacterial community composition (BCC) in Lake Taihu, China, using terminal restriction fragment length polymorphism (T‐RFLP) and 454‐tag pyrosequencing of 16S rRNA gene. We generated a total of 218,027 high quality non‐cyanobacterial sequence reads that resulted in 4940 OTUs (97% cutoff), with Actinobacteria, β‐and α‐proteobacteriabeing the predominant taxa. Although PA communities contained significantly higher alpha‐diversity than FL ones, we found that 59% of OTUs, that accounted for 96% of the total reads, were shared by both communities. The high degree of overlap between FL and PA communities indicates a high rate of dispersal potential, highlighting an underestimated connectivity and potentially similar ecological role for these two components. Distinct seasonal trends were recorded in both FL and PA communities, while spatial differences in BCC were small. In addition, both FL and PA bacterial communities exhibited similar patterns and synchrony, correlated to water temperature, nitrate and total suspended solids (TSS). Accordingly, the effects of eutrophication and hydrodynamics on the phylogenetic overlap and diversity between FL and PA communities were discussed.

Castleman disease (CD) is a group of rare and heterogenous lymphoproliferative disorders including unicentric CD (UCD), human herpesvirus-8(HHV-8)-associated multicentric CD (HHV8-MCD), and HHV-8-negative/idiopathic multicentric CD (iMCD). Knowledge of CD mainly comes from case series or retrospective studies, but the inclusion criteria of these studies vary because the Castleman Disease Collaborative Network (CDCN) diagnostic criteria for iMCD and UCD were not available until 2017 and 2020, respectively. Further, these criteria and guidelines have not been systematically evaluated.

A vertical type twin roll caster with two side dams was used to cast aluminium alloy strip with a thickness of about 5mm at speed higher than 10m/min. The characteristics of the twin roll caster with two side dams are as follows: The diameter of the copper roll is 500mm, the width of the copper roll is 110mm and the thickness of the copper roll sleeve is 25mm.The maximum casting speed is up to 60m/min. Using the vertical type twin roll caster, a 4.5mm thickness of 6111 strip could be cast at a speed of 30m/min. The microstructure of the as-cast strip was equiaxed and spherical, not columnar. The mechanical properties of the strip casted from the vertical type twin roll caster were almost as same as that of the strip made from the conventional cast ingot.

In this paper, the asymptotic solutions about the origin and infinity are formulated via Laplace transform for a two-term linear Caputo fractional differential equation. The asymptotic expansion about the origin describes the complete singular information of the solution, which is also a good approximation of the solution near the origin. The expansion at infinity exhibits the structure of the solution, as well as the stable or unstable property of the solution, which becomes more accurate as the variable tends to larger. Based on the asymptotic solution about the origin, a singularity-separation Legendre collocation method is designed to validate the methods in this paper. Numerical examples show the easy calculation and high accuracy of the truncated expansions and their Padé approximations when the variable is suitably small or sufficiently large. As an application, the method is used to solve the initial value problem of the Bagley–Torvik equation, and the oscillatory property of the solution is displayed. • The series solutions with logarithms about the origin and infinity are formulated. • The series solution at the origin is used to design a Legendre collocation method. • The expansion at infinity reveals the stable or unstable property of the solution. • The method can be applied to solve general multi-term linear fractional problems. [ABSTRACT FROM AUTHOR]

Objective We investigated the effect of dexmedetomidine anesthesia on postoperative cognitive function after pulmonary surgery.Methods A blinded, prospective, randomized, placebo-controlled study was performed on 60 patients (age range 65–74 years) undergoing lobectomy by video-assisted thoracoscopic surgery (29 in the dexmedetomidine group; 31 in the placebo group). Dexmedetomidine group patients received dexmedetomidine, and placebo group patients received an equal volume of physiological saline 20 minutes before anesthesia induction. Cognitive function was evaluated using the Montreal Cognitive Assessment 1 day before surgery and on postoperative day (POD)1, POD3, and POD7. The regional cerebral oxygen saturation (rSO2) was monitored continuously by near-infrared spectroscopy before anesthesia.Results The Montreal Cognitive Assessment score was significantly different between the two groups on POD1 (dexmedetomidine 26.4  ±  0.73 vs. placebo 25.5 ± 0.96) and POD3 (dexmedetomidine 27.1 ± 0.79 vs. placebo 26.6 ± 0.80). Specifically, attention and orientation scores were increased in the dexmedetomidine group on POD1 and POD3. The rSO2was not significantly different between the dexmedetomidine and placebo groups.Conclusion Dexmedetomidine given before induction of anesthesia could reduce the risk of postoperative cognitive dysfunction and might not decrease rSO2. Hence, dexmedetomidine could be employed in pulmonary surgical procedures, especially for older patients with a high risk of cognitive dysfunction.

Epitope mapping of the 3F3A mAb identified p38 MAPK phosphorylation of Ser-538 of the E3 ubiquitin ligase Gp78. p38 MAPK phosphorylation of Ser-538 prevents Gp78-dependent mitofusin degradation, mitochondrial fission, and ER–mitochondria association, defining a novel regulatory mechanism of Gp78 activity at the ER–mitochondria interface.

Purpose – The purpose of this paper is to develop a method for solving the multiple attribute decision-making (MADM) problem in which the decision maker can provide the five types of attribute aspirations, namely: benefit type with requirements; cost type with requirements; interval type; benefit type; and cost type. Design/methodology/approach – First, for each type of attribute aspiration, the calculation formula of utility values of alternative concerning attributes is given. Then, using the calculation formulae, the attribute values are transformed into the corresponding utility values. On the basis of this, the overall ranking value of each alternative is calculated. Further, a ranking order of alternatives can be determined according to the obtained overall ranking values. Findings – Research shows that it is necessary to develop the method for MADM with attribute aspirations. The example shows that the proposed method is applicable. Practical implications – The proposed method can be applied to the selection of wastewater treatment technologies or other areas. Originality/value – This paper proposes a new MADM method with multiple types of attribute aspirations. It develops and enriches the existing MADM methods. [ABSTRACT FROM AUTHOR]

It is very important to use the science, technology and cultural elements in the process is the landscape of expression, and advanced engineering technology is the basis for the development of the urban landscape. In the urban construction area of modern technology into the traditional culture of the city can do the development and continuation of traditional culture, and promote the development of the urban landscape systems. This paper presents a dynamic urban landscape design, a variety of traits city weather conditions, urban context, materials technology, biological populations, ecological flows were studied. Through analysis, can be used in shaping the city's landscape, and achieved good results.

In this paper, a 4 cylinder SI engine was fuelled with gasoline, M10, M30 and M85 methanol-gasoline blends, and the cold start transient performances were investigated under the ambient temperature of 15°C, -7°C, -15°C and-25°C, respectively. The engine speed curves indicate the existence of misfire and incomplete combustion, which are proved by the measured temperatures and the indicated mean effective pressure (IMEP) obtained from the cylinder pressure analyses. The addition of methanol increases the starting time at low temperature, but improves the combustion. The peak speed and the transient period increase with the increase of methanol fraction, while the speed fluctuation decreases.

The depth map is a basic diagram of the intrinsic; each pixel value represents the scene graph the elevation position of the object point. In this paper, the analysis methods for target classification elevation map. Figure elevation are visible depth image, the depth of the image is the distance from each point in the scene to the image capture device values ​​of the image as an image pixel value.

Increased expressions of fatty acid synthase (FASN) and epidermal growth factor receptor (EGFR) are common in cancer cells. De novo synthesis of palmitate by FASN is critical for the survival of cancer cells via mechanisms independent of its role as an energy substrate. Besides the plasma membrane and the nucleus, EGFR can also localize at the mitochondria; however, signals that can activate mitochondrial EGFR (mtEGFR) and the functions of mtEGFR of cancer cells remain unknown. The present study characterizes mtEGFR in the mitochondria of cancer cells (prostate and breast) and reveals that mtEGFR can promote mitochondrial fusion through increasing the protein levels of fusion proteins PHB2 and OPA1. Activation of plasma membranous EGFR (pmEGFR) stimulates the de novo synthesis of palmitate through activation of FASN and ATP-citrate lyase (ACLy). In vitro kinase assay with isolated mitochondria shows that palmitate can activate mtEGFR. Inhibition of FASN blocks the mtEGFR phosphorylation and palmitoylation induced by EGF. Mutational studies show that the cysteine 797 is important for mtEGFR activation and palmitoylation. Inhibition of FASN can block EGF induced mitochondrial fusion and increased the sensitivity of prostate cancer cells to EGFR tyrosine kinase inhibitor. In conclusion, these results suggest that mtEGFR can be activated by pmEGFR through de novo synthesized palmitate to promote mitochondrial fusion and survival of cancer cells. This mechanism may serve as a novel target to improve EGFR-based cancer therapy.

Telescopic jib is the key load-bearing component for both truck crane and all-terrain crane,seriously affect hoisting capacity of crane. Different stress feature or structural feature produce different affects on the hoisting capacity of telescopic jib. In order to study the mechanism and levels of different factors,multiple telescopic jib models with different factors are built based on nonlinear finite element method. Adopting Arc-length method to analysis structural nonlinear deformation in the whole course,the impact degree for hoisting performance of material yield strength, load eccentricity, lap length of telescopic jib and the support position of lifting hydraulic cylinder are acquired respectively. The results shows: A finite element method combined with arc-length method can be used to analysis the buckling problem of nonlinear deformation of telescopic jib. All the above four factors have affect on the hoisting performance of telescopic jib, but the levels are different. By analyzing change law of impact factors, corresponding measure are adopted in practical deign to reduce its impact and to strengthen the capacity of resisting local buckling of the telescopic jib.

The roof garden is a complex form of roofs landscape. Advanced green roof design played a huge ecological and economic benefits gradually being recognized for the significance of green roofs and classification, this paper study the roof garden design principles and key technologies for preliminary summary and discussion, proposed green roof functioning and performance arts beautiful landscape design methods.

For the bulging of sheet metals under hydraulic pressure on concave surface, constitutive relation, static equilibrium conditions, and approximate geometrical relation were discussed about the source of calculation error. Dimensionless deflection at the center of sheet was used as the intermediate variable, and a simple but efficient nomographic algorithm addressed for strain limit is presented in this paper. The results of the calculation were compared with that of the uniaxial tensile test, the bulge test, and the Finite Element Analysis (FEA). This method has the potential for industrial applications such as pressure forming, bulge test, and rupture disc manufacturing.

Aerobic biological wastewater treatment processes are difficult to be controlled because of their complex and nonlinear behavior, however, the control of the dissolved oxygen (DO) level in the reactors plays an important role in the operation of the facility, which affects the activity of activated sludge. A mathematical model of aeration system is established with the actual pulp and paper wastewater aerobic biological treatment process in Shandong as the background. Three control strategies for DO are designed. MATLAB simulation was carried out to compare the PID control, fuzzy control and fuzzy PID control of the step response. The robustness analysis of the three control systems is also researched. Conclusion is that the performance of Fuzzy PID control is the best.

As a new type of pulse width modulate converter,the input current of matrix rectifier consists of a great deal of high-frequency harmony current. The harmony has a bad influence on the net side. So a input filter is needed to eliminate it. Through the approach of Fourier transform, the harmony wave of the matrix rectifier is discussed, and the conclusion of the value of high-harmony and the induction in inverse proportion is deduced. The inactive power that the capacitance absorbe determines its value. The range of the resonance frequency determine the range of the induction. From above analysis a basic design of input LC filter of matrix converter is given. The input filter has been verified in the matlab/simulink and good performances are achieved.

The Split Hopkinson Pressure Bar (SHPB) is used to investigate the dynamic compressive mechanical behavior of a new foamed ceramic composite under impact loading. The stress versus strain curves are obtained under high strain rates. The test results are considered to be able to assure conformability of the tests, validate the stress equilibrium assumption, and show that the stress versus strain curves of foamed ceramic composite display strain hardening effect and damage softening effect as brittle materials. Meanwhile the curve includes short plateau region while no densification region.