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A series of progress has been made in the field of antimicrobial use of nanozymes due to their superior stability and decreased susceptibility to drug resistance. However, catalytically generated reactive oxygen species (ROS) are insufficient for coping with multidrug-resistant organisms (MDROs) in complex wound environments due to their low targeting ability and insufficient catalytic activity. To address this problem, chemically stable copper–gallic acid–vancomycin (CuGA–VAN) nanoneedles were successfully constructed by a simple approach for targeting bacteria; these nanoneedles exhibit OXD-like and GSH-px-like dual enzyme activities to produce ROS and induce bacterial cuproptosis-like death, thereby eliminating MDRO infections. The results of in vitroexperiments showed that the free carboxylic acid of GA could react with the free ammonia of teichoic acid in the methicillin-resistantStaphylococcus aureus(MRSA) cell wall skeleton. Thus, CuGA–VAN nanoneedles can rapidly “capture” MRSAin liquid environments, releasing ROS, VAN and Cu2+on bacterial surfaces to break down the MRSAbarrier, destroying the biofilm. In addition, CuGA–VAN effectively promoted wound repair cell proliferation and angiogenesis to facilitate wound healing while ensuring biosafety. According to transcriptome sequencing, highly internalized Cu2+causes copper overload toxicity; downregulates genes related to the bacterial glyoxylate cycle, tricarboxylic acid cycle, and oxidative respiratory chain; and induces lipid peroxidation in the cytoplasm, leading to bacterial cuproptosis-like death. In this study, CuGA–VAN was cleverly designed to trigger a cascade reaction of targeting, drug release, ROS-catalyzed antibacterial activity and cuproptosis-like death. This provides an innovative idea for multidrug-resistant infections.

Alkaline water electrolysis is one of the most promising solutions for large-scale hydrogen production from renewable energy sources (RESs) due to its low cost and maturity. However, the low-load performance of alkaline water electrolyzers (AWEs) is poor, which makes it difficult to follow fluctuant RESs in wide operating range. To address this problem, a novel equivalent circuit model of industrial AWESs is established based on its internal structure and operating principle. Then, a multimodal self-optimization control method and its prototype electrolysis converter are proposed to improve the efficiency of hydrogen production in low load. Compared with traditional methods, the proposed method can provide stable pulse current for the electrolyzer to realize efficiency improvement in low load. Finally, based on a 10 KW AWEs experimental platform, the correctness of the theoretical analysis is verified. The experimental results show that the proposed control strategy has a significant effect on the efficiency improvement of the 10 KW AWEs in low load.

Photoactivation is a phenomenon that could enhance the photoluminescence (PL) and photostability upon UV/vis light exposure, which is usually observed in CdSe/ZnS quantum dots (QDs). However, the photoactivation phenomenon has been scarcely reported in fluorescent carbon quantum dots (CQDs). Herein, the nitrogen-doped carbon quantum dots (N-CQDs) were prepared through a facile solvothermal approach with naphthalenetracarboxylic dianhydride and serine as precursors. Upon simple UV light irradiation for 10 min, the fluorescence quantum yield (QY) of N-CQDs could increase up to 10-fold. Based on this phenomenon, the N-CQDs were explored as an ultraviolet (UV) light sensor to assess the intensity of ultraviolet radiation in sunlight and indirectly evaluate the UV-blocking efficiency of various sunscreen products. Thus, this contribution not only provided an insight into developing a low-cost UV detector but also opened a door for the development of carbon quantum dots with converse-photobleaching properties.

Hsp70-Bim protein–protein interaction (PPI) is the most recently identified specific target in chronic myeloid leukemia (CML) therapy. Herein, we developed a new class of Hsp70-Bim PPI inhibitors via scaffold hopping of S1g-10, the most potent Hsp70-Bim PPI inhibitor thus far. Through structure–activity relationship (SAR) study, we obtained a biphenyl scaffold compound JL-15with a 5.6-fold improvement in Hsp70-Bim PPI suppression (Kd= 123 vs 688 nM) and a 4-fold improvement in water solubility (29.42 vs 7.19 μg/mL) compared to S1g-10. It maintains comparable apoptosis induction capability with S1g-10against both TKI-sensitive and TKI-resistant CML cell lines in an Hsp70-Bim-dependent manner. Additionally, through SAR, 1H–15N TRSOY-NMR, and molecular docking, we revealed that Lys319 is a “hot spot” in the Hsp70-Bim PPI interface. Collectively, these results provide a novel chemical scaffold and structural insights for the rational design of Hsp70-Bim PPI inhibitors.

Uncertainty exists about whether lowering systolic blood pressure to less than 120 mm Hg is superior to that of less than 140 mm Hg, particularly in patients with diabetes and patients with previous stroke.

In the rolling process of silicon steel strip of the five-stand UCMW tandem cold rolling line, the quality of finished profile is the result of cooperative control of five stands, the exit profiles of the first four stands jointly decide the exit profile of the fifth stand, so it is necessary to accurately control the strip profile in the rolling process. However, the shapemeter is only typically equipped at the exit of fifth stand, making it impossible to obtain the strip profile of the first four stands. A profile prediction model for the whole tandem cold rolling based on PSO-BP algorithm is established, compared with the finite element method, this model can satisfy the demand for fast prediction of strip profile and quickly analyzing the profile change characteristics for five stands according to the adjustment of profile control parameters in the industrial field. Firstly, a 3D elastic-plastic finite element model of rolls and strip for five stands is built, and a large number of profile calculation data are as the training sample sets to build the PSO-BP model. Through the transfer calculation of strip profile between adjacent stands, the PSO-BP model of five stands is established, and the validity is verified by comparing with the actual measured data. Secondly, to improve the quality of product profile, focusing on the unreasonable setting of production parameters, many improvement schemes of WRB and WRS for five stands are designed, and the PSO-BP model is used to quickly calculate the strip profile, then comparing the result of each scheme, the optimum improvement scheme is selected, which is furtherly carried out rolling experiments in the industrial field, and the quality of strip profile is well improved. At present, the new scheme has been successfully applied to industrial production.

Diesel particulate filter (DPF) made from cordierite with a porous filter media structure has become an essential component in diesel engines to meet the increasingly the strict emission standards. Hence, a more accurate and universal DPF porous filter media model is necessary to analyze the complex mechanism and optimize its performance. In this work, a new optimization method was proposed for the initial DPF model constructed by the quartet structure generation set (QSGS), and the fractal and spectral dimension were used to quantify the actual effects of the optimized DPF model. Results showed that the method could effectively repair dead zones and eliminate burr boundaries, thus decreasing the complexity of the pore structure and increasing the effective flow area of the DPF model. The increase in porosity decreased the fractal dimension and increased the spectral dimension in porous media. Additionally, simulation results showed that the proposed method was more effective on burr boundaries. This allows the optimization method to be adopted more effectively in porous media modeling and provides improved guidance for optimization. Not only DPF, the proposed method offers a new idea for the structure optimization of porous filter media.

The association between dysfunctional microglia and amyloid-ß (Aß) is a fundamental pathological event and increases the speed of Alzheimer’s disease (AD). Additionally, the pathogenesis of AD is intricate and a single drug may not be enough to achieve a satisfactory therapeutic outcome. Herein, we reported a facile and effective gene therapy strategy for the modulation of microglia function and intervention of Aß anabolism by ROS-responsive biomimetic exosome-liposome hybrid nanovesicles (designated as TSEL). The biomimetic nanovesicles codelivery ß-site amyloid precursor protein cleaving enzyme-1 (BACE1) siRNA (siBACE1) and TREM2 plasmid (pTREM2) gene drug efficiently penetrate the blood–brain barrier and enhance the drug accumulation at AD lesions with the help of exosomes homing ability and angiopep-2 peptides. Specifically, an upregulation of TREM2 expression can reprogram microglia from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 phenotype while also restoring its capacity to phagocytose Aß and its nerve repair function. In addition, siRNA reduces the production of Aß plaques at the source by knocking out the BACE1 gene, which is expected to further enhance the therapeutic effect of AD. The in vivo study suggests that TSEL through the synergistic effect of two gene drugs can ameliorate APP/PS1 mice cognitive impairment by regulating the activated microglial phenotype, reducing the accumulation of Aß, and preventing the retriggering of neuroinflammation. This strategy employs biomimetic nanovesicles for the delivery of dual nucleic acids, achieving synergistic gene therapy for AD, thus offering more options for the treatment of AD.

The diesel particulate filter (DPF) with porous media structure has become an essential component for diesel engines to satisfy increasingly strict emission standards. This study constructed a porous media structure model of DPF, and optimized its boundary to conduct a simulation on the flow characteristic with different influencing parameters using the lattice Boltzmann method (LBM). Results showed that the increase of the average flow velocity of the DPF model reduced the pressure drop, indicating that the flow probability of model improved. In addition, the porosity application range was expanded. The visualization and quantization of the velocity and pressure distribution with the DPF revealed that an increase of the wall thickness resulted in a higher pressure drop of the DPF, but a lower flow velocity. Further, the fractal dimension of the porous media exhibited no direct relationship with the DPF pressure and velocity performance; however, the outlet velocity and pressure drop of the model were optimized within the different porosity. Moreover, both the increase in the spectral dimension and model optimization improved the DPF permeability. The impact of increasing the inlet velocity on the pressure drop was particularly significant as it accelerated the rate of pressure drop, illustrating that a smoother porous media boundary was conducive to improve the flow performance of DPF, which facilitated a better scheme for the design of DPF porous media.

Atomically precise doping of metal nanoclusters provides excellent opportunities not only for subtly tailoring their properties but also for in-depth understanding of composition (structure)–property correlation of metal nanoclusters and has attracted increasing interest partly due to its significance for fundamental research and practical applications. Although single and multiple metal atom doping of metal nanoclusters (NCs) has been achieved, sequential single-to-multiple metal atom doping is still a big challenge and has not yet been reported. Herein, by introducing a second ligand, a novel multistep synthesis method was developed, controlled sequential single-to-multiple metal atom doping was successfully achieved for the first time, and three doped NCs Au25Cd1(p-MBT)17(PPh3)2, Au18Cd2(p-MBT)14(PPh3)2, and [Au19Cd3(p-MBT)18]−(p-MBTH: para-methylbenzenethiol) were obtained, including two novel NCs that were precisely characterized via mass spectrometry, single-crystal X-ray crystallography, and so forth. Furthermore, sequential doping-induced evolutions in the atomic and crystallographic structures and optical and catalytic properties of NCs were revealed.

The integration of predictive, preventive, personalized, and participatory (P4) healthcare advocates proactive intervention, including dietary supplements and lifestyle interventions for chronic disease. Personal profiles include deep phenotypic data and genetic information, which are associated with chronic diseases, can guide proactive intervention. However, little is known about how to design an appropriate intervention mode to precisely intervene with personalized phenome-based data. Here, we report the results of a 3-month study on 350 individuals with metabolic syndrome high-risk that we named the Pioneer 350 Wellness project (P350). We examined: (1) longitudinal (two times) phenotypes covering blood lipids, blood glucose, homocysteine (HCY), and vitamin D3(VD3), and (2) polymorphism of genes related to folic acid metabolism. Based on personalized data and questionnaires including demographics, diet and exercise habits information, coaches identified 'actionable possibilities', which combined exercise, diet, and dietary supplements. After a 3-month proactive intervention, two-thirds of the phenotypic markers were significantly improved in the P350 cohort. Specifically, we found that dietary supplements and lifestyle interventions have different effects on phenotypic improvement. For example, dietary supplements can result in a rapid recovery of abnormal HCY and VD3levels, while lifestyle interventions are more suitable for those with high body mass index (BMI), but almost do not help the recovery of HCY. Furthermore, although people who implemented only one of the exercise or diet interventions also benefited, the effect was not as good as the combined exercise and diet interventions. In a subgroup of 226 people, we examined the association between the polymorphism of genes related to folic acid metabolism and the benefits of folate supplementation to restore a normal HCY level. We found people with folic acid metabolism deficiency genes are more likely to benefit from folate supplementation to restore a normal HCY level. Overall, these results suggest: (1) phenome-based data can guide the formulation of more precise and comprehensive interventions, and (2) genetic polymorphism impacts clinical responses to interventions. Notably, we provide a proactive intervention example that is operable in daily life, allowing people with different phenome-based data to design the appropriate intervention protocol including dietary supplements and lifestyle interventions.

Hydrogen production from photovoltaic arrays is a promising way to fully utilize the solar energy and to relieve consumption pressure of the power system. The low-cost and mature alkaline water electrolysis is suitable for large-scale hydrogen production. However, the low-load inefficiency of alkaline water electrolyzers greatly limits their operation range (usually 40%–100% of rated load). Hence, alkaline water electrolyzers are hard to follow the fluctuating photovoltaic power in full range. Focusing on this problem, this article analyzes the inefficiency mechanism of low-load alkaline water electrolyzers. It is found that through modifying the excitation electric field, the low-load performance of alkaline water electrolyzers can be greatly enhanced. Based on this, an optimal current pulsewidth modulation control strategy and the corresponding prototype converter are proposed to regulate alkaline water electrolyzers directly driven by photovoltaic arrays. The effectiveness of the proposed method is verified by a 2 Nm3/h commercial alkaline water electrolyzer. Experimental results show that compared to the conventional dc power supply, 1) the maximum efficiency improvement can exceed two times, and 2) the alkaline water electrolyzer can follow the fluctuating photovoltaic power well.

Assessing CD38 expression in vivo has become a significant element in multiple myeloma (MM) therapy, as it can be used to detect lesions and forecast the effectiveness of treatment. Accurate diagnosis requires a multifunctional, high-throughput probe screening platform to develop molecular probes for tumor-targeted multimodal imaging and treatment. Here, we investigated a microarray chip-based strategy for high-throughput screening of peptide probes for CD38. We obtained two new target peptides, CA-1 and CA-2, from a 105peptide library with a dissociation constant (KD) of 10–7M. The specificity and affinity of the target peptides were confirmed at the molecular and cellular levels. Peptide probes were labeled with indocyanine green (ICG) dye and 68Ga-DOTA, which were injected into a CD38-positive Ramos tumor-bearing mouse via its tail vein, and small animal fluorescence and positron emission tomography (PET) imaging showed that the peptide probes could show specific enrichment in the tumor tissue. Our study shows that a microchip-based screening of peptide probes can be used as a promising imaging tool for MM diagnosis.

The idle start-go (ISG) system has been widely used, but there have been few relevant studies of its effect on emissions. This paper investigates fuel economy, total hydrocarbon (THC), carbon monoxide (CO), nitrogen oxides (NOx), particulate mass (PM), and particle number (PN) emissions from China VI gasoline direct injection (GDI) vehicles with and without ISG. Three test cycles were performed under hot start conditions, that is, the worldwide harmonized light vehicle test cycle (WLTC), the China light-duty vehicle test cycle (CLTC), and the USA federal test procedure-75 (FTP-75). About 28 idling phases were selected to specifically analyze the influence of ISG system. The results reveal that ISG system helps decrease fuel consumption, THC and CO emissions but aggravates NOxand solid PN emissions. Also, ISG system increases the proportions of sub-23 nm and nucleation-mode particle emission. Idling time plays a role in fuel economy, THC and CO emissions, while accelerated speed affects the emissions of THC, CO, NOx, and PN.

In vivo quantitative assessment of oxyhaemoglobin saturation (sO2) status in tumour-associated vessels could provide insights into cancer metabolism and behaviour. Here we develop a non-invasive in vivo sO2imaging technique to visualize the sO2levels of healthy and tumour tissue based on photoluminescence bioimaging in the near-infrared IIb (NIR-IIb; 1,500–1,700 nm) window. Real-time dynamic sO2imaging with a high frame rate (33 Hz) reveals the cerebral arteries and veins through intact mouse scalp/skull, and this imaging is consistent with the haemodynamic analysis results. Utilizing our non-invasive sO2imaging, the tumour-associated-vessel sO2levels of various cancer models are evaluated. A positive correlation between the tumour-associated-vessel sO2levels and the basal oxygen consumption rate of corresponding cancer cells at the early stages of tumorigenesis suggests that cancer cells modulate the tumour metabolic microenvironment. We also find that a positive therapeutic response to the checkpoint blockade cancer immunotherapy could lead to a dramatic decrease of the tumour-associated-vessel sO2levels. Two-plex dynamic NIR-IIb imaging can be used to simultaneously observe tumour-vessel sO2and PD-L1, allowing a more accurate prediction of immunotherapy response.

Selectively targeting the cancer-specific protein–protein interaction (PPI) between Hsp70 and Bim has been discovered as a promising strategy for treating chronic myeloid leukemia (CML). The first Hsp70–Bim PPI inhibitor, S1g-2, has been identified to overcome the on-target toxicity of known Hsp70 inhibitors when it induces apoptosis of CML cells. Herein, we carried out a hit-to-lead optimization of S1g-2, yielding S1g-10, which exhibited a 10-fold increase in Hsp70/Bim suppressing potency. Furthermore, S1g-10not only exhibited a 5- to 10-fold stronger antitumor activity in the sub-μM range against CML cells than S1g-2in vitro, but it also overcame BCR-ABL-independent tyrosine kinase inhibitor resistance in CML in vivo depending on the Hsp70–Bim signaling pathway. Moreover, through structure–activity relationship analysis, TROSY-HSQC NMR, molecular dynamics simulation, and point mutation validation, two hydrophobic pockets composed of eight key residues were demonstrated to produce predominant interactions with either Bim or S1g-10, regarded as the “hot-spots” in the Hsp70–Bim PPI interface.

A flexible and dual-channel sensing system is proposed for monitoring nasal and oral respiration simultaneously during sleep. The system consists of a respiratory sensor and a signal processing circuit. The sensitive units of the respiratory sensor are composed of folding metal resistances, which are deposited on flexible substrate by micro-electromechanical system (MEMS) technology, and the working principle is based on the thermal resistance effect. The simulation demonstrates that there is a remarkable temperature difference in the sensitive units between inhalation and exhalation (10 °C and 19 °C for nasal and oral channel, respectively), and the performance tests illustrate that the sensing system has superior sensitivity (9.4 and 19.6 mV for nasal and oral channel, respectively), stability, and anti-interference ability. Also, the system is proved to be able to identify and distinguish various kinds of respiratory diseases, including hypopnea, mouth breathing, and apnea. Therefore, the proposed sensing system can serve as an effective method for health monitoring and early screening of respiratory diseases in the future.

The effects of mechanical stress on the magnetic characteristics of materials indicates it possible to quantitatively measure and evaluate stress via the testing of stress-induced magnetic component. At present, however, the stress-associated magnetic component is extracted from the inducting magnetic field, which is mingled with the environmental magnetic field and the residual magnetic field of the materials. Both factors are difficult to be isolated, leading to: 1) poor stress measuring precision and 2) misunderstanding of the mechanism between stress and the magnetic characteristics. In this article, the relationships between the stresses and the excitation magnetic fields of three materials are investigated, with a proposed method to extract the stress-induced component. The results show that: 1) the stress effect on the excitation magnetic field is evident, and a method to extract the stress-induced magnetic component is proposed and 2) the relationship between the stress and the stress-induced magnetic component is affected by the material’s permeability and conductivity. The findings and proposed methods are helpful to enrich the understanding of the magneto-mechanical effect and improve the stress measurement.

Non-noble metal catalysts have great potential for controlling soot emissions due to their effective oxidation properties and low cost. This study investigated the characteristics of Cs-V-based non-noble metal soot catalyst and Ce doping enhancement effect through comprehensive characterization of physicochemical properties, catalytic activity evaluation, and density functional theory (DFT) theoretical calculations. The results demonstrate that Ce doping improves the degree of surface particle aggregation and the spatial distribution morphology of Cs-V-based catalyst, with a 36.7 % increase in the specific surface area. Additionally, Ce doping enhances the probability of oxygen adsorption and dissociation activation on the Cs-V-based catalyst, accelerating the soot-oxidation process, improving the soot-oxidation activity, with a decrease in the characteristic temperature T10(temperature at 10 % conversion rate of soot) from 349.7 ℃ to 281.1 ℃, and decreases the activation energy for soot-oxidation to 5.8 kJ/mol. DFT calculations reveal that Ce doping strengthens the pulling effect of interatomic chemical bonds, facilitating the removal of oxygen atoms and dissociated reactive oxygen (Oasd), resulting in an increase in the adsorption energy of C4molecules and a shorter bond length between C4molecules and the catalytic surface, facilitating the desorption of post-oxidation soot products.

The combination of diesel oxidation catalyst (DOC), catalyzed diesel particulate filter (CDPF) and selective catalytic reduction (SCR) is the most effective way to reduce particulate emission and nitrogen oxide (NOx) from diesel engines. In this study, the effects of a DOC+CDPF+SCR system on the emissions including carbon monoxide (CO) total hydrocarbon (THC), NOx, particle number (PN) and particle mass (PM) from a heavy-duty diesel engine were evaluated. In addition, the influences of ammonia (NH3) slip catalyst (ASC) coating and SCR catalyst downsizing on the NOx conversion efficiency, nitrous oxide (N2O) emissions and NH3slip were also investigated. Results showed that the installation of the after-treatment system had negligible effect on the power and BSFC of the engine. The upstream DOC reduced by an average of 97.0% of the CO and 67.5% of the THC, in combination with CDPF, the CO and THC emission further decreased with an average drop of 97.8% and 72.5%, respectively. In terms of particulate emissions, the single DOC reduced 48.0% of the PN and 50.9% of the PM, and the combination of DOC and CDPF led to a reduction of 98.0% in the PN and 96.9% in the PM on average. The SCR was effective in reducing NOx emission, but resulted in higher N2O emission by more than 3 times, meanwhile led to an average NH3slip of 3.80 ppm. Downsizing the SCR length by 1/3 could still ensure a 91.9% conversion efficiency of NOx, and produced less N2O, but led to an increase of the NH3slip by 2 times, reaching 7.63 ppm on average. By coating Pt-based ASC catalyst on the back end of the SCR could eliminate the NH3slip. Considering the cost and performance, the combination of DOC, CDPF and a downsized SCR with ASC coating may be a better choice.

Single-cell RNA sequencing (scRNA-seq) is one of the most efficient technologies for human tumor research. However, data analysis is still faced with technical challenges, especially the difficulty in efficiently and accurately discriminating cancer/normal cells in the scRNA-seq expression matrix. If we can address these challenges, we can have a deeper understanding of the intratumoral and intertumoral heterogeneity. In this study, we developed a cancer/normal cell discrimination pipeline called pan-Cancer Seeker (CaSee) devoted to scRNA-seq expression matrix, which is based on the traditional high-quality pan-cancer bulk sequencing data using transfer learning. CaSee is the first tool directly used to discriminate cancer/normal cells in the scRNA-seq expression matrix, with much wider application fields and higher efficiency than copy number variation (CNV) method which requires corresponding reference cells. CaSee is user-friendly and can adapt to a variety of data sources, including but not limited to scRNA tissue sequencing data, scRNA cell line sequencing data, scRNA xenograft cell sequencing data and scRNA circulating tumor cell sequencing data. It is compatible with mainstream sequencing technology platforms, 10× Genomics Chromium, Smart-seq2, and Microwell-seq. Here, CaSee pipeline exhibited excellent performance in the multicenter data evaluation of 11 retrospective cohorts and one independent dataset, with an average discrimination accuracy of 96.69%. In general, the development of a deep-learning based, pan-cancer cell discrimination model, CaSee, to distinguish cancer cells from normal cells will be compelling to researchers working in the genomics, cancer, and single-cell fields.

Total Quality Management (TQM) is instrumental in augmenting the quality and efficacy of healthcare service delivery, but a comprehensive evaluation of present and evolving TQM research trends within healthcare research articles is notably absent. This study provides an insightful view into the prevailing international scenarios and upcoming research frontiers in healthcare TQM research field, utilizing bibliometric mapping through VOSviewer. Drawing data from 360 publications in the Web of Science core citation database, it delineates a steady growth in the field over the last 30 years. Research outputs span 51 countries and regions, with notable contributions from the United States, United Kingdom, Netherlands, and Italy. The top five research institutions and numerous authors predominantly hail from the United States. Key keywords in near years encompass healthcare safety, healthcare quality assurance, quality indicators, and the application of Six Sigma management principles. This exploration serves as a pivotal reference for understanding the global research landscape and future trends in healthcare TQM, particularly in guaranteeing quality and safety. Future scientific endeavors will build upon these focus areas, exploring and connecting research gaps in more specialized fields.

Corrosion fatigue is considered as one of the most detrimental threat to steel structures subjected to the coupled effects of cyclic load and corrosive environment, but the scientific data collected in an authentic service environment has been rarely reported. The corrosion fatigue behaviors of 10CrNiCu shipbuilding steel with a prefabricated stress field under authentic marine environments was investigated in this study. The results demonstrate that the shapes of pits in steel specimens can be simplified as conical, trapezoidal and ellipsoidal. Furthermore, the shapes, radius-to-depth ratios and corrosion rates of these pits are not consistent under different wettability conditions. Notably, the specimens corrode the most severely under semi-wettable conditions. A corrosion fatigue life prediction model for 10CrNiCu shipbuilding steel has been proposed by leveraging the profound principles of continuum damage mechanics. When the corrosion duration reaches 10 years, the corrosion fatigue life of steel specimens under wettable conditions will be decreased by 36.3 % in comparison with that of uncorroded specimens. This study provides a constructive insight on the interaction mechanism of mechanical fatigue stress and corrosion environment and the more realistic lifetime estimation of steel structures under authentic marine environments.

Acute wounds are converted to chronic wounds due to advanced age and diabetic complications. Nanozymes catalyze ROS production to kill bacteria without causing drug resistance, while microneedles (MNs) can break through the skin barrier to deliver drugs effectively. Nanozymes can be intergrateded into MNs delivery systems to improve painless drug delivery. It can also reduce the effective dose of drug sterilization while increasing delivery efficiency and effectively killing wounded bacteria while preventing drug resistance. This paper describes various types of metal nanozymes from previous studies and compares their mutual enhancement with nanozymes. The pooled results show that the MNs, through material innovation, are able to both penetrate the scab and deliver nanozymes and exert additional anti‐inflammatory and bactericidal effects. The catalytic effect of some of the nanozymes can also accelerate the lysis of the MNs or create a cascade reaction against inflammation and infection. However, the issue of increased toxicity associated with skin penetration and clinical translation remains a challenge. This study reviews the latest published results and corresponding challenges associated with the use of MNs combined with nanozymes for the treatment of wounds, providing further information for future research. The review presents new ideas for painless drug delivery and reducing adverse effects through the use of microneedles for treating chronic wounds by deep delivering nanozymes through skin‐scab barriers or by forming cascade reactions through material innovations, resulting in painless drug delivery and reduction of adverse effects.

In this work, we fabricated cobalt-doped carbon quantum dots (Co-CQDs) by a one-pot hydrothermal method with cobalt tetraphenylporphyrin and 1,2-ethanediamine as precursors. The morphology and structure of the Co-CQDs were characterized through transmission electron microscopy, X-ray diffraction spectra, Fourier transform infrared, and X-ray photoelectron spectra. The Co-CQDs emitted intense blue luminescence under ultraviolet irradiation and exhibited a typical excitation-dependent emission property. Moreover, they can act as a fluorescent probe for the detection of Fe3+and ascorbic acid (AA) with high selectivity and sensitivity through an “on–off–on” mode. The limit of detection (LOD) of Fe3+was measured as 38 μM (S/N = 3). The quenched emission of carbon quantum dots can be recovered with the addition of ascorbic acid (AA) to the Co-CQDs/Fe3+system. The change of fluorescence was linear with the concentration of AA (0.6–1.6 mM) with the LOD of 18 μM. Furthermore, the Co-CQDs exhibited high oxidase-like catalytic behavior, which could convert transparent 3,3′,5,5′-tetramethylbenzidine (TMB) into blue ox-TMB by dissolved oxygen. After adding ascorbic acid to the Co-CQDs/TMB system, the blue color of the solution faded due to the reduction of blue ox-TMB to colorless TMB. Based on this phenomenon, the Co-CQDs were capable of detecting AA (10–400 μM) with the LOD of 0.27 μM. The fluorometric and colorimetric assays based on the Co-CQDs for the AA detection were then successfully applied in fresh fruits. Furthermore, the high biocompatibility of the Co-CQDs against HeLa cells was verified by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Thus, the Co-CQDs could be used as a powerful tool for the detection of AA in real samples through a dual-mode method.

Rotors with active flap control have considerable potential in reducing vibration and noise and improving aerodynamic performance. However, due to the movement of the flap, there are unavoidable gaps between the components that will lead to significant changes in the aerodynamic characteristics. Moreover, considering the difficulties in motion modeling and the accuracy of the simulation of the flow field in such a narrow gap, carrying out related research is challenging; thus, there has been inadequate targeted research, and that which does exist requires supplementation. To carry out this challenging flow field simulation, the overset assembly algorithm proposed by the author in previous research is adopted in the present study. It is used to successfully assemble the narrow gap, and the accuracy of the simulation is fully verified by comparing the results with the actual experimental results and a grid study. Furthermore, to compensate for the lack of research and experiments on the gap effect, cases considering a complete range of gap widths from an absence of a gap to a width of 10% of the chord length are set up and carried out under the following three case groups: steady cases with a fixed trailing-edge deflection angle, unsteady cases in which only the trailing-edge flap is flapping, and full-motion cases characterized by the periodic flap of the main airfoil and the trailing-edge flap. The results show that the gap increases the drag of the trailing-edge flap and decreases aerodynamic efficiency, especially at low speeds and high angles of attack. Nevertheless, when the gap is unavoidable, there is a range of the gap width that makes unapparent the decrease of aerodynamic efficiency. Moreover, the decrease of aerodynamic efficiency can be reduced as much as possible by a well-designed gap region geometry to ensure that the airfoil and the trailing-edge flap fit together when moving.

The pairing of heavy and light chains of an antibody decides the specificity of monoclonal antibodies (mAbs). Acquisition of the genes encoding variable regions of paired heavy and light chains (VH:VL) is crucial, but it is a labor- and cost-intensive process in traditional methods. The emerging microfluidic chips have brought us to a portal of directly acquiring natively paired VH:VLgenes by sequencing single target cells. This study presents a novel method in which all processing steps for acquiring natively paired VH:VLgenes from single cells are finished in a single microfluidic chip, not multiple discrete devices. The microfluidic chip performs single-cell trapping/in situfluorescence examination of antibody specificity/cell lysis/gene amplification all at a single-cell level. By a proof-of-concept validation of efficiently acquiring paired VH:VLgenes of anti-CD45 mAbs from single hybridoma cells, the microfluidic chip has been proved capable of trapping/screening/lysing single antibody-secreting cells and performing an on-chip reverse transcription-polymerase chain reaction. The presented method has realized remarkably improved cell loss/human labor/time cost, and more importantly, determinacy of native VH:VLgene pairing, which is one of the most decisive factors of effectiveness for antibody discovery.

The fragile electrolyte/Li interface is responsible for the long-lasting consumption of Li resources and fast failure of Li metal batteries. The polymer artificial interface with high mechanical flexibility is a promising candidate to maintain the stability of the electrolyte/Li interface; however, sluggish Li-ion transportation of the conventional polymer interface hinders the application. In this work, Li-functionalized graphene oxide (GO-ADP-Li3), which is synthesized by covalent grafting of adenosine 5′-diphosphate lithium on GO nanosheets, is used as a functional additive to improve the Li-ion conductivity of the polymer artificial interface based on PVDF-HFP/LiTFSI. The enhanced Li-ion conductivity is contributed by accelerated Li-ion hopping at the surface between polymer chains and functionalized GO as well as the reduced crystallization degree of PVDF-HFP by this novel additive. The use of this modified polymer as an artificial interface on Li foil enables highly reversible Li stripping/plating and a high capacity retention of 78.4% after 150 cycles for a 0.2 A h Li metal pouch cell (Li/NCM811, strictly following practical conditions). This Li-grafted strategy on GO sheets provides an alternative for designing a compatible electrolyte/Li interface for practical Li metal batteries.

The monitoring of circulating tumor cells (CTCs) has recently served as a promising approach for assessing prognosis and evaluating cancer treatment. We have already developed a CTCs enrichment platform by EpCAM recognition peptide-functionalized magnetic nanoparticles (EP@MNPs). However, considering heterogeneous CTCs generated through epithelial-mesenchymal transition (EMT), mesenchymal CTCs would be missed with this method. Notably, N-cadherin, overexpressed on mesenchymal CTCs, can facilitate the migration of cancer cells. Hence, we screened a novel peptide targeting N-cadherin, NP, and developed a new CTCs isolation approach via NP@MNPs to complement EpCAM methods’ deficiencies. NP@MNPs had a high capture efficiency (about 85%) of mesenchymal CTCs from spiked human blood. Subsequently, CTCs were captured and sequenced at the single-cell level via NP@MNPs and EP@MNPs, RNA profiles of which showed that epithelial and mesenchymal subgroups could be distinguished. Here, a novel CTCs isolation platform laid the foundation for mesenchymal CTCs isolation and subsequent molecular analysis.

ABSTRACTIndustrial trials and thermodynamic analysis were performed to investigate the transient influence of cerium on inclusions in an Al-killed non-oriented electrical steel. Inclusions were statistically analyzed using an automatic scanning electron microscope. Without cerium addition, inclusions in the molten steel were predominately MgO·Al2O3ones as well as a small number of Al2O3–MgO–CaO ones, and precipitates of AlN and MgS formed in the continuous casting slab. In the steel with approximately 10 ppm total oxygen and 10 ppm total sulphur, inclusions of MgO·Al2O3were modified into homogeneous Ce2O2S ones and Ce–Al–Mg–Ca–S–O dual-phase ones by 35 ppm cerium. With increasing time, the content of cerium decreased to 23 ppm in the tundish and dual-phase inclusions of Ce–Al–Mg–Ca–S–O transformed into CeAlO3ones. During cooling, inclusions of CeAlO3transformed into dual-phase MgO–CexS ones in the steel with approximately 14 ppm total magnesium. Thermodynamic analysis was in good agreement with observed results.

Industrial trials and thermodynamic analysis were performed to investigate the transient influence of cerium on inclusions in an Al-killed non-oriented electrical steel. Inclusions were statistically analyzed using an automatic scanning electron microscope. Without cerium addition, inclusions in the molten steel were predominately MgO·Al2O3ones as well as a small number of Al2O3–MgO–CaO ones, and precipitates of AlN and MgS formed in the continuous casting slab. In the steel with approximately 10 ppm total oxygen and 10 ppm total sulphur, inclusions of MgO·Al2O3were modified into homogeneous Ce2O2S ones and Ce–Al–Mg–Ca–S–O dual-phase ones by 35 ppm cerium. With increasing time, the content of cerium decreased to 23 ppm in the tundish and dual-phase inclusions of Ce–Al–Mg–Ca–S–O transformed into CeAlO3ones. During cooling, inclusions of CeAlO3transformed into dual-phase MgO–CexS ones in the steel with approximately 14 ppm total magnesium. Thermodynamic analysis was in good agreement with observed results.

Gastric cancer (GC) is a major global cancer burden, and only HER2-targeted therapies have been approved in first line clinical therapy. CLDN18.2 has been regarded as a potential therapeutic target for gastrointestinal tumors, and global clinical trials have been in process. Hence, the precise, efficient, and noninvasive detection of CLDN18.2 expression is important for the effective application of this attractive target. A high similarity of protein sequence between CLDN18.1 and -18.2 made RNA become more suitable for the detection of CLDN18.2 expression. In this study, CLDN18.2 molecular beacon (MB) with a stem-loop hairpin structure was optimized by phosphorothioate and 2′-O-methyl for stability and efficiency. The MB could recognize CLDN18.2RNA rapidly. Its resolution and selectivity has been verified in several model cells, demonstrating that MB can distinguish CLDN18.2 expression in several model cells. Furthermore, it was applied successfully to the circulating tumor cell (CTC) assay. The concordance in the expression of CLDN18.2 between CTCs and tissue biopsy is 100% (negative: 3 vs 3; positive: 7 vs 7), indicating that CLDN18.2RNA detection in CTCs based on a MB will be a promising approach for searching potential patients to CLDN 18.2 targeted drug.

Alzheimer’s disease (AD) is the most common neurodegenerative disorder with a continuous pathophysiological process starting from the preclinical and mild cognitive impairment (MCI) phases to the dementia phase. Early diagnosis is prerequisite for the early intervention of AD but meanwhile challenging. Amyloid-beta 1–42 (Aβ42) plays a crucial part in AD pathology. Positron-emission tomography (PET) imaging of Aβ42in the brain and the measurement of Aβ42in the cerebrospinal fluid (CSF) have been adopted for the auxiliary diagnosis of AD, but their widespread clinical application has been limited due to the radiation and the high-cost of PET and the invasive lumbar puncture for collecting CSF. Noninvasive and cost-effective blood-based assay is desirable for the early diagnosis of AD. Here, a label-free assay for the quantification of blood Aβ42was developed using the high-throughput surface plasmon resonance imaging method with the aid of an antibody-mimetic peptoid nanosheet equipping Aβ42-recognizing loops. We demonstrated that this nanosheet-based sensor system could distinguish the plasma and sera from normal individuals and patients suffering AD and amnestic MCI with high sensitivity and specificity, preceding the diagnostic performance of the Aβ42-recognizing molecule and the antibody specific to Aβ42. This work provides a label-free, cost-effective, highly sensitive, and high-throughput blood-based assay for early detection of AD.

Alzheimer’s disease (AD) starts decades before cognitive symptoms develop. Easily accessible and cost-effective biomarkers that accurately reflect AD pathology are essential for both monitoring and therapeutics of AD. Neurofilament light chain (NfL) levels in blood and cerebrospinal fluid are increased in AD more than a decade before the expected onset, thus providing one of the most promising blood biomarkers for monitoring of AD. The clinical practice of employing single-molecule array (Simoa) technology for routine use in patient care is limited by the high costs. Herein, we developed a microarray chip-based high-throughput screening method and screened an attractive self-assembling peptide targeting NfL. Through directly “imprinting” and further analyzing the sequences, morphology, and affinity of the identified self-assembling peptides, the Pep-NfL peptide nanosheet with high binding affinity toward NfL (KD= 1.39 × 10–9mol/L), high specificity, and low cost was characterized. The superior binding ability of Pep-NfL was confirmed in AD mouse models and cell lines. In the clinical setting, the Pep-NfL peptide nanosheets hold great potential for discriminating between patients with AD (P< 0.001, n= 37), mild cognitive impairment (P< 0.05, n= 26), and control groups (n= 30). This work provides a high-throughput, high-sensitivity, and economical system for noninvasive tracking of AD to monitor neurodegeneration at different stages of disease. The obtained Pep-NfL peptide nanosheet may be useful for assessing dynamic changes in plasma NfL concentrations to evaluate disease-modifying therapies as a surrogate end point of neurodegeneration in clinical trials.

The T-plastin (PLS3) has a significant implication in epithelial-mesenchymal transition (EMT) and breast cancer prognosis. Using one-bead-one-compound library strategy, a novel peptide TP1 (KVKSDRVC) toward PLS3 was screened and exhibited the specificity for identifying PLS3-expressed cancer cells. Moreover, we found Fluorescein isothiocyanate-labeled TP1 (FITC-TP1) could act as a novel probe for EMT-induced cancer cells, preferentially in the leading edge. It also has satisfactory specificity for PLS3-expressed cancer cells spiked in the blood. FITC-TP1 was expected to become a diagnostic tool to identify PLS3-expressed circulating tumor cells and predict prognosis for patients with breast cancer in the future.

Ligand-targeting specific liposomal probes are increasingly used as imaging and delivery vehicles for in vivo diagnosis. Thereinto, the ligand variety and density profoundly affect the binding behaviors toward the target. The synergetic effect of different ligands could be achieved only when the optimized molecular-recognition configuration occurred. In this study, we construct a dual-peptides-targeting liposomal probe named BTLS that could synergistically bind two different sites of prominin-1, a cancer stem cell marker. At the distance of 11 Å between the two new peptides, ligands could insert into the hollow pocket of prominin-1 and BTLS could achieve the appropriate spatial structure, showing the strong binding affinity in both cellular and in vivo levels. It is indicated that the design of density-optimized peptide-targeted liposomes could be promising to maximize the multifunctional targeting effects on the cancer theranostics.

Metastasis is a complex multistep process that involves critical interactions between cancer cells and a variety of stromal components in the tumor microenvironment, which profoundly influence the different aspects of the metastatic cascade and organ tropism of disseminating cancer cells. Ovarian cancer is the most lethal gynecological malignancy and is characterized by peritoneal disseminated metastasis. Evidence has demonstrated that ovarian cancer possesses specific metastatic tropism for the adipose-rich omentum, which has a pivotal role in the creation of the metastatic tumor microenvironment in the intraperitoneal cavity. Considering the distinct biology of ovarian cancer metastasis, the elucidation of the cellular and molecular mechanisms underlying the reciprocal interplay between ovarian cancer cells and surrounding stromal cell types in the adipose-rich metastatic microenvironment will provide further insights into the development of novel therapeutic approaches for patients with advanced ovarian cancer. Herein, we review the biological mechanisms that regulate the highly orchestrated crosstalk between ovarian cancer cells and various cancer-associated stromal cells in the metastatic tumor microenvironment with regard to the omentum by illustrating how different stromal cells concertedly contribute to the development of ovarian cancer metastasis and metastatic tropism for the omentum.

The study of fallopian tube (FT) function in health and disease has been hampered by limited knowledge of FT stem cells and lack of in vitromodels of stem cell renewal and differentiation. Using optimized organoid culture conditions to address these limitations, we find that FT stem cell renewal is highly dependent on WNT/β-catenin signaling and engineer endogenous WNT/β-catenin signaling reporter organoids to biomark, isolate, and characterize these cells. Using functional approaches, as well as bulk and single-cell transcriptomics analyses, we show that an endogenous hormonally regulated WNT7A-FZD5 signaling axis is critical for stem cell renewal and that WNT/β-catenin pathway-activated cells form a distinct transcriptomic cluster of FT cells enriched in extracellular matrix (ECM) remodeling and integrin signaling pathways. Overall, we provide a deep characterization of FT stem cells and their molecular requirements for self-renewal, paving the way for mechanistic work investigating the role of stem cells in FT health and disease.

Mild acidic environment and angiogenesis are two typical characteristics of tumor. The specific response toward both lower pH and angiogenesis may enhance the targeting ability both for drug and diagnostic probe delivery. Herein, we present a kind of dual responding self-assembled nanotransformation material that is tumor angiogenesis targeting and pH triggered based on amphiphilic conjugation between peptides (STP) and aromatic molecules (tetraphenylethylene (TPE)). The morphology of the self-assembled peptide conjugates is responsibly changed from nanoparticles in neutral condition to nanofibers in acidic condition, which “turn on” the in vivo targeting imaging and accelerate the efficient drug delivery and in vivo therapy. On the basis of the well-controlled nanotransformation both in vitro and in vivo, we envisioned the successful demonstration of the responding materials would open a new avenue in turn on targeting imaging diagnostics and specific cancer therapeutics.

Cloud manufacturing is a new type of modern manufacturing mode. The Cloud Manufacturing Service Composition (CMSC) is one of the key issues of cloud manufacturing. The quality and efficiency of cloud manufacturing services are influenced by the rationality of the optimisation model. Previous studies have rarely considered the impact of cooperation between services on the quality of the manufacturing service composition. In this paper, a Service Cooperation Level (SCL) evaluation mechanism and a corresponding update model are proposed to dynamically measure the level of cooperation between services. Furthermore, a novel Cloud Manufacturing Service Composition model with Service Cooperation Level Evaluation (CMSC-SCLE) is established by introducing the SCL evaluation value as a new objective. Finally, an Improved Strength Pareto Evolutionary Algorithm 2 (ISPEA2) is proposed to solve the CMSC-SCLE problem. The experimental results show that the CMSC-SCLE model is more practical than the CMSC model. In addition, compared with four other classical multi-objective optimisation algorithms, ISPEA2 achieves better performance when solving CMSC-SCLE problem.

EGFR mutations companion diagnostics have been proved to be crucial for the efficacy of tyrosine kinase inhibitor targeted cancer therapies. To uncover multiple mutations occurred in minority of EGFR-mutated cells, which may be covered by the noises from majority of un-mutated cells, is currently becoming an urgent clinical requirement. Here we present the validation of a microfluidic-chip-based method for detecting EGFR multi-mutations at single-cell level. By trapping and immunofluorescently imaging single cells in specifically designed silicon microwells, the EGFR-expressed cells were easily identified. By in situ lysing single cells, the cell lysates of EGFR-expressed cells were retrieved without cross-contamination. Benefited from excluding the noise from cells without EGFR expression, the simple and cost-effective Sanger’s sequencing, but not the expensive deep sequencing of the whole cell population, was used to discover multi-mutations. We verified the new method with precisely discovering three most important EGFR drug-related mutations from a sample in which EGFR-mutated cells only account for a small percentage of whole cell population. The microfluidic chip is capable of discovering not only the existence of specific EGFR multi-mutations, but also other valuable single-cell-level information: on which specific cells the mutations occurred, or whether different mutations coexist on the same cells. This microfluidic chip constitutes a promising method to promote simple and cost-effective Sanger’s sequencing to be a routine test before performing targeted cancer therapy.

Peptide nanomaterials have recently attracted considerable interest in the biomedical field. However, their poor bioavailability and less powerful therapeutic efficacy hamper their further applications. Herein, we discovered reconfigurable and activated nanotherapeutics in the tumor microenvironment. Two peptides, that is, a pH-responsive peptide HLAH and a matrix metalloprotease-2 (MMP2)-sensitive peptide with a poly(ethylene glycol) (PEG) terminal were conjugated onto the hydrophobic poly(β-thioester)s backbones to gain the copolymer P–S–H. The therapeutic activity of the HLAH peptide could be activated in tumors owing to its reconfiguration under microenvironmental pH. The resultant copolymers self-assembled into nanoparticles under physiological condition, with HLAH in cores protected by PEG shells. The moderate size (∼100 nm) and negative potential enabled the stable circulation of P–S–Hin the bloodstream. Once arrived at the tumor site, the P–S–Hnanoparticles were stimulated by overexpressed MMP2 and acidic pH, and subsequently the shedding of the PEG shell and protonation of the HLAH peptide induced the reassembly of nanoparticles, resulting in the formation of nanoparticles with activated cytotoxic peptides on the surface. In vivo experiments demonstrated that the reorganized nanoassembly contained three merits: (1) effective accumulation in the tumor site, (2) enhanced antitumor capacity, and (3) no obvious toxic effect at the treatment dose. This on-site reorganization strategy provides an avenue for developing high-performance peptide nanomaterials in cancer treatment.

Aminopeptidase N (APN/CD13) is closely related to the growth of cancers and is suggested as a suitable target for anti-cancer therapy. Based on the “one-bead-one-compound” (OBOC) approach on a microarray device, we screened out a novel affinity peptide LN (YEVGHRC). It was determined that LN could specifically recognize and bind to APN. Moreover, LN-functionalized liposomes (LN-LS) could achieve efficient nano-encapsulated drug delivery under APN-overexpressing tumor conditions in vitroand in vivo. We expect that LN-LS could provide a new strategy for APN-positive tumor diagnosis and therapy.

Human papillomaviruses (HPV) are oncogenic DNA viruses implicated in squamous cell carcinomas of several anatomic sites, as well as endocervical adenocarcinomas. Identification of HPV is an actionable finding in some carcinomas, potentially influencing tumor classification, prognosis, and management. We incorporated capture probes for oncogenic HPV strains 16 and 18 into a broader next-generation sequencing (NGS) panel designed to identify actionable mutations in solid malignancies. A total of 21 head and neck, genitourinary, and gynecologic squamous cell carcinomas and endocervical adenocarcinomas were sequenced as part of the UNCSeq project. Using p16 immunohistochemical results as the gold standard, we set a cutoff for proportion of aligned HPV reads that maximized performance of our NGS assay (92% sensitive, 100% specific for HPV). These results suggest that sequencing of oncogenic pathogens can be incorporated into targeted NGS panels, extending the clinical utility of genomic assays.

One switchable nanodelivery system was constructed. Liposomes were functionalized by a novel dual-recognition peptide STP, which is pH-responsive as well as the affinity ligand of tumor marker VEGFR2 (the angiogenesis marker vascular endothelial growth factor receptor 2). Efficient drug delivery and in vivo therapy could be “turned on” and accelerated only in the conditions of VEGFR2 overexpression and a mild acidic environment. We envisioned that the successful demonstration of this switchable nanocarrier system would open a new avenue on rapid cytoplasmic delivery for specific cancer diagnostics and therapeutics.

Previous studies have shown that Saharan dust can be transported thousands of miles, affecting regional climates, environments, and ecosystems. However, research on the long‐range transport of Saharan dust in Asia remains limited. We systematically investigated the long‐range transportation of Saharan dust over East Asia from 2007 to 2020 using WRF‐Chem model simulations, space‐borne CALIPSO lidar observations, NCEP/NCAR reanalysis data, as well as HYSPLIT trajectory analysis. The results show that one quarter (24.3 ± 6.2%) of dust events in East Asia during 2007–2020 originated from the Sahara Desert. Moreover, long‐range transported Saharan dust over East Asia was usually distributed in the upper troposphere. The average total amount of transported Saharan dust over East Asia between 2010 and 2015 was estimated at 33.05 ± 9.78 Tg/yr. Additionally, Saharan dust could be transported eastward all year and contributed about 35.8% of dust loading in the upper troposphere in Northern China in spring, which is almost the same amount of dust aerosols lifted up from East Asian dust sources. This study provides new sights on the important role of Saharan dust over East Asia, and elucidates the influence of long‐range transported dust on regional climate and the water cycle. About one fourth of dust cases in East Asia from 2007 to 2020 originated from the Sahara DesertLong‐range transported Saharan dust over East Asia was usually distributed in the upper troposphere where is >5 km above sea levelOver East Asia, Saharan dust contributes 35.8% of total dust concentration in the upper troposphere in spring About one fourth of dust cases in East Asia from 2007 to 2020 originated from the Sahara Desert Long‐range transported Saharan dust over East Asia was usually distributed in the upper troposphere where is >5 km above sea level Over East Asia, Saharan dust contributes 35.8% of total dust concentration in the upper troposphere in spring

Abraxane, an FDA-approved albumin-bound nanoparticle (NP) form of paclitaxel (PTX) to treat breast cancer and nonsmall cell lung cancer (NSCLC), has been demonstrated to be more effective than the original Taxol, the single molecule form. We have established a cell line from NSCLC A549 cells to be resistant to Abraxane. To further understand the molecular mechanisms involved in the NP drug resistance, global protein expression profiles of Abraxane sensitive (A549) and resistant cells (A549/Abr), along with the treatment of Abraxane, have been obtained by a quantitative proteomic approach. The most significantly differentially expressed proteins are associated with lipid metabolism, cell cycle, cytoskeleton, apoptosis pathways and processes, suggesting several mechanisms are working synergistically in A549 Abraxane-resistant cells. Overexpression of proteins in the lipid metabolism processes, such as E3 ubiquitin-protein ligase RNF139 (RNF139) and Hydroxymethylglutaryl-CoA synthase (HMGCS1), have not been reported previously in the study of paclitaxel resistance, suggesting possibly different mechanism between nanoparticle and single molecular drug resistance. In particular, RNF139 is one of the most up-regulated proteins in A549 Abraxane-resistant cell line, but remains no change when the resistant cells were further treated with Abraxane and down-regulated in the sensitive cells after 4 h treatment of Abraxane. This study shows the use of a proteomic strategy to understand the unique response of drug resistant cells to a nanoparticle therapeutic.