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Wearable magnetoencephalography (MEG) using optical-pumped magnetometers (OPMs) array, i.e., OPM-MEG, has drawn extensive interests due to its merits such as reduced stand-off distance, flexible layout, and enhanced wearability. The mismatch response (MMR), a neurophysiological marker indicative of psychiatric disorders, has yet to be explored with OPM-MEG in focal layouts using univariate statistical tests in the time domain. To reveal the performance of different univariate methods on OPM data, here we first simulated mismatch effects in OPM arrays with different numbers of sensors covering left hemisphere and tested the effects in two univariate methods, i.e., false discovery rate (FDR)-corrected t-test and channelwise permutation t-test on OPM-MEG evoked data to address multiple comparison problem (MCP). Then, we adopted a paradigm to assess the performance of OPM array in distinguishing the response for two different tones (i.e., flat and low dipping) of Mandarin in oddball manner. We validated statistical results of simulated data with real data. Mismatch effects yielded different results across test methods and layouts. What is more, cortical activation to mismatch stimuli is consistent with sensor-level results. Our study provides preference on univariate statistical tests, thereby paving way for future cognitive and clinical applications.

The development of engineered or modified autologous stem cells is an effective strategy to improve the efficacy of stem cell therapy. In this study, the stemness and functionality of adipose stem cells derived from type 1 diabetic donors (T1DM-ASC) were enhanced by treatment with Cu(II)-baicalein microflowers (Cu-MON). After treatment with Cu-MON, T1DM-ASC showed enhanced expression of the genes involved in the cytokine-cytokine receptor interaction pathway and increased cytokine secretion. Among the top 13 differentially expressed genes between T1DM-ASC and Cu-MON-treated T1DM-ASC (CMTA), some genes were also expressed in HUVEC, Myoblast, Myofibroblast, and Vascular Smooth Muscle cells, inferring the common role of these cell types. In vivo experiments showed that CMTA had the same therapeutic effect as adipose-derived stem cells from non-diabetic donors (ND-ASC) at a 15% cell dose, greatly reducing the treatment cost. Taken together, these findings suggest that Cu-MON promoted angiogenesis by promoting the stemness and functionality of T1DM-ASC and influencing multiple overall repair processes, including paracrine effects.

Magnetoencephalography (MEG) is an important development in the field of noninvasive brain imaging. Nevertheless, MEG recordings are prone to contamination from background noise and other artifacts. The advantage of wearability and mobility of the optically pumped magnetometer (OPM) system has resulted in higher requirements for reducing interference. However, under the new OPM-MEG measurement system with limited channels, the effects of different interference suppression methods on background noise suppression have not been fully studied. We investigate six background noise suppression methods, including signal space projection, common temporal subspace projection (CTSP), signal space separation (SSS), spatiotemporal SSS (tSSS), dual signal subspace projection (DSSP), and extended SSS (eSSS). The relationships and differences between these methods are summarized. In addition, the sensitivity to its parameter and its robustness to noise of different intensities for each algorithm are verified via adequate simulation experiments. Finally, the performance of these methods is analyzed and evaluated by the semi-physical simulation experiments and the somatosensory evoked experiments of OPM-MEG for four subjects. We proposed, meanwhile, a new evaluation method for real OPM-MEG experiments. The results show that the improved CTSP method has the strongest noise reduction robustness based on the comprehensive evaluation of waveform reconstruction degree, signal-to-noise ratio (SNR), root mean square error (RMSE), power spectral density reconstruction degree, source localization error, and expected source location deviation (ESLD). This study provides a reference for the anti-jamming and evaluation of OPM-MEG.

Photocatalytic reduction of CO2to high value-added chemicals and fuels has received widespread attention. However, the higher thermodynamic stability of CO2greatly limits its conversion efficiency. Frustrated Lewis pairs (FLPs) have been well-established to be very effective in CO2activation. In this work, we prepared ZnIn2S4–AlOOH (ZIS–AlOOH) composites for visible-light-driven CO2reduction. The Lewis basic OHvsites on the AlOOH surface (one H removed from OH) and an adjacent Lewis acidic unsaturated Al site (Al3+unsatur.) form the FLPs. The composite structure facilitated light absorption, CO2adsorption activation, and separation of photogenerated carriers, thus improving the CO2photoreduction activity (CO generation rate of 510.3 μmol g−1h−1), and suppressing hydrogen evolution with the CO/H2ratio increasing from 0.38 for ZnIn2S4(ZIS) to 0.84 for ZIS–AlOOH. This work elucidates a rational strategy for the construction of efficient photocatalysts and provides insight into the mechanism of the photocatalytic CO2reduction reaction.

The transverse-dislocated magnetic-field modulated brushless contra-rotating machine (TDMFM-BCRM), composed of stator, transverse-dislocated modulation (TDM) rotor, and permanent-magnet (PM) rotor, is a novel contra-rotating machine (CRM) for contra-rotating propulsion system (CRPS). Compared with conventional CRMs, the TDMFM-BCRM is the only one that has the following advantages at the same time: no rotating winding, no brushes and slip rings, and equal-opposite torque at any time. In this article, the air-gap magnetic-field modulated behaviors of the proposed TDMFM-BCRMs with different PM rotor structures including surface-mounted PM rotor, consequent-pole PM rotor and spoke-type PM rotor, and different TDM rotor structures with multi-unit topologies are comparatively investigated by the analytical analysis. Then, the key parameters in the TDMFM-BCRMs with different rotor structures those influence the air-gap magnetic-field modulated effect are studied by the theoretical and simulated analysis. The electromagnetic performances of the TDMFM-BCRMs with different rotor structures are compared. The comparison results show that the spoke-type TDMFM-BCRM with 1-4-5-3 has the best comprehensive performance. Finally, the theoretical analysis are verified by one TDMFM-BCRM prototype with spoke-type PM rotor and 1-4-5-3.

Malignant tumors represent a formidable global health challenge, compelling the pursuit of innovative treatment modalities. Oncolytic therapy has emerged as a promising frontier in antitumor strategies. However, both natural agents (such as oncolytic bacteria or viruses) and synthetic oncolytic peptides confront formidable obstacles in clinical trials, which include the delicate equilibrium between safety and efficacy, the imperative for systemic administration with targeted therapy, and the need to counteract oncolysis-induced immunosuppression. To overcome these dilemmas, we have developed biomimetic nanoengineering to create oncolytic bacteria-inspired nanosystems (OBNs), spanning from hierarchical structural biomimicry to advanced bioactive biomimicry. Our OBNs harbor inherent oncolytic potential, including functionalized oligosaccharides mimicking bacterial cell walls for optimal blood circulation and tumor targeting, tumor acidity-switchable decoration for tumor-specific oncolysis, stereospecific tryptophan-rich peptides for robust oncolytic activity, encapsulated tumor immunomodulators for enhanced immunotherapy, and innate multimodal imaging potential for biological tracing. This work elucidates the efficacy and mechanisms of OBNs, encompassing primary tumor suppression, metastasis prevention, and recurrence inhibition. Systemic administration of d-chiral OBNs has demonstrated superior oncolytic efficacy, surpassing intratumoral injections of clinical-grade oncolytic peptides. This work heralds an era in biomimetic engineering on oncolytic agents, promising the revolutionization of contemporary oncolytic therapy paradigms for clinical translation.

Reasonable design of winding can improve the performance of the machine without increasing the weight and cost. The toroidal (TO) and tooth-coil (TC) windings have different spatial positions in the electromagnetic field and generate vertical magnetic field. If the characteristics of both winding factor and the unified analysis method can be researched, the windings with better performance can be obtained. Based on this, the winding characteristics considering harmonics and the design methods of single winding and combination of windings are analyzed. The “Halbach winding” with the same effect as Halbach permanent magnet (PM) is designed and researched based on the study of TO, TC windings, and their combination. According to the characteristics of the magnetic field mentioned above, the improved method of the machine using only winding to generate the traveling wave of Halbach magnetic field is proposed and analyzed. By improving the Halbach winding, it is possible to achieve a magnetic field that enhances one side and weakens the other side while reducing the minimum repetitive unit, and the feasibility of the above methods is verified by finite element analysis (FEA).

This article proposes a transverse-dislocated magnetic-field modulated brushless contra-rotating machine (TDMFM-BCRM) with a multiunit structure for the contra-rotating propulsion system (CRPS). Compared with the existing contra-rotating machines (CRMs), it has the advantages of equal and opposite torque at any time, no brushes, and no slip rings. The improved 3-D magnetic-field modulation (MFM) principle by considering the multiunit structure of the TDMFM-BCRM is investigated. Then, due to the structural complexity of the TDMFM-BCRM, there are some challenges in its manufacturing. Therefore, the performance of the TDMFM-BCRM adopting different core material combinations including electrical steel (ES) and soft magnetic composite (SMC) material is investigated. Meanwhile, a prototype is manufactured and tested to validate the theoretical analysis, finally, more manufacturing methods for the TDMFM-BCRM are comparatively studied.

The effect of the salient rotor on magnetic field is important for the performance of propulsion motors with saliency. Thus, a novel analytical model and a fast calculation method for magnetic field considering the saliency and slot effect are proposed. Also, the different effects of the structure with saliency on the $d$ - and $q$ -axis magnetic field and corresponding rules are investigated. The calculation, the analysis process of $d$ - and $q$ -axis magnetic fields, and the mapping relationship between their difference and energy conversion are elaborated on load. Finally, the accuracy and adaptability of the proposed analysis and calculation method are verified by a finite-element analysis (FEA) under the combination of various parameters. According to the rule of error distribution, the reason for the difficulty in analyzing the motor with saliency is explained. Also, the results show that the proposed one is in good agreement with the results of FEA in a wide range of parameters.

Synthesizing biomimetic systems with stereospecific architectures and advanced bioactivity remains an enormous challenge in modern science. To fundamentally eliminate biosafety issues of natural oncolytic viruses, the development of synthetic virus-inspired particles with high oncolytic activity is urgently needed for clinical antitumor treatments. Here, we describe the design and synthesis of enantiomeric virus-inspired particles for efficient oncolytic therapy from homochiral building blocks to stereospecific supramolecular constructions. The L-virus-inspired oncolytic particles (L-VOPs) and D-VOPs possess similar biomimetic nanostructures but mirror-imaged enantiomeric forms. It is important that both L-VOPs and D-VOPs successfully mimic the pharmacological activity of oncolytic viruses, including direct tumor lysis and antitumor immune activation. D-VOPs provide quite better oncolytic efficacy than that of clinical-grade oncolytic agents (LTX-315, IC50= 53.00 μg mL–1) with more than 5-fold decrease in IC50value (10.93 μg mL–1) and close to 100% tumor suppression (98.79%) against 4T1 tumor-bearing mice, attributed to the chirality-dependent tumor recognition, interaction, antidegradation, and immunotherapy. This work provides a strategy for the synthesis of stereospecific biomimetic material systems as well as develops an advanced candidate for biomimetic oncolytic agents without biosafety risks.

Anovel hollow carbon derived from biomass lotus-root has been prepared by a one-step carbonization method. The carbon anode obtained at 900 °C showed the best electrochemical performance, corresponding to a high specific capacity of 445 mA·h/g at 0.1 C, as well as excellent cycling stability after 500 cycles. Further investigation exhibits that the lithium storage of hollow carbon involves Li+adsorption in the defect sites and Li+insertion. The results showed that the intrinsic structure of lotus root can inspire us to prepare biomass carbon with a hollow structure as an excellent anode for lithium-ion batteries.

It is of great significance for coal mining and utilization to study the adsorption process of mixed gas in coal. In this paper, the Monte Carlo method (MC) is employed to study the competitive saturation adsorption of oxygen and water vapor inside coal particles, and then the convection, diffusion and adsorption inside and between particles are studied by lattice Boltzmann method (LBM). In addition, this study examines the impacts of porosity, average particle size, and gas concentration on the process of adsorption in coal porous media. The research results show that oxygen and water vapor present in the mixed gas experience increased permeability, diffusion rate, and saturated adsorption capacity as the porosity and average particle size of the coal porous medium increase. However, the time required to achieve saturated adsorption decreases. Under the condition of maintaining the proportion of gas components and altering the initial gas concentrations from 4.087 to 53.131 mol/m3, saturated adsorption capacity of both gases remains nearly unchanged. Yet, the effective diffusivity of gases declines with increasing initial concentration. Additionally, it is also found that water vapor diffuses more quickly than oxygen in the mixed gas and achieves adsorption saturation faster.

U-type evacuated tube collector (ETC) is one of the most popular types of solar collectors for solar thermal applications. However, ETCs suffer from drawbacks caused by the intermittency of solar radiation. The addition of phase change materials (PCMs) inside ETC can reduce the energy fluctuations by storing the excess thermal energy during the daytime and releasing it to meet the supply deficit in the absence of sunlight. Therefore, a numerical model was conducted to assess the thermal performance of a PCM-filled U-type ETC with fins and experimentally validated. The design of different energy storage solutions, including the melting point of the PCM, the flow rate of heat transfer fluid (HTF) and the diameter of the inner glass tube were optimized. A two-fold beneficial effect of extending the hot water supply period and a reduction of the peak outlet temperature of HTF is achieved by filling PCM inside U-type ETC with fins. When the melting temperature of the PCM is 323 K, the reduction of the HTF peak outlet temperature is 7.4 K and the liquid fraction of the PCM approaches to a relatively high value, while the thermal efficiency and the thermal storage efficiency of the ETC are 50.72% and 19.20%, respectively. Meanwhile, the hot water supply time over 308 K extends by 160 min, compared to the case without PCM. It is also found that a high rate of the HTF inlet flow can shorten the hot water supply time with a smaller liquid fraction of the PCM. Furthermore, enlarging the glass tube leads to a higher thermal efficiency and thermal storage efficiency. This work shows that filling PCM with appropriate designs in the ETC with fins can promote the performance of ETC .

Frustrated Lewis pairs (FLPs) have demonstrated remarkable efficacy in metal-free hydrogenation, yet necessitate rigorous anhydrous reaction conditions. To address this concern, we propose a novel approach to enhance the water resistance of FLP by establishing a hydrophobic microenvironment. The inclusion of B(C6F5)3within a MIL-101 framework, enveloped by hydrophobic polydimethylsiloxane (PDMS) coating, facilitates the in-situ formation of FLP in a solvent of 1,4-dioxane. The hydrophobic PDMS effectively prevents the ingress of water into the MOF nanocages, while simultaneously enabling the diffusion of 1,4-dioxane into the MOF nanocages for FLP formation. Consequently, the as-prepared FLP/MIL-101@PDMS composite exhibits superior water tolerance in the hydrogenation of benzaldehyde and can be utilized directly in commercially available solvents without necessitating stringent inert conditions. Remarkably, FLP/MIL-101@PDMS showcases unparalleled water tolerance even in the presence of 15 equivalents of water relative to B(C6F5)3. This research introduces innovative concepts for designing water-tolerant FLP.

Peritoneal adhesion is the most common adverse effect following abdominal surgery or inflammation. The occurrence in clinical trials has been successfully reduced using barriers. However, the shortcomings of frequently used adhesion barriers, such as rapid degradation rate of gel barrier and inadequate operation ability of solid barrier, cannot be ignored. In this study, a fibrous membrane with an ECM-like structure was prepared. The adhesion properties were reduced significantly by changing the surface structure. The fibrous membrane caused less inflammatory response and much less peripheral adhesion and intestinal obstruction compared to the casting film and the commercial film with smooth surface, though with the same components. Because of the auto-soft bionic structure and similarity in the mechanical modulus of the tissues, the fibrous membrane was more flexible when it adhered to the tissues, showed excellent effectiveness and biocompatibility. In addition to the rat and miniature pig models, a randomized, placebo-controlled, and multicenter clinical pilot study with 150 patients confirmed that because of its flexibility, biodegradability, and similarity to mechanical modulus and structure with tissues involved, the fibrous membrane served as a favorable implant for preventing post-operation adhesion.

Assessing the effect of alcohol consumption on biological age is essential for understanding alcohol use‐related comorbidities and mortality. Previously developed epigenetic clocks are mainly based on DNA methylation in heterogeneous cell types, which provide limited knowledge on the impacts of alcohol consumption at the individual cellular level. Evidence shows that monocytes play an important role in both alcohol‐induced pathophysiology and the aging process. In this study, we developed a novel monocyte‐based DNA methylation clock (MonoDNAmAge) to assess the impact of alcohol consumption on monocyte age. A machine learning method was applied to select a set of chronological age‐associated DNA methylation CpG sites from 1202 monocyte methylomes. Pearson correlation was tested between MonoDNAmAge and chronological age in three independent cohorts (Ntotal= 2242). Using the MonoDNAmAge clock and four established clocks (i.e., HorvathDNAmAge, HannumDNAmAge, PhenoDNAmAge, GrimDNAmAge), we then evaluated the effect of alcohol consumption on epigenetic aging in the three cohorts [i.e., Yale Stress Center Community Study (YSCCS), Veteran Aging Cohort Study (VACS), Women's Interagency HIV Study (WIHS)] using linear and quadratic models. The MonoDNAmAge, comprised of 186 CpG sites, was moderately to strongly correlated with chronological age in the three cohorts (r= 0.90, p= 3.12E−181 in YSCCS; r= 0.54, p= 1.75E−96 in VACS; r= 0.66, p= 1.50E−60 in WIHS). More importantly, we found a nonlinear association between MonoDNAmAge and alcohol consumption (pmodel= 4.55E−08, px2= 7.80E−08 in YSCCS; pmodel= 1.85E−02, px2= 3.46E−02 in VACS). Heavy alcohol consumption increased EAAMonoDNAmAgeup to 1.60 years while light alcohol consumption decreased EAAMonoDNAmAgeup to 2.66 years. These results were corroborated by the four established epigenetic clocks (i.e., HorvathDNAmAge, HannumDNAmAge, PhenoDNAmAge, GrimDNAmAge). The results suggest a nonlinear relationship between alcohol consumption and its effects on epigenetic age. Considering adverse effects of alcohol consumption on health, nonlinear effects of alcohol use should be interpreted with caution. The findings, for the first time, highlight the complex effects of alcohol consumption on biological aging. Evidence shows that monocyte plays an important role in both alcohol‐induced pathophysiology and aging process. In this study, we developed a novel monocyte‐based DNA methylation clock to assess the impact of alcohol consumption on monocyte age. We found that alcohol use affects epigenetic aging in a nonlinear manner, with heavy consumption increasing and nonheavy use decreasing the epigenetic age. Our study expands previous knowledge and provides new insights into the effect of a spectrum of alcohol use on epigenetic aging.

• Upon annealing, the microstructure, not only in short range order but also in medium range order, contributes to the magnetic softness in Fe-based amorphous alloy. • Exchange coupling of homogeneous weak and strong magnetic regions generate excellent magnetic softness. • A configuration with energetically stabilization is formed annealed at optimized temperature, resulting in heating-rate independence of coercivity. The underlying structural origin of magnetic properties is still elusive in Fe-based amorphous alloys. In this study, distinctive soft magnetic properties were developed in Fe 76 Si 9 B 10 P 5 amorphous ribbons through systematic design of annealing process. Combining with synchrotron radiation, high-resolution transmission electron microscopy and first principle ab initio molecular dynamic simulation, it is found that the atomic structural evolution both in short range order and medium range order is responsible for the magnetic softness at proper annealing temperature. In short range, formation of separated and densely coordinated Fe-metalloid clusters is instigated to adapt energy minimization, resulting in strengthening of ferromagnetic exchange interaction locally. In medium range, a homogeneous exchange-coupling from the uniformly strong and weak ferromagnetic regions is generated, which significantly weakens magnetic heterogeneity and leads to the excellent magnetic softness. Our findings may provide an effective/promising pathway to modulate the magnetic properties for Fe-based amorphous alloys, and give a comprehensive and quantitative understanding of the structure-properties relationship in amorphous materials. [Display omitted] [ABSTRACT FROM AUTHOR]

The photocatalytic reduction of CO2into valuable fuels and sustainable energy has a promising future, yet remains a challenge due to low charge separation efficiency and inadequate active sites. We find that ZnIn2S4-loaded secondary amine-functionalized organic silica (ZnIn2S4/NH–SiO2) was effective for visible-light driven CO2photocatalytic reduction. The ZnIn2S4/NH–SiO2with 40% ZnIn2S4content achieves a CO production rate of 1304.8 μmol g−1h−1at room temperature, which is about 3 times higher than that of pristine ZnIn2S4. The thin ZnIn2S4nanosheet accelerates the separation of photogenerated electron pairs, and the amine groups on ZnIn2S4/NH–SiO2act as active sites for adsorption and activation of CO2, hence facilitating the photoreduction of CO2.

Protein-based drugs have been demonstrating great potential for the treatment of various diseases, but most of them encounter many difficulties in clinical trials or uses, such as instability, low bioavailability, and poor in vivoefficacy. In this work, we developed virus-mimetic nanocapsules (VMNs) for improving protein systemic delivery and pharmaceutical effects through bioinspired macromolecular and supramolecular engineering. These VMNs possessed hierarchical nanostructures including artificial capsids, encapsulated proteins, and synthetic envelopes. These dynamic-responsive VMNs can harbor protein drugs, resist protein adsorption, target solid tumors, penetrate into deep tissue, and site-specifically unpack protein drugs. Through surmounting the sequential physio-pathological barriers, protein-loaded VMNs successfully maximized the in vitroand in vivotherapeutic efficacy of proteins, giving a promising strategy to address dilemmas on clinical TRAIL therapy. This study is expected to promote in vivotreatment outcomes and clinical transformation of protein drugs.

Large-scale genome-wide association studies (GWAS) have been successfully applied to a wide range of genetic variants underlying complex diseases. The network-based regression approach has been developed to incorporate a biological genetic network and to overcome the challenges caused by the computational efficiency for analyzing high-dimensional genomic data. In this paper, we propose a gene selection approach by incorporating genetic networks into case-control association studies for DNA sequence data or DNA methylation data. Instead of using traditional dimension reduction techniques such as principal component analyses and supervised principal component analyses, we use a linear combination of genotypes at SNPs or methylation values at CpG sites in a gene to capture gene-level signals. We employ three linear combination approaches: optimally weighted sum (OWS), beta-based weighted sum (BWS), and LD-adjusted polygenic risk score (LD-PRS). OWS and LD-PRS are supervised approaches that depend on the effect of each SNP or CpG site on the case-control status, while BWS can be extracted without using the case-control status. After using one of the linear combinations of genotypes or methylation values in each gene to capture gene-level signals, we regularize them to perform gene selection based on the biological network. Simulation studies show that the proposed approaches have higher true positive rates than using traditional dimension reduction techniques. We also apply our approaches to DNA methylation data and UK Biobank DNA sequence data for analyzing rheumatoid arthritis. The results show that the proposed methods can select potentially rheumatoid arthritis related genes that are missed by existing methods.

The short wavelength of X-rays makes them attractive for high-resolution imaging systems in fields ranging from medicine to industry. The thin-film grating required for X-ray imaging can be created using printing, which is a cost-effective method for large-area imaging. Since the grating resolution (line/space, or L/S) influences the imaging resolution, it is crucial to enhance the L/S through printing methods. In this study, thin-film gratings were fabricated from silver nanoparticles using letterpress inversion printing, achieving a maximum L/S grating resolution of 1 μm/1 μm (the highest resolution achieved through printing). Subsequently, the cross-section of a pine needle was successfully imaged.

The process of diagnosing hazardous alcohol drinking (HAD) is based on self-reported data and is thereby vulnerable to bias. There has been an interest in developing epigenetic biomarkers for HAD that might complement clinical assessment. Because alcohol consumption has been previously linked to DNA methylation (DNAm), we aimed to select DNAm signatures in blood to predict HAD from two demographically and clinically distinct populations (Ntotal= 1,549). We first separately conducted an epigenome-wide association study (EWAS) for phosphatidylethanol (PEth), an objective measure of alcohol consumption, and for self-reported alcohol consumption in Cohort 1. We identified 83 PEth-associated CpGs, including 23 CpGs previously associated with alcohol consumption or alcohol use disorder. In contrast, no CpG reached epigenome-wide significance on self-reported alcohol consumption. Using a machine learning approach, two CpG subsets from EWAS on PEth and on self-reported alcohol consumption from Cohort 1 were separately tested for the prediction of HAD in Cohort 2. We found that a subset of 143 CpGs selected from the EWAS on PEth showed an excellent prediction of HAD with the area under the receiver operating characteristic curve (AUC) of 89.4% in training set and 73.9% in validation set of Cohort 2. However, CpGs preselected from the EWAS on self-reported alcohol consumption showed a poor prediction of HAD with AUC 75.2% in training set and 57.6% in validation set. Our results demonstrate that an objective measure for alcohol consumption is a more informative phenotype than self-reported data for revealing epigenetic mechanisms. The PEth-associated DNAm signature in blood could serve as a robust biomarker for alcohol consumption.

Compared with paclitaxel, sirolimus has been more used in the treatment of vascular restenosis gradually as an anti-proliferative drug, but few basic studies have elucidated its mechanism. The anti-proliferative effects of sirolimus or paclitaxel have been demonstrated by numerous studies under normoxia, but few studies have been achieved focusing hypoxia. In this study, porcine carotid artery injury model and classical cobalt chloride hypoxia cell model were established. Sirolimus nanoparticles (SRM-NPs), paclitaxel nanoparticles (PTX-NPs) and blank nanoparticles (Blank-NPs) were prepared respectively. The effect of RPM-NPs on the degree of stenosis, proliferative index and the expression of PCNA after 28 days of porcine carotid artery injury model was evaluated. Compared with saline group and SRM groups, SRM-NPs group suppressed vascular stenosis, proliferative index and the expression of PCNA (P < 0.01 and P < 0.05). Endothelial cell (EC) and smooth muscle cell (SMC) were pre-treated with cobaltous chloride, followed by SRM-NPs, PTX-NPs, Blank-NPs or PBS control treating, the effects on cell proliferation, HIF-1 expression and glycolysis were detected. SRM-NPs could inhibit EC and SMC proliferation under hypoxia, while PTX-NPs couldn't (P < 0.001). Significant differences between sirolimus and paclitaxel NPs in anti-proliferation effect under normoxia and hypoxia may due to the different inhibitory effects on HIF-1α expression and glycolysis. In conclusion, these results suggest that sirolimus can inhibit the proliferation of hypoxic cells more effectively than paclitaxel. These observations may provide a basis for understanding clinical vascular stenosis therapeutic differences between rapamycin and paclitaxel.

CD8+T cell exhaustion dampens antitumor immunity. Although several transcription factors have been identified that regulate T cell exhaustion, the molecular mechanisms by which CD8+T cells are triggered to enter an exhausted state remain unclear. Here, we show that interleukin-2 (IL-2) acts as an environmental cue to induce CD8+T cell exhaustion within tumor microenvironments. We find that a continuously high level of IL-2 leads to the persistent activation of STAT5 in CD8+T cells, which in turn induces strong expression of tryptophan hydroxylase 1, thus catalyzing the conversion to tryptophan to 5-hydroxytryptophan (5-HTP). 5-HTP subsequently activates AhR nuclear translocation, causing a coordinated upregulation of inhibitory receptors and downregulation of cytokine and effector-molecule production, thereby rendering T cells dysfunctional in the tumor microenvironment. This molecular pathway is not only present in mouse tumor models but is also observed in people with cancer, identifying IL-2 as a novel inducer of T cell exhaustion.

Micron-sized single crystal particles could be used to intensify structural changes between bulk and surface area during the charge–discharge process owing to their long-range order. In this study, the effects of Mn3+formation–migration and oxygen loss on the structure change from the bulk side to the near surface in single crystalline Li1.2Mn0.54Ni0.13Co0.13O2were decoupled by regulating the voltage windows of 2–4.5, 3–4.8, and 2–4.8 V because Mn3+formation–migration and oxygen loss mainly occurred below 3 V and beyond 4.5 V, respectively. It is found that oxygen vacancies and phase transformation can be retarded by suppressing the formation–migration of Mn3+. Finally, we also conducted an important insight that boron ion doping in tetrahedral site could be used to suppress Mn3+migration from octahedral site to tetrahedral site and disrupt the synergistic effect of Mn3+migration and oxygen loss.

The successful treatment of limb ischemia requires that promote angiogenesis along with microenvironment improvement. Zinc ions have been reported to stimulate angiogenesis, but application was limited to the toxicity concerns. We hypothesized that zinc based metal-EGCG capsule (EGCG/Zn Ps) can achieve sustained release Zn2+resulting in reduced toxicity and improve angiogenesis as well as the improvement of microenvironment by ROS scavenging of EGCG. The surface morphology, zeta potential, infrared absorbance peaks and zinc ion release profile of the EGCG/Zn Ps were measured. In vitro, EGCG/Zn showed significantly antioxidant, anti-inflammatory and induced cell migration effect. In addition, EGCG/Zn Ps enabled the sustained release of zinc ions, which reduced cytotoxicity and enhanced the secretion of vascular endothelial growth factor (VEGF) in vitro andin vivo. In mouse models of limb ischemia, EGCG/Zn Ps promoted angiogenesis and cell proliferation in ischemic tissues. Moreover, EGCG/Zn Ps group exhibited the most significant recovery of limb ischemic score, limb temperature and blood flow than other groups. In conclusion, EGCG/Zn Ps is a safe and promising approach to combine the merit of Zn2+and EGCG, thus enabling the direct application to limb ischemia.

The application of inductive energy storage in the generation of high-current pulses has attracted considerable attention during recent years. In this article, a new inductive high-current pulse generator circuit is proposed based on XRAM (MARX spelled backword) current multiplier converter concept and multistage pulse transformers by using power electronic switches. This circuit is capable to recover the residual energy and generate repetitive high-current pulses with a flexible output pattern. To verify the circuit operation, simulation and experimental results of a two-stage laboratory prototype are presented. The results confirm the theoretical analysis and show the validity of the converter scheme.

Stimulus-responsive polymer materials have attracted much attention as drug carriers because of the ability to deliver drugs to the active site. Reactive oxygen species (ROS) play crucial roles in cellular signaling and regulation of oxygen homeostasis. However, ROS are present in abnormally high levels in many pathological environments. Based on the above points, three-arm poly(lactic-co-glycolic acid)-PO-poly(ethylene glycol) (3s-PLGA-PO-PEG or simply PP) was synthesized by using peroxalate esters (PO) as hydrogen peroxide-responsive linkages. PP was used to deliver promote hematopoietic recovery drugs erythropoietin (EPO) and EPO nanoparticles (EPO NPs) were prepared. We established a hematopoietic system injury model by ionizing radiation (IR) and unexpectedly found the good therapeutic effect of blank PP. Moreover, the administration of EPO NPs obviously decreased IR-induced ROS in bone marrow cells (BMCs) and reconstituted hematopoietic stem cells in BMCs. This study reveals a novel ROS-responsive polymer material that could be employed to remove excess ROS in the lesion and promote the efficacy of drug therapy.

Solar-driven CO2conversion into fuels and sustainable energy has attracted increasing attention around the world. However, the efficiency of the transformation remains relatively low due to the rapid recombination of photogenerated charge carriers. In this work, we prepared a ZnIn2S4–ZnAlOxnanocomposite for visible light driven CO2reduction. The thin layered structure facilitated the photoinduced charge carrier separation and transfer, and also gave excellent adsorption ability towards CO2molecules. Such a nanocatalyst exhibited excellent activity in visible-light driven CO2reduction with a CO optimal formation rate of 1100 μmol g−1h−1, which is 5 times that over bulk ZnIn2S4, and the CO/H2ratio was increased from 0.2 over bulk ZnIn2S4to 1.5 over the ZnIn2S4–ZnAlOxcomposite. In situFT-IR experiments indicated that CO2was reduced on ZnIn2S4–ZnAlOxfollowing a COOH* pathway. This work gives insights into the mechanism of the photocatalytic CO2reduction reaction and inspiration to construct novel heterostructure materials for application in energy and environmental catalysis.

Poly[lactic-co-(glycolic acid)] (PLGA) is arguably one of the most versatile synthetic copolymers used for biomedical applications. In vivo delivery of multiple substances including cells, pharmaceutical compounds, and antigens has been achieved by using PLGA-based micro-/nanoparticles although, presently, the exact biological impact of PLGA particles on the immune system remains controversial. Type 1 diabetes (T1D) is one subtype of diabetes characterized by the attack of immune cells against self-insulin-producing pancreatic islet cells. Considering the autoimmune etiology of T1D and the recent use of PLGA particles for eliciting desired immune responses in various aspects of immunotherapy, for the present study, a combination of Ins29–23peptide (a known autoantigen of T1D) and PLGA microparticles was selected for T1D prevention assessment in nonobese diabetic (NOD) mice, a well-known animal model with spontaneous development of T1D. Thus, inoculation of PLGA microparticles + Ins29–23completely prevented T1D development, significantly better than untreated controls and mice treated by either PLGA microparticles or Ins29–23per se. Subsequent mechanistic investigation further revealed a facilitative role of PLGA microparticles in immune tolerance induction. In summary, our data demonstrate an adjuvant potential of PLGA microparticles in tolerance induction and immune remodulation for effective prevention of autoimmune diseases such as T1D.

Glycogen has long been considered to have a function in energy metabolism. However, our recent study indicated that glycogen metabolism, directed by cytosolic phosphoenolpyruvate carboxykinase Pck1, controls the formation and maintenance of CD8+memory T (Tmem) cells by regulating redox homeostasis1. This unusual metabolic program raises the question of how Pck1 is upregulated in CD8+Tmemcells. Here, we show that mitochondrial acetyl coenzyme A is diverted to the ketogenesis pathway, which indirectly regulates Pck1expression. Mechanistically, ketogenesis-derived β-hydroxybutyrate is present in CD8+Tmemcells; β-hydroxybutyrate epigenetically modifies Lys 9 of histone H3 (H3K9) of Foxo1and Ppargc1a(which encodes PGC-1α) with β-hydroxybutyrylation, upregulating the expression of these genes. As a result, FoxO1 and PGC-1α cooperatively upregulate Pck1expression, therefore directing the carbon flow along the gluconeogenic pathway to glycogen and the pentose phosphate pathway. These results reveal that ketogenesis acts as an unusual metabolic pathway in CD8+Tmemcells, linking epigenetic modification required for memory development.

The design and evaluation experiments of a multibeam X-ray tomography optical system that can be used with synchrotron radiation from sources with a narrow energy bandwidth, i.e. undulator sources, are reported. It consists of silicon single crystals that diffract the incident X-rays to 27 beams, which are used to image a sample. The energy of the beams was aligned with an accuracy sufficient for use at typical undulator beamlines. Projection images of a test sample were collected and successfully reconstructed, showing the feasibility of a high-speed X-ray tomography instrument based on the optical system.

In this study, we report the preparation of AZ31/TiC composites by laser cladding based on elemental vaporization and supplementation and investigate the effects of laser process parameters and mixed powder ratio on the vaporization and spattering. It was found that the capillary pressure generated by using TiC could effectively suppress the molten pool sputtering during laser cladding. In addition, TiC particles promoted the recrystallisation behavior of the molten pool, and the grains were significantly refined from 61.58 μm to 6.46 μm. The random orientation of the recrystallized grains led to a weaker texture, decrease from 12.349 to 1.964. The microhardness of the composites higher than AZ31 from 46 to 86.2 HV0.2, and the average wear rate was reduced by 21.9%.

Complete reendothelialization followed by inhibition of smooth muscle cell (SMC) proliferation is considered as an effective therapeutic option to prevent restenosis. We have designed poly(lactide-co-glycolide)-loaded bilayered nanoparticles (NPs) with the ability to sequentially release vascular endothelial growth factor (VEGF)-encoding plasmids from the outer layer and paclitaxel (PTX) from the core to promote endothelial regeneration as well as prevent restenosis. Comparing with conventional NPs, which release VEGF plasmid and PTX simultaneously, we expect that the bilayered NPs could release the VEGF plasmid more rapidly, followed by a delayed release of PTX, resulting in an efficient VEGF gene transfection, which ideally could promote reendothelialization and inhibit excessive SMC growth. Indeed, in the present study, we have observed efficient gene transfection using a model plasmid as well as cell growth attenuation in vitro using Chinese hamster ovary cells. Therapeutic efficacy of the bilayered NPs on restenosis was further evaluated in vivo using a rabbit model of atherosclerosis. The bilayered NPs were administered locally via balloon angioplasty to the injured aortic wall through perfusion. Twenty-eight days after the NP administration, rabbits treated with the bilayered NPs exhibited rapid reendothelialization and inhibition of restenosis, as demonstrated by histological analysis. Increased level of VEGF and decreased level of C-reactive protein, a biological marker that is closely related to atherosclerosis, were also observed from animals treated with the bilayered NPs, implicating ameliorated atherosclerosis. Our results suggest that the VEGF plasmid-/PTX-loaded bilayered NPs exert a beneficial impact on atherosclerotic restenosis by sequentially releasing VEGF and PTX in vivo.

A soft sensor based on a self-organizing model and conditional probability density analysis is proposed for a nonlinear multimode process, the operation of which switches between multiple nonlinear modes. The self-organizing model is based on multiple kernel partial least-squares (KPLS) models, with each KPLS model associated with a specific mode. It is assumed that no a priori information is available; that is, neither the number of modes nor mode labels of the training samples are known. During the training stage, both the assigned modes of training samples and model parameters are updated, so that mode assignment and model training can be achieved simultaneously. For the purpose of online estimation, the conditional density p(y|x) of the outputs yconditional on inputs xis estimated based on samples assigned into each mode. When a query sample is available, several candidate output predictions are obtained using the trained models. The prediction that yields the most significant conditional probability is assigned as the final estimation. The introduction of conditional density estimation produces an appropriate similarity measure for the nonlinear multimode process. The performance of the proposed soft sensor is validated using a simulation example and an industrial process.