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• Coating entered the pre-existing cracks and formed the subterranean river feature. • The base metal rod experienced softening during thermal spray and fusion heating. • Debonding and pinholes are observed in the as-sprayed materials. • Stress concentrations magnified bending and residual stresses to cause overload. • Defects, residual stresses, and the applied stress result in the final fracture. A straightening fracture of an AISI 1045 pump rod with a fused coating by thermal spray welding was investigated. The fracture surface was surveyed for pinhole-related defects in the coating, debonding at the coating/substrate interface, and fracture initiation points. The base metal and coating were also examined using an optical microscope, scanning electron microscope with energy dispersive spectroscopy, tensile testing, and microhardness testing. The base metal rod experienced softening due to the thermal effect of spray welding and fusion. Large residual stress has been found in the outer coating layer using finite element analysis. The open-to-surface crack in the base metal was found to be partially filled by the hard coating. The brittle fracture is believed to be initiated at defects near the coating/rod interface and driven by a combined loading of thermal residual stresses and the applied straightening stress. [ABSTRACT FROM AUTHOR]

Fluorine (F) and its compounds produced from industrial production and coal combustion can cause air, water and soil contamination, which can accumulate in animals, plants and humans via food chain threatening public health. Fluoride exposure affects liver, kidney, gastrointestinal and reproductive system in humans and animals. Literature regarding fluoride influence on intestinal structure and microbiota composition in ducks is scarce. This study was designed to investigate these effects by using simple and electron microscopy and 16S rRNA sequencing techniques. Results indicated an impaired structure with reduced relative distribution of goblet cells in the fluoride exposed group. Moreover, the gut microbiota showed a significant decrease in alpha diversity. Proteobacteria , Firmicutes and Bacteroidetes were the most abundant phyla in both control and fluoride-exposed groups. Specifically, fluoride exposure resulted in a significant decrease in the relative abundance of 9 bacterial phyla and 15 bacterial genera. Among them, 4 phyla (Latescibacteria , Dependentiae , Zixibacteria and Fibrobacteres) and 4 genera (Thauera , Hydrogenophaga , Reyranella and Arenimonas) weren't even detectable in the gut microbiota of the ducks. In summary, higher fluoride exposure can significantly damage the intestinal structure and gut microbial composition in ducks. • Intestinal structure and gut microbial composition and diversity depends on various animal and environment related factors. • Fluoride and its compounds can accumulate in animals and plants and threaten public health through the food chain. • Simple and electron microscopy coupled with 16S rRNA sequencing revealed that excessive fluoride exposure can significantly impair the intestinal structure and the gut microbial diversity and composition in ducks. [ABSTRACT FROM AUTHOR]

Abstract: Although gonadal hormone mostly causes genotropic actions through the members of nuclear receptor family, it also can regulate these actions via membrane receptor. To explore the possibility of plasma membrane estrogen receptors (mER) mediating genotropic events, we have investigated estrogen''s effect on nicotine-stimulated adhesion molecule expression and evaluated whether this effect depends on calcium, MAPK signal pathway. Fluorescence Spectroscopy analysis of Ca2+ from human umbilical vein endothelial cells (HUVECs) showed through mER, estrogen induced a rapid rise of intracellular free Ca2+ concentration and this rise could not be inhibited by tamoxifen (classic ER inhibitor). In the context of nicotine stimulating, however, estrogen attenuated phosphorylation of mitogen-activated protein kinase (MAPK) family members, extracellular signal regulated kinase 1/2 (ERK1/2), p38 but not c-Jun-N-terminal kinase (JNK) in HUVECs and this effect could not still be prevented by tamoxifen. In the meantime, estrogen also down-regulated surface/soluble vascular cell adhesion molecule (VCAM-1, sVCAM-1) and endothelial selectin (E-selectin, sE-selectin) levels, which was not abolished by tamoxifen either. Moreover, calcium chelator BAPTA, ERK1/2 inhibitor PD98059, p38 inhibitor SB203580 significantly reduced the production of nicotine-activated surface/soluble VCAM-1 and E-selectin and both of the remained levels were no longer regulated by estrogen. Our study here provides the information of decrease effect of mER-mediated estrogen through Ca2+ and ERK1/2, p38 MAPK signaling pathway on nicotine-stimulated expression of surface/soluble VCAM-1 and E-selectin in HUVECs. [Copyright &y& Elsevier]

Abstract: To evaluate the effect of nicotine on endothelium dysfunction and development of vascular diseases, we investigated the influence on adhesion molecular expression mediated by nicotine and the mechanism of this effect in human umbilical vein endothelial cells (HUVECs). The result showed that nicotine could induce surface/soluble vascular cell adhesion molecule (VCAM-1) and endothelial selectin (E-selectin) expression in a time-response decline manner and the peak appeared at 15min. This action could be mediated by mitogen-activated protein kinase/extracellular signal regulated kinase 1/2 (MAPK/ERK1/2) and MAPK/p38 because their activation could be distinctly blocked by MAPK inhibitors, PD098059 or SB203580. Mecamylamine (non-selective nicotinic receptor inhibitor), α-bungarotoxin (α7 nicotinic receptor inhibitor) could block Ca2+ accumulation, and then, prevented the phosphorylation on ERK1/2 and p38. They also inhibited the surface/soluble VCAM-1, E-selectin production of HUVECs modulated by nicotine. Therefore, we concluded that: (i) nicotine obviously up-regulates VCAM-1 and E-selectin expression at 15min in HUVECs, (ii) nicotine activates HUVECs triggered by the ERK1/2 and p38 phosphorylation with an involvement of intracellular calcium mobilization chiefly mediated by α7 nicotinic receptor, (iii) intracellular Ca2+ activates a sequential pathway from α7 nicotinic receptor to the phosphorylation of ERK1/2, p38. These elucidate that nicotine activates HUVECs through fast signal transduction pathway and arguments their capacity of adhesion molecular production. Further more nicotine may contribute its influence to the progression of vascular disease such as atherosclerotic lesion. [Copyright &y& Elsevier]

Nicotine, the major immunomodulatory components of cigarette smoking, is among the leading risk factors in atherosclerosis and various other diseases. The subject of this study is to observe how nicotine affects the function of macrophages and vascular endothelial cells. The changes of nicotine on releasing of cytokines from Ana-1 were detected by radio-immunoassay (RIA) or enzyme-link immunosorbent assay (ELISA). The adhesion of monocytes to human umbilical vein endothelial cells (HUVECs) with Ana-1 supernatant-activated was evaluated through adhesion experiments. ELISA and RT-PCR methods examined expression of soluble adhesion molecular protein and their mRNA. Which cytokines in Ana-1 supernatant affecting HUVECs ability to express adhesion molecular were tested by adhesion blockade analysis and ELISA. The results showed TNF-α, IL-1β could reach the peak with 0.06mM nicotine treated for 24 and 12 h on Ana-1, respectively, but IL-8 and IFN-γ had no significant alter. Adhesion experiments proved treatment of HUVECs with supernatant of Ana-1 for 24 h obviously augmented the adhesion of monocytes to HUVECs. ELISA and PCR demonstrated expression of soluble intracellular adhesion molecule-1 protein (sICAM-1) increased sharply at 24 h, while soluble vascular cell adhesion molecule-1 protein (sVCAM-1) and soluble endothelial selectin protein (sE-selectin) rose at 9 h; ICAM-1, VCAM-1 and E-selectin mRNA had a similar tendency. Treatment of HUVECs with anti-TNF-α, anti-IL-1β antibodies pre-neutralized supernatant of Ana-1 could block monocytes adhesion. In conclusion, our findings suggest that nicotine could augment macrophages releasing TNF-α and IL-1β, furthermore TNF-α and IL-1β could up-regulate the expression of adhesion molecule and increase adhesion of monocytes to HUVECs. These might be one of the reasons that leaded to endothelial dysfunction. [Copyright &y& Elsevier]

R2166 --> There is limited and discordant evidence on the association of diabetic vascular disease and nicotine. Compared to diabetic nonsmokers, acerbated endothelial cell dysregulation in diabetic smokers has been confirmed. Adiponectin (APN) possesses vascular protective, anti‐inflammatory and anti‐diabetic properties. However, whether and how nicotine causes and aggravates diabetic vascular disorders remain uncertain. In this study, we evaluated the alteration of APN level in high fat diet (HFD) mice with nicotine administration. The vascular pathophysiological response was evaluated with vascular ring assay. Confocal and co‐immunoprecipitation analysis were applied to identify the signal interaction and transduction. The results indicated that addition of nicotine in HFD groups (NIC + HFD) significantly reduced the vascular relaxation response to adiponectin. The circulating APN level raised at 4 weeks and reached the peak at 6 weeks, 2 weeks earlier than that of diabetic mice. In addition, in aortic vascular ring assay, the detrimental APN signaling response was characterized by worse relaxation capability. Mechanistically, APN receptor 1 (AdipoR1) level was decreased in NIC and further significantly reduced in NIC + HFD group at 6 weeks, while suppressor of cytokine signaling 3 (SOCS3) expression was induced in NIC treated group and further increased in NIC + HFD group. Similar results were also observed in human umbilical vein endothelial cells (HUVECs) treated with high glucose and high lipid (HG/HL) combined with nicotine. The reduction of ERK1/2 activation manifested APN signaling response was attenuated. The increase of ubiquitinated AdipoR1 was determined by administration of MG132 (proteasome inhibitor). Inhibition of SOCS3 partially preserved the reduction of AdipoR1 induced by nicotine or NIC + HG/HL, which indicated that SOCS3 is the key molecule to induce the degradation of ubiquitinated AdipoR1, subsequent to detrimental APN signaling and worsen diabetic vascular injury. [ABSTRACT FROM AUTHOR]

Particle size inversion of dynamic light scattering (DLS) is a typically ill-posed problem. Regularization is an effective method to solve the problem. The regularization involves imposing constraints on the fitted autocorrelation function data by adding a norm. The classical regularization inversion for DLS data is constrained by the L2 norm. In the optimization equation, the norm determines the smoothness and stability of the inversion result, affecting the inversion accuracy. In this paper, the Lp norm regularization model is constructed. When p is 1, 2, 10, 50, 100, 1000, and ∞, respectively, the influence of their norm models on the inversion results of data with different noise levels is studied. The results prove that overall, the inversion distribution errors show a downward trend with the increase of p. When p is larger than 10, there is no significant difference in distribution error. Compared with L2, L∞ can provide better performance for unimodal particles with strong noise, although this does not occur in weak noise cases. Meanwhile, L∞ has lower sensitivity to noise and better peak resolution, and its inverse particle size distribution is closer to the true distribution for bimodal particles. Thus, L∞ is more suitable for the inversion of DLS data. [ABSTRACT FROM AUTHOR]

Anaerobic digestion technology, effective for sustainable waste management and renewable energy, but challenged by slow reaction rates and low biogas yields, could benefit from advancements in magnetic nanomaterials. This review explores the potential of magnetic nanomaterials, particularly magnetic biochar nanocomposites, to address these challenges by serving as electron conduits and providing essential iron. This review contributes a thorough overview of the application of magnetic nanoparticles loaded into biochar in anaerobic digestion and engages in a comprehensive discussion regarding the synthesis methods and characterization of various magnetic nanoparticles, elucidating their mechanisms of action in both the absence and presence of magnetic fields. Our review underscores the predominance of co-precipitation (53%) and commercially sourced nanoparticles (29%) as the main synthesis methods, with chemical reduction, pyrolysis, and green synthesis pathways less commonly utilized (8%, 5%, and 5%, respectively). Notably, pyrolysis is predominantly employed for synthesizing magnetic biochar nanocomposites, reflecting its prevalence in 100% of cases for this specific application. By offering a critical evaluation of the current state of knowledge and discussing the challenges and future directions for research in this field, this review can help researchers and practitioners better understand the potential of magnetic biochar nanocomposites for enhancing anaerobic digestion performance and ultimately advancing sustainable waste management and renewable energy production. Highlights: Critical insights into using magnetic nanoparticles within biochar as a solution to sustainable waste management. Fe3O4, nZVI, and Fe2O3 are prevalent in enhancing anaerobic digestion processes. Insights offered on nanoparticle utilization, magnetic field impacts, and sustainable solutions integrating biochar. [ABSTRACT FROM AUTHOR]

An annular thermoelectric generator (ATG) contributes to energy utilization in round structures. An accurate prediction of thermoelectric (TE) performance is key to the design of the ATG. By using the perturbation theory and the equivalent substitution of integrals method, an analytical model is proposed, which can easily deal with the nonlinear heat equation induced by temperature-dependent material properties. The TE performance of the ATG including the Thomson effect is studied by the proposed model, and the effect of structural parameters and operating conditions on the TE behavior is analyzed. The results indicate that if the Thomson effect is neglected, the predicted power output and efficiency will be much higher than the actual cases. Significantly, in both working conditions, the relative error of the predicted temperature field of the proposed model is less than 0.1%, far below the available theoretical models. In addition, the influence of side surface heat convection is also analyzed using a numerical method. Remarkably, the maximum power output may increase as the heat convection coefficient grows. [ABSTRACT FROM AUTHOR]

Efficient utilization of crop straw is a determining factor for cleaner production and sustainable development in Ghana's agricultural sector. However, extensive field burning of crops straw is hampering the effective utilization of straw resources in the Northern region of Ghana. The aim of this research was to identify rural households' crops straw utilization methods and investigate the occurrence as well as effects of crops straw burning. Cross-sectional data collected from 384 farmer households' in Yendi municipality, Saboba and Tatale-Sanguli districts in the Northern region of Ghana were analyzed with Statistical Package of Social Sciences (SPSS). The total crop yield for major cereals and legumes produced was 1.29 kton with a total crop straw yield of 3.05 kton. Cereals straw contributed the highest yield percentage of 56.4% while legume straw contribution was 43.6%. About 1.23kton (40.3%) of straws from major cereals and legumes were utilized for different purposes such as returning to the field to enrich the soil, fodder for livestock, cooking fuel, sale and other traditional purposes. The remaining 1.82kton (59.7%) of crop straws were burnt on the field. The percentages of straw burnt on the field for each crop were 77.6% for maize, 58.6% for sorghum, 56.5% groundnut, 49.7% for millet, 47.4% cowpea, 42.2% for rice and 41.4% for soybean. Farming and farm size are the key influencing factors that affect straw burning. Open field burning of straws caused a decline in yield for about 65.7% of respondents. The present findings indicates that utilization of crop straw in the Northern region of Ghana is poorly practiced and needs to be encouraged because of its associated benefits. Government of Ghana needs to develop appropriate policies and legislative measures to encourage effective utilization of straw and prohibit field burning of straws. • Different straw utilization methods are identified in the study area. • Straw utilization methods identified are poorly practiced. • Large proportions of straw are burnt on the farm by farmers or hunters. • Straw burning has negative effects on human and the environment. • Farming and farm size are determinant for future occurrence of burning. [ABSTRACT FROM AUTHOR]

Lightweight, strong and broadband microwave absorbents are urgently demanded for practical applications. Exploring magnetic/dielectric composites by anchoring magnetic nanostructures on lightweight dielectric carbon is an effective way, due to their possible good impedance matching condition. Herein, one-dimensional FeCo/C nanofibers are fabricated by electrospinning method and subsequent anoxic annealing treatment, which are used as difunctional magnetic/dielectric microwave absorbents. The nanofibers have a large aspect ratio, in which tiny magnetic FeCo nanocrystals are uniformly decorated in the amorphous dielectric C nanofibers. Benefiting from good impedance matching condition, enhanced microwave attenuation ability and synergistic effect between ferromagnetic FeCo and dielectric C, the FeCo/C nanofibers exhibit boosting microwave absorption performance, which is related to the absorber thickness and filling ratio. The optimal FeCo/C/paraffin composites with 40 wt% of functional fillers show a minimum reflection loss value of −59.9 dB with broad effective absorption bandwidth of 6.0 GHz at 13.2 GHz when the absorber thickness is only 2.6 mm. The FeCo/C nanofibers have a small density of only about 1.1 g/cm3, much smaller than the bulk FeCo (7.4–7.6 g/cm3). Owing to the characteristics of low density, strong absorption and broad effective absorption bandwidth, the FeCo/C nanofibers are promised to be good candidates as microwave absorbents. Image 1 • The FeCo/C nanofibers were prepared by electrospinning and annealing treatment. • The carbon nanofibers were uniformly decorated by tiny FeCo nanocrystals. • The FeCo/C nanofibers have a small density of only 1.1 g/cm3. • The absorption bandwidth of FeCo/C reaches 6.0 GHz with a thickness of 2.6 mm. • The FeCo/C composites show a minimum reflection loss value of −59.9 dB at 13.2 GHz. [ABSTRACT FROM AUTHOR]

Accurate real-time evaluation of human physiological state is significant for safety guidance and early warning for people in high temperature environments. The constant weight method often makes the evaluation results deviating from reality. In this paper, the variable weight theory is adopted to solve above problem. Firstly, a human physiological state evaluation system is proposed. Secondly, the constant weight and variable weight methods are used to obtain the weights of the indexes. Thus, the comprehensive evaluation score is obtained to quantify the human physiological state. Finally, a case study is conducted to demonstrate and verify the proposed evaluation system. It indicates that, the variable weight of rectal temperature, skin temperature, systolic pressure and heart rate is 0.2∼0.77, 0.11∼0.61, 0.03∼0.31, 0.03∼0.31, respectively. And the weights of the skin temperature and the rectal temperature account for a relatively large proportion, ranging from 50% to 92%. The physiological parameters with small constant weight may account for a larger percentage in the evaluation when the physiological parameters reach an extremely harmful condition. This paper can provide more reasonable and scientific method in physiological state quantification for people in high temperature environments. • Physiological state evaluation is significant for human safety guidance. • A physiological safety evaluation system is established. • The variable weight theory is adopted to improve the weight determination. • The weights of skin temperature and rectal temperature range from 50% to 92%. • The results demonstrate the effectiveness of this proposed method. [ABSTRACT FROM AUTHOR]

In this paper, Moso bamboo (Phyllostachys heterocycle) before and after heat treatment were used as raw materials to prepare transparent bamboo (TB). In an acidic environment, the lignin contained in the bamboo material was removed to obtain a bamboo template, and an epoxy resin similar to the cellulose refractive index was used for vacuum impregnation into the bamboo template to obtain a transparent bamboo material. The purpose of this study was to compare the physical and chemical properties of TB and original bamboo and the differences between TBs before and after heat treatment, taken from different parts of bamboo, in order to explore the performance advantages and disadvantages of TB as a new material. The Fourier transform infrared spectroscopy analysis (FTIR), scanning electron microscope testing (SEM), three elements analysis, light transmittance testing, and mechanical strength testing were used to study the molecular composition, microstructure, chemical composition, light transmittance, and tensile strength of the TB samples. The results showed that the lignin content of the delignified bamboo templates was greatly reduced. In addition, the SEM images showed that a large amount of epoxy resin (type E51 and type B210 curing agent) was covered on the cross-section surface and pores of the TB samples. The FTIR showed that the epoxy molecular groups appeared on the TB, and the delignified bamboo template and the resin had a good synergy effect. According to the light transmittance testing, the original bamboo samples hardly contained light transmittance under visible light. The transmittance of transparent inner bamboo (TIB) and transparent heat-treated inner bamboo (THIB) could reach about 11%, and the transmittance of transparent outer bamboo (TOB) and transparent heat-treated outer bamboo (THOB) was about 2%. The light transmittance had been significantly improved when compared with the original bamboo samples. The transmittances of the TB samples before and after heat treatment in different parts of bamboo were different. In the visible light irradiation range, the light transmittances of TB samples were as follows: TIB > THIB and THOB > TOB. Meanwhile, the tensile strength of TB was reduced, especially for TOB and THOB. In addition, TB has a wide range of raw materials, and the preparation process is environmentally friendly. It can be used for decorative materials in homes, buildings, etc., and has a great application potential. [ABSTRACT FROM AUTHOR]

Chemical looping reforming of methane (CLRM) technology is a new approach for syngas and pure hydrogen generation. During the whole reaction, methane is first partially oxidized to syngas by the lattice oxygen of the oxygen carrier, and then the lattice oxygen of the reduced oxygen carrier is recovered by thermal water splitting, with pure hydrogen produced. LaMnO 3 is used as an oxygen carrier for the CLRM. It obtains a high resistance to carbon deposition, while a lower CH 4 conversion due to the unstable structure. Fe ion substitution in LaMnO 3 can be used to improve its reactivity and thermal stability. La 1-x MnFe x O 3 /LaMn 1-x Fe x O 3 (x = 0.05, 0.1, 0.15, 0.2) oxygen carriers own higher reactivity and better resistance to carbon deposition, producing high purity syngas and hydrogen. La 0.85 MnFe 0.15 O 3 sample exhibits the highest CO selectivity (~99%), syngas productivity (3.78 mmol g−1) and H 2 productivity (1.76 mmol g−1) due to the higher oxygen vacancy concentration, and its H 2 /CO molar ratio is maintained at the ideal ratio of 2.0 (1.93–2.07) during the whole process. Notably, no carbon deposition is generated over LaMnO 3 , La 0.85 MnFe 0.15 O 3 and LaMn 0.9 Fe 0.1 O 3 oxygen carriers even after 20 redox cycles, and La 0.85 MnFe 0.15 O 3 exhibits superior resistance to carbon deposition due to the better structural and thermal stability. Image 1 • The doping of Fe to LaMnO 3 promotes the production of syngas and pure hydrogen. • La–Mn–Fe–O oxygen carriers possess higher reactivity and ideal H 2 /CO molar ratio. • La 0.85 MnFe 0.15 O 3 exhibits the optimal performance during 20 redox cycles. [ABSTRACT FROM AUTHOR]

Research has explored the effects of illuminance and correlated color temperature (CCT) of indoor lighting on visual performance, mood and physiological parameters of the elderly. Yet, these investigations did not render a consistent finding on visual and non-visual effects of lighting from a holistic perspective. The present study systemically explored the comprehensive effects of illuminance (300 lx, 500 lx, 750 lx, 1000 lx and 1500 lx) and CCT (3000 K, 5000 K and 6500 K) on electrocardiogram (ECG), visual performance and subjective mood of the elderly. The findings revealed that the ECG indicators of the elderly did not change significantly under most lighting conditions though the heart rate was more sensitive to light than waveform time. In addition, an increase in CCT elicited statistically significant benefits on task performance, however, participants' task performance was not significantly enhanced with the increase of illuminance, and the light of 750 lx seemed to be the most unfavorable for the visual task of the elderly. Furthermore, the participants' subjective appraisals were inclined to be positive and satisfactory and were not significantly different between different lighting conditions. The results of this study showed that short duration (i.e. 20 min) of light exposure had little effect on the physiological rhythm of the elderly, but it did affect the visual performance and psychological feelings of the elderly. Therefore, in the places where the elderly stay for a short time, the first consideration of lighting design should be to meet the visual and psychological needs of the elderly. [ABSTRACT FROM AUTHOR]

As the demand for Internet services continues to rise, large-scale Internet companies have expanded their data center infrastructure across multiple global regions. The inherent spatial-temporal flexibility in scheduling workloads allows data center clusters to dynamically adjust their power consumption without overloading the transmission network. In this work, we introduce a novel approach for treating a geo-distributed data center cluster as a non-wire alternative resource and explore its potential role in the energy balancing market. Our methodology manages a geographically distributed data center cluster as a balance-responsible entity by employing optimal workload scheduling that considers its inherent spatial-temporal flexibility and market arbitrage opportunities. To achieve this, we develop a two-layer stochastic receding horizon control optimization algorithm to formulate a strategic bidding strategy for the data center cluster. To validate the effectiveness of our proposed approach, we conduct numerical experiments using real-world data center production traces and data from the Nordic balancing market, demonstrating its practical applicability and performance. • Explored spatial-temporal flexibility of data center cluster as non-wire alternative. • Applied a two-layer SRHC algorithm for online biddings and workload schedules. • Applied real-world data traces to illustrate the effectiveness and accuracy. • Real-world data showed the scheme's impact on cost reduction in balancing markets. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to develop machine learning (ML) models based on diffusion- and perfusion-weighted imaging fusion (DP fusion) for identifying stroke within 4.5 h, to compare them with DWI- and/or PWI-based ML models, and to construct an automatic segmentation-classification model and compare with manual labeling methods.ML models were developed from multimodal MRI datasets of acute stroke patients within 24 h of clear symptom onset from two centers. The processes included manual segmentation, registration, DP fusion, feature extraction, and model establishment (logistic regression (LR) and support vector machine (SVM)). A segmentation-classification model (X-Net) was proposed for automatically identifying stroke within 4.5 h. The area under the receiver operating characteristic curve (AUC), sensitivity, Dice coefficients, decision curve analysis, and calibration curves were used to evaluate model performance.A total of 418 patients (≤ 4.5 h: 214; > 4.5 h: 204) were evaluated. The DP fusion model achieved the highest AUC in identifying the onset time in the training (LR: 0.95; SVM: 0.92) and test sets (LR: 0.91; SVM: 0.90). The DP fusion-LR model displayed consistent positive and greater net benefits than other models across a broad range of risk thresholds. The calibration curve demonstrated the good calibration of the DP fusion-LR model (average absolute error: 0.049). The X-Net model obtained the highest Dice coefficients (DWI: 0.81; Tmax: 0.83) and achieved similar performance to manual labeling (AUC: 0.84).The automatic segmentation-classification models based on DWI and PWI fusion images had high performance in identifying stroke within 4.5 h.Perfusion-weighted imaging (PWI) fusion images had high performance in identifying stroke within 4.5 h. The automatic segmentation-classification models based on DWI and PWI fusion images could provide clinicians with decision-making guidance for acute stroke patients with unknown onset time.• The diffusion/perfusion-weighted imaging fusion model had the best performance in identifying stroke within 4.5 h.• The X-Net model had the highest Dice and achieved performance close to manual labeling in segmenting lesions of acute stroke.• The automatic segmentation-classification model based on DP fusion images performed well in identifying stroke within 4.5 h.Methods: We aimed to develop machine learning (ML) models based on diffusion- and perfusion-weighted imaging fusion (DP fusion) for identifying stroke within 4.5 h, to compare them with DWI- and/or PWI-based ML models, and to construct an automatic segmentation-classification model and compare with manual labeling methods.ML models were developed from multimodal MRI datasets of acute stroke patients within 24 h of clear symptom onset from two centers. The processes included manual segmentation, registration, DP fusion, feature extraction, and model establishment (logistic regression (LR) and support vector machine (SVM)). A segmentation-classification model (X-Net) was proposed for automatically identifying stroke within 4.5 h. The area under the receiver operating characteristic curve (AUC), sensitivity, Dice coefficients, decision curve analysis, and calibration curves were used to evaluate model performance.A total of 418 patients (≤ 4.5 h: 214; > 4.5 h: 204) were evaluated. The DP fusion model achieved the highest AUC in identifying the onset time in the training (LR: 0.95; SVM: 0.92) and test sets (LR: 0.91; SVM: 0.90). The DP fusion-LR model displayed consistent positive and greater net benefits than other models across a broad range of risk thresholds. The calibration curve demonstrated the good calibration of the DP fusion-LR model (average absolute error: 0.049). The X-Net model obtained the highest Dice coefficients (DWI: 0.81; Tmax: 0.83) and achieved similar performance to manual labeling (AUC: 0.84).The automatic segmentation-classification models based on DWI and PWI fusion images had high performance in identifying stroke within 4.5 h.Perfusion-weighted imaging (PWI) fusion images had high performance in identifying stroke within 4.5 h. The automatic segmentation-classification models based on DWI and PWI fusion images could provide clinicians with decision-making guidance for acute stroke patients with unknown onset time.• The diffusion/perfusion-weighted imaging fusion model had the best performance in identifying stroke within 4.5 h.• The X-Net model had the highest Dice and achieved performance close to manual labeling in segmenting lesions of acute stroke.• The automatic segmentation-classification model based on DP fusion images performed well in identifying stroke within 4.5 h.Results: We aimed to develop machine learning (ML) models based on diffusion- and perfusion-weighted imaging fusion (DP fusion) for identifying stroke within 4.5 h, to compare them with DWI- and/or PWI-based ML models, and to construct an automatic segmentation-classification model and compare with manual labeling methods.ML models were developed from multimodal MRI datasets of acute stroke patients within 24 h of clear symptom onset from two centers. The processes included manual segmentation, registration, DP fusion, feature extraction, and model establishment (logistic regression (LR) and support vector machine (SVM)). A segmentation-classification model (X-Net) was proposed for automatically identifying stroke within 4.5 h. The area under the receiver operating characteristic curve (AUC), sensitivity, Dice coefficients, decision curve analysis, and calibration curves were used to evaluate model performance.A total of 418 patients (≤ 4.5 h: 214; > 4.5 h: 204) were evaluated. The DP fusion model achieved the highest AUC in identifying the onset time in the training (LR: 0.95; SVM: 0.92) and test sets (LR: 0.91; SVM: 0.90). The DP fusion-LR model displayed consistent positive and greater net benefits than other models across a broad range of risk thresholds. The calibration curve demonstrated the good calibration of the DP fusion-LR model (average absolute error: 0.049). The X-Net model obtained the highest Dice coefficients (DWI: 0.81; Tmax: 0.83) and achieved similar performance to manual labeling (AUC: 0.84).The automatic segmentation-classification models based on DWI and PWI fusion images had high performance in identifying stroke within 4.5 h.Perfusion-weighted imaging (PWI) fusion images had high performance in identifying stroke within 4.5 h. The automatic segmentation-classification models based on DWI and PWI fusion images could provide clinicians with decision-making guidance for acute stroke patients with unknown onset time.• The diffusion/perfusion-weighted imaging fusion model had the best performance in identifying stroke within 4.5 h.• The X-Net model had the highest Dice and achieved performance close to manual labeling in segmenting lesions of acute stroke.• The automatic segmentation-classification model based on DP fusion images performed well in identifying stroke within 4.5 h.Conclusions: We aimed to develop machine learning (ML) models based on diffusion- and perfusion-weighted imaging fusion (DP fusion) for identifying stroke within 4.5 h, to compare them with DWI- and/or PWI-based ML models, and to construct an automatic segmentation-classification model and compare with manual labeling methods.ML models were developed from multimodal MRI datasets of acute stroke patients within 24 h of clear symptom onset from two centers. The processes included manual segmentation, registration, DP fusion, feature extraction, and model establishment (logistic regression (LR) and support vector machine (SVM)). A segmentation-classification model (X-Net) was proposed for automatically identifying stroke within 4.5 h. The area under the receiver operating characteristic curve (AUC), sensitivity, Dice coefficients, decision curve analysis, and calibration curves were used to evaluate model performance.A total of 418 patients (≤ 4.5 h: 214; > 4.5 h: 204) were evaluated. The DP fusion model achieved the highest AUC in identifying the onset time in the training (LR: 0.95; SVM: 0.92) and test sets (LR: 0.91; SVM: 0.90). The DP fusion-LR model displayed consistent positive and greater net benefits than other models across a broad range of risk thresholds. The calibration curve demonstrated the good calibration of the DP fusion-LR model (average absolute error: 0.049). The X-Net model obtained the highest Dice coefficients (DWI: 0.81; Tmax: 0.83) and achieved similar performance to manual labeling (AUC: 0.84).The automatic segmentation-classification models based on DWI and PWI fusion images had high performance in identifying stroke within 4.5 h.Perfusion-weighted imaging (PWI) fusion images had high performance in identifying stroke within 4.5 h. The automatic segmentation-classification models based on DWI and PWI fusion images could provide clinicians with decision-making guidance for acute stroke patients with unknown onset time.• The diffusion/perfusion-weighted imaging fusion model had the best performance in identifying stroke within 4.5 h.• The X-Net model had the highest Dice and achieved performance close to manual labeling in segmenting lesions of acute stroke.• The automatic segmentation-classification model based on DP fusion images performed well in identifying stroke within 4.5 h.Clinical relevance statement: We aimed to develop machine learning (ML) models based on diffusion- and perfusion-weighted imaging fusion (DP fusion) for identifying stroke within 4.5 h, to compare them with DWI- and/or PWI-based ML models, and to construct an automatic segmentation-classification model and compare with manual labeling methods.ML models were developed from multimodal MRI datasets of acute stroke patients within 24 h of clear symptom onset from two centers. The processes included manual segmentation, registration, DP fusion, feature extraction, and model establishment (logistic regression (LR) and support vector machine (SVM)). A segmentation-classification model (X-Net) was proposed for automatically identifying stroke within 4.5 h. The area under the receiver operating characteristic curve (AUC), sensitivity, Dice coefficients, decision curve analysis, and calibration curves were used to evaluate model performance.A total of 418 patients (≤ 4.5 h: 214; > 4.5 h: 204) were evaluated. The DP fusion model achieved the highest AUC in identifying the onset time in the training (LR: 0.95; SVM: 0.92) and test sets (LR: 0.91; SVM: 0.90). The DP fusion-LR model displayed consistent positive and greater net benefits than other models across a broad range of risk thresholds. The calibration curve demonstrated the good calibration of the DP fusion-LR model (average absolute error: 0.049). The X-Net model obtained the highest Dice coefficients (DWI: 0.81; Tmax: 0.83) and achieved similar performance to manual labeling (AUC: 0.84).The automatic segmentation-classification models based on DWI and PWI fusion images had high performance in identifying stroke within 4.5 h.Perfusion-weighted imaging (PWI) fusion images had high performance in identifying stroke within 4.5 h. The automatic segmentation-classification models based on DWI and PWI fusion images could provide clinicians with decision-making guidance for acute stroke patients with unknown onset time.• The diffusion/perfusion-weighted imaging fusion model had the best performance in identifying stroke within 4.5 h.• The X-Net model had the highest Dice and achieved performance close to manual labeling in segmenting lesions of acute stroke.• The automatic segmentation-classification model based on DP fusion images performed well in identifying stroke within 4.5 h.Key Points: We aimed to develop machine learning (ML) models based on diffusion- and perfusion-weighted imaging fusion (DP fusion) for identifying stroke within 4.5 h, to compare them with DWI- and/or PWI-based ML models, and to construct an automatic segmentation-classification model and compare with manual labeling methods.ML models were developed from multimodal MRI datasets of acute stroke patients within 24 h of clear symptom onset from two centers. The processes included manual segmentation, registration, DP fusion, feature extraction, and model establishment (logistic regression (LR) and support vector machine (SVM)). A segmentation-classification model (X-Net) was proposed for automatically identifying stroke within 4.5 h. The area under the receiver operating characteristic curve (AUC), sensitivity, Dice coefficients, decision curve analysis, and calibration curves were used to evaluate model performance.A total of 418 patients (≤ 4.5 h: 214; > 4.5 h: 204) were evaluated. The DP fusion model achieved the highest AUC in identifying the onset time in the training (LR: 0.95; SVM: 0.92) and test sets (LR: 0.91; SVM: 0.90). The DP fusion-LR model displayed consistent positive and greater net benefits than other models across a broad range of risk thresholds. The calibration curve demonstrated the good calibration of the DP fusion-LR model (average absolute error: 0.049). The X-Net model obtained the highest Dice coefficients (DWI: 0.81; Tmax: 0.83) and achieved similar performance to manual labeling (AUC: 0.84).The automatic segmentation-classification models based on DWI and PWI fusion images had high performance in identifying stroke within 4.5 h.Perfusion-weighted imaging (PWI) fusion images had high performance in identifying stroke within 4.5 h. The automatic segmentation-classification models based on DWI and PWI fusion images could provide clinicians with decision-making guidance for acute stroke patients with unknown onset time.• The diffusion/perfusion-weighted imaging fusion model had the best performance in identifying stroke within 4.5 h.• The X-Net model had the highest Dice and achieved performance close to manual labeling in segmenting lesions of acute stroke.• The automatic segmentation-classification model based on DP fusion images performed well in identifying stroke within 4.5 h. [ABSTRACT FROM AUTHOR]

Aging in humans is associated with abdominal distribution and remodeling of body fat and a parallel gradual increase in the prevalence of metabolic diseases such as obesity, type 2 diabetes mellitus and fatty liver disease, as well as the risk of developing metabolic complications. Current treatments might be improved by understanding the detailed mechanisms underlying the onset of age-related metabolic disorders. Neddylation, a post-translational modification that adds the ubiquitin-like protein NEDD8 to substrate proteins, has recently been linked to age-related metabolic diseases, opening new avenues of investigation and raising a potential target for treatment of these diseases. In this review, we will focus on the potential role of NEDD8-mediated neddylation in age-related metabolic dysregulation, insulin resistance, obesity, type 2 diabetes mellitus and fatty liver. We propose that alterations in NEDD8-mediated neddylation contribute to triggering insulin resistance and the development of age-related metabolic dysregulation, thus highlighting NEDD8 as a promising therapeutic target for preventing age-related metabolic diseases. • The elevation of NEDD8-mediated neddylation plays a critical role in the development of age-associated metabolic diseases. • NEDD8-mediated neddylation increases macrophage inflammation and adipogenesis and inhibits the browning of adipose tissue. • NEDD8-mediated neddylation increases hepatic gluconeogenesis, steatosis and fibrosis. [ABSTRACT FROM AUTHOR]

Tikhonov regularization, or truncated singular value decomposition (TSVD), is usually used for dynamic light scattering (DLS) inversion of particles in suspension. The Tikhonov regularization method uses a regularization matrix to modify all singular values in the kernel matrix. The modification of large singular values cannot effectively reduce the variance of the estimated values but may introduce bias in the solution, resulting in poor disturbance resistance in the inversion results. The TSVD method, on the other hand, truncates all small singular values, which leads to the loss of particle size information during the inversion process. The shortcomings of the two methods mentioned above do not have a significant impact on the inversion of high signal-to-noise ratio data. However, compared to the classical DLS particle size inversion for non-flowing suspended particles, the DLS inversion of flowing aerosols is more significantly affected by noise, and the extraction of particle size information is more difficult due to the effect of flow velocity, resulting in worse inversion results with increasing aerosol flow velocity for both methods. To improve the accuracy of the particle size distribution (PSD) of flowing aerosols, we introduced a kernel matrix into the regularization matrix, and based on the principles of the two methods, the spectral information of the kernel matrix was utilized to make the modification of small singular values by the regularization matrix. Correspondingly, weak or no modification was made according to the values of large singular values to reduce the introduction of bias. The inversion results of simulated and measured data indicate that the reconstruction of the regularization matrix improves the anti-disturbance performance and avoids the loss of particle size information during the regularization inversion process, thereby significantly improving the PSD accuracy, which is affected by the dual effects of flow velocity and noise in the DLS measurement of flowing particles. The peak error and distribution error of the inversion results by reconstructing the regularization matrix are lower than those of Tikhonov regularization. [ABSTRACT FROM AUTHOR]

Introduction: We present a new surgical technique of Krackow suture combined with vertical Nice knot for the treatment of inferior patellar fractures and report the clinical results. Patients and Methods: Seventeen consecutive patients admitted with inferior patellar fractures over a 2-year period from June 2019 to February 2022 were prospectively enrolled. The AO classification was 34-A1. All patients underwent open reduction and fixation with Krackow sutures in combination with vertical Nice knot. Postoperative follow-up was performed for at least 1 year to evaluate knee function. Results: The mean age of seventeen patients was 53.2 ± 9.5 years (39–68 years), and all patients were followed up for more than 12 months. The operation time was 54.6 ± 7.7 min (42–68 min). No patients had nonunion, joint stiffness, and joint pain. All cases achieved bony union at an average of 9.9 ± 1.5 weeks (8–13 weeks) after surgery. At the last follow-up, there was no significant difference in range of motion between the injured knee (129.7 ± 3.3°, range 125–135°) and the unaffected knee (130.8 ± 3.8°, range 126–137°) (t = 0.28, P > 0.05). The mean Bostman score of the knee joint was 29.6 ± 0.7, including 15 excellent cases (88.2%) and two good case (11.8%). Conclusion: Krackow sutures combined with vertical Nice knots are stable and reliable in the treatment of inferior patellar fractures. Knee rehabilitation can be performed immediately after surgery and satisfactory knee function can be achieved. It is a safe, simple, and reliable alternative surgical method, and patients do not need to bear the secondary surgical injury of removing the internal fixation material. Therefore, it is suitable for the application of clinical promotion. [ABSTRACT FROM AUTHOR]

Metal‐organic frameworks provide versatile templates for the fabrication of various metal/carbon materials, but most of the derived composites possess only microspores, limiting the accessibility of embedded active sites. Herein, we report the construction of cobalt/nitrogen‐doped carbon composites with a three‐dimensional (3D) ordered macroporous and hollow‐wall structure (H‐3DOM‐Co/NC) using a single‐crystal ordered macropore (SOM)‐ZIF‐8@ZIF‐67 as precursor. During the pyrolysis, the interconnected macroporous structure of SOM‐ZIF‐8@ZIF‐67 is mostly preserved, whereas the pore wall achieves a solid‐to‐hollow transformation with Co nanoparticles formed in the hollow walls. The 3D‐ordered macroporous carbon skeleton may effectively promote long‐range mass transfer and the hollow wall can facilitate local accessibility of active sites. This unique structure can greatly boost its catalytic activity in the selective hydrogenation of biomass‐derived furfural to cyclopentanol, much superior to its counterparts without this well‐designed hierarchically porous structure. [ABSTRACT FROM AUTHOR]

Metal‐organic frameworks provide versatile templates for the fabrication of various metal/carbon materials, but most of the derived composites possess only microspores, limiting the accessibility of embedded active sites. Herein, we report the construction of cobalt/nitrogen‐doped carbon composites with a three‐dimensional (3D) ordered macroporous and hollow‐wall structure (H‐3DOM‐Co/NC) using a single‐crystal ordered macropore (SOM)‐ZIF‐8@ZIF‐67 as precursor. During the pyrolysis, the interconnected macroporous structure of SOM‐ZIF‐8@ZIF‐67 is mostly preserved, whereas the pore wall achieves a solid‐to‐hollow transformation with Co nanoparticles formed in the hollow walls. The 3D‐ordered macroporous carbon skeleton may effectively promote long‐range mass transfer and the hollow wall can facilitate local accessibility of active sites. This unique structure can greatly boost its catalytic activity in the selective hydrogenation of biomass‐derived furfural to cyclopentanol, much superior to its counterparts without this well‐designed hierarchically porous structure. [ABSTRACT FROM AUTHOR]

Drought is an important abiotic stress that seriously restricts crop productivity. An understanding of drought tolerance mechanisms offers guidance for cultivar improvement. In order to understand how a well-known wheat genotype Jinmai 47 responds to drought, we adopted the iTRAQ and LC/MS approaches and conducted proteomics analysis of leaves after exposure to 20% of polyethylene glycol-6000 (PEG)-induced stress for 4 days. The study identified 176 differentially expressed proteins (DEPs), with 65 (36.5%) of them being up-regulated, and 111 (63.5%) down-regulated. DEPs, located in cellular membranes and cytosol mainly, were involved in stress and redox regulation (51), carbohydrate and energy metabolism (36), amino acid metabolism (24), and biosynthesis of other secondary metabolites (20) primarily. Under drought stress, TCA cycle related proteins were up-regulated. Antioxidant system, signaling system, and nucleic acid metabolism etc. were relatively weakened. In comparison, the metabolism pathways that function in plasma dehydration protection and protein structure protection were strongly enhanced, as indicated by the improved biosynthesis of 2 osmolytes, sucrose and Proline, and strongly up-regulated protective proteins, LEA proteins and chaperones. SUS4, P5CSs, OAT, Rab protein, and Lea14-A were considered to be important candidate proteins, which deserve to be further investigated. [ABSTRACT FROM AUTHOR]

Objectives: Globular domain isotype adiponectin (gAPN) exerts cardioprotective effect against cardiac ischemia injury. It is known that adiponectin-mediated cardioprotection is dependent upon the T-Cadherin (TCad) and adiponectin receptors. However, whether these receptors mediate the cardioprotective effects of gAPN, the isotype with more potent biological activity, most commonly utilized in metabolic/cardiovascular investigations, remains unclear. Methods and Results: Adult male WT, AdipoR1KO, and TCadKO mice were subjected to MI, treated with vehicle or gAPN, and observed for 4 weeks. Knockout of AdipoR1, but not Tcad, abolished the cardioprotective effects of gAPN observed in WT mice, indicating that AdipoR1, but not Tcad, mediates gAPN cardioprotection. Unexpectedly, we observed that gAPN cardioprotection was significantly attenuated in animals pre-treated with GW4869 (an exosome generation inhibitor). To further determine whether gAPN regulates exosome biogenesis and/or uptake and the precise involvement of AdipoR1, cardiomyocytes were isolated from adult AdipoR1KO and TCadKO mice. The effects of gAPN and HMW (high molecular weight APN isoform) upon exosome generation and uptake were determined. Surprisingly, cardiomyocyte exosome production increased markedly (8-fold) when cells were treated with gAPN, but not with HMW (at 5-fold dose of gAPN). Moreover, gAPN increases cardiomyocyte exosome production in a receptor-independent fashion, via regulation of the ESCRT-multivesicular body (MVB) pathway. Furthermore, gAPN-stimulated exosome uptake and cellular protection in WT cardiomyocytes was abolished in cardiomyocytes derived from AdipoR1KO, but not TCadKO, mice. Conclusions: These data demonstrate that gAPN and HMW cardioprotection exhibits differential receptor dependence, and is mediated by distinct mechanisms. Whereas HMW protects the heart via TCad-dependent mechanisms, gAPN promotes exosome biogenesis in a receptor-independent fashion, and stimulating exosome uptake and cardioprotection in an AdipoR1-dependent manner. Our results suggest gAPN is superior to HMW with respect to cardioprotection against ischemia heart injury, and represents a promising therapeutic strategy in patients with coronary artery disease. [ABSTRACT FROM AUTHOR]

[Display omitted] • A mathematics-based method was developed to determine the boundaries of thermal effects. • Microwave non-thermal effects was differentiated from thermal effects that occur simultaneously. • Microwave non-thermal effects on 22 amino acids were determined. • Sterilization was carried out using a low frequency (896 MHz) microwave processing system. The aim of this study was to investigate the impact of microwave non-thermal effects on thermal sensitive amino acids in rainbow trout (Oncorhynchus mykiss) fillets. To distinguish non-thermal effects from thermal effects occurring simultaneously, a Double Side Approximating Method (DSAM) derived from computational mathematics was developed. Two corresponding water bath treatments were designed for each microwave processing to approximate the time–temperature profiles at the hot and cold spots of the microwave processed samples while maintaining a comparable thermal intensity (F 0). The microwave non-thermal effects on amino acids were determined by comparing the amount of each of 22 amino acids between the microwave processed and the two corresponding water bath treated rainbow trout fillets. The results indicated that the DSAM was successfully implemented, as the amino acid contents' order curve in the microwave processed samples was clearly exceeded the boundary formed by the two corresponding water bath treated samples. This finding confirmed the occurrence of microwave non-thermal effects on amino acids. The non-thermal effect resulted in a notable increase in the quantity of most amino acids, while it reduced the content of Lys and Hyp. Longer microwave processing times intensified these effects, while higher thermal processing intensities resulted in more damage to each amino acid. [ABSTRACT FROM AUTHOR]

Poly(ADP-ribose) polymerase 1 (PARP1) inhibitors can selectively kill homologous recombination (HR) deficient cancer cells and elicit anticancer effect through a mechanism of synthetic lethality. In this study, we designed, synthesized and pharmacologically evaluated a series of [1,2,4]triazolo[4,3- a ]pyrazine derivatives as a class of potent PARP1 inhibitors. Among them, compounds 17m , 19a , 19c , 19e , 19i and 19k not only displayed more potent inhibitory activities (IC 50 s < 4.1 nM) than 9 and 1 against PARP1, but also exhibited nanomolar range of antiproliferative effects against MDA-MB-436 (BRCA1−/−, IC 50 s < 1.9 nM) and Capan-1 (BRCA2−/−, IC 50 s < 21.6 nM) cells. Notably, 19k significantly inhibited proliferation of resistant Capan-1 cells (IC 50 s < 0.3 nM). Collectively, the newly discovered PARP1 inhibitors act as a useful pharmacological tool for investigating the mechanism of acquired resistance to PARP1 inhibitors, and may also represent promising therapeutic agents for the treatment of HR deficient cancers with the potential to overcome the acquired resistance. [Display omitted] • Several series of [1,2,4]triazolo[4,3-a]pyrazine derivatives have been designed and synthesized. • 17m, 19a, 19i and 19k are identified as potent and novel PARP1 inhibitors. • 19k exhibited potent antiproliferative effects against BRCA-mutated cells. • 19k showed promising antiproliferative efficacy against PARP1 inhibitor-resistant cells. [ABSTRACT FROM AUTHOR]

[Display omitted] • A mathematics-based method was developed to determine the boundaries of thermal effects. • Microwave non-thermal effects was differentiated from thermal effects that occur simultaneously. • Microwave non-thermal effects on 22 amino acids were determined. • Sterilization was carried out using a low frequency (896 MHz) microwave processing system. The aim of this study was to investigate the impact of microwave non-thermal effects on thermal sensitive amino acids in rainbow trout (Oncorhynchus mykiss) fillets. To distinguish non-thermal effects from thermal effects occurring simultaneously, a Double Side Approximating Method (DSAM) derived from computational mathematics was developed. Two corresponding water bath treatments were designed for each microwave processing to approximate the time–temperature profiles at the hot and cold spots of the microwave processed samples while maintaining a comparable thermal intensity (F 0). The microwave non-thermal effects on amino acids were determined by comparing the amount of each of 22 amino acids between the microwave processed and the two corresponding water bath treated rainbow trout fillets. The results indicated that the DSAM was successfully implemented, as the amino acid contents' order curve in the microwave processed samples was clearly exceeded the boundary formed by the two corresponding water bath treated samples. This finding confirmed the occurrence of microwave non-thermal effects on amino acids. The non-thermal effect resulted in a notable increase in the quantity of most amino acids, while it reduced the content of Lys and Hyp. Longer microwave processing times intensified these effects, while higher thermal processing intensities resulted in more damage to each amino acid. [ABSTRACT FROM AUTHOR]

The impedance matching is a very important part to influence materials' microwave absorption performance. However, a way to further discuss the impedance matching is still weak. We build a novel dielectric–magnetic impedance matching (DMIM) model to analyze the real part and imaginary part of materials' impedance matching. To verify the practicality of the DMIM model, using MIL-100(Fe) as precursor, a series of FexNi1−x@C are synthesized via one-step pyrolysis by controlling the samples' Fe–Ni ratio, changing their dielectric loss tangent and magnetic loss tangent and successfully regulating their impedance matching to optimize microwave absorption properties. In addition, the minimum reflection loss for MOF-derived Fe0.8Ni0.2@C can arrive at -71.3 dB at 10.3 GHz with a thickness of 3.1 mm, and the effective absorption bandwidth is 5.3 GHz. And combining with the RLGC equivalent circuit model to further indicate the FexNi1−x@C's energy loss mechanism. The method of using DMIM model and RLGC model to discuss materials' impedance matching and energy loss mechanism paves a new way to fabricate high-performance microwave materials with balanced electromagnetic distribution and further reveal the materials' microwave absorbing mechanism. [ABSTRACT FROM AUTHOR]

LSD1 (KDM1A), a histone demethylase, plays important roles in breast cancer. The breast cancer patients with LSD1 mutation show significantly worse outcomes compared to those without LSD1 mutation. The R251Q mutation of LSD1 increases the invasion and migration of luminal breast cancer cells. Furthermore, the R251Q mutation of LSD1 alters the expression of genes that modulates the epithelial to mesenchymal transition. Additionally, the R251Q mutation impairs the H3K4me2 demethylation activity of LSD1 by abolishing the interaction between LSD1 and CoREST, which leads to the increased expression of TRIM37, a histone H2A ubiquitin ligase that regulates the expression of E-cadherin. Collectively, our results suggest that the R251Q mutation abolishes the tumor suppressive effects of LSD1 on luminal breast cancer cells by disrupting the formation of functional LSD1/CoREST/HDAC complexes. • The R251Q mutation of LSD1 is identified from TCGA Breast Invasive Carcinoma Dataset. • The R251Q mutation abolishes the suppression of LSD1 on the migration and invasion of luminal breast cancer cells. • The R251Q mutation of LSD1 causes the upregulation of TRIM37. • The R251Q mutation abolishes the interaction between LSD1 and CoREST. [ABSTRACT FROM AUTHOR]

Sluggish water dissociation step severely constraints the efficiency of alkaline hydrogen evolution reaction (HER). Inspired by the merits of the favorable water dissociation ability of Ni(OH)2 and moderate hydrogen bonding strength on NiMo alloy, in this paper, NiMo/Ni(OH)2 nanohybrid on carbon cloth (CC) was synthesized by hydrothermal method and subsequent electrodeposition technique. XRD, SEM and XPS confirmed NiMo alloy was electrodeposited on Ni(OH)2 nanosheet surface. Alkaline HER measurement unveiled that NiMo/Ni(OH)2/CC exhibited the highest alkaline HER performance with overpotential of 132 mV at 10 mA/cm2 among as‐prepared samples, Tafel slope and EIS spectra verified the HER kinetics and the water dissociation rate were enhanced after embedding NiMo alloy into Ni(OH)2 nanosheets. The outstanding alkaline HER performance can be assigned to the coupling effect between NiMo alloy and Ni(OH)2, and Ni alloying with Mo. The preeminent HER performance and facile preparation method of NiMo/Ni(OH)2/CC endow it with prospect application in alkaline water splitting. [ABSTRACT FROM AUTHOR]

With the rapidly increased penetration of renewable generations, the incentive-based demand-side management (DSM) shows great value in alleviating the uncertainty and providing flexibility for a microgrid. However, how to price those demand resources becomes one of the most significant challenges for promoting the incentive-based DSM under microgrid environments. In this article, a flexible demand resource pricing scheme is proposed. Instead of using the utility function of end-users like most existing literature, the economic benefit of the flexible demand resources is evaluated by the operation performance enhancement of the microgrid, and correspondingly, the resource is priced based on a benefit-sharing approach. An iteration-based chance-constrained method is established to calculate the economic benefit and shared compensation for the demand resource providers. Meanwhile, the financial risks for the microgrid operator due to uncertain factors are mitigated by the chance-constrained criterion. The proposed scheme is examined by an experimental microgrid to illustrate its effectiveness. [ABSTRACT FROM AUTHOR]

• The skin dynamics development of two pear cultivars and their mutants were analyzed. • The key genes and metabolites involved in russet skin formation were identified. • A set of TFs was predicted as putative regulators of russet skin formation. • We emphasis on exploring the underlying mechanisms of russet pear skin formation. Different periderm development makes the partial and full russet skin of pear fruit, which negatively influence pear fruit appearance quality. The switch gene for russet skin formation and the functional conservation of the homologs among different species showed to have multiple significance to clarify the transcriptional network underlying russet skin formation. In this study, two pear cultivars coupled with their mutants were used to explore the underlying molecular regulatory network of russet skin formation. RNA-sequencing and metabolomics were used to identify the key pathways and switch genes involved in russet skin formation, and identified genes involved in lignin biosynthesis, suberin biosynthesis, and suberin transporters. Additionally, a set of transcription factors was identified via coexpression network analysis and differential expression analysis, including PbMYB308, PbbHLH49, PbWRKY24 , and PbNAC40 , which had a high correlation with russet skin-related genes. These genes were predicted as putative regulators involved in russet pear skin formation. qRT–PCR was performed to validate the transcriptome data. Two varieties and their mutants were used for the first time to explore the switch genes and underlying mechanisms of russet formation. We concentrated on the russet skin development in pear fruit, with an emphasis on exploring the underlying regulatory mechanisms. [ABSTRACT FROM AUTHOR]

Highly reversible sodium metal anodes are still regarded as a stubborn hurdle in ester‐based electrolytes due to the issue of uncontrollable dendrites and incredibly unstable interphase. Evidently, a strong protective film on sodium is decisive, while the quality of the protective film is mainly determined by its components. However, it is challenging to actively adjust the expected components. This work can regulate the solid electrolyte interphase (SEI) components by introducing a functional electrolyte additive (2‐chloro‐1,3‐dimethylimidazoline hexafluorophosphate (CDIH, namely CDI++PF6−)) into FEC/PC ester‐based electrolyte. Specifically, the chloride element in the CDI+ can easily react to form a NaF/NaCl‐rich SEI together with the decomposition products of FEC; then the CDI+ without chlorine as a gripper to capture the organic–molecule intermediates generated during FEC decomposition to greatly reduce the content of unstable organic components in SEI, which can be confirmed by molecular dynamic simulation and experiment. Eventually, a highly reversible Na deposition behavior can be delivered. As expected, under the action of CDIH additives, the Na||Na symmetrical cell performs an excellent long‐term cycling (>800 h, 0.5 mA cm−2–0.5 mAh cm−2) and rate performance (0.5–4 mA cm−2). Furthermore, the Na||PB full cell exhibits the outstanding electrochemical performance with small polarization. [ABSTRACT FROM AUTHOR]

Simple Summary: Dietary neutral detergent fiber (NDF) is commonly used as an indicator of the fiber content in animal diets, particularly in ruminant nutrition. NDF plays a crucial role in the digestive process of ruminant animals, as it affects feed intake, rumen fermentation, and nutrient utilization. The levels of NDF affect feeding behavior, rumen fermentation, and production performance during the period of peak lactation in dairy cows. To prove it, four Holstein dairy cows were subjected to a feeding experiment with varying NDF levels in their diets. The results indicated that increased NDF levels resulted in reduced dry matter intake, while the time spent eating and ruminating increased. Moreover, higher NDF levels led to increased pH value and acetate concentration, as well as changes in the proportions of certain bacteria in the rumen. Milk yield, protein percentage, and nitrogen efficiency decreased with increasing NDF levels, while milk fat percentage and milk urea nitrogen concentration increased. Notably, diets with 25% and 34% NDF had negative effects on feeding behavior, rumen fermentation, and production performance. However, the diet with 28% NDF was effective in enhancing the production performance compared to the one with 31% NDF. These findings offer a valuable strategy for optimizing the provision of dietary NDF to cattle, thereby enhancing their overall performance. This study investigated the impact of dietary neutral detergent fiber (NDF) levels (25.49%, 28.65%, 31.66%, and 34.65%, respectively) on the feeding behavior, rumen fermentation, cellulolytic bacteria, and production performance of dairy cows during peak lactation. A feeding experiment was conducted using four fistulated Holstein dairy cows (600 ± 25 kg) with days in milk (50 ± 15 days), employing a 4 × 4 Latin square design to assign the cows to four groups. The results demonstrated that increasing NDF levels in the diet had the following effects: (1) A linear decrease in dry matter intake (DMI), NDF intake, and physically effective NDF8.0 (peNDF8.0) intake; a linear increase in the average time spent eating and ruminating, as well as the time spent eating and ruminating per kilogram of dry matter (DM); a quadratic response in the time spent ruminating per kilogram of NDF and peNDF8.0. (2) A linear increase in average pH value, acetate concentration, and the proportions of Fibrobacter succinogenes and Ruminococcus flavefaciens among total bacteria; a linear decrease in ammonia nitrogen (NH3-N) concentration, microbial crude protein (MCP), total volatile fatty acid (TVFA), propionate, butyrate, and lactate. (3) A linear decrease in milk yield, milk protein percentage, and nitrogen efficiency of dairy cows; a linear increase in milk fat percentage and milk urea nitrogen (MUN) concentration. Based on the combined results, it was found that diets with 25% and 34% NDF had detrimental effects on the feeding behavior, rumen fermentation, and production performance of dairy cows. However, the diet with 28% NDF showed superior outcomes in production performance compared to the one with 31% NDF. Therefore, it is strongly recommended to include a diet containing 28% NDF during the critical peak lactation period for dairy cows. [ABSTRACT FROM AUTHOR]

Diabetes enhances myocardial ischemic/reperfusion (MI/R) injury via an incompletely understood mechanism. Adiponectin (APN) is a cardioprotective adipokine suppressed by diabetes. However, how hypoadiponectinemia exacerbates cardiac injury remains incompletely understood. Dysregulation of miRNAs plays a significant role in disease development. However, whether hypoadiponectinemia alters cardiac miRNA profile, contributing to diabetic heart injury, remains unclear. Methods and Results: Wild-type (WT) and APN knockout (APN-KO) mice were subjected to MI/R. A cardiac microRNA profile was determined. Among 23 miRNAs increased in APN-KO mice following MI/R, miR-449b was most significantly upregulated (3.98-fold over WT mice). Administrating miR-449b mimic increased apoptosis, enlarged infarct size, and impaired cardiac function in WT mice. In contrast, anti-miR-449b decreased apoptosis, reduced infarct size, and improved cardiac function in APN-KO mice. Bioinformatic analysis predicted 73 miR-449b targeting genes, and GO analysis revealed oxidative stress as the top pathway regulated by these genes. Venn analysis followed by luciferase assay identified Nrf-1 and Ucp3 as the two most important miR-449b targets. In vivo administration of anti-miR-449b in APN-KO mice attenuated MI/R-stimulated superoxide overproduction. In vitro experiments demonstrated that high glucose/high lipid and simulated ischemia/reperfusion upregulated miR-449b and inhibited Nrf-1 and Ucp3 expression. These pathological effects were attenuated by anti-miR-449b or Nrf-1 overexpression. In a final attempt to validate our finding in a clinically relevant model, high-fat diet (HFD)-induced diabetic mice were subjected to MI/R and treated with anti-miR-449b or APN. Diabetes significantly increased miR-449b expression and downregulated Nrf-1 and Ucp3 expression. Administration of anti-miR-449b or APN preserved cardiac Nrf-1 expression, reduced cardiac oxidative stress, decreased apoptosis and infarct size, and improved cardiac function. Conclusion: We demonstrated for the first time that hypoadiponectinemia upregulates miR-449b and suppresses Nrf-1/Ucp3 expression, promoting oxidative stress and exacerbating MI/R injury in this population. Dysregulated APN/miR-449b/oxidative stress pathway is a potential therapeutic target against diabetic MI/R injury. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Depression is a common mental health problem among veterans, with high mortality. Despite the numerous conducted investigations, the prediction and identification of risk factors for depression are still severely limited. This study used a deep learning algorithm to identify depression in veterans and its factors associated with clinical manifestations. Methods: Our data originated from the National Health and Nutrition Examination Survey (2005–2018). A dataset of 2,546 veterans was identified using deep learning and five traditional machine learning algorithms with 10-fold cross-validation. Model performance was assessed by examining the area under the subject operating characteristic curve (AUC), accuracy, recall, specificity, precision, and F1 score. Results: Deep learning had the highest AUC (0.891, 95%CI 0.869–0.914) and specificity (0.906) in identifying depression in veterans. Further study on depression among veterans of different ages showed that the AUC values for deep learning were 0.929 (95%CI 0.904–0.955) in the middle-aged group and 0.924(95%CI 0.900-0.948) in the older age group. In addition to general health conditions, sleep difficulties, memory impairment, work incapacity, income, BMI, and chronic diseases, factors such as vitamins E and C, and palmitic acid were also identified as important influencing factors. Conclusions: Compared with traditional machine learning methods, deep learning algorithms achieved optimal performance, making it conducive for identifying depression and its risk factors among veterans. [ABSTRACT FROM AUTHOR]

Background: Primary Sjögren's syndrome (pSS) is an autoimmune disease that leads to the destruction of exocrine glands and multisystem lesions. Abnormal proliferation, apoptosis, and differentiation of CD4+ T cells are key factors in the pathogenesis of pSS. Autophagy is one of the important mechanisms to maintain immune homeostasis and function of CD4+ T cells. Human umbilical cord mesenchymal stem cell-derived exosomes (UCMSC-Exos) may simulate the immunoregulation of MSCs while avoiding the risks of MSCs treatment. However, whether UCMSC-Exos can regulate the functions of CD4+ T cells in pSS, and whether the effects via the autophagy pathway remains unclear. Methods: The study analyzed retrospectively the peripheral blood lymphocyte subsets in pSS patients, and explored the relationship between lymphocyte subsets and disease activity. Next, peripheral blood CD4+ T cells were sorted using immunomagnetic beads. The proliferation, apoptosis, differentiation, and inflammatory factors of CD4+ T cells were determined using flow cytometry. Autophagosomes of CD4+ T cells were detected using transmission electron microscopy, autophagy-related proteins and genes were detected using western blotting or RT-qPCR. Results: The study demonstrated that the peripheral blood CD4+ T cells decreased in pSS patients, and negatively correlated with disease activity. UCMSC-Exos inhibited excessive proliferation and apoptosis of CD4+ T cells in pSS patients, blocked them in the G0/G1 phase, inhibited them from entering the S phase, reduced the Th17 cell ratio, elevated the Treg ratio, inhibited IFN-γ, TNF-α, IL-6, IL-17A, and IL-17F secretion, and promoted IL-10 and TGF-β secretion. UCMSC-Exos reduced the elevated autophagy levels in the peripheral blood CD4+ T cells of patients with pSS. Furthermore, UCMSC-Exos regulated CD4+ T cell proliferation and early apoptosis, inhibited Th17 cell differentiation, promoted Treg cell differentiation, and restored the Th17/Treg balance in pSS patients through the autophagy pathway. Conclusions: The study indicated that UCMSC-Exos exerts an immunomodulatory effect on the CD4+ T cells, and maybe as a new treatment for pSS. [ABSTRACT FROM AUTHOR]

Highlights • CoOx@N-doped graphene structure with tunable Co oxidation state was prepared. • Co d-band center can be manipulated by altering Co oxidation state, facilitating ORR. • Electron structure of graphene shell was tuned by inner CoOx. • Core-shell structure prevent CoOx core from etching out, enhancing ORR stability. Abstract Metal@nitrogen-doped carbon core-shell structure, processing both the stability of inner metal species and manipulated electron structure of outer carbons, is regarded as a promising catalysts for oxygen reduction reaction. In the traditional fabrication of such materials, metal ions are reduced into metallic particles, which make it hard to control oxidation state of metals. In this work, we report tunable oxidation state of Co in CoOx@N-doped graphene simply by changing the pyrolysis temperature of Co 3 O 4 /polyaniline. Under high temperature, polyaniline decompose and release various organic gases, which can partially reduce Co 3 O 4 and serve as gaseous precursors for the in-situ growth of graphene in the meantime. The balance of these two reactions is crucial to control the oxidation state of Co. Thus, its catalytic activity towards oxygen reduction reaction can be easily tuned by inner CoOx core with different electron structure. [ABSTRACT FROM AUTHOR]

Background: Previous investigations into the effect of dietary forage on calf performance have been inconsistent, and there is a paucity of information exploring the effect of age on the growth performance and rumination of calves. Eighty-four female Holstein calves (41.5 ± 4.2 kg) were enrolled at birth, a subset of the calves were fed calf starter only (CON, n = 21) while the rest (n = 63) were classified into three treatment groups: the early (EHAY, n = 26, 5.1 ± 0.8 d), the middle (MHAY, n = 21, 7.9 ± 0.8 d) and the late (LHAY, n = 16, 12.1 ± 1.4 d) hay consumers. The short-term effect of the age at first forage consumption (AFF) on calves' feed intake was monitored until d 84. In addition, the long-term effects of AFF on body weight, structural growth and rumination behavior were recorded until d 196. Rumen samples were collected on d 1, 7, 35, 84 and 196 to analyze the rumen fermentation, while fecal samples were collected from d 78 to 84 to estimate digestibility parameters. Results: Treatment had no effect on feed intake. While, the EHAY calves tended to have lower BW and ADG compared to LHAY and CON calves. Several total-tract apparent digestibility parameters and digestible nutrients intake were significantly lower in EHAY calves compared with CON and LHAY calves. Calves in the EHAY group tended to begin ruminating ealier, while CON calves were the latest (12.3 vs. 15.5 days of age). A treatment and time interaction was present for rumination time due to greater rumination in calves consuming hay compared to CON calves in week 10 to 12, the differences in rumination disappeared afterwards, no long-lasting significant differences in the rumination and rumen fermentation parameters were found between treatments. Conclusions: In conclusion, this study showed that hay consumption earlier in life (in the first week, around 5 days of life) could negatively affect the growth of the calf in the short and long term. Compared to consuming hay from the second week (around 12 days of life) or feeding concentrate only without hay, starting to consume hay from the first week could compromise nutrient digestibility and digestible nutrient intake independent of developing rumination behaviour and rumen fermentation. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the effects of the inclusion of whole-plant corn silage (WPCS) in a starter or total mixed ration (TMR) on growth, blood metabolites, ruminal fermentation, and microbial community in preweaning dairy calves. A total of 45 healthy dairy calves were blocked by date of birth and randomly assigned to 1 of 3 treatments: 100% calf starter (CONS), a mix of 85% calf starter and 15% WPCS [dry matter (DM) basis; CSCS], or 100% WPCS-based lactation TMR (CTMR). Pasteurized normal milk was fed to all the animals under the same regimen. The experiment ran from when the calves were 2 d old to weaning at 63 d. Milk and feed intakes were recorded daily. Growth performance data and blood samples were collected on wk 3, 5, 7, and 9 of the experiment. Rumen fluid was sampled at 40 and 60 d. The 3 treatments had different particle size fractions. The CSCS group had greater medium fraction (<19 mm, >8 mm) and particles retained on 8-mm sieves than the other 2 groups, whereas the CTMR group had the greatest long (>19 mm) and fine (<4 mm) fractions and physically effective neutral detergent fiber (NDF) on 8- and 4-mm sieves, but had the smallest short fraction (<8 mm, >4 mm) and particles retained on 4-mm sieves. The 24-h in vitro digestibility of DM, crude protein (CP), NDF, and acid detergent fiber (ADF) were decreased in order by the CONS, CSCS, and CTMR groups. Compared with the CONS group, the digestibility of ether extract (EE) was lower in the CSCS and CTMR groups, whereas the digestibility of starch was similar among treatments. During the experimental period, the DM, CP, and metabolizable energy intakes from milk, solid feed, and total feed were not affected by treatments. The NDF, ADF, and EE intakes and potentially digestible intakes were greater in the CTMR group than in the other 2 groups. With the exception that body barrel was greater for calves fed CSCS, growth parameters and blood metabolites were similar among treatments. Compared with the CSCS group, the CTMR group had greater rumen pH and total volatile fatty acids, propionate, and isovalerate concentrations, but a lower acetate:propionate ratio. The CTMR group had greater relative abundances of some cellulolytic bacteria (Rikenellaceae RC9 gut group, Christensenellaceae R7, Ruminococcaceae NK4A214, Ruminococcaceae UCG, Ruminococcus , and Erysipelotrichaceae UCG) in the rumen, which may be beneficial for the early acquisition of specific adult-associated microorganisms. In summary, a WPCS-based lactation TMR, but not the WPCS-included starter, had the potential to be an alternative starter in preweaning calves without having significant adverse effects. These findings provide theoretical and practical implications for the rational application of TMR in the early life of dairy calves. [ABSTRACT FROM AUTHOR]

Constructing low cost and efficient electrochemical sensors for highly sensitive detection of hydrazine has a great significance in the field of environmental monitoring and protection. Herein, metal–organic framework derived Co3S4 nanosheets grown on Ti mesh (Co3S4/TM) were successfully synthesized by employing a facile anion exchange reaction and hydrothermal vulcanization with Co-MOF as the precursor. The crystalline structure and morphology of as-synthesized samples were characterized by XRD, SEM, Raman, XPS and TEM analysis. It was found that Co3S4 nanosheets were stacked loosely and irregularly on each other to form a three-dimensional (3D) porous structure. The electrochemical sensing performance of Co3S4/TM toward hydrazine was investigated in 0.1 M NaOH solution. The results showed that Co3S4/TM presented a better electrocatalytic activity toward hydrazine oxidation than Co-MOF/TM and Co(OH)2/TM, owing to the high electrical conductivity of Co3S4 for enhancing electron transfer and the 3D porous structure for providing many more accessible active sites and shortening ion diffusion length as well as promoting mass transfer for hydrazine electrooxidation. As a result, Co3S4/TM exhibited a superior analytical performance with a wide linear range of 0.005–2.0 mM, a high sensitivity of 2956 μA mM−1 cm−2 and a low detection limit of 0.7 μM (S/N = 3), which was superior or comparable to that of the recently reported sensor. Because of the good selectivity and reproducibility, Co3S4/TM was applied to detection of hydrazine in tap water and it showed good recovery, indicating that it could be a promising candidate for analyzing hydrazine in practical application. [ABSTRACT FROM AUTHOR]

Exploring environmentally friendly, efficient, cheap and recyclable catalysts are essential for the development of green, sustainable and mild processes for the liquid-phase Beckmann rearrangement. Herein, a novel caprolactam-based Brønsted acidic ionic liquid ([CPL][2MSA]) was developed for the conversion of cyclohexanone oxime (CHO) to caprolactam (CPL), not only as a catalyst, but also as a mild reaction medium. Under the reaction conditions for the reaction temperature (90 °C), reaction time (2 h) and mole ratio ([CPL][2MSA]: CHO = 3:1), [CPL][2MSA] possesses plenty of high sulfonate groups, which exhibit high conversion (100%) and selectivity (95%) without any other co-catalysts or metals. Based on the thermogravimetric (TGA) and differential scanning calorimetry (DSC) analyses, the decomposition and glass transition temperatures are gradually increased with the increase in MSA mole content, revealing the existence of hydrogen-bonded clusters. Interestingly, the occurrent route of the liquid-phase Beckmann rearrangement for CHO in [CPL][2MSA] is revealed by in situ FT-Raman. In addition, the dominating H-bond combination between CHO and [CPL][2MSA] is further confirmed by COSMO-RS model. The activation energy (Ea) of the reaction is calculated by the first-order reaction kinetics. Thus, the [CPL][2MSA] with plenty of acidic catalytic active species is an environmentally friendly and efficient candidate for the liquid-phase Beckmann rearrangement. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR) T-cell therapy has made remarkable progress in cancer immunotherapy, but several challenges with unclear mechanisms hinder its wide clinical application. Single-cell sequencing technologies, with the powerful unbiased analysis of cellular heterogeneity and molecular patterns at unprecedented resolution, have greatly advanced our understanding of immunology and oncology. In this review, we summarize the recent applications of single-cell sequencing technologies in CAR T-cell therapy, including the biological characteristics, the latest mechanisms of clinical response and adverse events, promising strategies that contribute to the development of CAR T-cell therapy and CAR target selection. Generally, we propose a multi-omics research mode to guide potential future research on CAR T-cell therapy. [ABSTRACT FROM AUTHOR]

Genetically modified (GM) mice are essential tools in biomedical research. Traditional methods for generating GM mice are expensive and require specialized personnel and equipment. The use of clustered regularly interspaced short palindromic repeats (CRISPR) coupled with improved-Genome editing via Oviductal Nucleic Acids Delivery (i-GONAD) has highly increased the feasibility of producing GM mice in research laboratories. However, genetic modification in inbred mouse strains of interest such as C57BL/6 (B6) is still challenging because of their low fertility and embryo fragility. We have successfully generated multiple novel GM mouse strains in the B6 background while attempting to optimize i-GONAD. We found that i-GONAD reduced the litter size in superovulated pregnant females but did not impact pregnancy rates. Natural mating or low-hormone dose did not increase the low fertility rate observed in superovulated B6 females. However, diet enrichment had a positive effect on pregnancy success. We also optimized breeding conditions to increase the survival of small litters by co-housing i-GONAD-treated pregnant B6 females with synchronized pregnant FVB/NJ companion mothers. Thus, GM mice generation was increased by an enriched diet and shared pup rearing with highly fertile females such as FVB/NJ. In the present study, we generated 16 GM mice using a CRISPR/Cas system to target individual and multiple loci simultaneously or consecutively. We also compared homology-directed repair efficiency using different methods for LoxP insertion for conditional knockout mouse production. We found that a two-step serial LoxP insertion, in which each LoxP sequence was inserted individually in different i-GONAD procedures, was a low-risk high-efficiency method for generating floxed mice. [ABSTRACT FROM AUTHOR]

Abstract: The objective of this study was using a wide range of dietary concentrate levels to investigate the major effects of limit‐feeding on heifers. Twenty‐four Holstein heifers were blocked into six groups and fed with one of four diets containing different levels of concentrate (20%, 40%, 60% and 80% on a dry matter (DM) basis) but with same intakes of metabolizable energy for 28 days. Increasing levels of dietary concentrate caused decreased (P ≤ 0.02) intakes of dry matter (DMI) and neutral detergent fiber and total rumination time, but increased (P < 0.01) nonfiberous carbohydrates intake, ruminal concentrations of NH3‐N, propionate and butyrate, and digestibility of DM and crude protein. Dietary concentrate levels had no significant effect on most plasma concentrations and body measurements. The corrected average daily gain (CADG) and feed efficency (ADG/DMI, CFE) were linearly increased (P < 0.01) with increasing dietary concentrate levels when gut fill impact was removed. In conclusion, heifers limit‐fed high concentrate diets increased most ruminal fermentation parameters, CADG and CFE with similar body growth and blood metabolites as heifers fed low concentrate diets, and had the potential to be used as an effective feeding strategy in dairy heifers. [ABSTRACT FROM AUTHOR]

The present study has examined the virulence potential of Escherichia coli isolates harboring at least one virulence gene (associated with ExPEC or InPEC pathotype and belonging to different phylogenetic groups: A, B1, B2 or D), isolated from free ranging Tibetan yak feces. The E. coli isolates (n = 87) were characterized for different serogroups and a mouse model of subcutaneous–infection was used to envisage the virulence within these E. coli strains. Of the 87 E. coli isolates examined, 23% of the E. coli isolates caused lethal infections in a mouse model of subcutaneous infection and were classified as killer. Moreover, the majority of the killer strains belonged to phylogroup A (65%) and serogroup O 60 or O 101 (35%). Phylogroup B1, serogroups O 60 and O 101 were statistically associated with the killer status ( P < 0.05). However, positive associations (OR >1) were observed between the killer status isolates and all other bacterial virulence traits. This study comprises the first report on the virulence potential of E. coli strains isolated from free-ranging Tibetan yaks feces. Our findings suggest that pathogenic E. coli of free ranging yaks is highly worrisome, as these feces are used as manures by farmers and therewith pose a health risk to humans upon exposure. [ABSTRACT FROM AUTHOR]

[Display omitted] Recently, hybrid two-dimensional (2D) Ruddlesden-Popper (RP) phase layered halide perovskite structures of (BA) 2 Cs n-1 Pb n Br 3n+1 (BA is the butylammonium organic chain and n is the number of inorganic perovskite-like layers) have been experimental synthesized and indicated superior optical properties. Here, we reported an investigation of the above series of layered halide perovskites (n = 1, 2, 3 and ∞). Their structural, electronic and optical properties were calculated using first-principle approaches, including the bond angles, band structures, formation energy, carrier effective masses, density of states, differential charge densities, Bader charge analysis, optical absorption spectra and transition dipole moment. As a consequence of these findings, with the increase in the number of inorganic layers, perovskite materials showed lower bandgaps, improved light absorption and poorer stability. Hence, tuning the inorganic layer thickness of layered 2D RP phase perovskites is a suitable method to enhance their optoelectronic properties. This work provides a theoretical basis for layered 2D perovskite materials with large-scale and low-cost applications in the photoluminescent device light-emitting diodes. [ABSTRACT FROM AUTHOR]

Background: Myocardial insulin resistance is a hallmark of diabetic cardiac injury. However, the underlying molecular mechanisms remain unclear. Recent studies demonstrate that the diabetic heart is resistant to other cardioprotective interventions, including adiponectin and preconditioning. The "universal" resistance to multiple therapeutic interventions suggests impairment of the requisite molecule(s) involved in broad prosurvival signaling cascades. Cav (Caveolin) is a scaffolding protein coordinating transmembrane signaling transduction. However, the role of Cav3 in diabetic impairment of cardiac protective signaling and diabetic ischemic heart failure is unknown. Methods: Wild-type and gene-manipulated mice were fed a normal diet or high-fat diet for 2 to 12 weeks and subjected to myocardial ischemia and reperfusion. Insulin cardioprotection was determined. Results: Compared with the normal diet group, the cardioprotective effect of insulin was significantly blunted as early as 4 weeks of high-fat diet feeding (prediabetes), a time point where expression levels of insulin-signaling molecules remained unchanged. However, Cav3/insulin receptor-β complex formation was significantly reduced. Among multiple posttranslational modifications altering protein/protein interaction, Cav3 (not insulin receptor-β) tyrosine nitration is prominent in the prediabetic heart. Treatment of cardiomyocytes with 5-amino-3-(4-morpholinyl)-1,2,3-oxadiazolium chloride reduced the signalsome complex and blocked insulin transmembrane signaling. Mass spectrometry identified Tyr73 as the Cav3 nitration site. Phenylalanine substitution of Tyr73 (Cav3Y73F) abolished 5-amino-3-(4-morpholinyl)-1,2,3-oxadiazolium chloride–induced Cav3 nitration, restored Cav3/insulin receptor-β complex, and rescued insulin transmembrane signaling. It is most important that adeno-associated virus 9–mediated cardiomyocyte-specific Cav3Y73F reexpression blocked high-fat diet–induced Cav3 nitration, preserved Cav3 signalsome integrity, restored transmembrane signaling, and rescued insulin-protective action against ischemic heart failure. Last, diabetic nitrative modification of Cav3 at Tyr73 also reduced Cav3/AdipoR1 complex formation and blocked adiponectin cardioprotective signaling. Conclusions: Nitration of Cav3 at Tyr73 and resultant signal complex dissociation results in cardiac insulin/adiponectin resistance in the prediabetic heart, contributing to ischemic heart failure progression. Early interventions preserving Cav3-centered signalsome integrity is an effective novel strategy against diabetic exacerbation of ischemic heart failure. [ABSTRACT FROM AUTHOR]