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The mechanical properties and insulation damage of stator end windings in permanent magnet synchronous generator (PMSG) are investigated by theoretical analysis, finite element analysis (FEA) and experiment verification. First, a theoretical model of the winding electromagnetic force (EF) and vibration response before and after eccentricity faults are established. Then, the stress/strain distribution of the end windings under different working conditions is analyzed. Finally, the insulation damage behavior of end windings with initial cracks is studied and characterized using the stress intensity factor (SIF). The results indicate that the winding EF and vibration responses vary under different faults. The stress/strain at the joint of the winding is the largest, and the insulation layer has the maximum stress/strain under the same section. Additionally, the SIF amplitude of the crack at the winding joint is the largest. And the SIF amplitude of the crack will increase with the increase of fault degree/crack depth/crack length. The contribution of this paper lies in the comprehensive analysis of the winding EF distribution, vibration response, stress and strain, and insulation damage before and after eccentricity. This analysis can provide valuable reference for the health monitoring of PMSG eccentricity faults and the prevention of winding insulation damage.

Static air-gap eccentricity (SAGE) is a common fault in generators. Current researches primarily focus on the parallel SAGE types, while the inclined static air-gap eccentricity (ISAGE) has been rarely investigated. This paper proposes an improved air-gap eccentricity model and presents a study on the electromagnetic-mechanical properties in synchronous generators under typical ISAGE running conditions. Such electromagnetic-mechanical properties include not only the magnetic flux density (MFD) variations, but also the mechanical responses of the electromagnetic torque (EMT) and rotor unbalanced magnetic pulls (UMP). The typical ISAGE factors include: 1) a varied rotor inclined angle θ, and 2) different values of axial inclined distance z (indicates the offset combination case of the two rotor ends). This work is based on the MFD analysis calculation. Theoretical analysis, finite element analysis, and experimental study are carried out, respectively, by taking a 5 kVA two-pole prototype generator as the study object. It is shown that the electromagnetic-mechanical properties of the generator will change when the inclined eccentricity occurs. The EMT, and the rotor UMP as well as the vibrations will increase as the rotor inclined θ and z increase. Specifically, the 2nd harmonic has the most significant variation.

ABSTRACT: Spermatogenesis is a continuous process in which functional sperm are produced through a series of mitotic and meiotic divisions and morphological changes in germ cells. The aberrant development and fate transitions of spermatogenic cells cause hybrid sterility in mammals. Cattle-yak, a hybrid animal between taurine cattle (Bos taurus) and yak (Bos grunniens), exhibits male-specific sterility due to spermatogenic failure. In the present study, we performed single-cell RNA sequencing analysis to identify differences in testicular cell composition and the developmental trajectory of spermatogenic cells between yak and cattle-yak. The composition and molecular signatures of spermatogonial subtypes were dramatically different between these 2 animals, and the expression of genes associated with stem cell maintenance, cell differentiation and meiotic entry was altered in cattle-yak, indicating the impairment of undifferentiated spermatogonial fate decisions. Cell communication analysis revealed that signaling within different spermatogenic cell subpopulations was weakened, and progenitor spermatogonia were unable to or delayed receiving and sending signals for transformation to the next stage in cattle-yak. Simultaneously, the communication between niche cells and germ cells was also abnormal. Collectively, we obtained the expression profiles of transcriptome signatures of different germ cells and testicular somatic cell populations at the single-cell level and identified critical regulators of spermatogonial differentiation and meiosis in yak and sterile cattle-yak. The findings of this study shed light on the genetic mechanisms that lead to hybrid sterility and speciation in bovid species.

Drug discovery is a sophisticated process that incorporates scientific innovations and cutting-edge technologies. Compared to traditional bioactivity-based screening methods, encoding and display technologies for combinatorial libraries have recently advanced from proof-of-principle experiments to promising tools for pharmaceutical hit discovery due to their high screening efficiency, throughput, and resource minimization. This review systematically summarizes the development history, typology, and prospective applications of encoding and displayed technologies, including phage display, ribosomal display, mRNA display, yeast cell display, one-bead one-compound, DNA-encoded, peptide nucleic acid-encoded, and new peptide-encoded technologies, and examples of preclinical and clinical translation. We discuss the progress of novel targeted therapeutic agents, covering a spectrum from small-molecule inhibitors and nonpeptidic macrocycles to linear, monocyclic, and bicyclic peptides, in addition to antibodies. We also address the pending challenges and future prospects of drug discovery, including the size of screening libraries, advantages and disadvantages of the technology, clinical translational potential, and market space. This review is intended to establish a comprehensive high-throughput drug discovery strategy for scientific researchers and clinical drug developers.

The adiabatic shear band is a common dynamic failure mechanism in metal materials at high strain rates. In this work, a new approach was proposed to improve mechanical properties and inhibit the formation and propagation of the adiabatic shear band in the pure Mo single crystal. The microstructure evolution of the pure Mo and Mo-Nb single crystals subjected to the dynamic load was investigated by EBSD and TEM. At a strain rate of 2500 s−1, the developed adiabatic shear band was totally distributed in the pure Mo single crystal, and the slip is the main deformation mechanism. A thinner adiabatic shear band was distributed in the Mo-3Nb single crystal accompanied by a few bands of deformation twins and then disappeared in the Mo-6Nb single crystal, replaced by the {112} deformation twinning. At high strain rates, the dynamic deformation mechanism of the Mo single crystal is sensitive to the Nb element, which attributes to the reduction of the generalized stacking fault energy.

This study examines the hot deformation behavior of Mo-14Re alloy at various true strains (15%, 35%, 65%) and strain rates (0.01 s−1, 10 s−1) at a temperature of 1400K. The findings indicate that dynamic recovery (DRV) and dynamic recrystallization (DRX) occur concomitantly as strain increases at a low strain rate of 0.01 s−1, with DRV being the predominant softening mechanism. At a strain of 65%, DRX emerges as the primary softening process. Conversely, under high strain rates of 10 s−1, DRX is inhibited, and the Mo-14Re alloy experiences work hardening due to an increase in dislocation density. Microscopic analysis shows that the high-density dislocations facilitate the continued nucleation and growth of recrystallized grains at low strain rates. At high strain rates, tangled dislocations hinder dislocation motion and recrystallization. Regarding texture evolution, stronger {100}//CD and weaker {111}//CD fiber texture is observed at low strain rates of 0.01 s−1, while stronger {111}//CD and weaker {100}//CD fiber texture forms at high strain rates of 10 s−1, with enhanced texture intensity. Mechanistic analysis confirms the activation of the {110}, {112}, and {123} dislocation slip systems at elevated temperatures, with the {123} system being the most dominant.

Current cytotoxic T lymphocyte (CTL) activating immunotherapy requires a major histocompatibility complex I (MHC-I)-mediated presentation of tumor-associated antigens, which malfunctions in around half of patients with triple-negative breast cancer (TNBC). Here, we create a LCL161-loaded macrophage membrane decorated nanoparticle (LMN) for immunotherapy of MHC-I-deficient TNBC. SIRPα on the macrophage membrane helps LMNs recognize CD47-expressing cancer cells for targeted delivery of LCL161, which induces the release of high mobility group protein 1 and proinflammatory cytokines from cancer cells. The released cytokines and high mobility group protein 1 activate antitumor immunity by increasing the intratumoral density of the phagocytic macrophage subtype by 15 times and elevating the intratumoral concentration of CTL lymphotoxin by 4.6 folds. LMNs also block CD47-mediated phagocytosis suppression. LMNs inhibit the growth of MHC-I-deficient TNBC tumors, as well as those resistant to combined therapy of anti-PDL1 antibody and albumin-bound paclitaxel, and prolong the survival of animals, during which process CTLs also play important roles. This macrophage membrane-decorated nanoparticle presents a generalizable platform for increasing macrophage-mediated antitumor immunity for effective immunotherapy of MHC-I-deficient cancers.

Natural slopes usually display complicated exposed rock surfaces that are characterized by complex and substantial terrain undulation and ubiquitous undesirable phenomena such as vegetation cover and rockfalls. This study presents a systematic outcrop research of fracture pattern variations in a complicated rock slope, and the qualitative and quantitative study of the complex phenomena impact on three-dimensional (3D) discrete fracture network (DFN) modeling. As the studies of the outcrop fracture pattern have been so far focused on local variations, thus, we put forward a statistical analysis of global variations. The entire outcrop is partitioned into several subzones, and the subzone-scale variability of fracture geometric properties is analyzed (including the orientation, the density, and the trace length). The results reveal significant variations in fracture characteristics (such as the concentrative degree, the average orientation, the density, and the trace length) among different subzones. Moreover, the density of fracture sets, which is approximately parallel to the slope surface, exhibits a notably higher value compared to other fracture sets across all subzones. To improve the accuracy of the DFN modeling, the effects of three common phenomena resulting from vegetation and rockfalls are qualitatively analyzed and the corresponding quantitative data processing solutions are proposed. Subsequently, the 3D fracture geometric parameters are determined for different areas of the high-steep rock slope in terms of the subzone dimensions. The results show significant variations in the same set of 3D fracture parameters across different regions with density differing by up to tenfold and mean trace length exhibiting differences of 3–4 times. The study results present precise geological structural information, improve modeling accuracy, and provide practical solutions for addressing complex outcrop issues.

To study temperature and rate-dependent behaviors of molybdenum-rhenium (Mo–Re) alloys, compressive tests at variable temperatures and strain rates were conducted. After the same machining and thermal annealing processes, fully recrystallization happens in Mo and Mo–Re alloys with low Re content (5 wt %), while recovery occurs in Mo–Re alloys with high Re content (14 wt% and 42 wt %). The strength increases as Re content rises at all temperatures (300 °C, 600 °C and 1200 °C), meaning sufficient strengthening effect of Re. The rate-dependent behaviors, however, show different trends between Mo and Mo–Re alloys. Positive strain rate sensitivity is detected in Mo and low Re Mo–Re alloys in all temperatures, which is consistent to other research. While, near zero strain rate sensitivity is found in high Re Mo–Re alloys at 600 °C. Such an unusual phenomenon may be contributed to high stored dislocation density during mechanical processes. The stored dislocations are activated at a proper temperature to accommodate plastic flow, which weakens the influence of strain rate on strength.

An environment-friendly solvent debinding process for polyoxymethylene (POM) for metal injection molding (MIM) is presented as an alternative to the traditional catalytic debinding method. This study investigated the influence of various acid solvents and debinding temperature. The optimal debinding parameters were 5 M nitric acid solution at 60 °C. Based on the calculation of effective diffusivity and activation energy, the solvent-debinding mechanism for POM is proposed. The removal of POM was controlled by three processes: dissolution, diffusion, and chemical reaction. The resulting final titanium parts have a high density of over 95% and an ultimate tensile strength of 406 MPa.

Summary: Pulmonary arterial hypertension (PAH) is a life-threatening disease induced by abnormal activation of pulmonary adventitial fibroblasts (PAFs) in the early stage. The association between selenium deficiency and PAH is not yet fully understood. In this study, we found that the serum selenium content of PAH patients was significantly lower than that of healthy volunteers in two independent cohorts. Moreover, PAH patients with lower selenium levels may present poorer prognosis. Prophylactic selenium supplementation could effectively improve hemodynamics and pulmonary vascular remodeling in monocrotaline-induced pulmonary hypertension rat models. Mechanistically, selenium supplementation restored the level of selenium binding protein 1 (SELENBP1) which could exert an antagonistic effect on PAF activation. The rescue assay further proved that selenium supplementation worked in a SELENBP1-dependent manner. These findings demonstrated that selenium deficiency is an important risk factor in PAH, and the selenium-SELENBP1 axis represents a promising target for PAH prevention.

The viral metagenomics approach is an effective technique for investigating and analysing both existing and emerging viruses in humans and diverse animal samples. The ruddy shelduck, a nationally protected secondary key species of wild animals, has become the predominant species among overwintering waterbirds in Qinghai Lake. Viruses carried by ruddy shelducks can potentially infect humans or other animals; however, limited research on the faecal virome of ruddy shelducks is currently available. In the present study, faecal samples of ruddy shelducks collected from Saga County, Shigatse City, Tibet, China, were subjected to viral metagenomic analysis. The predominant viral families identified in ruddy shelduck samples were Picornaviridae, Parvoviridae, Microviridae, Vilyaviridae, Astroviridae, and Caliciviridae. Among these, two picornavirus genomes have been identified as new strains of the genus Megrivirus in the family Parvoviridae. In addition, viruses that infect parasites and bacteria have been identified and characterised. The present study enhances our comprehension of the composition of the viral community in ruddy shelducks faeces and highlights the dynamic nature of viral evolution and the significance of continuous monitoring to assess potential risks to wildlife and public health.

Enteritis often limits intensive aquaculture, where bile acids (BAs), a group of steroid molecules, are used to prevent intestinal diseases. However, the functions of certain BAs are poorly understood. In this study, grass carp with enteritis (EGC) and healthy grass carp (HGC) were sampled, and the BAs' composition was analyzed. Results showed distinct differences in the BA profiles: EGC exhibited significantly elevated levels of taurodeoxycholic acid (TDCA), lithocholic acid (LCA), glycoursodeoxycholic acid (GUDCA), and glycohyocholic acid (GHCA) (P < 0.05), and decreased levels of TCDCA, taurocholic acid (TCA), and cholic acid (CA) in the intestine compared with their levels in HGC. Subsequently, five diets containing four typical BAs (CA, chenodeoxycholic acid [CDCA], deoxycholic acid [DCA], and LCA) at the same concentration (0.1 %) were formulated to feed the juvenile grass carps (6.29 ± 0.05 g) for 8 weeks. DCA alone increased body weight, reduced the feed conversion ratio (FCR), and ameliorated histological intestinal inflammatory hallmarks. Conversely, individual supplementation with CDCA, LCA, or CA decreased body weight and increased FCR and exacerbated the histological hallmarks of enteritis. Furthermore, DCA markedly reduced the mRNA expression levels of endoplasmic reticulum stress (ERS)-related genes in the intestine, including glucose-regulated protein 78 (GPR78), activating transcription factor 6 (ATF6), inositol-requiring enzyme 1, and protein kinase RNA-like ER kinase, as well as genes encoding proinflammatory cytokines, such as interleukin (IL)-1 beta, IL-8, and tumor necrosis factor α (TNF-α). Supplementation with CDCA, LCA, or CA promoted the expression of ERS- and proinflammatory-cytokine-related genes. Additionally, Actinobacteriota abundance negatively correlated with intestinal mRNA expression levels of TNF-α, ATF6, IL-1β, GPR78, and IL-8, and Candidatus-Arthromitus abundance positively correlated with these inflammatory markers (P < 0.05). In conclusion, our results demonstrated that BAs play differential roles in modulating the enteritis process and that DCA may have a specific anti-inflammatory role in grass carp.

Material design is essential for the development and preparation of new materials. In this paper, a new two-dimensional heterostructure material (B@Si) consisting of boronene and silicene is designed and used as an anode material for lithium-ion batteries in order to improve the performance of lithium-ion batteries, and the structural properties, stability, electronic properties, and performance as an anode material for lithium-ion batteries are systematically investigated by first-principle calculations of the B@Si heterostructure. The results show that the B@Si heterostructure is energetically, thermodynamically and dynamically stable, and although the Dirac cone in the energy band structure of silicene disappears after the formation of the heterojunction, the overall electrical conductivity of the material improves considerably and the electron transport rate is faster. Due to the synergistic effect, Li has more stable adsorption sites and lower diffusion barriers than boronene and silicene in the B@Si heterostructure, higher theoretical specific capacity (1208 mAhg−1), and stronger mechanical properties (C11 = 296.6 N/m, C22 = 142.8 N/m). The volume expansion in the fully lithiated state is also only 8 %. These advantages indicate that B@Si heterostructures are good potential anode materials for high-performance Li-ion batteries.

Objective: This study aims to investigate variances in renal ultrasound parameters between fetuses experiencing fetal growth restriction (FGR) and those with normal intrauterine development, with the intent to offer actionable insights for clinical management. Method: Forty-five pregnant women diagnosed with FGR between 28 and 36 weeks of gestation, who underwent examination at Wenzhou People's Hospital from September 2021 to June 2023, constituted the FGR group. Concurrently, 65 pregnant women with normal intrauterine development at matching gestational weeks formed the control group. Renal ultrasound parameters, encompassing renal artery peak systolic velocity (PSV), end diastolic velocity (EDV), time averaged maximum velocity (TAMX), resistive indices (S/D, PI, RI), ratios of renal volume to gestational age (RV/WEEK) and estimated fetal weight (RV/EFW), vascular indices (VI, FI, VFI), were compared between the two groups. All parameters represented the mean values of bilateral kidneys. Result: In the FGR group, fetal renal artery PSV (37.71 ± 9.93 cm/s), EDV (6.19 ± 1.50 cm/s), TAMX (15.10 ± 3.83 cm/s), RV/WEEK (0.45 ± 0.12), RV/EFW (7.53 ± 3.24), VI (22.19 ± 15.00), and VFI (5.53 ± 3.63) were significantly lower compared to the control group (PSV: 47.11 ± 11.24 cm/s, EDV: 7.13 ± 2.00 cm/s, TAMX: 17.85 ± 3.85 cm/s, RV/WEEK: 0.66 ± 0.19, RV/EFW:9.20 ± 3.17, VI: 28.67 ± 14.72, VFI: 7.40 ± 3.68). Conversely, fetal renal artery resistive indices (S/D: 9.09 ± 2.58, PI: 2.71 ± 0.56, RI: 0.92 ± 0.04) in the FGR group were notably higher than those in the control group (S/D: 6.22 ± 1.93, PI: 2.20 ± 0.73, RI: 0.87 ± 0.04), with statistical significance (P 0.05). Receiver operating characteristic (ROC) curve analysis revealed higher diagnostic efficacy for RV/WEEK and RI among individual indicators, while combined parameter application yielded the highest diagnostic efficiency. Conclusion: Utilizing a comprehensive evaluation of fetal kidney ultrasound parameters with multiple indices facilitates early screening and diagnosis of FGR fetuses, thereby aiding clinical decision-making and enhancing newborn birth outcomes.

Background: Dayuan Yin (DYY) is a classical formula used for treating plague, known for anti-inflammatory and antioxidant effects. It has shown potential in alleviating acute lung injury (ALI), though its mechanisms remain unclear. This study aimed to investigate the effects and mechanisms of DYY in treating ALI. Methods: Network pharmacology and molecular docking techniques were used to elucidate the potential targets and mechanisms of DYY in treating ALI. Subsequently, in vivo experiment was performed to verify the findings from bioinformatics analysis. λ-Carrageenan (λ-Car) was used to establish the ALI model. At 1 h before 2% λ-Car injection, 3 g/kg or 9 g/kg DYY were administered orally. 4 h after λ-Car-induced injury, the efficacy of DYY in treating ALI was assessed using several methods, including Wright-Giemsa staining to examine inflammatory cells in mouse pleural exudates, hematoxylin and eosin staining of lung tissues, and serum cytokine levels, cytokine mRNA levels in lung tissues, key protein levels were detected. Results: Network pharmacology and molecular docking analyses suggested that signal transducer and activator of transcription 3 (STAT3), interleukin-6, and tumor necrosis factor alpha might be the key regulated proteins, while the nuclear factor kappa-B (NF-κB) pathway could be the pathway involved. In vivo, the lung injury score of mice decreased to 0.78 from 3.44 after treating 9 g/kg DYY. Compared with the λ-Car group, the number of inflammatory cells in the DYY groups were decreased by 63 - 73% in pleural effusion. Further analysis showed that DYY could reduce the release of inflammatory cytokines, inhibit the activation of NF-κB signaling pathway, and downregulate the expression of p-janus kinase 2 (JAK2), p-STAT3, and matrix metalloproteinase-9 (MMP-9), thereby protecting against ALI. Conclusion: The study revealed remarkable potential of DYY in alleviating λ-Car-induced ALI through inhibiting the JAK2/STAT3/MMP-9 and NF-κB signaling pathways.

The combination of straw return and nitrogen (N) fertilization is an effective strategy for increasing farmland productivity and improving soil structure while mitigating climate change. However, although straw return practices are widely recommended in agroecosystems targeting sustainable agriculture, few studies have explored changes in grain yield, resource use efficiency, water productivity, and potential interactions between these variables. A field experiment was conducted during 2022–2023 in Northeast China to study the effects of straw return modes and N fertilizer input on maize grain yield and the efficient use of radiation, water, and N. We investigated two straw return tillage methods (rotary tillage with straw returning, RTS; plow tillage with straw returning, PTS) and five N fertilizer levels (0, 112, 187, 262, and 337 kg N ha−1) based on a field location experiment that started in 2015. Compared with RTS treatment, the PTS treatment resulted in a higher photosynthetic capacity by regulating the leaf area index and photosynthetic metabolism, resulting in increased dry matter accumulation and transportation. Such physiological improvements are conducive to increasing the nutrient use efficiency, water productivity, and grain yield. Specifically, PTS combined with the N3 treatment was an efficient tillage mode that increased radiation use efficiency of grain by 123.48 % and 207.41 % and by 153.44 % and 167.37 % in 2022 and 2023, respectively, compared with the PTS and N0 treatment. Together with partial least squares path modeling, regression analysis, and random forest, the variations in the above parameters led to high productivity in terms of N uptake, water productivity, leaf area index, radiation use efficiency, N use efficiency, and dry matter accumulation. Our results highlight the key roles of straw return methods in affecting grain yield, and further suggest that PTS combined with optimized N fertilizer input can enhance resource utilization, leading to a productive, efficient, and sustainable maize population.

Background: Colorectal cancer is a predominant contributor to global cancer-related morbidity and mortality. The oncogene PTOV1 has been linked to various human malignancies, yet its specific role in CRC pathogenesis requires further elucidation. Methods: Our study used a comprehensive array of authoritative bioinformatics tools, such as TIMER, UCSC Xena, GEO, Human Protein Atlas, UALCAN, CIBERSORTx and others which used to investigate the complex effects of PTOV1 on gene expression profiles, diagnostic and prognostic biomarkers, tumor immunology, signaling pathways, epigenetic alterations, and genetic mutations. Gene expression validation was conducted using Western blot and qRT-PCR. The in vitro proliferative and migratory potentials of CRC cells were evaluated using CCK-8 assays, colony formation, and transwell migration assays, respectively. MSP was applied to assess the methylation status of the PTOV1 promoter region. Results: Our results reveal a significant association between increased PTOV1 expression, driven by promoter hypomethylation, and poor patient prognosis in CRC. Elevated PTOV1 levels were positively correlated with the enrichment of diverse immune cell subsets and immune-related molecules within the tumor microenvironment. In vitro assays demonstrated that PTOV1 knockdown markedly reduced CRC cell proliferation, colony formation, and migration, while ectopic PTOV1 expression had the opposite effect. Importantly, PTOV1 was shown to regulate the PI3K-AKT signaling pathway, significantly influencing the phosphorylation of AKT1 and the expression of cell cycle regulators P21 and P27. The pharmacological inhibition of AKT1 phosphorylation using MK2206 effectively counteracted the proliferative effects induced by PTOV1 overexpression. Conclusion: The ability of PTOV1 to enhance CRC cell proliferation via modulation of the AKT1 signaling pathway establishes it as a potential therapeutic target and a promising biomarker for prognostic stratification in CRC.

Ten percent of non-small cell lung cancer patients with epidermal growth factor receptor (EGFR) mutations harbor uncommon variants. These mutations are mainly involved in lung adenocarcinomas but are rare in lung squamous cell carcinoma (LSCC). In 2018, the Food and Drug Administration-approved afatinib for this specific patient population. However, there is limited information regarding the effectiveness of afatinib for LSCC with EGFR mutations. This case report documented a unique case of a patient with LSCC, which had a rare compound EGFR mutation (G719C and S768I) and showed significant response to afatinib treatment, with 10 months of progression-free survival. New NTRK1 and RET gene mutations may play a potential role in the development of acquired resistance to afatinib following clinical progression. This case highlights the importance of genetic profiling in patients with LSCC. Although these patients have a low positive rate of EGFR mutations, searching for EGFR mutations in these patients might broaden their treatment options.

Myocardial ischemia (MI) is a significant contributor to ischemic heart diseases like angina pectoris and myocardial infarction. Reactive oxygen species produced during MI can trigger lipid peroxidation, damaging cell structure and function. Salvia miltiorrhiza (SM) has been widely used clinically in the treatment of cardiovascular diseases. However, in the process of rooting, the aboveground parts of this plant are usually discarded by tons. To make better use of these plant resources, the phenolic acids extracted and purified from the aerial part of SM were studied and chemically transformed, and the potential protective effect and possible mechanism of salvianolic acids containing a higher content of salvianolic acid A on MI were obtained. The transformed products of SM stem-leaves total phenolic acids with 8.16 % salvianolic acid A showed a better protective effect on the isoproterenol (ISO)-induced acute MI injury rat model. It can improve ST segment changes and has good antioxidant, anti-inflammatory and anticoagulant effects. In addition, the dysbiosis of gut microbiota and the related metabolic levels of short chain fatty acids (SCFAs), phenylalanine and glycerophospholipids were improved. This was achieved by reducing the abundance of Bacteroides, Faecalibaculum, and L-phenylalanine levels. In addition, the abundance of probiotics in Butyricoccus, Roseburia, and norank_f_Eubacterium_coprostanoligenes_group, as well as the contents of propionic acid and isobutyric acid, LPCs and PCs were increased. In conclusion, total phenolic acids of SM stem-leaves showed protective effects against ISO-induced rats, especially the strongest effect after conversion, which is a new option for the prevention and treatment of MI.

Osteoarthritis (OA) is a degenerative disease potentially exacerbated due to inflammation, cartilage degeneration, and increased friction. Both mesenchymal stem cells (MSCs) and pro-inflammatory macrophages play important roles in OA. A promising approach to treating OA is to modify multi-functional hydrogel microspheres to target the OA microenvironment and structure. Arginyl-glycyl-aspartic acid (RGD) is a peptide widely used in bioengineering owing to its cell adhesion properties, which can recruit BMSCs and macrophages. We developed TLC-R, a microsphere loaded with TGF-β1-containing liposomes. The recruitment effect of TLC-R on macrophages and BMSCs was verified by in vitro experiments, along with its function of promoting chondrogenic differentiation of BMSCs. And we evaluated the effect of TLC-R in balancing OA metabolism in vitro and in vivo. When TLC-R was co-cultured with BMSCs and lipopolysaccharide (LPS)-treated macrophages, it showed the ability to recruit both cells in substantial numbers. As the microspheres degraded, TGF-β1 and chondroitin sulfate (ChS) were released to promote chondrogenic differentiation of the recruited BMSCs, modulate chondrocyte metabolism and inhibit inflammation induced by the macrophages. Furthermore, in vivo analysis showed that TLC-R restored the narrowed space, reduced osteophyte volume, and improved cartilage metabolic homeostasis in OA rats. Altogether, TLC-R provides a comprehensive and novel solution for OA treatment by dual-modulating inflammatory and chondrocyte metabolism.

The static air gap eccentricity is one of the prevalent faults in permanent magnet synchronous generators. In previous studies, the variation of magnetic flux density, stator current and vibration have been studied mostly. However, the temperature characteristic of winding insulation under 3D static air gap eccentricity fault is rarely investigated. As a supplement, this paper comprehensively analyzes the influence of radial static air gap eccentricity, axial static air gap eccentricity and the combined static air gap eccentricity (radial static air gap eccentricity and axial static air gap eccentricity) fault on the winding insulation thermal response. The whole work is based on not only the loss of core and windings but also the temperature rise of the winding insulation, which is carried out through theoretical analysis, finite element calculation, and experiment verification. It is shown that radial static air gap eccentricity will increase the winding insulation temperature whatever in singe radial static air gap eccentricity or combined static air gap eccentricity, while axial static air gap eccentricity has the opposite effect. Specifically, the winding insulation temperature in radial static air gap eccentricity 0.1 mm, 0.2 mm and 0.3 mm cases are 57.18℃, 59.10℃ and 61.04℃, respectively, which is 3.29℃, 5.21℃ and 7.15℃ higher than that under normal condition. However, under axial static air gap eccentricity, winding insulation temperature will decrease by 1.84℃, 4.11℃ and 5.9℃, respectively. When axial static air gap eccentricity is unchanged and radial static air gap eccentricity is increased, the winding insulation temperature will increase by 1.5℃ and 3.23℃, respectively. On the contrary, when radial static air gap eccentricity is unchanged and axial static air gap eccentricity increases, the winding insulation temperature decreases by 2.54℃ and 5.66℃, respectively. The end part and the join between the end and line parts of the winding insulation are the most dangerous positions to suffer from static thermal wear.

Abstracts: The Internet of Things (IoT) has been growing quickly since the 5 G era arrived, which has boosted the quantity of data stream and computational demands. Ultra-dense Edge Computing (UDEC) is a result of the growing popularity of Mobile Edge Computing (MEC) and Ultra-dense Network (UDN), two vital technologies with bright futures. Task offloading is viewed in the UDEC network as a successful strategy to offer mobile users low-latency and flexible computing capabilities. However, the edge cloud's constrained computing capacity and mobile users' dynamically shifting computing requirements present difficulties for the reasonable scheduling of computing requests to the edge cloud. The Power Allocation (PA) problem for mobile users to address this issue. This problem attempts to use quasiconvex technique to minimize energy consumption. Next, the Joint Request Offloading and Resource Scheduling (JRORS) problem is treated as a mixed-integer nonlinear programming problem to minimize request delay and improve welfare. The request offloading problem and the computational resource scheduling challenge are two subproblems of the JRORS problem that can be further broken down, the JRORS issue is therefore viewed as a dual decision-making problem. A Ratio of Power Consumption to Welfare (RCW) problem through mathematical modeling. An improved snake optimizer (SO) is therefore proposed, which was added with oscillation factor to optimize the location of the weight parameter in the location update and the variation of food production. It can enhance the global search capability and local search ability. By conducting simulation experiments, divide the mobile users into nine groups for testing, select energy consumption, welfare, and RCW as the objective functions, respectively, and compare them with other swarm optimization algorithms, such as Differential Evolution (DE), Particle Swarm Optimization (PSO), Ant-Lion Optimizer (ALO), Butterfly Optimization Algorithm (BOA), and Gray Wolf Optimizer (GWO). The improved algorithm achieved minimal energy consumption and optimal welfare in nearly every test case, contributing to the enhanced effectiveness and cost-efficiency of edge systems, thereby achieving the optimization of task offloading and scheduling.

It is economically desirable to develop a material that can simultaneously detect and recover uranium. Herein, a CC-bridged two-dimensional metal-covalent organic framework (Cu-BTAN-AO MCOF) was constructed by condensation of metal single crystals with a rigid structure (Cu3(PyCA)3) and cyano monomers (BTAN) via Knoevenagel reaction for simultaneous detection and adsorption of uranium. The amidoxime group within the pore and the presence of unsaturated Cu(I) in the framework facilitate the adsorption of uranyl ions onto the amidoxime group, leading to fluorescence quenching via the photoinduced electron transfer (PET) mechanism, achieving a detection limit of as low as 167 nM uranyl ions. Furthermore, Cu-BTAN-AO demonstrates exceptional efficiency in capturing uranium from wastewater characterized by rapid kinetics and superior selectivity. It is noteworthy that Cu-BTAN-AO is the first example of simultaneous detection, adsorption and chemical reduction of uranium using metal centers and functional groups in MCOF, indicating that Cu-BTAN-AO has great potential for the detection and recovery of uranium-containing wastewater. This design strategy may also be applicable to advancing sensing and energy materials for other important metal ions.

Background: Epigenetic dysregulation has been implicated in the development and progression of a variety of human diseases, but epigenetic changes are reversible, and epigenetic enzymes and regulatory proteins can be targeted using small molecules. Histone deacetylase inhibitors (HDACis), as a class of epigenetic drugs, are widely used to treat various cancers and other diseases involving abnormal gene expression. Results: Specially, HDACis have emerged as a promising strategy to enhance the therapeutic effect of non-neoplastic conditions, including neurological disorders, cardiovascular diseases, renal diseases, autoimmune diseases, inflammatory diseases, infectious diseases and rare diseases, along with their related mechanisms. However, their clinical efficacy has been limited by drug resistance and toxicity. Conclusions: To date, most clinical trials of HDAC inhibitors have been related to the treatment of cancer rather than the treatment of non-cancer diseases, for which experimental studies are gradually underway. Discussions regarding non-neoplastic diseases often concentrate on specific disease types. Therefore, this review highlights the development of HDACis and their potential therapeutic applications in non-neoplastic diseases, either as monotherapy or in combination with other drugs or therapies.

Transforming growth factor β 1 (TGF-β1), as the most abundant signaling molecule in bone matrix, is essential for bone homeostasis. However, the signaling transduction of TGF-β1 in the bone-forming microenvironment remains unknown. Here, we showed that microRNA-191 (miR-191) was downregulated during osteogenesis and further decreased by osteo-favoring TGF-β1 in bone marrow mesenchymal stem cells (BMSCs). MiR-191 was lower in bone tissues from children than in those from middle-aged individuals and it was negatively correlated with collagen type I alpha 1 chain (COL1A1). MiR-191 depletion significantly increased osteogenesis and bone formation in vivo. Hydrogels embedded with miR-191-low BMSCs displayed a powerful bone repair effect. Mechanistically, transcription factors BMI1 and SMAD2 coordinately controlled miR-191 level. In detail, BMI1 and pSMAD2 were both upregulated by TGF-β1 under osteogenic condition. SMAD2 activated miR-191 transcription, while BMI1 competed with SMAD2 for binding to miR-191 promoter region, thus disturbing the activation of SMAD2 on miR-191 and reducing miR-191 level. Altogether, our findings reveal that miR-191 regulated by TGF-β1-induced BMI1 and SMAD2 negatively modulated bone formation and regeneration, and inhibition of miR-191 might be therapeutically useful to enhance bone repair in clinic.

Summary: Co-immunoprecipitation (coIP) is an experimental technique to study protein-protein interactions (PPIs). However, single-step coIP can only be used to identify the interaction between two proteins and does not solve the interaction testing of ternary complexes. Here, we present a protocol to test for the formation of ternary protein complexes in vivo or in vitro using a two-step coIP approach. We describe steps for cell culture and transfection, elution of target proteins, and two-step coIP including western blot analyses.For complete details on the use and execution of this protocol, please refer to Li et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Summary: Biomarker screening is critical for precision oncology. However, one of the main challenges in precision oncology is that the screened biomarkers often fail to achieve the expected clinical effects and are rarely approved by regulatory authorities. Considering the close association between cancer pathogenesis and the evolutionary events of organisms, we first explored the evolutionary feature underlying clinically approved biomarkers, and two evolutionary features of approved biomarkers (Ohnologs and specific evolutionary stages of genes) were identified. Subsequently, we utilized evolutionary features for screening potential prognostic biomarkers in four common cancers: head and neck squamous cell carcinoma, liver hepatocellular carcinoma, lung adenocarcinoma, and lung squamous cell carcinoma. Finally, we constructed an evolution-strengthened prognostic model (ESPM) for cancers. These models can predict cancer patients’ survival time across different cancer cohorts effectively and perform better than conventional models. In summary, our study highlights the application potentials of evolutionary information in precision oncology biomarker screening.

Brain apoptosis is one of the main causes of epileptogenesis. The antiapoptotic effect and potential mechanism of Q808, an innovative anticonvulsant chemical, have never been reported. In this study, the seizure stage and latency to reach stage 2 of pentylenetetrazol (PTZ) seizure rat model treated with Q808 were investigated. The morphological change and neuronal apoptosis in the hippocampus were detected by hematoxylin and eosin (HE) and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining, respectively. The hippocampal transcriptomic changes were observed using RNA sequencing (RNA-seq). The expression levels of hub genes were verified by quantitative reverse-transcription PCR (qRT-PCR). Results revealed that Q808 could allay the seizure score and prolong the stage 2 latency in seizure rats. The morphological changes of neurons and the number of apoptotic cells in the DG area were diminished by Q808 treatment. RNA-seq analysis revealed eight hub genes, including Map2k3, Nfs1, Chchd4, Hdac6, Siglec5, Slc35d3, Entpd1, and LOC103690108, and nine hub pathways among the control, PTZ, and Q808 groups. Hub gene Nfs1 was involved in the hub pathway sulfur relay system, and Map2k3 was involved in the eight remaining hub pathways, including Amyotrophic lateral sclerosis, Cellular senescence, Fc epsilon RI signaling pathway, GnRH signaling pathway, Influenza A, Rap1 signaling pathway, TNF signaling pathway, and Toll-like receptor signaling pathway. qRT-PCR confirmed that the mRNA levels of these hub genes were consistent with the RNA-seq results. Our findings might contribute to further studies exploring the new apoptosis mechanism and actions of Q808.

High-k hafnium oxide (HfO2) film was prepared by high power impulse magnetron sputtering (HiPIMS). The influences of oxygen supply on the plasma state, film properties and TFT performance were investigated. The films are near-stoichiometric and preferentially (−1 1 1)-orientated. When the oxygen supply increased from 1% to 3%, the excitation/ionization rate of the plasma species increased, leading to higher crystallinity, higher density, and lower oxygen vacancy defect concentration of the film, therefore improving the dielectric properties of the film. When the oxygen supply further increased to 5%, the excitation/ionization rate decreased, thereby leading to lower crystallinity, lower density, and higher oxygen vacancy defect concentration of the film, therefore deteriorating the dielectric properties of the film. The film deposited at 3% oxygen supply exhibited the best dielectric properties with the highest k value of 24 and the highest breakdown-electric field (4.7 MV/cm), which should be attributed to the high crystallinity, high density and low oxygen vacancy defect concentration of the film. Finally, transparent thin film transistors (TFTs) with ITO gate electrode, HfO2 gate dielectric layer and indium-gallium-zinc oxide channel were fabricated on flexible colorless polyimide substrate at full room temperature by all HiPIMS process. The fixed positive charges and k value of HfO2 film have significant effects on the TFT performance. The best TFT exhibited good electrical performance, featuring a remarkably low subthreshold swing of 0.13 V/decade. It also exhibited fair stability against bending and gate bias stress.

ABSTRACT: Avian infectious bronchitis virus (IBV) still causes serious economic losses in the poultry industry. Currently, there are multiple prevalent genotypes and serotypes of IBVs. It is imperative to develop a new diagnosis method that is fast, sensitive, specific, simple, and broad-spectrum. A monoclonal hybridoma cell, N2D5, against the IBV N protein was obtained after fusion of myeloma SP2/0 cells with spleen cells isolated from the immunized Balb/c mice. The N2D5 monoclonal antibody (mAb) and the previously prepared mouse polyclonal antibody against the IBV N protein were used to target IBV as a colloidal gold–mAb conjugate and a captured antibody, respectively, in order to develop an immunochromatographic strip. The optimal pH and minimum antibody concentration in the reaction system for colloidal gold–mAb N2D5 conjugation were pH 6.5 and 30 μg/mL, respectively. Common avian pathogens were tested to evaluate the specificity of the strip and no cross-reaction was observed. The sensitivity of the strip for detecting IBV was 10−1.4522 EID50/mL. The strip showed a broad-spectrum cross-reactive capacity for detecting IBV antigens, including multiple IBV genotypes in China and all of the seven serotypes of IBV that are currently prevalent in southern China. Additionally, the result can be observed within 2 min without any equipment. The throat and cloacal swab samples of chickens that were artificially infected with three IBV strains were tested using the developed strip and the qPCR method; the strip test demonstrated a high consistency in detecting IBV via qPCR gene detection. In conclusion, the immunochromatographic strip that was established is rapid, sensitive, specific, simple, practical, and broad-spectrum; additionally, it has the potential to serve as an on-site rapid detection method of IBV and can facilitate the surveillance and control of the disease, especially in resource-limited areas.

High-performance P-type cuprous oxide (Cu2O) film was prepared at room temperature by high power impulse magnetron sputtering. Optical emission spectra revealed that the ratio of Cu radicals/ions in the plasma significantly decreased with increasing process pressure due to the reduction of sputtering yield as the Cu target surface was oxidized by the increased oxygen radicals/ions. In addition, the increase of self-sputtering yield for Cu cations with increasing process pressure reduced the arrival ratio of Cu species at the substrate surface. As a result, the film crystal phase transformed from Cu2O to Cu4O3 and CuO with increasing process pressure. X-ray photoelectron spectra and Hall effect test results revealed that the oxygen vacancy defects in the films were passivated by the increased oxygen species at higher process pressure, leading to the inhibition of electron background and the emergence of net hole concentration. A mobility of 37.3 cm2/V·s was achieved, which is very high for room-temperature-deposited Cu2O film and comparable to high-temperature (300–600 °C) deposited/post-annealed Cu2O film. Finally, Cu2O thin film transistors (TFTs) exhibited reasonable switching characteristics with a low off-current of 0.3 nA without post-annealing treatment, showing an advantage in low-temperature preparation.

Nature-based solutions to ecological challenges have continued to draw significant attention, and are connected to the increased establishment of protected areas as a means for climate and ecological crisis mitigation. This study presents an innovative approach that combines spatial and statistical analysis of land cover change and drivers to evaluate land use management and effectiveness of 22 designated protected areas (PAs) across the tropical coastal regions of sub-Saharan Africa. While the results provided insight into land use management and conservation priorities, it highlighted (1) the use of these protected areas for food production is prevalent, irrespective of its designation. Nevertheless, there is evidence of a decline in cropland in some of the protected areas, suggesting a shift in policy towards conservation land use. (2) The occurrence of forest loss suggests that conservation is weak in most of the protected areas, while wetland conservation efforts are stronger due to their land cover expansion. (3) Population density (human factor) is the most significant driver of land cover change in these protected areas, followed by elevation (natural environment), precipitation (climate), nighttime light (socio-economic), and slope (natural environment). (4) In terms of Ecosystem value, only 15 of the 22 protected areas exhibited an increase in their total ecosystem service value according to land cover change, indicating sustainable land use and measures effectiveness in these protected areas. However, based on an individual land cover assessment, most protected areas showed signs of loss, especially in forests. Given the projected population growth in Africa, a regular assessment of protected areas should be initiated to enable effective and timely management decisions. Additionally, policies to improve the management effectiveness of African protected areas through funding should be a top priority, while taking into consideration the livelihoods of the indigenous people in the area in order to find a sustainable balance.

According to the Standard of Chinese Medicinal Materials of Shaanxi Province (2015 edition), Salvia miltiorrhiza caulis et folium is the dried stems and leaves of Salvia miltiorrhiza, which could activate blood and dispell blood stasis, clear the mind and remove annoyance. In this study, the dynamic absorption changes of phenolic acids (FS) and phenolic acids-flavonoids (FT) in rats after oral administration were studied by UPLC-TQ/MS/MS, to elucidate the pharmacokinetics of seven major bioactive components of the stem-leaf of Salvia miltiorrhiza in vivo. The results showed that the pharmacokinetic parameters of FS and FT were significantly different in normal rats and model rats. Compared with the control group, after injecting 10 % polymer dextran 500 into the tail vein to establish a model of microcirculation disturbance, the Cmax of caffeic acid decreased. The Cmax of rosmarinic acid and lithospermic acid increased. Danshensu showed a decrease in CLz/F, accompanied by an increase in both AUC0-t and AUC0-∞. The AUC0-t of lithospermic acid was also increased. These results indicated that microcirculation disturbance could decrease the absorption of caffeic acid while increasing the absorption of danshensu, rosmarinic acid and lithospermic acid. After oral administration of FT, the Cmax of danshensu and the AUC0-t of caffeic acid were increased significantly, suggesting that the presence of flavonoids may promote the absorption and exposure of phenolic acids in vivo. This study provides a reference for the elucidation of the in vivo substances and the mechanisms of action of FS and FT from the stem-leaf of Salvia miltiorrhiza.

A diagnosis based on multiple nuclear medicine imaging (NMI) was more comprehensive in approaching the nature of pathological changes. In this research, a method to realize triple NMIs within one day was developed based on the reasonable arrangements of 68Ga-RGD PET/CT specialized on neovascularization, 99mTc-HL-91 SPECT/CT specialized on hypoxia and 18F-FDG PET/CT specialized on tumor metabolism. Feasibility was verified in evaluating the therapeutic effects of transarterial embolization (TAE) performed on rabbit models with VX2 tumor. Radiation dosimetry was carried out to record the radiation exposure from multiple injections of radiopharmaceuticals. In results, the one-day examination of triple NMIs manifested the diversity of the postoperative histological changes, including the local neovascularization induced by embolization, hypoxic state of embolized tissues, and suppression of tumor metabolism. More importantly, radiation dosage from radiopharmaceuticals was limited below 5.70 ± 0.90 mSv. In conclusion, the strong timeliness and complementarity of one-day examination of triple nuclear medicine imaging made it clinically operative and worthy of popularizing. There was flexibility in combining distinct NMIs according to the clinical demands, so as to provide comprehensive information for diagnosis.

Maternal diet is indispensable for the proper development of offspring, and the establishment of a well-functioning intestinal barrier is crucial for normal growth and development. Edible bird’s nest (EBN) has positive impacts on intestinal health, but the underlying mechanisms are unknown. Our study showed that maternal EBN supplementation downregulated the serum levels of diamine oxidase and D-lactate, elevated expression of tight junction proteins ZO-1, Occludin, and Claudin-1, and regulated the intestinal microbiota in rat offspring. Spearman’s correlation analysis revealed that Claudin-1, transforming growth factor-β (TGF-β), and transcription factor RUNX3 were positively correlated with changes in intestinal bacteria. EBN may upregulate the expression of TGF-β by modulating the intestinal microbiota composition, enhancing RUNX3 binding to the Claudin-1 promoter region to upregulate its expression. In conclusion, we demonstrated that maternal EBN supplementation during gestation and lactation enhanced intestinal barrier function by upregulating Claudin-1 in rat offspring.

Electroacupuncture (EA) is a neuroregulatory therapy for depression. Nonetheless, the effects of EA on the gut microbiome in mice models of depression are not well established. Here, using a chronic unpredictable mild stress (CUMS) model in mice, we evaluated the antidepressant effects of EA and changes in gut microbiota with behavioral tests and 16S rRNA gene sequencing. The results found that EA increased the time spent in the center area of the open-field test and the percentage of sucrose preference and reduced the immobility time in the tail suspension test in CUMS-treated mice. Furthermore, the genus Lachnoclostridium, Ruminococcaceae_UCG-002 and Rikenellaceae_RC9_gut_group were enriched in the CUMS group, which was positively correlated with depressive-like behaviors. Whereas phylum Actinobacteria and genus Allobaculum, Bifidobacterium, Dubosiella, Rikenella and Ileibacterium were enriched in the EA and CUMS + EA groups, all of which were negatively correlated with depressive-like behaviors. This study characterizes gut microbiota under EA treatment and provides new insights into the association of anti-depressive-like effects of EA and gut microbiota.

Most studies on building height estimation using remote sensing imagery mainly focus on urban buildings with relatively regular shape and relatively flat terrain, and pay little attention to large buildings with complex terrain like dams. A new dam height measurement method was proposed in this paper, which used shadow measurement data and metadata from multiple image sources. The method not only considers the geometric relationship between the sun, the satellite and the dam, but also considers the influence of the satellite zenith and introduces the correction factor, which brings the higher precision. Two dams with a maximum height of more than 200 m were studied, and the dam height is estimated by considering the topography around the dam and the shape of the dam. The experimental results show that the Mean Relative Error (MRE) of the estimated dam height using our proposed method are 3.1% and 4.7% for our two study areas, while the MRE of the traditional models is more than 13%. By doing so, we are able to calculate dam height and obtain information on temporal changes in dam height during the construction process, even in situations without a Digital Surface Model (DSM). Therefore, the proposed method will be propitious to the dynamic supervision of the construction process of the dams effectively.

Th2-high asthma is characterized by elevated levels of type 2 cytokines, such as interleukin 13 (IL-13), and its prevalence has been increasing worldwide. Ferroptosis, a recently discovered type of programmed cell death, is involved in the pathological process of Th2-high asthma; however, the underlying mechanisms remain incompletely understood. In this study, we demonstrated that the serum level of malondialdehyde (MDA), an index of lipid peroxidation, positively correlated with IL-13 level and negatively correlated with the predicted forced expiratory volume in 1 s (FEV1%) in asthmatics. Furthermore, we showed that IL-13 facilitates ferroptosis by upregulating of suppressor of cytokine signaling 1 (SOCS1) through analyzing immortalized airway epithelial cells, human airway organoids, and the ovalbumin (OVA)-challenged asthma model. We identified that signal transducer and activator of transcription 6 (STAT6) promotes the transcription of SOCS1 upon IL-13 stimulation. Moreover, SOCS1, an E3 ubiquitin ligase, was found to bind to solute carrier family 7 member 11 (SLC7A11) and catalyze its ubiquitinated degradation, thereby promoting ferroptosis in airway epithelial cells. Last, we found that inhibiting SOCS1 can decrease ferroptosis in airway epithelial cells and alleviate airway hyperresponsiveness (AHR) in OVA-challenged wide-type mice, while SOCS1 overexpression exacerbated the above in OVA-challenged IL-13-knockout mice. Our findings reveal that the IL-13/STAT6/SOCS1/SLC7A11 pathway is a novel molecular mechanism for ferroptosis in Th2-high asthma, confirming that targeting ferroptosis in airway epithelial cells is a potential therapeutic strategy for Th2-high asthma.

Aluminum nitride (AlN) film is a promising material which is used in various fields. In this study, AlN films with different plasma powers were grown by remote plasma atomic layer deposition. Saturation experiments have been applied in the plasma power between 1000 and 3000 W. The influence of plasma power on preferential orientation, chemical, optical, and electrical properties of AlN films are investigated. AlN films displayed multiphase hexagonal wurtzite crystal structure with (002) preferential orientation for higher plasma power, while the predominant orientation shifted toward (100) at lower plasma power. The optical emission spectroscopy analyses show that NH and NH2 radicals conduce to the deposition of AlN films and H radicals selectively dissociate Al–OH bonds which were on AlN film surface and etch deposition films. Atomic force microscopy measurements show that the 1500 W prepared AlN film with smallest surface roughness may be related to the relatively smaller concomitant crystal grains of (100) and (002). X-ray photoelectron spectroscopy investigation presents that oxygen content decreases as the plasma power increases. The obtained maximum value of dielectric constant and breakdown electrical field of AlN film deposited at 3000 W is 8.23 and 5.42 MV/cm, respectively.

Fe–TiB2 composite shows great potential in lightweight materials for automotive parts due to its lightweight, high strength and high specific modulus etc. However, challenges remain with regard to establishing a fine hot working process of Fe–TiB2 composites. Here, a series of isothermal hot compression tests was conducted to systematically investigate the microstructure evolution and the dynamic recrystallization (DRX) mechanisms of as-cast Fe–TiB2 composites at different sets of hot deformation parameters. The results indicate the true stress drops more significantly after reaching its peak at low temperatures compared to high temperatures, since low temperatures favors the DRX through particle stimulated nucleation (PSN) in Fe–TiB2 composites, as featured by layers of DRXed grains surrounding TiB2 particles. Continuous dynamic recrystallization (CDRX) process gradually dominates as strain rate increase from 0.01 s−1 to 1 s−1 in Fe–TiB2 composites hot compressed to the true strain of 0.69 at 900 °C, as evidenced by the presence of DRXed grains with larger size and uniform distribution in matrix. DRX through PSN is the primary DRX mechanism at low temperature and low strain rate, while CDRX dominates the DRX mechanism at high temperature and high strain rate. Both DRX behaviors deepen with the increase of the strain. Different hot deformation parameters favor different DRX mechanisms. The increase in temperature and strain rate leads to a transition of the dominant recrystallization mechanism from the DRX through PSN to CDRX which is attributed to the competition for stored energy between the DRX through PSN and CDRX process.

The enteric virome, comprising a complex community of viruses inhabiting the gastrointestinal tract, plays a significant role in health and disease dynamics. In this study, the fecal sample of a wild snow leopard was subjected to viral metagenomic analysis using a double barcode Illumina MiSeq platform. The resulting reads were de novo assembled into contigs with SOAPdenovo2 version r240. Additional bioinformatic analysis of the assembled genome and genome annotation was done using the Geneious prime software (version 2022.0.2). Following viral metagenomic analysis and bioinformatic analysis, a total of 7 viral families and a novel specie of bocaparvovirus tentatively named Panthera uncia bocaparvovirus (PuBOV) with GenBank accession number OQ627713 were identified. The complete genome of PuBOV was predicted to contain 3 open reading frames (ORFs), contains 5433 nucleotides and has a G + C content of 47.40 %. BLASTx analysis and pairwise sequence comparison indicated the novel virus genome was a new species in the genus Bocaparvovirus based on the species demarcation criteria of the International Committee on the Taxonomy of Viruses. This study provides valuable insights into the diversity and composition of the enteric virome in wild endangered snow leopards. The identification and characterization of viruses in wildlife is crucial for developing effective strategies to manage and mitigate potential zoonotic and other viral disease threats to human and animal health.

Diabetic kidney disease (DKD) is leading causes and one of the fastest growing causes of chronic kidney disease worldwide, and leads to high morbidity and mortality. Emerging evidences have revealed gut microbiota dysbiosis and related metabolism dysfunction play a dominant role in DKD progression and treatment through modulating inflammation. Our previous studies showed that Tangshen Formula (TSF), a Chinese herbal prescription, exhibited anti-inflammatory effect on DKD, but underlying mechanism that involved gut microbiota and related metabolism in aged model remained obscure. Here, BTBR ob/ob mice were used to establish aged DKD model, and 16S rRNA sequence and untargeted metabolomic analyses were employed to investigate the correlation between colonic microbiota and serum metabolism. The aged ob/ob mice exhibited obvious glomerular and renal tubule injury and kidney function decline in kidney, while TSF treatment significantly attenuated these abnormalities. TSF also exhibited potent anti-inflammatory effect in aged ob/ob mice indicating by reduced proinflammatory factor IL-6 and TNF-α, MCP-1 and COX-2 in serum, kidney and intestine, which suggested the involvement of gut microbiota with TSF effect. The 16S rDNA sequencing of the colonic microbiome and untargeted serum metabolomics analysis revealed significant differences in gut microbiota structure and serum metabolomic profiles between WT and ob/ob mice. Notably, TSF treatment reshaped the structure of gut microbiota and corrected the disorder of metabolism especially tryptophan metabolism and arginine biosynthesis. TSF increased Anaeroplasma and Barnesiella genera and decreased Romboutsia, Akkermansia, and Collinsella genera, and further elevated tryptophan, 5-hydroxyindoleacetate, glutamic acid, aspartate and reduced 4-hydroxy-2-quinolinecarboxylic acid, indole-3-acetic acid, xanthurenic acid, glutamine. Further correlation analysis indicated that disturbed gut microbiota was linked to tryptophan metabolism and arginine biosynthesis to regulate inflammation in aged DKD. Our data revealed that TSF attenuated renal inflammation by modulating gut microbiota and related amino acid metabolism in aged DKD model, highlighting gut microbiota and related metabolism functioned as potential therapeutic target for DKD in elderly patients.

Sleep is essential to animals with circadian rhythms. Sleep deprivation causes serious pathophysiological consequences, such as DNA damage and oxidative stress. Pyrroloquinoline quinone (PQQ) is a bioactive food ingredient with antioxidant properties. Here, we used zebrafish continuous swimming paradigm sleep deprivation model to investigate the effect of PQQ on DNA damage. We found that DNA damage and neuronal activity increase following sleep deprivation. PQQ pretreatment reduced DNA damage in the zebrafish dorsal pallium. As an antioxidant, PQQ effectively inhibited reactive oxygen species (ROS) production induced by 2,2′-azobis-2-methyl-propanimidamide dihydrochloride (AAPH) and sleep deprivation, and upregulated the expression of antioxidant genes sod1 and gpx4b. Also, PQQ ameliorated the decreased silent information regulator 1 (SIRT1) expression level, suggesting that PQQ may remove excessive ROS by activating SIRT1, thereby reducing DNA damage within neurons. This study indicates that PQQ has strong antioxidant function, provides ideas for further development of ingredients for sleep recovery.

Background & Aims: Thrombospondin-2 (THBS2) expression is associated with liver fibrosis regardless of etiology. However, the role of THBS2 in the pathogenesis of liver fibrosis has yet to be elucidated. Methods: The in vivo effects of silencing Thbs2 in hepatic stellate cells (HSCs) were examined using an adeno-associated virus vector (serotype 6, AAV6) containing short-hairpin RNAs targeting Thbs2, under the regulatory control of cytomegalovirus, U6 or the α-smooth muscle promoter, in mouse models of carbon tetrachloride or methionine-choline deficient (MCD) diet-induced liver fibrosis. Crosstalk between THBS2 and toll-like receptor 4 (TLR4), as well as the cascaded signaling, was systematically investigated using mouse models, primary HSCs, and human HSC cell lines. Results: THBS2 was predominantly expressed in activated HSCs and dynamically increased with liver fibrosis progression and decreased with regression. Selective interference of Thbs2 in HSCs retarded intrahepatic inflammatory infiltration, steatosis accumulation, and fibrosis progression following carbon tetrachloride challenge or in a dietary model of metabolic dysfunction-associated steatohepatitis. Mechanically, extracellular THBS2, as a dimer, specifically recognized and directly bound to TLR4, activating HSCs by stimulating downstream profibrotic focal adhesion kinase (FAK)/transforming growth factor beta (TGF-β) pathways. Disruption of the THBS2-TLR4-FAK/TGF-β signaling axis notably alleviated HSC activation and liver fibrosis aggravation. Conclusions: THBS2 plays a crucial role in HSC activation and liver fibrosis progression through TLR4-FAK/TGF-β signaling in an autocrine manner, representing an attractive potential therapeutic target for liver fibrosis. Impact and implications: Thrombospondin-2 (THBS2) is emerging as a factor closely associated with liver fibrosis regardless of etiology. However, the mechanisms by which THBS2 is involved in liver fibrosis remain unclear. Here, we showed that THBS2 plays a prominent role in the pathogenesis of liver fibrosis by activating the TLR4-TGF-β/FAK signaling axis and hepatic stellate cells in an autocrine manner, providing a potential therapeutic target for the treatment of liver fibrosis.

In recent years, several monoclonal antibodies (mAbs) targeting PD-L1 have been licensed by the FDA for use in the treatment of cancer, demonstrating the effectiveness of blocking immune checkpoints, particularly the PD-1/PD-L1 pathway. Although mAb-based therapies have made great strides, they still have their limitations, and new small-molecule or PROTAC-molecule inhibitors that can block the PD-1/PD-L1 axis are desperately needed. Therefore, it is crucial to translate initial in vitro discoveries into appropriate in vivo animal models when creating PD-L1-blocking therapies. Due to their widespread availability and low experimental expenses, classical immunocompetent mice are appealing for research purposes. However, it is yet unclear whether the mouse (m) PD-L1 interaction with human (h) PD-1 in vivo would produce a functional immunological checkpoint. In this review, we summarize the in vitro and in vivo experimental studies of small molecules and PROTAC molecules, particularly the distinctions between mPD-L1 as a target and hPD-L1 as a target.

Pigs are natural host to various zoonotic pathogens including viruses. In this study, we analyzed the viral communities in the feces of 89 piglets with diarrhea under one month old which were collected from six farms in Jiangsu Province of the Eastern China, using the unbiased virus metagenomic method. A total of 89 libraries were constructed, and 46937894 unique sequence reads were generated by Illumina sequencing. Overall, the family Picornaviridae accounted for the majority of the total reads of putative mammalian viruses. Ten novel virus genomes from different family members were discovered, including Parvoviridae (n = 2), Picobirnaviridae (n = 4) and CRESS DNA viruses (n = 4). A large number of phages were identified, which mainly belonged to the order Caudovirales and the family Microviridae. Moreover, some identified viruses were closely related to viruses found in non-porcine hosts, highlighting the potential for cross-species virus dissemination. This study increased our understanding of the fecal virus communities of diarrhea piglets and provided valuable information for virus monitoring and preventing.