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Summary: Sleep deprivation (SD) has been reported to induce intestinal damage by several mechanisms, yet its role in modulating epithelial repair remains unclear. In this study, we find that chronic SD leads to colonic damage through continuous hypoxia. However, HIF1α, which generally responds to hypoxia to modulate barrier integrity, was paradoxically dysregulated in the colon. Further investigation revealed that a metabolic disruption during SD causes accumulation of α-ketoglutarate in the colon. The excessive α-ketoglutarate degrades HIF1α protein through PHD2 (prolyl hydroxylase 2) to abolish the intestinal repair functions of HIF1α. Collectively, these findings provide insights into how SD can exacerbate intestinal damage by fine-tuning metabolism to abolish HIF1α-mediated repair.

Plasmid-mediated conjugative transfer of antibiotic resistance genes (ARGs) within the human and animal intestine represents a substantial global health concern. linoleic acid (LA) has shown promise in inhibiting conjugation in vitro, but its in vivo effectiveness in the mammalian intestinal tract is constrained by challenges in efficiently reaching the target site. Recent advancements have led to the development of waterborne polyurethane nanoparticles for improved drug delivery. In this study, we synthesized four waterborne polyurethane nanoparticles incorporating LA (WPU@LA) using primary raw materials, including N-methyldiethanolamine, 2,2'-(piperazine-1,4-diyl) diethanol, isophorone diisocyanate, castor oil, and acetic acid. These nanoparticles, identified as WPU0.89@LA, WPU0.99@LA, WPU1.09@LA, and WPU1.19@LA, underwent assessment for their pH-responsive release property and biocompatibility. Among these, WPU0.99@LA displayed superior pH-responsive release properties and biocompatibility towards Caco-2 and IPEC-J2 cells. In a mouse model, a dosage of 10 mg/kg/day WPU0.99@LA effectively reduced the conjugation of IncX4 plasmids carrying the mobile colistin resistance gene (mcr-1) by more than 45.1-fold. In vivo toxicity assessment demonstrated that 10 mg/kg/day WPU0.99@LA maintains desirable biosafety and effectively preserves gut microbiota homeostasis. In conclusion, our study provides crucial proof-of-concept support, demonstrating that WPU0.99@LA holds significant potential in controlling the spread of antibiotic resistance within the mammalian intestine.

Abstract Photonic quantum computation plays an important role and offers unique advantages. Two decades after the milestone work of Knill-Laflamme-Milburn, various architectures of photonic processors have been proposed, and quantum advantage over classical computers has also been demonstrated. It is now the opportune time to apply this technology to real-world applications. However, at current technology level, this aim is restricted by either programmability in bulk optics or loss in integrated optics for the existing architectures of processors, for which the resource cost is also a problem. Here we present a von-Neumann-like architecture based on temporal-mode encoding and looped structure on table, which is capable of multimode-universal programmability, resource-efficiency, phase-stability and software-scalability. In order to illustrate these merits, we execute two different programs with varying resource requirements on the same processor, to investigate quantum signature of chaos from two aspects: the signature behaviors exhibited in phase space (13 modes), and the Fermi golden rule which has not been experimentally studied in quantitative way before (26 modes). The maximal program contains an optical interferometer network with 1694 freely-adjustable phases. Considering current state-of-the-art, our architecture stands as the most promising candidate for real-world applications.

Soft hydrogels are excellent candidate materials for repairing various tissue defects, yet the mechanical strength, anti-swelling properties, and biocompatibility of many soft hydrogels need to be improved. Herein, inspired by the nanostructure of collagen fibrils, we developed a strategy toward achieving a soft but tough, anti-swelling nanofibrillar hydrogel by combining the self-assembly and chemical crosslinking of nanoparticles. Specifically, the collagen fibril-like injectable hydrogel was subtly designed and fabricated by self-assembling methylacrylyl hydroxypropyl chitosan (HM) with laponite (LAP) to form nanoparticles, followed by the inter-nanoparticle bonding through photo-crosslinking. The assembly mechanism of nanoparticles was elucidated by both experimental and simulation techniques. Due to the unique structure of the crosslinked nanoparticles, the nanocomposite hydrogels exhibited low stiffness (G’< 2 kPa), high compressive strength (709 kPa), and anti-swelling (swelling ratio of 1.07 in PBS) properties. Additionally, by harnessing the photo-crosslinking ability of the nanoparticles, the nanocomposite hydrogels were processed as microgels, which can be three-dimensionally (3D) printed into complex shapes. Furthermore, we demonstrated that these nanocomposite hydrogels are highly biocompatible, biodegradability, and can effectively promote fibroblast migration and accelerate blood vessel formation during wound healing. This work presents a promising approach to develop biomimetic, nanofibrillar soft hydrogels for regenerative medicine applications.

Rheumatoid arthritis (RA) is a prevalent autoimmune disease that involves the overgrowth and inflammation of synovial tissue, leading to the degeneration and impairment of joints. In recent years, numerous studies have shown a close relationship between the hypoxic microenvironment in joints and the occurrence and progression of RA. The main cause of the pathological changes in RA is widely believed to be the abnormal expression of hypoxia-inducible factor-1 (HIF-1) in joints. This paper describes and illustrates the structure and primary functions of HIF-1 and explains the main regulatory methods of HIF-1, including the PHDs/HIF-1/pVHL pathway, factor-inhibiting HIF (FIH), regulation of inflammatory cytokines, and the NF-B pathway. Furthermore, this paper discusses the mechanism of HIF-1 and its impact on inflammation, angiogenesis, and cartilage destruction in greater detail. We summarize previous research findings on the mechanism of HIF-1 and propose new potential treatments for RA based on the pathogenesis of HIF-1 in RA.

Abstract Background The triglyceride glucose-body mass index (TyG-BMI index) has been suggested as a novel predictor of insulin resistance. However, its predictive value for slow coronary flow phenomenon (SCFP) in patients with ischemia and nonobstructive coronary arteries (INOCA) remains unclear. Methods We consecutively recruited 1625 patients with INOCA from February 2019 to February 2023 and divided them into two groups based on thrombolysis in myocardial infarction (TIMI) frame counts (TFCs): the SCFP group (n = 79) and the control group. A 1:2 age-matched case–control study was then performed. The TyG-BMI index was calculated as ln [plasma triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2] × BMI. Results TyG-BMI index in the SCFP group (218.3 ± 25.2 vs 201.0 ± 26.5, P

Essential oils are potential alternatives to antibiotics for preventing Candida albicans (C. albicans) infection which is responsible for economic losses in the pigeon industry. Cymbopogon martini essential oil (EO) can inhibit pathogens, particularly fungal pathogens but its potential beneficial effects on C. albicans-infected pigeons remain unclear. Therefore, we investigated the impact of C. martini EO on antioxidant activity, immune response, intestinal barrier function, and intestinal microbiota in C. albicans-infected pigeons. The pigeons were divided into four groups as follows: (1) NC group: C. albicans uninfected/C. martini EO untreated group; (2) PC group: C. albicans infected/C. martini EO untreated group; (3) LPA group: C. albicans infected/1% C. martini EO treated group; and (4) HPA group: C. albicans infected/2% C. martini EO treated group. The pigeons were infected with C. albicans from day of age 35 to 41 and treated with C. martini EO from day of age 42 to 44, with samples collected on day of age 45 for analysis. The results demonstrated that C. martini EO prevented the reduction in the antioxidant enzymes SOD and GSH-Px causes by C. albicans challenge in pigeons. Furthermore, C. martini EO could decrease the relative expression of IL-1β, TGF-β, and IL-8 in the ileum, as well as IL-1β and IL-8 in the crop, while increasing the relative expression of Claudin-1 in the ileum and the crop and Occludin in the ileum in infected pigeons. Although the gut microbiota composition was not significantly affected by C. martini EO, 2% C. martini EO increased the abundance of Alistipes and Pedobacter. In conclusion, the application of 2% C. martini EO not only enhanced the level of antioxidant activity and the expression of genes related to intestinal barrier function but also inhibited inflammatory genes in C. albicans-infected pigeons and increased the abundance of gut bacteria that are resistant to C. albicans.

Abstract Despite the diverse roles of tripartite motif (Trim)-containing proteins in the regulation of autophagy, the innate immune response, and cell differentiation, their roles in skeletal diseases are largely unknown. We recently demonstrated that Trim21 plays a crucial role in regulating osteoblast (OB) differentiation in osteosarcoma. However, how Trim21 contributes to skeletal degenerative disorders, including osteoporosis, remains unknown. First, human and mouse bone specimens were evaluated, and the results showed that Trim21 expression was significantly elevated in bone tissues obtained from osteoporosis patients. Next, we found that global knockout of the Trim21 gene (KO, Trim21 −/−) resulted in higher bone mass compared to that of the control littermates. We further demonstrated that loss of Trim21 promoted bone formation by enhancing the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and elevating the activity of OBs; moreover, Trim21 depletion suppressed osteoclast (OC) formation of RAW264.7 cells. In addition, the differentiation of OCs from bone marrow-derived macrophages (BMMs) isolated from Trim21 −/− and Ctsk-cre; Trim21 f/f mice was largely compromised compared to that of the littermate control mice. Mechanistically, YAP1/β-catenin signaling was identified and demonstrated to be required for the Trim21-mediated osteogenic differentiation of BMSCs. More importantly, the loss of Trim21 prevented ovariectomy (OVX)- and lipopolysaccharide (LPS)-induced bone loss in vivo by orchestrating the coupling of OBs and OCs through YAP1 signaling. Our current study demonstrated that Trim21 is crucial for regulating OB-mediated bone formation and OC-mediated bone resorption, thereby providing a basis for exploring Trim21 as a novel dual-targeting approach for treating osteoporosis and pathological bone loss.

The genus Amomum includes over 111 species, 6 of which are widely utilized as medicinal plants and have already undergone taxonomic revision. Due to their morphological similarities, the presence of counterfeit and substandard products remains a challenge. Accurate plant identification is, therefore, essential to address these issues. This study utilized 11 newly sequenced samples and extensive NCBI data to perform molecular identification of the six medicinal “Doukou” species. The plastomes of these species exhibited a typical quadripartite structure with a conserved gene content. However, independent variation shifts of the SC/IR boundaries existed between and within species. The comprehensive set of genetic sequences, including ITS, ITS1, ITS2, complete plastomes, matK, rbcL, psbA-trnH, and ycf1, showed varying discrimination of the six “Doukou” species based on both distance and phylogenetic tree methods. Among these, the ITS, ITS1, and complete plastome sequences demonstrated the highest identification success rate (3/6), followed by ycf1 (2/6), and then ITS2, matK, and psbA-trnH (1/6). In contrast, rbcL failed to identify any species. This research established a basis for a reliable molecular identification method for medicinal “Doukou” plants to protect wild plant resources, promote the sustainable use of medicinal plants, and restrict the exploitation of these resources.

Objectives. Traditional Chinese medicine Cortex Eucommiae has been used to treat bone fracture for hundreds of years, which exerts a significant improvement in fracture healing. Aucubin, a derivative isolated from Cortex Eucommiae, has been demonstrated to possess anti-inflammatory, immunoregulatory, and antioxidative potential. In the present study, our aim was to explore its function in bone regeneration and elucidate the underlying mechanism. Materials and Methods. The effects of Aucubin on osteoblast and osteoclast were examined in mouse bone marrow-derived mesenchymal stem cells (BM-MSCs) and RAW 264.7 cells, respectively. Moreover, the lncRNA H19 and Wnt/β-catenin signaling were detected by qPCR examination, western blotting, and luciferase activity assays. Using the femur fracture mice model, the in vivo effect of Aucubin on bone formation was monitored by X-ray, micro-CT, histomorphometry, and immunohistochemistry staining. Results. In the present study, Aucubin was found to significantly promote osteogenic differentiation in vitro and stimulated bone formation in vivo. Regarding to the underlying mechanism, H19 was found to be obviously upregulated by Aucubin in MSCs and thus induced the activation of Wnt/β-catenin signaling. Moreover, H19 knockdown partially reversed the Aucubin-induced osteogenic differentiation and successfully suppressed the activation of Wnt/β-catenin signaling. We therefore suggested that Aucubin induced the activation of Wnt/β-catenin signaling through promoting H19 expression. Conclusion. Our results demonstrated that Aucubin promoted osteogenesis in vitro and facilitated fracture healing in vivo through the H19-Wnt/β-catenin regulatory axis.

Abstract Hexagonal boron nitride (hBN) is a remarkable two-dimensional (2D) material that hosts solid-state spins and has great potential to be used in quantum information applications, including quantum networks. However, in this application, both the optical and spin properties are crucial for single spins but have not yet been discovered simultaneously for hBN spins. Here, we realize an efficient method for arraying and isolating the single defects of hBN and use this method to discover a new spin defect with a high probability of 85%. This single defect exhibits outstanding optical properties and an optically controllable spin, as indicated by the observed significant Rabi oscillation and Hahn echo experiments at room temperature. First principles calculations indicate that complexes of carbon and oxygen dopants may be the origin of the single spin defects. This provides a possibility for further addressing spins that can be optically controlled.

Background: Mixed lineage kinase 3 (MLK3) is a member of a serine/threonine MAP3K family, and it has been demonstrated to play critical roles in various biological activities and disease progression. Previous studies showed that impaired skeletal mineralization and spontaneous tooth fracture in the MLK3-deficient mice, suggesting MLK3 actively participated in the bone formation. However, the detailed function and underlying mechanisms remain obscure. Methods: The MLK3 knockout (KO) mouse was applied in the present study, and multi-omics were performed to compare the metabolites and gene expression between wild type (WT) and KO mice. The bone fracture model was successfully established, and the healing process was evaluated by X-ray, micro-CT examination, histomorphometry and immunohistochemistry (IHC) staining. On the other hand, the effects of MLK3 on osteogenic differentiation were assessed by alkaline phosphatase (ALP) activity, Alizarin red S (ARS) staining and qRT-PCR examination. Finally, the downstream signaling pathways were screened out by RNA-sequencing (RNA-seq) and then validated by Western blotting. Results: In the present study, imbalanced bone metabolism was observed in these MLK3 KO mice, suggesting MLK3 may participate in bone development. Moreover, MLK3 −/− mice displayed abnormal bone tissues, impaired bone quality, and delayed fracture healing. Further investigation showed that the inhibition of MLK3 attenuated osteoblast differentiation in vitro. According to the RNA-seq data, MAPK signaling was screened out to be a downstream pathway, and its subfamily members extracellular signal-regulated kinase (ERK), p38 and Jun N-terminal protein kinase (JNK) were subjected to Western blotting examination. The results revealed that although no differences in their expression were observed between MSCs derived from WT and KO mice, their phosphorylated protein levels were all suppressed in MLK3 −/− MSCs. Conclusion: In conclusion, our results demonstrated that loss of MLK3 suppressed osteoblast differentiation and delayed bone formation via influencing metabolism and disturbing MAPK signaling. The translational potential of this article: The findings based on the current study demonstrated that MLK3 promoted osteogenesis, stimulated new bone formation and facilitated fracture healing, suggesting that MLK3 may serve as a potential therapeutic target for bone regeneration. MLK3 activator therefore may be developed as a therapeutic strategy for bone fracture.

Abstract Hexagonal boron nitride (hBN) has recently been demonstrated to contain optically polarized and detected electron spins that can be utilized for implementing qubits and quantum sensors in nanolayered-devices. Understanding the coherent dynamics of microwave driven spins in hBN is of crucial importance for advancing these emerging new technologies. Here, we demonstrate and study the Rabi oscillation and related phenomena of a negatively charged boron vacancy (V $${}_{{{{{{{{\rm{B}}}}}}}}}^{-}$$ B − ) spin ensemble in hBN. We report on different dynamics of the V $${}_{{{{{{{{\rm{B}}}}}}}}}^{-}$$ B − spins at weak and strong magnetic fields. In the former case the defect behaves like a single electron spin system, while in the latter case it behaves like a multi-spin system exhibiting multiple-frequency dynamical oscillation as beat in the Ramsey fringes. We also carry out theoretical simulations for the spin dynamics of V $${}_{{{{{{{{\rm{B}}}}}}}}}^{-}$$ B − and reveal that the nuclear spins can be driven via the strong electron nuclear coupling existing in V $${}_{{{{{{{{\rm{B}}}}}}}}}^{-}$$ B − center, which can be modulated by the magnetic field and microwave field.

Abstract Background China has successfully reduced tuberculosis (TB) incidence rate over the past three decades, however, challenges remain in improving the quality of TB diagnosis and treatment. In this paper, we assess the effects of the implementation of “China National Health Commission (NHC) and Gates Foundation TB Prevention and Control Project” on the quality of TB care in the three provinces. Methods We conducted the baseline study in 2016 and the final evaluations in 2019 in the 12 selected project counties. We obtained TB patients’ information from the TB Information Management System and reviewed medical records of TB cases in the TB designated hospitals. We compared TB diagnosis and treatment services with the national practice guideline and used Student’s t-test and Pearson χ 2 tests or Fisher’s exact tests to compare the difference before and after the project implementation. Results The percentage of sputum smear-negative (SS–) patients taking culture or rapid molecular test (RMT) doubled between 2015 and 2018 (from 35% to 87%), and the percentage of bacteriologically confirmed pulmonary TB cases increased from 36% to 52%. RMT has been widely used and contributed an additional 20% of bacteriologically confirmed TB cases in 2018. The percentage of TB patients taking drug susceptibility tests (DST) also doubled (from 40% in 2015 to 82% in 2018), and the proportion of TB patients receiving adequate diagnosis services increased from 85% to 96%. Among all SS– TB patients, over 86% received the recommended diagnostic services at the end of the study period, an improvement from 75% prior to the project implementation. However, the proportion of TB patients treated irrationally using second-line anti-TB drugs (SLDs) increased from 12.6% in 2015 to 19.9% in 2018. The regional disparities remained within the project provinces, albeit the gaps between them narrowed down for almost all indicators. Conclusions The quality of TB diagnosis services has been improved substantially, which is attributable to the coverage of new diagnosis technology. However, irrational use of SLDs remains a concern after the project implementation. Graphic abstract

Abstract Background The China National Health Commission-Gates TB Project Phase III implemented a comprehensive TB control model including multiple interventions to address the burden of drug-resistant TB (DRTB). This study aims to evaluate the quality of DRTB clinical services and assess the financial burden of DRTB patients during the intervention period. Methods A mixed-methods approach was used to evaluate the effectiveness of interventions in the three project provinces: Zhejiang, Jilin and Ningxia Hui Autonomous Region. The quantitative data included de-identified DRTB registry data during 2015–2018 in project provinces from China CDC, medical records of DRTB patients registered in 2018 (n = 106) from designated hospitals, and a structured DRTB patient survey in six sample prefectures in 2019. The quality of clinical services was evaluated using seven indicators across patient screening, diagnosis and treatment. Logistic regression was conducted to explore factors associated with the extremely high financial burden. Semi-structured in-depth interviews with policymakers and focus group discussions with physicians and DRTB patients were conducted to understand the interventions implemented and their impacts. Results The percentage of bacterially confirmed patients taking a drug susceptibility test (DST) increased significantly between 2015 and 2018: from 57.4 to 93.6% in Zhejiang, 12.5 to 86.5% in Jilin, and 29.7 to 91.4% in Ningxia. The treatment enrollment rate among diagnosed DRTB patients also increased significantly and varied from 73 to 82% in the three provinces in 2018. Over 90% of patients in Zhejiang and Jilin and 75% in Ningxia remained in treatment by the end of the first six months’ treatment. Among all survey respondents 77.5% incurred extremely high financial burden of treatment. Qualitative results showed that interventions on promoting rapid DST technologies and patient referral were successfully implemented, but the new financing policies for reducing patients’ financial burden were not implemented as planned. Conclusions The quality of DRTB related clinical services has been significantly improved following the comprehensive interventions, while the financial burden of DRTB patients remains high due to the delay in implementing financing policies. Stronger political commitment and leadership are required for multi-channel financing to provide additional financial support to DRTB patients.

Leveraging the properties of the first three linear moments (L-moments), this study proposes an effective normal transformation for structural reliability analysis considering correlated input random variables, in which the admissible range of the initial correlation matrix when employing this transformation is also presented. Subsequently, a practical procedure for structural reliability analysis, grounded in the proposed transformation and first-order reliability method (FROM), is proposed, accommodating instances wherein the joint probability density functions (PDFs) or marginal PDFs of the relevant random variables remain unknown. In comparison to the technique premised on the first three central moments (C-moments), the proposed method, based on the first three L-moments, exhibits a more extensive applicability. Various practical scenarios showcase the method’s effectiveness and precision in calculating the structural reliability index, considering diverse distributions, numerous variables, and complex structures.

An experimental study was carried out to investigate the flame propagation and thermal hazard of the premixed N2O/fuel mixtures, including NH3, C3H8 and C2H4. The study provided the high speed video images and data about the flame locations, propagation patterns, overpressures and the quenching diameters during the course of combustion in different channels to elucidate the dynamics of various combustion processes. The onset decomposition temperature was determined using high-performance adiabatic calorimetry. It was shown that the order of the flame acceleration rate and thermal hazard was N2O/C2H4>N2O/C3H8>N2O/NH3.

The continuous improvement of people’s living standards and quality puts higher and higher demands on polymer materials, and damping materials such as polyurethane elastomer used for vibration and noise reduction have also received increasing attention. However, the application of polyurethanes is limited to some extent owing to the narrow effective damping temperature range of polyurethane. Therefore, polyurethane containing a branched chain has been prepared from the perspective of its structural designability, in which the prepolymer synthesized by the reaction of polyethylene glycol monomethyl ether (MPEG) with toluene 2,4-diisocyanate (TDI) is performed as a branched chain. Herein, the long branched chain with one end fixed at the end gives its unique movement and relaxation, contributing to the superior damping performance of polyurethane to some extent, and the presence of TDI not only prolongs the length of the branch and increases the entanglement degree between the branches and the molecules but also makes the branches contain a strong polar electron-withdrawing isocyanate group and a urethane group, impacting the branch and the main chain with strong hydrogen bonding effect. Herein, the influencing factors of polyurethane on damping property are explored separately from the perspective of hydrogen bonding and microphase separation. By means of Fourier transform infrared spectroscopy (FTIR), dynamic mechanical analysis (DMA), atomic force microscopy (AFM), and broadband dielectric relaxation spectroscopy, the results show that E'30 °C/E'70 °C is able to reach 268.28 with the increased proportion of branches, indicating the dropped degree of microphase separation of polyurethanes. Furthermore, the hydrogen bonding effect is enhanced by characterization with FTIR. The two aforementioned effects make the damping properties of polyurethanes more excellent; the effective damping (tan δ ≥ 0.3) can even exceed 150 °C (−50−100 °C). Simultaneously, the polyurethane has a certain self-healing property after the introduction of branches, which is of great significance to extend the service life of polyurethanes

Abstract Gravitational wave (GW) ringdown waveforms may contain “echoes” that encode new physics in the strong gravity regime. It is commonly assumed that the new physics gives rise to the GW echoes whose intervals are constant. We point out that this assumption is not always applicable. In particular, if the post-merger object is initially a wormhole, which slowly pinches off and eventually collapses into a black hole, the late-time ringdown waveform exhibit a series of echoes whose intervals are increasing with time. We also assess how this affects the ability of Advanced LIGO/Virgo to detect these new signals.

Polysaccharides are considered the main active ingredient for the immune-enhancing effect of Radix Astragali, which is popularly used as medicinal food supplementary. The signal pathways involved in immune-enhancing effect remain unclear. This study is to investigate the role and regulation relation of Akt pathway with downstream kinases of TLR4 receptor in macrophages induced by Astragalus polysaccharide, RAP. The results showed that RAP induced phosphorylation of Akt, NFκB, IRF3 and MAPKs in RAW264.7 cells, and their individual inhibitors not only inhibited their inflammatory factors production and gene expression, but also suppressed the Akt phosphorylation, while Akt inhibitor exerted no effect on MAPKs, NFκB, and IRF3 phosphorylation. Taken together, these results suggested that Akt and IRF3 exerted activation role in RAP induced macrophage, and Akt exerted effect downstream of MyD88 dependent and independent pathway. This study will provide a deeper insight into the signal transduction induced by Astragalus polysaccharides.

As a kind of food supplementary, polysaccharide-rich tonic herbs become more and more popular. However, little is known regarding the interaction between known active molecules with these polysaccharides. This study aims to investigate effects of luteolin on RAW264.7 cells induced by Astragalus polysaccharide RAP in comparison with lipopolysaccharide (LPS). The results showed that luteolin suppressed inflammatory meditors in LPS-induced RAW264.7 cells. While in the RAP-induced RAW264.7 cells, luteolin only decreased the NO production and iNOS gene expression, but only inhibit IL-6 at high concentration, and was ineffective in term of TNF-α. The results of western blot analysis suggested that luteolin only inhibited the phosphorylation of NF-κB p65 and Akt, but not MAPKs and IRF3 in RAP-induced RAW264.7 cells. Taken together, lutelion exerted less inhibitory effect on macrophage induced by RAP than by LPS. This study demonstrated the luteolin-containing foods may not strongly interfere the immunoregulation effect of polysaccharide RAP.

Rice area has been expanding rapidly during the past 30 years under the influence of global change in northeastern China, which is the northernmost region of rice cultivation in China. However, the spatio-temporal dynamic changes in rice area are still unclear, although they may have important policy implications for environmental protection and adaptation to climate change. In this study, we aimed to identify the dynamic changes of the rice area in Heilongjiang Province of northeastern China by extracting data from multiple Landsat images. The study used ground quadrats selected from Google Earth and the extraction of a confusion matrix to verify the accuracy of extraction. The overall accuracy of the extracted rice area was higher than 95% as a result of using the artificial neural network (ANN) classification method. The results showed that the rice area increased by approximately 2.4×106 ha during the past 30 years at an annual rate of 8.0×104 ha, and most of the increase occurred after 2000. The central latitude of the rice area shifted northwards from 46 to 47°N during the study period, and moved eastwards from 130 to 133°E. The rice expansion area accounted for 98% of the total change in rice area, and rice loss was notably rare. The rice expansion was primarily from dryland. In addition, rice cultivation in marshland and grassland played a minor role in the rice expansion in this region.

Purpose: The purpose of this study was to determine if an Astragalus polysaccharide (RAP) can protect immune cells from the toxic side effects of paclitaxel (Taxol), a powerful anti-tumor drug whose equally powerful side effects limit its clinical use.Methods: We hypothesized that RAP can reduce the toxic effects induced by Taxol. To test this hypothesis, we conducted a series of studies in vivo and in vitro. First, we confirmed RAP’s effects in vivo utilizing BALB/c mice inoculated with 4T1 mouse breast cancer cells as the tumor model. Mice were treated with RAP and/or Taxol, and the differences in the life spans were recorded. Second, a co-culture cell model was used to study the protective effect of RAP on cells vis-a-vis Taxol. The cell cycle and apoptosis of RAW 264.7 cells that were treated with RAP with/without Taxol were checked by flow cytometry and Hoechst staining. Proteins involved in the cell cycle and apoptosis were also tested by Western blot to reveal the probable mechanism.Results: RAP prolonged the life span of tumor-bearing mice treated with Taxol. The in vitro experiments showed that Taxol suppressed the proliferation of RAW 264.7 cells while RAP protected the RAW 264.7 cells from Taxol-induced suppression. The protection is selective because RAP had no effect on 4T1 cells. Furthermore, Taxol clearly led to cell cycle arrest mainly at the G2/M phase and generated cytotoxicity against RAW 264.7 cells, while RAP blocked cell cycle arrest and protected cells from apoptosis. Taxol up-regulated the protein levels of P-H2A, PARP, Chk1, p53, and p21 and down-regulated Bcl-Xl and Mcl-1, and RAP reversed the expression of all these proteins.Conclusion: These results suggested that RAP can protect immune cells from Taxol-induced toxicity, by changing the cell cycle and apoptosis.

Electron energy loss spectroscopy (EELS) has been widely used as a chemical analysis technique to characterize materials chemical properties, such as element valence states, atoms/ions bonding environment. This study provides a new method to characterize physical properties (i.e., film uniformity, grain orientations) of non-oxide thin films in the magnetic device by using EELS microanalysis on scanning transmission electron microscope. This method is based on analyzing white line ratio of spectra and related extended energy loss fine structures so as to correlate it with thin film uniformity. This new approach can provide an effective and sensitive method to monitor/characterize thin film quality (i.e., uniformity) at atomic level for thin film development, which is especially useful for examining ultra-thin films (i.e., several nanometers) or embedded films in devices for industry applications. More importantly, this technique enables development of quantitative characterization of thin film uniformity and it would be a remarkably useful technique for examining various types of devices for industrial applications.

Acupuncture can induce changes in the brain. However, the majority of studies to date have focused on a single acupoint at a time. In the present study, we observed activity changes in the brains of healthy volunteers before and after acupuncture at Taichong (LR3) and Taixi (KI3) using resting-state functional magnetic resonance imaging. Fifteen healthy volunteers underwent resting-state functional magnetic resonance imaging of the brain 15 minutes before acupuncture, then received acupuncture at Taichong and Taixi using the nail-pressing needle insertion method, after which the needle was retained in place for 30 minutes. Fifteen minutes after withdrawal of the needle, the volunteers underwent a further session of resting-state functional magnetic resonance imaging, which revealed that the amplitude of low-frequency fluctuation, a measure of spontaneous neuronal activity, increased mainly in the cerebral occipital lobe and middle occipital gyrus (Brodmann area 18/19), inferior occipital gyrus (Brodmann area 18) and cuneus (Brodmann area 18), but decreased mainly in the gyrus rectus of the frontal lobe (Brodmann area 11), inferior frontal gyrus (Brodmann area 44) and the center of the posterior lobe of the cerebellum. The present findings indicate that acupuncture at Taichong and Taixi specifically promote blood flow and activation in the brain areas related to vision, emotion and cognition, and inhibit brain areas related to emotion, attention, phonological and semantic processing, and memory.

In order to explore the rules of the deformation force during the launching of a small-diameter steel cartridge, the semi-closed bomb test method is used to test the greatest strains on chamber outer wall under the different chamber pressures. The pressure curves of cartridge chamber are measured in experiment, and the tensile test data of cartridge are loaded into the numerical calculation to compare with the experimental data. The conclusion was obtained that the calculated results match better with the experimental results by considering strain rate bilinear kinematic hardening material constitutive model. The forces on the various parts of the cartridge during launching and their deformation rules are achieved, in which the equivalent plastic strain decreases and the cylinder ring withstands the maximum equivalent stress when the cartridge case clings to the bore from the mouth to the bottom.

Macrophages occur in polarized phenotypes, whose characteristics determine the role they play in tumor growth. The M1 phenotype macrophages promote tumoricidal responses and suppress tumor growth. Our previous study showed that a polysaccharide isolated from Radix Astragali, named RAP, was itself non-cytotoxic but induced RAW264.7 cells’ cytotoxicity against cancer cells. The current study was undertaken to determine its mechanism. Series studies was conducted to show that RAP is able to induce much higher gene expression of M1 markers, including iNOS, IL-6, TNF-a, and CXCL10, compared with the control group. When RAP-induced BMDMs were transplanted together with 4T1 tumor cells in BALB/c mice, both tumor volume and tumor weight decreased. Further studies indicated that RAP induces the Notch signaling pathway in RAW264.7 cells. The function of Notch signaling in macrophage polarization was confirmed by using γ-secretase inhibitor. These results suggested that Astragalus polysaccharide RAP induces macrophage’s polarization to M1 phenotype via the Notch signaling pathway.

Polysaccharides, which exert immunoregulatory effects, are becoming more and more popular as food supplements; however, certain components of ordinary foods could be reducing the polysaccharides beneficial effects. Quercetin, a flavonoid found in common fruits and vegetables, is one such component. This study investigated the effects of quercetin on Astragalus polysaccharide RAP induced-macrophage activation. The results show quercetin decreases the NO production and iNOS gene expression in RAW264.7 cells, and it inhibits the production of cytokines in RAW264.7 cells and peritoneal macrophages. Western blot analysis results suggest that quercetin inhibits the phosphorylation of Akt/mTORC1, MAPKs, and TBK1, but has no effect on NF-κB in RAP-induced RAW264.7 cells. Taken together, the results show that quercetin partly inhibits macrophage activation by the Astragalus polysaccharide RAP. This study demonstrates that quercetin-containing foods may interfere with the immune-enhancing effects of Astragalus polysaccharide RAP to a certain extent.

Li-ion battery systems, synthesized as epitaxial thin films, can provide powerful insights into their electrochemical processes. Crystallographic analysis shows that many important cathode oxides have an underlying similarity: their structures can be considered as different ordering schemes of Li and transition metal ions within a pseudo-cubic sublattice of oxygen anions arranged in a face-center cubic (FCC) fashion. This oxygen sublattice is compatible with SrTiO3 and similar perovskite oxides, thus perovskites can be used as supporting substrates for growing epitaxial cathode films. The predicted epitaxial growth and crystallographic relations were experimentally verified for different oxide films deposited by pulsed laser deposition (PLD) on SrTiO3 or SrRuO3/SrTiO3 of different orientations. The results based on cross-sectional high-resolution TEM of the following films are presented in the paper: (a) trigonal LiCoO2; (b) orthorhombic LiMnO2; (c) monoclinic Li2MnO3; (d) compositionally-complex monoclinic Li1.2Mn0.55Ni0.15Co0.1O2. All results demonstrated the feasibility of epitaxial growth for these materials, with the growth following the predicted cube-on-cube orientation relationship between the cubic and pseudo-cubic oxygen sublattices of a substrate and a film, respectively.

Dendrobium officinale extract shows potent anti-fatigue effects; however, the active substance responsible for these effects remains undetermined. A glucomannan with a huge molecular size of 730 kDa, called DOP, was identified as the unique authentication marker of this expensive herb. DOP exhibited immunomodulating effects on macrophages and lymphocytes in our previous study. Clinical reports also showed that people with fatigue syndrome have a disturbed immune system. Because DOP is the unique and dominant component of D. officinale, we hypothesize that DOP may also have anti-fatigue activity. The present study aims to evaluate the anti-fatigue activity of DOP on BALB/c mice, with Rhodiola rosea extract as a positive control. DOP and Rhodiola rosea extract were orally administered at doses of 50 mg/kg and 100 mg/kg, respectively, for four weeks, and the anti-fatigue activity of DOP on BALB/c mice was evaluated using the weight-loaded swimming test. The contents of lactic dehydrogenase (LDH), creatine phosphokinase (CK), triglyceride (TG), blood urea nitrogen (BUN), superoxide dismutase (SOD), malondialdehyde (MDA), lactic acid (LD), and glutathione peroxidase (GSH-Px) in serum, glycogen of liver and gastrocnemius muscle were also determined. Their effects on variability of T cells and B cells were determined by using tetrazolium compound (MTS) method. The weight-loaded swimming exercise caused fatigue syndrome, mainly including the decreases of serum SOD/GSH-Px and gastrocnemius glycogen, as well as the increases of LDH, BUN, MDA, CK, TG, and LD in serum. All of these indicators of fatigue were inhibited to a certain extent by both DOP and Rhodiola rosea extract; however, the effects of DOP were much stronger than those of Rhodiola rosea extract. Compared to the positive control, mice dosed with DOP showed increases in endurance, body weight, and food intake. Furthermore, DOP-feeding mice significantly increased the cell variability of T lymphocytes and B lymphocytes, compared with that of mice in control group. This study indicates that the unique and dominant polysaccharide DOP of D. officinale has stronger anti-fatigue activity than Rhodiola rosea extract. As such, DOP has promising potential for pharmaceutical development into health products to reduce fatigue.

The accumulation of misfolded a-synuclein is mechanistically linked to neurodegeneration in Parkinson’s disease (PD) and other alpha-synucleinopathies. However, how alpha-synuclein causes neurodegeneration is unresolved. Several studies have supported the involvement of dynein, the major motor for retrograde axonal transport in alpha-synuclein-dependent neurodegeneration, especially in the nigrostriatal system. Therefore, we examined the nigrostriatal dyneins in transgenic mice that overexpress human A53T alpha-synuclein and recapitulate key features of a PD-like neuronal synucleinopathy. Age-matched nontransgenic littermates were used as controls. The results demonstrated that the protein level of dynein was decreased in the striatum, whereas it was elevated in the substantia nigra. Double immunostaining results revealed that the reduction in dynein level was associated with aggregation of A53T a-synuclein in the striatum. Furthermore, we performed a quantitative analysis of motor behaviors in A53T alpha-synuclein transgenic mice and controls using a modified open field test. We demonstrated that the protein level of dynein in the striatum was significantly correlated with the motor behaviors. Together, our data indicate that dynein changes in the nigrostriatal system of A53T alpha-synuclein transgenic mice may contribute to their severe movement disorder.

In the title compound, C11H14ClNO, the herbicide propachlor, there are significant differences between the three N—C bond lengths [N—Ccarbonyl = 1.354 (3) Å, N—Cphenyl = 1.444 (2) Å and N—Cisopropyl = 1.496 (3) Å], indicating the presence of π delocalization involving the carbonyl group. The N atom lies 0.074 (2) Å from the plane defined by the the three bonded C atoms.