Urbanization impacts on evapotranspiration change across seven typical urban agglomerations in China.

Evaluating the differences in evapotranspiration between urban and surrounding non-urban areas (i.e., ∆ET) has critical implications for urban ecological planning and water resources management. However, it is unclear how the magnitude of changes in ∆ET caused by urbanization varies under different climatic conditions in China. Here, using the remotely ET estimates at 1 km spatial resolution, we firstly estimated the magnitude of changes in ∆ET and then quantified the main driving factors influencing variations in ∆ET of 7 national-level urban agglomerations (UAs) across China during 2003-2020. Results showed that all annual ETurban values were smaller than ETnon-urban of 7 UAs, and the absolute ∆ET values of cities in South China were generally higher than those in North China. There is an apparent effect of urbanization on ∆ET increase in Guanzhong Plain City Group, Central Plain UA and Guangdong-Hong Kong-Macao Greater Bay Area (GHKMGBA), while ∆ET decrease in Chengdu-Chongqing City Group and Yangtze River Delta (YRDUA) were primarily due to the climate change. The suppressing effects of temperature and NDVI on ∆ET decrease in YRDUA were enhanced, and the promoting effect of GDP on ∆ET increase in GHKMGBA was weakened. Considering nonstationary features, urbanization appears to heighten extreme ∆ET by 0.83 %, 4.83 % and 10.39 % under 5-year, 20-year, and 50-year return periods over all the 7 UAs, respectively. Collectively, our findings confirm that urbanization is a significant factor that leads to ∆ET increase, and the factors affecting the response of urban water circulation system need to be deeply decomposed.

Genome-Driven Discovery of Antiviral Atralabdans A-C from the Soil-Dwelling Streptomyces atratus.

Heterologous expression of an atr terpenoid gene cluster derived from Streptomyces atratus Gö66 in S. albus J1074 led to the discovery of three novel labdane diterpenoids featuring an unprecedented 6/6/5-fused tricyclic skeleton, designated as atralabdans A-C (1-3), along with a known compound, labdanmycin A. Compounds 1-3 were identified through extensive spectroscopic analysis, including NMR calculations with DP4+ probability analysis, and a comparative assessment of experimental and theoretical electronic circular dichroism (ECD) spectra. A plausible biosynthetic pathway for these compounds was proposed. Compounds 1-3 exhibited inhibitory activity against the human neurotropic coxsackievirus B3 (CVB3); 1 was the most potent, surpassing the positive control ribavirin with a higher therapeutic index.

Assessment of monthly runoff simulations based on a physics-informed machine learning framework: The effect of intermediate variables in its construction.

Hydrological forecasting is of great importance for water resources management and planning, especially given the increasing occurrence of extreme events such as floods and droughts. The physics-informed machine learning (PIML) models effectively integrate conceptual hydrologic models with machine learning (ML) models. In this process, the intermediate variables of PIML models serve as bridges between inputs and outputs, while the impact of intermediate variables on the performance of PIML models remains unclear. To fill this knowledge gap, this study aims to encompass the construction of PIML models based on various hydrologic models, conduct comparative analyses of different intermediate variables based on a case study of 205 CAMELS basins, and further explore the relationship between the performance of PIML models and catchment characteristics. The optimal ML model for constructing PIML is first selected among four ML models within the 205 basins. The PIML models are then developed based on five monthly water balance models, namely TM, XM, MEP, SLM, and TVGM. To quantify the potential impact of difference in intermediate variables, two sets of experiments are further designed and performed, namely S1 with actual evapotranspiration as the intermediate variable and S2 with soil moisture as the intermediate variable. Results show that five PIML models generally outperformed the optimal standalone ML models, i.e., the Lasso model. Specifically, regardless of the choice of intermediate variables, the PIML-XM model consistently outperformed the other models within the same basins. Almost all constructed PIML models are affected by the intermediate variables in monthly runoff simulations. Typically, S1 exhibited better performance compared to S2. A greater impact of aridity index, forest fraction, and catchment area on model performance is observed in S2. These findings improve our understanding of constructing PIML models in hydrology by emphasizing their excellent performance in runoff simulations and highlighting the importance of intermediate variables.

Joint cooperative caching and power control for UAV-assisted internet of vehicles.

In view of the current problems of spectrum resource scarcity, return congestion, and insufficient energy utilization in the unmanned aerial vehicle (UAV)-assisted Internet of Vehicles (IoV), this paper investigates the cooperative caching and power control, and proposes a joint optimization method to improve the overall Energy Efficiency (EE) . In this method, we first propose a communication establishment threshold to control the V2V communication distance and serve as a joint optimization factor. Then we derive the closed form expressions of offloading ratio and EE of the UAV-assisted IoV, and formulate the optimization problem of maximizing EE. Due to the coupling relationship between caching strategy and transmission power, it is difficult for us to directly solve the optimization problem. Furthermore, we propose an alternating optimization algorithm for solving the optimization problem. Finally, the experimental simulation compare the propose joint optimization method with other existing optimization methods, and the simulation results prove the effectiveness and superiority of the propose joint optimization method.

Indole alkaloids isolated from the Nicotiana tabacum-derived Aspergillus fumigatus 0338 as potential inhibitors for tobacco powdery mildew and their mode of actions.

To explore active natural products against tobacco powdery mildew caused by Golovinomyces cichoracearum, an extract from the fermentation of endophytic Aspergillus fumigatus 0338 was investigated. The mechanisms of action for active compounds were also studied in detail. As a result, 14 indole alkaloid derivatives were isolated, with seven being newly discovered (1-7) and the remaining seven previously described (8-14). Notably, compounds 1-3 are rare linearly fused 6/6/5 tricyclic prenylated indole alkaloids, with asperversiamide J being the only known natural product of this kind. The isopentenyl substitutions at the 5-position in compounds 4 and 5 are also rare, with only compounds 1-(5-prenyl-1H-indol-3-yl)-propan-2-one (8) and 1-(6-methoxy-5-prenyl-1H-indol3-yl)-propan-2-one currently available. In addition, compounds 6 and 7 are new framework indole alkaloid derivatives bearing a 6-methyl-1,7-dihydro-2H-azepin-2-one ring. The purified compounds were evaluated for their activity against G. cichoracearum, and the results revealed that compounds 7 and 9 demonstrated obvious anti-G. cichoracearum activities with an inhibition rate of 82.6% and 85.2%, respectively, at a concentration of 250 µg/mL, these rates were better than that of the positive control agent, carbendazim (78.6%). The protective and curative effects of compounds 7 and 9 were also better than that of positive control, at the same concentration. Moreover, the mechanistic study showed that treatment with compound 9 significantly increased the structural tightness of tobacco leaves and directly affect the conidiospores of G. cichoracearum, thereby enhancing resistance. Compounds 7 and 9 could also induce systemic acquired resistance (SAR), directly regulating the expression of defense enzymes, defense genes, and plant semaphorins, which may further contribute to increased plant resistance. Based on the activity experiments and molecular dockings, the indole core structure may be the foundation of these compounds' anti-G. cichoracearum activity. Among them, the indole derivative parent structures of compounds 6, 7, and 9 exhibit strong effects. Moreover, the methoxy substitution in compound 7 can enhance their activity. By isolating and structurally identifying the above indole alkaloids, new candidates for anti-powdery mildew chemical screening were discovered, which could enhance the utilization of N. tabacum-derived fungi in pesticide development.

Enabling robust blue circularly polarized organic afterglow through self-confining isolated chiral chromophore.

Creating circularly polarized organic afterglow system with elevated triplet energy levels, suppressed non-radiative transitions, and effective chirality, which are three critical prerequisites for achieving blue circularly polarized afterglow, has posed a formidable challenge. Herein, a straightforward approach is unveiled to attain blue circularly polarized afterglow materials by covalently self-confining isolated chiral chromophore within polymer matrix. The formation of robust hydrogen bonds within the polymer matrix confers a distinctly isolated and stabilized molecular state of chiral chromophores, endowing a blue emission band at 414 nm, lifetime of 3.0 s, and luminescent dissymmetry factor of ~ 10-2. Utilizing the synergistic afterglow and chirality energy transfer, full-color circularly polarized afterglow systems are endowed by doping colorful fluorescent molecules into designed blue polymers, empowering versatile applications. This work paves the way for the streamlined design of blue circularly polarized afterglow materials, expanding the horizons of circularly polarized afterglow materials into various domains.

Mechanism Behind the Programmed Biosynthesis of Heterotrimeric Fungal Depside Thielavin A.

Thielavin A (1) is a fungal depside composed of one 3-methylorsellinic acid and two 3,5-dimethylorsellinic acid units. It displays diverse biological activities. However, the mechanism underlying the assembly of the heterotrimeric structure of 1 remains to be clarified. In this study, we identified the polyketide synthase (PKS) involved in the biosynthesis of 1. This PKS, designated as ThiA, possesses an unusual domain organization with the C-methyltransferase (MT) domain situated at the C-terminus following the thioesterase (TE) domain. Our findings indicated that the TE domain is solely responsible for two rounds of ester bond formation, along with subsequent chain hydrolysis. We identified a plausible mechanism for TE-catalyzed reactions and obtained insights into how a single PKS can selectively yield a specific heterotrimeric product. In particular, the tandem acyl carrier protein domains of ThiA are critical for programmed methylation by the MT domain. Overall, this study highlighted the occurrence of highly optimized domain-domain communication within ThiA for the selective synthesis of 1, which can advance our understanding of the programming rules of fungal PKSs.

Mdpg: a novel multi-disease diagnosis prediction method based on patient knowledge graphs.

Diagnosis prediction, a key factor in enhancing healthcare efficiency, remains a focal point in clinical decision support research. However, the time-series, sparse and multi-noise characteristics of electronic health record (EHR) data make it a great challenge. Existing methods commonly address these issues using RNNs and incorporating medical prior knowledge from medical knowledge bases, but they neglect the local spatial characteristics and spatial-temporal correlation of the data. Consequently, we propose MDPG, a diagnosis prediction model based on patient knowledge graphs. Initially, we represent the electronic visit records of patients as a patient-centered temporal knowledge graph, capturing the local spatial structure and temporal characteristics of the visit information. Subsequently, we design the spatial graph convolution block, temporal self-attention block, and spatial-temporal synchronous graph convolution block to capture the spatial, temporal, and spatial-temporal correlations embedded in them, respectively. Ultimately, we accomplish the prediction of patients' future states through multi-label classification. We conduct comprehensive experiments on two real-world datasets independently and evaluate the results using visit-level precision@k and code-level accuracy@k metrics. The experimental results demonstrate that MDPG outperforms all baseline models, yielding the best performance.

Effects of aerobic exercise on cognitive function in adults with major depressive disorder: A systematic review and meta-analysis.

Background: Major Depressive Disorder (MDD) is a highly prevalent psychiatric disorder that impairs the cognitive function of individuals. Aerobic exercise stands out as a promising non-pharmacological intervention for enhancing cognitive function and promoting brain health.While positive impacts of aerobic exercise on executive function in adults with depression have been documented, a comprehensive understanding of its benefits on overall cognitive function, including memory, attention, and processing speed, along with key moderating factors in adults with MDD, remains unexplored. The purpose of the systematic review and meta-analysis was to investigate the effects of aerobic exercise on overall cognitive function in adults with MDD, and to explore whether cognitive sub-domains, aerobic exercise characteristics, and study and sample variables modify the effects of aerobic exercise on cognition. Methods: Six English electronic databases (Embase, Cochrane Central, Scopus, APA PsycInfo, PubMed, Web of Science) were searched from inception to 2 April 2023. Randomized trials, including adults aged 18 years or above with a diagnosis of clinical depression, of the effects of aerobic exercise on cognitive function in adults with MDD compared to non-aerobic exercise groups were included. A three-level meta-analysis was conducted utilizing a random-effects model in R. The quality of the studies was evaluated using the Physiotherapy Evidence Database (PEDro) scale. The PROSPERO registration number is CRD42022367350. Results: Twelve randomized trials including 945 adults with MDD were included. Results indicated that aerobic exercise significantly improved overall cognitive function (g = 0.21; 95 % confidence intervals [CI] = 0.07, 0.34), and the sub-domains of memory (g = 0.25; 95 % CI = 0.06, 0.44) and executive function (g = 0.12; 95 % CI = 0.04, 0.20). Significant benefits in cognitive function were found from moderate-to-vigorous (mixed) intensity (g = 0.19; 95 % CI = 0.02, 0.37), aerobic exercise conducted 3 times per week (g = 0.23; 95 % CI = 0.10, 0.38), in sessions < 45 min (g = 0.59; 95 % CI = 0.28, 0.90), and 45-60 min (g = 0.16; 95 % CI = 0.07, 0.26), in aerobic exercise intervention ≤ 12 weeks (g = 0. 26; 95 % CI = 0.08, 0.44). Limitations: This review only included peer-reviewed English-language studies, which may lead to a language bias. The results of the Egger's test suggested a potential publication bias. Conclusions: Aerobic exercise is efficacious in improving overall cognitive function and the sub-domains of memory and executive function in adults with major depressive disorder.

Transition from positive to negative indirect CO2 effects on the vegetation carbon uptake.

Although elevated atmospheric CO2 concentration (eCO2) has substantial indirect effects on vegetation carbon uptake via associated climate change, their dynamics remain unclear. Here we investigate how the impacts of eCO2-driven climate change on growing-season gross primary production have changed globally during 1982-2014, using satellite observations and Earth system models, and evaluate their evolution until the year 2100. We show that the initial positive effect of eCO2-induced climate change on vegetation carbon uptake has declined recently, shifting to negative in the early 21st century. Such emerging pattern appears prominent in high latitudes and occurs in combination with a decrease of direct CO2 physiological effect, ultimately resulting in a sharp reduction of the current growth benefits induced by climate warming and CO2 fertilization. Such weakening of the indirect CO2 effect can be partially attributed to the widespread land drying, and it is expected to be further exacerbated under global warming.

The effect of graphene and graphene oxide induced reactive oxygen species on polycaprolactone scaffolds for bone cancer applications.

Bone cancer remains a critical healthcare problem. Among current clinical treatments, tumour resection is the most common strategy. It is usually effective but may present several limitations such as multiple operations, long hospital time, and the potential recurrence caused by the incomplete removal of cancer cells. To address these limitations, three-dimensional (3D) scaffolds fabricated through additive manufacturing have been researched for both bone cancer treatment and post-treatment rehabilitation. Polycaprolactone (PCL)-based scaffolds play an important role in bone regeneration, serving as a physical substrate to fill the defect site, recruiting cells, and promoting cell proliferation and differentiation, ultimately leading to the regeneration of the bone tissue without multiple surgical applications. Multiple advanced materials have been incorporated during the fabrication process to improve certain functions and/or modulate biological performances. Graphene-based nanomaterials, particularly graphene (G) and graphene oxide (GO), have been investigated both in vitro and in vivo, significantly improving the scaffold's physical, chemical, and biological properties, which strongly depend on the material type and concentration. A unique targeted inhibition effect on cancer cells was also discovered. However, limited research has been conducted on utilising graphene-based nanomaterials for both bone regeneration and bone cancer treatment, and there is no systematic study into the material- and dose-dependent effects, as well as the working mechanism on 3D scaffolds to realise these functions. This paper addresses these limitations by designing and fabricating PCL-based scaffolds containing different concentrations of G and GO and assessing their biological behaviour correlating it to the reactive oxygen species (ROS) release level. Results suggest that the ROS release from the scaffolds is a dominant mechanism that affects the biological behaviour of the scaffolds. ROS release also contributes to the inhibition effect on bone cancer due to healthy cells and cancer cells responding differently to ROS, and the osteogenesis results also present a certain correlation with ROS. These observations revealed a new route for realising bone cancer treatment and subsequent new bone regeneration, using a single dual-functional 3D scaffold.

Integrative analysis reveals chemokines CCL2 and CXCL5 mediated shear stress-induced aortic dissection formation.

Background: Aortic dissection (AD) is a critical emergency in cardiovascular disease. AD occurs only in specific sites of the aorta, and the variation of shear stress in different aortic segments is a possible cause not reported. This study investigated the key molecules involved in shear stress-induced AD through quantitative bioinformatic analysis of a public RNA sequencing database and clinical tissue sample validation. Methods: Gene expression data from the GSE153434, GSE147026, and GSE52093 datasets were downloaded from the Gene Expression Omnibus. Next, differently expressed genes (DEGs) in each dataset were identified and integrated to identify common AD DEGs. STRING, Cytoscape, and MCODE were used to identify hub genes and crucial clustering modules, and Connectivity Map (CMap) was used to identify positive and negative agents. The same procedure was performed for the GSE160611 dataset to obtain shear stress-induced human aortic endothelial cell (HAEC) DEGs. After the integration of these two DEGs sets to identify shear stress-associated hub DEGs in AD, Gene Ontology Enrichment Analysis was performed. The common chemokine receptors and ligands in AD were identified by analyzing AD's three RNA sequencing datasets. Their origin was verified by analyzing AD single-cell sequencing data and validated by immunoblotting and immunofluorescence. Results: We identified 100 down-regulated and 50 up-regulated AD common DEGs. Enrichment results showed that common DEGs were closely related to blood vessel morphogenesis, muscle structure development, muscle tissue development, and chemotaxis. Among those DEGs, MYC, CCL2, and SPP1 are the three molecules with the highest degree. A crucial cluster of 15 genes was identified using MCODE, which contained inflammation-related genes with elevated expression and muscle cell-related genes with decreased expression, and CCL2 is central to immune-related genes. CMap confirmed MEK inhibitors and ALK inhibitors as possible therapeutic agents for AD. Moreover, 366 shear stress-associated DEGs in HAEC were identified in the GSE160611 dataset. After taking the intersection, we identified five shear stress-associated hub DEGs in AD (ANGPTL4, SNAI2, CCL2, GADD45B, and PROM1), and the enrichment analysis indicated they were related to the endothelial cell apoptotic process. Chemokine CCL2 was the molecule with a high degree in both DEG sets. Besides CCL2, CXCL5 was the only chemokine ligand differentially expressed in the three datasets. Additionally, immunoblotting confirmed the increased expression of CCL2 and CXCL5 in clinical tissue samples. Further research at the single-cell level revealed that CCL2 has multiple origins, and CXCL5 is macrophage-derived. Conclusion: Through integrative analysis, we identified core common AD DEGs and possible therapeutic agents based on these DEGs. We elucidated that the chemokine CCL2 and CXCL5-mediated "Endothelial-Monocyte-Neutrophil" axis may contribute to the development of shear stress-induced AD. These findings provide possible therapeutic targets for the prevention and treatment of AD.

Projecting the impact of climate change and elevated CO2 concentration on rice irrigation water requirement in China.

Climate change and elevated CO2 concentrations significantly affect rice growth and water consumption. Understanding the specific impacts of climate change and elevated CO2 concentrations on rice physiological phenology, crop water demand (ETC), and irrigation water requirement (IR) is of great significance for the sustainable utilization of water resources and food security. This is particularly true in China, the world's largest rice producer. In this study, with the help of two rice phenological models, the modified Penman-Monteith equation, and the paddy water balance model, we project the changes in rice phenological period, ETC, and IR in four main rice-producing regions of China in the period 2015-2100 based on the 11 GCM outputs. The results show that the rice growing period is shortened in most rice-producing regions, except for the parts of the middle and lower reaches of the Yangtze River. Meanwhile, the trend of ETC and IR of rice varies slightly among regions in the future scenario, with almost all regions decreasing yearly except for the middle and lower reaches of the Yangtze River, where the trend is increasing. The progressively increasing atmospheric CO2 concentration has a "fertilization effect" on the crop, which can reduce the water requirements of rice. In the SSP585 scenario, the " CO2 fertilization effect" can reduce up to 8.87 × 108 m3 of ETC and 6.94 × 108 m3 of IR in the middle and lower reaches of the Yangtze River in the period of 2090s. This study provides beneficial references to understand the response of rice ETC and IR to future climate change and CO2 concentration elevation in China and highlights that the simulation in terms of crop irrigation must account for the "CO2 fertilization effect".

MSGF-GLP: fusion method of visible and hyperspectral data for early detection of discolored standing trees.

Pest and disease damage to forests cannot be underestimated, so it is essential to detect diseased trees in time and take measures to stop their spread. The detection of discoloration standing trees is one of the important means to effectively control the spread of pests and diseases. In the visible wavelength range, early infected trees do not show significant color changes, which poses a challenge for early detection and is only suitable for monitoring middle and late discolor trees. The spectral resolution of hyperspectral restricts the improvement of its spatial resolution, and there are phenomena of different spectral of the same and foreign objects in the same spectrum, which affect the detection results. In this paper, the method of hyperspectral and CCD image fusion is used to achieve high-precision detection of discoloration standing trees. This paper proposes an improved algorithm MSGF-GLP, which uses multi-scale detail boosting and MTF filter to refine high-resolution data. By combining guided filtering with hyperspectral images, the spatial detail difference is enhanced, and the injection gain is interpolated into the difference of each band, so as to obtain high-resolution and high-quality hyperspectral images. This research is based on hyperspectral and CCD data obtained from LiCHy, Chinese Academy of Forestry, Maoershan Experimental Forest Farm, Shangzhi City, Heilongjiang Province. The evaluation framework is used to compare with the other five fusion algorithms to verify the good effect of the proposed method, which can effectively preserve the canopy spectrum and improve the spatial details. The fusion results of forestry remote sensing data were analyzed using the vegetation Normalized Difference Water Index and Plant Senescence Reflectance Index. The fused results can be used to distinguish the difference between discoloration trees and healthy trees by the multispectral vegetation index. The research results can provide good technical support for the practical application of forest remote sensing data fusion, and lay the foundation for promoting the scientific, automatic and intelligent forestry control.

Extraction and characterization of anti-virus anthraquinones from Nicotiana tabacum-derived Aspergillus oryzae YNCA1220.

In this study, seven novel anthraquinones (1-7) and four described anthraquinones (8-11) were purified from Nicotiana tabacum-derived Aspergillus oryzae YNCA1220. It is worth noting that only analogs of 4 and 5 have been reported as natural products to date, while the nuclei of compounds 1-3, 6 and 7 were isolated for the first time in nature. Among them, compounds 1-3 bear an unusual anthra[2,3-b]furan-9,10-dione nucleus, 4 and 5 possess a rare 3-methyl-1H-pyrrol-2-yl substituent, and 6 and 7 are new framework anthraquinones bearing a 6-methyl-1,7-dihydro-2H-azepin-2-one ring. Interestingly, the in vivo assays indicated that 1, 4 and 5 had inactivation effects against tobacco mosaic virus (TMV) with inhibition rates of 41.6%, 55.4% and 38.6%, respectively, at a concentration of 50 µg/mL, which were better than that of the positive control agent, ningnanmycin (33.8%). Compounds 1, 4 and 5 also had protective effects with inhibition rates of 48.7%, 60.2% and 43.5% at the same concentration, while 4 had a better curative effect than ningnanmycin at a concentration of 100 µg/mL. In addition, mechanistic studies also revealed that a potent direct effect on TMV, the induction of SAR in tobacco plants, and the effective regulation of defense enzymes, defense genes, and defense hormones may be the reasons for the significant effects of 4 against TMV. At the same time, downregulation of the expression of total NtHsp70 protein by inhibiting the related Hsp70 genes may also be involved in tobacco resistance to TMV. To evaluate whether compounds have broader antiviral activities, the antirotavirus activities of new isolates were also evaluated and found to be highly effective with a therapeutic index (TI) value ranging from 11.6 to 17.7. This study suggests that the above anthraquinone compounds, particularly 4, have broad spectrum antiviral activities. The successful isolation and structure identification of the above anthraquinones provide new materials for the screening of anti-TMV agents and contribute to the improved utilization of N. tabacum-derived fungi.

Virtual Design of 3D-Printed Bone Tissue Engineered Scaffold Shape Using Mechanobiological Modeling: Relationship of Scaffold Pore Architecture to Bone Tissue Formation.

Large bone defects are clinically challenging, with up to 15% of these requiring surgical intervention due to non-union. Bone grafts (autographs or allografts) can be used but they have many limitations, meaning that polymer-based bone tissue engineered scaffolds (tissue engineering) are a more promising solution. Clinical translation of scaffolds is still limited but this could be improved by exploring the whole design space using virtual tools such as mechanobiological modeling. In tissue engineering, a significant research effort has been expended on materials and manufacturing but relatively little has been focused on shape. Most scaffolds use regular pore architecture throughout, leaving custom or irregular pore architecture designs unexplored. The aim of this paper is to introduce a virtual design environment for scaffold development and to illustrate its potential by exploring the relationship of pore architecture to bone tissue formation. A virtual design framework has been created utilizing a mechanical stress finite element (FE) model coupled with a cell behavior agent-based model to investigate the mechanobiological relationships of scaffold shape and bone tissue formation. A case study showed that modifying pore architecture from regular to irregular enabled between 17 and 33% more bone formation within the 4-16-week time periods analyzed. This work shows that shape, specifically pore architecture, is as important as other design parameters such as material and manufacturing for improving the function of bone tissue scaffold implants. It is recommended that future research be conducted to both optimize irregular pore architectures and to explore the potential extension of the concept of shape modification beyond mechanical stress to look at other factors present in the body.

Tanshinone IIA attenuates valvular interstitial cells' calcification induced by oxidized low density lipoprotein via reducing endoplasmic reticulum stress.

Recent studies revealed that endoplasmic reticulum (ER) stress played an emerging role of in valve calcification. Tanshinone IIA (TanIIA) has been a research hotspot in cardiovascular diseases. Previously we found that sodium TanIIA dampened the pathological phenotype transition of valvular interstitial cells (VICs) by affecting ER stress published in Chinese Journal. Here, we test the hypothesis that TanIIA attenuates the pro-osteogenic effects of oxidized low-density lipoprotein (oxLDL) in VICs by reducing induction of ER stress. Patients' aortic valve (AV) was collected, and porcine VICs were cultured for in vitro model. ER stress markers were tested in human leaflets by immunostaining. Immunoblotting were used to test the osteoblastic factors such as Runx2, osteocalcin, and ER stress markers GRP78, CHOP, XBP1, etc. Alkakine phosphate (ALP) activity assay were used to test the activity of ALP kinase. Pro-inflammatory gene expression was detected by polymerase chain reaction. As a result, ER stress markers were elevated in patients' calcified AVs. OxLDL induced osteogenesis and inflammation via promoting ER stress. TanIIA attenuated oxLDL induced ER stress. TanIIA also inhibited theosteoblastic factors and inflammatory cytokine expressions in VICs. In conclusion, our data provide evidence that TanIIA exerts anti-inflammation and anti-osteogenic effects in VICs by attenuating ER stress, and ER stress acts as an important regulator in oxLDL induced VICs' phenotype transition.

Developing an efficient and visible prime editing system to restore tobacco 8-hydroxy-copalyl diphosphate gene for labdane diterpene Z-abienol biosynthesis.

Prime editing (PE) is a versatile CRISPR-Cas based precise genome-editing platform widely used to introduce a range of possible base conversions in various organisms. However, no PE systems have been shown to induce heritable mutations in tobacco, nor in any other dicot. In this study, we generated an efficient PE system in tobacco that not only introduced heritable mutations, but also enabled anthocyanin-based reporter selection of transgene-free T1 plants. This system was used to confer Z-abienol biosynthesis in the allotetraploid tobacco cultivar HHDJY by restoring a G>T conversion in the NtCPS2 gene. High levels of Z-abienol were detected in the leaves of homozygous T1 plants at two weeks after topping. This study describes an advance in PE systems and expands genome-editing toolbox in tobacco, even in dicots, for use in basic research and molecular breeding. And restoring biosynthesis of Z-abienol in tobacco might provide an efficient way to obtain Z-abienol in plants.

Two New Eudesmane-Type Sesquiterpene from Clonostachys sp. Y6-1and Their Cytotoxic Activity.

Two undescribed eudesmane-type sesquiterpenoids together with four known compounds were isolated from Clonostachys sp. Y6-1 associated. Their chemical structures were unambiguously determined by NMR, mass spectrometry, and 13 C-NMR calculation as well as DP4+ probability analyses. The absolute configurations of compounds 1 and 2 were determined by ECD calculation and X-ray single-crystal diffraction methods. Furthermore, all isolates were evaluated for in vitro cytotoxic activities against MCF-7, HCT-116, MDA-MB-231, and SW620 cancer cells. Among them, bioactivity evaluation of compound 5 revealed that weak activity (IC50 =66.55±0.82 µM) against SW620.

[The expression of autophagy-related proteins in peripheral blood mononuclear cells of patients with lupus nephritis is upregulated and related to kidney damage].

Objective To identify the relationship between nephritis activity, autophagy and inflammation in patients with SLE. Methods Western blot analysis was used to detect the expression of microtubule-associated protein 1 light chain 3 (LC3) and P62 in peripheral blood mononuclear cells (PBMCs) of SLE patients with lupus nephritis and non-lupus nephritis patients. Tumor necrosis factor α (TNF-α) and interferon γ (IFN-γ) in the serum of SLE patients were determined by ELISA. The correlation between LC3II/LC3I ratio and SLE disease activity score (SLEDAI), urinary protein, TNF-α and IFN-γ levels was analyzed by Pearson method. Results The expression of LC3 was increased and P62 was decreased in SLE patients. TNF-α and IFN-γ were increased in the serum of SLE patients. LC3II/LC3I ratio was positively correlated with SLEDAI (r=0.4560), 24 hour urine protein (r=0.3753), IFN-γ (r=0.5685), but had no correlation with TNF-α (r=0.04 683). Conclusion Autophagy is found in PBMCs of SLE, and the autophagy is correlated with renal damage and inflammation in patients with lupus nephritis.