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IntroductionEarly detection of leaf diseases is necessary to control the spread of plant diseases, and one of the important steps is the segmentation of leaf and disease images. The uneven light and leaf overlap in complex situations make segmentation of leaves and diseases quite difficult. Moreover, the significant differences in ratios of leaf and disease pixels results in a challenge in identifying diseases.MethodsTo solve the above issues, the residual attention mechanism combined with atrous spatial pyramid pooling and weight compression loss of UNet is proposed, which is named RAAWC-UNet. Firstly, weights compression loss is a method that introduces a modulation factor in front of the cross-entropy loss, aiming at solving the problem of the imbalance between foreground and background pixels. Secondly, the residual network and the convolutional block attention module are combined to form Res_CBAM. It can accurately localize pixels at the edge of the disease and alleviate the vanishing of gradient and semantic information from downsampling. Finally, in the last layer of downsampling, the atrous spatial pyramid pooling is used instead of two convolutions to solve the problem of insufficient spatial context information.ResultsThe experimental results show that the proposed RAAWC-UNet increases the intersection over union in leaf and disease segmentation by 1.91% and 5.61%, and the pixel accuracy of disease by 4.65% compared with UNet.DiscussionThe effectiveness of the proposed method was further verified by the better results in comparison with deep learning methods with similar network architectures.

Retinal vessel segmentation is critical for diagnosing related diseases in the medical field. However, the complex structure and variable size and shape of retinal vessels make segmentation challenging. To enhance feature extraction capabilities in existing algorithms, we propose PAM-UNet, a U-shaped network architecture incorporating a novel Plenary Attention Mechanism (PAM). In the BottleNeck stage of the network, PAM identifies key channels and embeds positional information, allowing spatial features within significant channels to receive more focus. We also propose a new regularization method, DropBlock_Diagonal, which discards diagonal regions of the feature map to prevent overfitting and enhance vessel feature learning. Within the decoder stage of the network, features from each stage are merged to enhance the segmentation accuracy of the final vessel. Experimental validation on two retinal image datasets, DRIVE and CHASE_DB1, shows that PAM-UNet achieves 97.15%, 83.16%, 98.45%, 83.15%, 98.66% and 97.64%, 85.82%, 98.46%, 82.56%, 98.95% on Acc, Se, Sp, F1, AUC, respectively, outperforming UNet and most other retinal vessel segmentation algorithms.

Remote sensing images are very vulnerable to cloud interference during the imaging process. Cloud occlusion, especially thick cloud occlusion, significantly reduces the imaging quality of remote sensing images, which in turn affects a variety of subsequent tasks using the remote sensing images. The remote sensing images miss ground information due to thick cloud occlusion. The thick cloud removal method based on a temporality global–local structure is initially suggested as a solution to this problem. This method includes two stages: the global multi-temporal feature fusion (GMFF) stage and the local single-temporal information restoration (LSIR) stage. It adopts the fusion feature of global multi-temporal to restore the thick cloud occlusion information of local single temporal images. Then, the featured global–local structure is created in both two stages, fusing the global feature capture ability of Transformer with the local feature extraction ability of CNN, with the goal of effectively retaining the detailed information of the remote sensing images. Finally, the local feature extraction (LFE) module and global–local feature extraction (GLFE) module is designed according to the global–local characteristics, and the different module details are designed in this two stages. Experimental results indicate that the proposed method performs significantly better than the compared methods in the established data set for the task of multi-temporal thick cloud removal. In the four scenes, when compared to the best method CMSN, the peak signal-to-noise ratio (PSNR) index improved by 2.675, 5.2255, and 4.9823 dB in the first, second, and third temporal images, respectively. The average improvement of these three temporal images is 9.65%. In the first, second, and third temporal images, the correlation coefficient (CC) index improved by 0.016, 0.0658, and 0.0145, respectively, and the average improvement for the three temporal images is 3.35%. Structural similarity (SSIM) and root mean square (RMSE) are improved 0.33% and 34.29%, respectively. Consequently, in the field of multi-temporal cloud removal, the proposed method enhances the utilization of multi-temporal information and achieves better effectiveness of thick cloud restoration.

Thick cloud and cloud shadow often exist in optical remote sensing (RS) images, which limit the application range of RS data. To solve this challenging problem, we propose a multitemporal-based method of cloud removal to reconstruct the large cloud-cover region in RS images. The method can combine the advantages of high accuracy of deep-learning method and low computation cost of traditional method, and reduce the difficulty of establishing multi-temporal dataset to a certain extent. In the proposed method, the complex problem of thick cloud removal is decomposed into two simple processes: coarse stage and refined stage. In the stage of coarse cloud removal, it is found that the cloud-cover images are distributed more regularly in frequency domain than in the space domain. Therefore, the frequency domain residual module is introduced, and the frequency domain attention module is designed to achieve more focused fusion of three-temporal features. In the stage of refined cloud removal, the refined network is designed to retain the effective features of the coarse stage and further refine the reconstruction result based on the image self-correlation. We carried out sufficient experiments to demonstrate the superiority of the proposed method compared with four classical methods, which include WLR, STSCNN, RFRnet and PSTCR. In qualitative experiments, the proposed method has obvious advantages in information accuracy, visual naturalness and semantic rationality. In quantitative experiments, compared with the best of four comparison methods, average values of Peak Signal to Noise Ratio (PSNR) on three-temporal images are improved by 5.1934 dB, 2.7729 dB and 7.2364 dB respectively, and average values of Correlation Coefficient (CC) on three-temporal images are increased by 0.1048, 0.0110 and 0.0966 respectively. Moreover, the proposed method has an obvious advantage in computation cost because it can reconstruct multiple cloud-cover images synchronously.

Abstract Porcine growth hormone (pGH) is a class of peptide hormones secreted from the pituitary gland, which can significantly improve growth and feed utilization of pigs. However, it is unstable and volatile in vitro. It needs to be encapsulated in liposomes when feeding livestock, whose high cost greatly limits its application in pig industry. Therefore we attempted to express pGH as intracellular soluble protein in Pichia pastoris and feed these yeasts with partial wall-breaking for swine, which could release directly pGH in intestine tract in case of being degraded in intestinal tract with low cost. In order to improve the intracellular soluble expression of pGH protein in Pichia pastoris and stability in vitro, we optimized the pGH gene, and screened molecular chaperones from E. coli and Pichia pastoris respectively for co-expressing with pGH. In addition, we had also explored conditions of mechanical crushing and fermentation. The results showed that the expression of intracellular soluble pGH protein was significantly increased after gene optimized and co-expressed with Ssa1–Sis1 chaperone from Pichia pastoris. Meanwhile, the optimal conditions of partial wall-breaking and fermentation of Pichia pastoris were confirmed, the data showed that the intracellular expression of the optimized pGH protein co-expressed with Ssa1–Sis1 could reach 340 mg/L with optimal conditions of partial wall-breaking and fermentation. Animal experiments verified that the optimized pGH protein co-expression with Ssa1–Sis1 had the best promoting effects on the growth of piglets. Our study demonstrated that Ssa1–Sis1 could enhance the intracellular soluble expression of pGH protein in Pichia pastoris and that partial wall-breaking of yeast could prevent pGH from degradation in vitro, release targetedly in the intestine and play its biological function effectively. Our study could provide a new idea to cut the cost effectively, establishing a theoretical basis for the clinic application of unstable substances in vitro.

High-quality remote sensing images play important roles in the development of ecological indicators’ mapping, urban-rural management, urban planning, and other fields. Compared with natural images, remote sensing images have more abundant land cover along with lower spatial resolutions. Given the embedded longitude and latitude information of remote sensing images, reference (Ref) images with similar scenes could be more accessible. However, existing traditional super-resolution (SR) approaches always depend on increases in network depth to improve performance, which limits the acquisition and application of high-quality remote sensing images. In this paper, we proposed a novel, reference-image-based, super-resolution method with feature compression module (FCSR) for remote sensing images to alleviate the above issue while effectively utilizing high-resolution (HR) information from Ref images. Specifically, we exploited a feature compression branch (FCB) to extract relevant features in feature detail matching with large measurements. This branch employed a feature compression module (FCM) to extract features from low-resolution (LR) and Ref images, which enabled texture transfer from different perspectives. To decrease the impact of environmental factors such as resolution, brightness and ambiguity disparities between the LR and Ref images, we designed a feature extraction encoder (FEE) to ensure accuracy in feature extraction in the feature acquisition branch. The experimental results demonstrate that the proposed FCSR achieves significant performance and visual quality compared to state-of-the-art SR methods. Explicitly, when compared with the best method, the average peak signal-to-noise ratio (PSNR) index on the three test sets is improved by 1.0877%, 0.8161%, 1.0296%, respectively, and the structural similarity (SSIM) index on four test sets is improved by 1.4764%, 1.4467%, 0.0882%, and 1.8371%, respectively. Simultaneously, FCSR obtains satisfactory visual details following qualitative evaluation.

Porcine gamma interferon is a cytokine produced by activated T cells and NK cells with broad-spectrum antiviral activity and immunomodulatory function. However, pIFN-γ is a secretory protein that has a short half-life in organisms and is easily inactivated, making it difficult to apply widely in clinics. Therefore, we tried to optimize the expression of pIFN-γ in Pichia pastoris to obtain a large amount of highly active, easily purified pIFN-γ protein in vitro. Through C-terminal sequence analysis, we found a signal sequence (EKREAEAE) that was easily enzymolysed by a signal peptide enzyme, resulting in degradation and inactivation of the pIFN-γ protein. In this study, we optimized the pIFN-γ gene recombination sequence and mutated the 3' end of the pIFN-γ gene, resulting in a higher expression level and stronger biological activity, as well as a significant upregulation in the expression of the interferon-stimulated genes Mx1 and OAS1 in IPEC-J2 jejunal epithelial cells. Our data also showed that the fermentation process could significantly improve productivity. A recombinant Pichia pastoris strain with the optimized pIFN-γ gene could obtain a high yield of pIFN-γ protein, up to 9536 mg/L, after staged incubation for 0-24 h at 28°C, pH 6.0, and 50% dissolved oxygen (DO), followed by incubation for 24-72 h at 25°C, pH 6.0 and 30% DO. These data demonstrated, for the first time, that the expression level of pIFN-γ in Pichia pastoris was improved significantly by gene optimization with 3' end mutation and a fermentation process that maintained good biological activity, which is beneficial to the application of pIFN-γ in animal husbandry.

Objective: Midaortic syndrome is a rare clinical condition that has been mainly studied in juveniles through case reports and series. This study aims to report the anatomic characteristics and long-term outcomes of 41 adult patients with midaortic syndrome who received open surgical treatment or endovascular treatment over a 14-year period. Methods: A consecutive cohort of 41 adult patients diagnosed with midaortic syndrome at our center between January 2008 and November 2021 were enrolled in the study. Patients’ baseline and anatomic characteristics were collected and analyzed. Primary follow-up outcomes included death and reintervention. Other follow-up outcomes included hypertension and complications. Results: The study enrolled 41 adult patients with midaortic syndrome with a mean age of 37.5 ± 13.4 years. Twenty-five patients received open surgical treatment, and 16 patients received endovascular treatment. Isolated infrarenal lesions were more likely to be found in the endovascular treatment group (P = .005), whereas patients with multiple (P = .002) or intravisceral involvement (P = .001) were more likely to be found in the open surgical treatment group. The open surgical treatment group was more likely to have a lower postoperative peak systolic pressure gradient (P = .020). The 5- and 10-year reintervention-free survivals were 87.7% and 71.7% in the open surgical treatment group and 92.3% and 79.1% in the endovascular treatment group, respectively. Conclusions: Both open surgical treatment and endovascular treatment showed satisfactory long-term efficacy outcomes for adult patients with midaortic syndrome. Given the patients’ relatively young age and long life expectancy, strict and regular lifelong follow-up is necessary.

The precise prediction of ship fuel consumption (SFC) not only serves to enhance energy efficiency to benefit shipping enterprises but also to provide quantitative foundations to aid in carbon emission reduction and ecological environment protection. On the other hand, SFC-related data represent typical multi-source characteristics and heterogeneous features, which lead to several methodological issues (e.g., feature alignment and feature fusion) in SFC prediction. Therefore, this paper proposes a dual-attention parallel network named DAPNet to solve the above issues. Firstly, we design a parallel network structure containing two kinds of long short-term memory (LSTM) and improved temporal convolutional networks (TCNs) for time-series analysis tasks so that different source data can be applied to suitable networks. Secondly, a local attention mechanism is included in each single parallel network so as to improve the ability of feature alignment from different-scale training data. Finally, global attention is employed for the fusion of all parallel networks, which can enrich representation features and simultaneously enhance the performance of SFC prediction. In experiments, DAPNet is compared with 10 methods, including baseline and attention models. The comparison results show that DAPNet and several of its variants obtain the highest accuracy in SFC prediction.

Abstract Background The aim of this study was to investigate the protective effect and mechanism of oridonin in an in vitro lipopolysaccharide (LPS)-induced human periodontal ligament stem cells (hPDLSCs) model of periodontitis. Methods Primary hPDLSCs were isolated and cultured, and then the expression of surface antigens CD146, STRO-1 and CD45 of hPDLSCs was detected by flow cytometry. The mRNA expression level of Runx2, OPN, Col-1, GRP78, CHOP, ATF4 and ATF6 in the cells was tested by qRT-PCR. MTT was taken to determine the cytotoxicity of oridonin at different concentrations (0–4 μM) on hPDLSCs. Besides, ALP staining, alizarin red staining and Oil Red O staining were utilized to assess the osteogenic differentiation (ALP concentration, mineralized calcium nodule formation) and adipogenic differentiation abilities of the cells. The proinflammatory factors level in the cells was measured by ELISA. The protein expression level of NF-κB/NLRP3 pathway-related proteins and endoplasmic reticulum (ER) stress-related markers in the cells were detected by Western blot. Results hPDLSCs with positive CD146 and STRO-1 expression and negative CD45 expression were successfully isolated in this study. 0.1–2 μM of oridonin had no significant cytotoxicity on the growth of hPDLSCs, while 2 μM of oridonin could not only greatly reduce the inhibitory effect of LPS on the proliferation and osteogenic differentiation of hPDLSCs cells, but also inhibit LPS-induced inflammation and ER stress in hPDLSCs cells. Moreover, further mechanism research showed that 2 μM of oridonin suppressed NF-κB/NLRP3 signaling pathway activity in LPS-induced hPDLSCs cells. Conclusions Oridonin promotes proliferation and osteogenic differentiation of LPS-induced hPDLSCs in an inflammatory environment, possibly by inhibiting ER stress and NF-κB/NLRP3 pathway. Oridonin may have a potential role in the repair and regeneration of hPDLSCs.

Regulating reactive oxygen species and inflammation are important for treating atherosclerosis. Here, the authors create a cell membrane coated zoledronic acid ceria nanocomposite loaded with probucol for synergistic drug and scavenging nanozyme treatment of atherosclerosis demonstrating application in vivo.

Prediction of water inflow in caverns has been a big problem for a long time, and the predication during construction has not been effectively combined with the water sealing by grouting, resulting in excessive grouting cost and difficulty in acceptance of storages during construction, which have caused great problems to the design, construction and operation of underground storages. Herein, a seepage field model was firstly established by FEFLOW software based on the actual geological conditions and the layout of underground works of a underground water-sealed storage, the water inflow of the storage during its operation without water-sealing by grouting was calculated by simulation, and the recommended water inflow value was finally determined to be 10 115 m3/d through the mutual verification with the calculation results of the empirical formula. Further, the permeability coefficient was calculated according to the requirements of relevant specifications. Definitely, the average permeability coefficient of the whole storage area needed to be reduced from 1.1×10-5 cm/s to 1.09×10-6 cm/s, which could guide the grouting design in a targeted way. The calculation of water inflow and seepage control were correlated in the research for the first time, capable of accurately estimating the quantity of pre-grouting and guiding the construction organization design, thus effectively overcoming the common difficulty in acceptance and commissioning of similar projects due to excessive water inflow.

Abstract Background Rare diseases have been increasingly recognized as unmet medical and health needs worldwide; a growing demand for the development of orphan drugs emerges subsequently. Therefore, it is of great interest for both the Chinese regulatory agency and pharmaceutical companies to keep tract on the clinical development of orphan drugs in China. Objective and method This study aims to reveal the current situation and trend of the clinical development of orphan drugs in China, based on the data collected from the Chinese official platform, dating from January 1, 2013 to December 31, 2021. Results A total of 331 clinical trials for orphan drugs were extracted from the platform, covering 31 rare diseases and 124 drugs. Increases were seen in the annual number of clinical trials and drugs being tested, with a sharp increase after 2018. About the disease types of the 331 trials, Parkinson disease (young-onset, early-onset) (86, 26%), hemophilia (70, 21%), homozygote hypercholesterolemia (60, 18%) were the most common. Furthermore, it was also observed that the largest number of clinical trial units for rare disease in east China (90, 41%) and the smallest number located in northwest China (18, 6%) and northeast China (18, 6%). Conclusions The growth trends illustrate the progress in clinical trial and drug development of rare diseases from 2013 to 2021. However, promoting orphan drugs development still is an important issue in China; at the same time, further efforts should be made for meet the unmet needs of disease types and balance the uneven distribution of medical resources for clinical trial on rare diseases.

Abstract Background The efficacy and validity of excimer laser ablation (ELA) in the in-stent restenosis (ISR) has been confirmed. However, its application in de novo atherosclerotic lesions of lower extremity artery disease (LEAD) has not been clearly defined and its procedure has not been standardized. Methods ELABORATE is a prospective, multicenter, real-world study designed to evaluate the efficacy and safety between ELA combined with drug-coated balloon (DCB) and DCB alone in de novo atherosclerotic lesions of LEAD. Discussion ELABORATE is a prospective, multicenter, real-world study designed to assess the efficacy and safety between ELA combined with drug-coated balloon (DCB) and DCB alone in patients with de novo atherosclerotic lesions of LEAD. According to the real-world situation, eligible patients will be allocated to ELA + DCB group (group E) and DCB group (group C). Baseline and follow-up information (at 3, 6, and 12 months) will be collected. The primary efficacy point is primary patency at 12-months, and the secondary efficacy points include clinically driven target lesion reintervention (CD-TLR), change of Rutherford class, ankle-brachial index and ulcer healing rate. These indexes will be assessed and recorded at 3, 6, and 12-month follow-up. Also, safety evaluation, including major adverse event, all-cause mortality through 30-day follow-up, unplanned major amputation, bailout stent and distal embolization, will also be evaluated by an independent core laboratory. All the data will be collected and recorded by the electric data capture system. This study will be finished in 3 years and the 12-month results will be available in 2023. All the patients will be followed for 5 years. Trial registration number Chinese Clinical Trial Registry (ChiCTR2100051263). Registered 17 September 2019. http://www.chictr.org.cn/listbycreater.aspx .

With the continuous expansion of national strategic reserve scale, less massive crystalline rock mass is available in China due to the limitation of various factors. Therefore, making a breakthrough in the construction technology of an underground water-sealed cavern in sandstone area can greatly broaden the site available for the underground caverns. In order to study the feasibility of cavern construction in sandstone area, the seepage field models of underground caverns in sandstone area under three working conditions of horizontal bedding, inclined 10° bedding and inclined 50° bedding were established with the FEFLOW software under the background of site selection for cavern construction in a sandstone area in southwest China. It is assumed that 2 to 3 layers of thick mudstone exist in the sandstone to amplify the damage degree of low-permeability mudstone layers to the water-sealed environment, so as to better study the design technology of water seal for the underground caverns in sandstone area. The simulation results show that the thick mudstone layers have the least influence on the inclined 50° bedding and the greatest influence on the horizontal bedding. The thick mudstone layers, as the water barrier in the groundwater environment, seriously affect or even destroy the water-sealed environment. By adjusting the model in a targeted way such as setting horizontal water curtain holes and a vertical or oblique water curtain system, the water-sealed effect is improved obviously. In the actual project, water seal can be realized by moving down the horizontal water curtain system, or setting a vertical or oblique water curtain system in specific areas. The results can provide theoretical reference for the design and site selection of underground water-sealed caverns in sandstone area.

Objectives: Rupture of a brain arteriovenous malformation (bAVM) can cause intracranial hemorrhage and severe clinical outcomes. At present, the mechanisms of bAVM-related hemorrhage are poorly understood. This study aimed to summarize the potential genetic risk factors for bAVM-related hemorrhage and appraise the methodological quality of existing genetic studies on bAVM-related hemorrhage using a cross-sectional design.Methods: A systematic literature search was conducted on genetic studies associated with bAVM-related hemorrhage published in PubMed, Embase, Web of Science, China National Knowledge Internet, and Wangfang databases, up to November 2022. Subsequently, a cross-sectional study was performed to describe the potential candidate genetic variants of bAVM associated with risk of hemorrhage and to evaluate the methodological quality of the identified studies using the Newcastle–Ottawa quality assessment scale and Q-genie tool.Results: Of the 1811 records identified in the initial search, nine studies met the filtering criteria and were included. Twelve single nucleotide polymorphisms (SNPs), including IL6 rs1800795, IL17A rs2275913, MMP9 rs9509, VEGFA rs1547651, and EPHB4 rs314353, rs314308, and rs314313, were associated with bAVM-related hemorrhage. However, only 12.5% of the evaluated SNPs showed statistical power> 0.80 (α = 0.05). Methodological quality assessment revealed significant flaws in the designs of the included studies, such as less reliable representativeness of recruited individuals, short follow-up periods in cohort studies, and less comparability between groups of hemorrhagic and non-hemorrhagic patients.Conclusion:IL1B, IL6, IL17A, APOE, MMP9, VEGFA and EPHB4 were potentially associated with bAVM-related hemorrhage. The methodological designs of the analyzed studies required improvement in order to obtain more reliable results. Regional alliances and rare disease banks need to be established to recruit large numbers of bAVM patients (especially familial and extreme-trait cases) in a multicenter, prospective cohort study with an adequate follow-up period. Furthermore, it is important to use advanced sequencing techniques and efficient measures to filter candidate genetic variants.

BackgroundHand grip strength (HGS) is a fast, useful, and inexpensive outcome predictor of nutritional status and muscular function assessment. Numerous demographic and anthropometric factors were reported to be associated with HGS, while which one or several factors produce greater variations in HGS has not been discussed in detail. This is important for answering how should HGS be normalized for eliminating the influence of individual differences in clinical practice.AimsTo compare the contribution of age, sex, height, weight, and forearm circumference (FCF) to variations in HGS based on a large-scale sample.MethodsWe enrolled 1,511 healthy undergraduate students aged 18–23 years. Age, weight, height, and sex were obtained. HGS was measured using a digital hand dynamometer, and FCF was measured at the point of greatest circumference using a soft ruler in both hands. Pearson’s or Spearman’s correlation coefficients were calculated with data of women and men separated and mixed for comparison. Partial correlation analysis and multivariate linear regression were used to compare the effect of variables on HGS.ResultsAnalysis results confirmed the correlates of higher HGS include higher height, heavier weight, being men and dominant hand, and larger FCF. The correlation between HGS and FCF was the highest, and the bivariate correlation coefficient between weight and HGS was largerata of women and men were mixed, than that between height and HGS. When data of women and men were mixed, there were moderate correlations between HGS and height and weight (r = 0.633∼0.682). However, when data were separated, there were weak correlations (r = 0.246∼0.391). Notably, partial correlation analysis revealed no significant correlation between height and HGS after eliminating the weight effect, while the correlation between weight and HGS was still significant after eliminating the height effect. Multivariate linear regression analyses revealed sex was the most significant contributor to the variation in HGS (Beta = –0.541 and –0.527), followed by weight (Beta = 0.243 and 0.261) and height (Beta = 0.102 and 0.103).ConclusionHGS and FCF reference values of healthy college students were provided. Weight was more correlate with hand grip strength, at least among the healthy undergraduates.Clinical trial registrationhttp://www.chictr.org.cn/showproj.aspx?proj=165914, identifier ChiCTR2200058586.

Background The treatment of chronic type B aortic dissection by thoracic endovascular aortic repair has some challenges, and its long‐term outcomes remain unclear. This study aimed to analyze the 5‐year clinical outcomes of thoracic endovascular aortic repair of chronic type B aortic dissection, compare the differences between patients with and without adverse aortic events (AAEs), and identify risk factors for AAEs. Methods and Results Patients who underwent thoracic endovascular aortic repair of chronic type B aortic dissection from January 2009 to June 2017 were retrospectively enrolled. The primary end points were AAEs, including aorta‐related death, procedural complications, and disease progression requiring reintervention. Clinical outcomes were described at the 5‐year follow‐up visit. The secondary end point was the comparison of the results between patients with and without AAEs. Univariable and multivariable logistic analyses were used to identify potential risk factors for AAEs. A total of 214 patients were enrolled. AAEs occurred in 46 (21.5%) patients. Compared with patients without AAEs, those with AAEs had higher rates of residual type A aortic dissection (26.1% versus 4.2%, P

Tumor microenvironment (TME) is intently related to tumor growth, progression and invasion, leading to drug resistance and insufficient therapeutic efficacy. However, remodeling TME and utilizing TME for exploring intelligent nanomaterials that can realize tumor theranostic is still challenging. Nowadays, the theranostic based on chemotherapy exposes some deficiencies, such as low targeting, weak permeability and premature clearance. Furthermore, it is challenging to cure drug-resistant tumors effectively. For the sake of solving these problems, a biomimetic decomposable nano-theranostic (MMV-Au-CDs-DOX) was well-established in this work. The Au-CDs are coated with macrophage-derived microvesicle to realize drug release accurately and enhance the biocompatibility of internal nanoparticles. Furthermore, MMV-Au-CDs-DOX would locate in the inflammation position of tumor, and disintegrate correspondingly into pieces with certain different functions stimulated by TME. Subsequently, the released anti-tumor nanodrugs were used for multimodal therapy, including chemotherapy and hemodynamic therapy. In addition, combined with the ability of Au-CDs to recognize GSH specifically, the off-on fluorescent probe was constructed to monitor the GSH of tumor cells and provided information on chemotherapy resistance.

A flexible strategy has been developed to synthesize divergent flavonoids bearing a chiral A-ring. As two key steps, the coupling via a boron-mediated aldol condensation and the cyclization via a highly stereoselective intramolecular Michael addition of 1,3-diketone proceed under mild conditions; thus, the chiral flavonoids bearing C-7 oxy functional groups or olefinic bonds are both easily accessible. Using this approach, the first synthesis of (+)-cryptogione F, (+)-cryptocaryanone B, and (+)-cryptochinones A and C, as well as stereoselective synthesis of (+)-cryptocaryone and (+)-cryptocaryanone A, were achieved from 2-deoxy-d-ribose in high overall yields. [ABSTRACT FROM AUTHOR]

In order to select the location of fire stations more scientifically and improve the efficiency of emergency management in chemical industry parks (CIPs), an improved risk calculation model for hazardous chemicals has been proposed by taking the domino effect and the identification of major hazardous installations for hazardous chemicals into account. In the analysis of the domino effect, the Monte Carlo simulation was used. Then, a location model of the fire stations was established with the optimization objectives of minimizing total cost and maximizing total risk coverage. The solving procedure of the location model is based on the augmented ε-constraint method combined with the TOPSIS method. Finally, a green chemical industry park was used as a case study for the validation and analysis of the location model. The results showed that the improved model could protect the high-risk areas, which is beneficial for the location decisions of fire stations.

Abstract Background Previous studies have demonstrated that no-option angiitis-induced critical limb ischemia (NO-AICLI) could be significantly improved by transplantation of peripheral blood-derived stem cells (PBDSCs). Additionally, a randomized controlled trial (RCT) recently conducted by us suggested that peripheral blood-derived purified CD34+ cells (PCCs) were not inferior to non-purified peripheral blood mononuclear cells (PBMNCs) at limb salvage in treatment of NO-AICLI. However, most of these clinical trials whether RCT or single-arm studies were characterized with a small sample size and absence of long-term outcomes. Methods To analyze long-term clinical outcomes of PBDSCs transplantation for NO-AICLI, we reviewed clinical data of patients with NO-AICLI receiving PBDSCs transplantation at our center during the past decade. Meanwhile, we first compared the long-term safety and efficacy of intramuscular transplantation of PCCs versus PBMNCs in a sizable number of patients with NO-AICLI. Results From May 2009 to December 2019, a total of 160 patients with NO-AICLI patients were treated by PBDSCs transplantation (82 with PCCs, 78 with PBMNCs) at our center. Baseline characteristics between two groups were similar. Up to June 2020, the mean follow-up period was 46.6 ± 35.3 months. No critical adverse events were observed in either group. There was one death during the follow-up period. A total of eight major amputations occurred. The cumulative major amputation-free survival (MAFS) rate at 5 years after PBDSCs transplantation was 94.4%, without difference between two groups (P = .855). Wound healing, rest pain, pain-free walking time, ankle-brachial index, transcutaneous oxygen pressure, and quality of life (QoL) also significantly improved after PBDSCs transplantation. Conclusions Autologous PBDSCs intramuscular transplantation could significantly decrease the major amputation rates and improve the QoL in patients with NO-AICLI. Long-term observation of a large sample of patients confirmed that the clinical benefits of PBDSCs transplantation were durable, without difference between the PCCs and PBMNCs groups.

Land cover information depicting the complex interactions between human activities and surface change is critically essential for nature conservation, social management, and sustainable development. Recent advances have shown great potentials of remote sensing data in generating high-resolution land cover maps, but it remains unclear how different models, data sources, and inclusive features affect the classification results, which hinders its applications in regional studies requiring more accurate land cover data. Informing these issues, here we developed a robust framework to improve the mapping results of 10 m resolution land cover classification in Guangdong Province, China using thousands of manually collected samples, multisource remote sensing data (Sentinel-1, Sentinel-2, and Luojia-1), machine learning algorithms, and a free cloud-based platform of Google Earth Engine. Results showed that an overall accuracy of 86.12% and a Kappa coefficient of 0.84 could be achieved for land cover classification in Guangdong for 2019. We found that random forest models achieved better performance than classification and regression trees, minimum distance, and support vector machine models. We also found that features derived from Sentinel-1 data and Sentinel-2 spectral indices greatly contributed to the classification process, while the feature of Luojia-1 data was not as much important as other configurations. A comparison between our results and several existing land cover products in terms of classification accuracy and visual interpretation further validated the effectiveness and robustness of the proposed framework. Our experiments and findings not only systematically elucidate the role of classification methods and data sources in deriving more accurate and reliable land cover maps but also provide certain guidelines for future land cover mapping from regional to global scales.

Background: Peripheral blood mononuclear cells (PBMNCs) showed encouraging short outcomes in the treatment of angiitis-induced no-option critical limb-threatening ischemia (AICLTI) in the pilot study. This study aimed to demonstrate the long-term outcomes of this treatment.Methods: From May 2014 to December 2018, patients diagnosed with AICLTI and treated by autotransplantation of PBMNCs in our center were enrolled and analyzed. The primary endpoint was major amputation-free survival (MAFS), the secondary endpoints included peak pain-free walking time (PPFWT), Wong-Baker FACES pain rating scale score (WFPRSS), labor recovery, ankle-brachial index (ABI), transcutaneous partial oxygen pressure (TcpO2), and SF-36v2 scores.Results: A total of 58 patients were enrolled. During a minimal follow-up of 36 months, the MAFS was 93.1% and the labor competence restored rate was 62.1%. The WFPRSS was decreased from 8.7 ± 1.6 to 1.6 ± 3.2, and PPFWT was significantly improved from 2.9 ± 4.2 min to 16.6 ± 6.9 min. The quality of life was also significantly improved at each follow-up point. Perfusion evaluating parameters, such as ABI and TcPO2, were also significantly improved. No critical adverse event was observed during the treatment and follow-up period.Conclusions: The treatment of AICLTI by autotransplantation of PBMNCs demonstrated encouraging long-term results. It could not only restore labor competence, improve the quality of life, but also significantly reduce the major amputation rate.

Critical limb ischemia (CLI) is the most advanced clinical stage of peripheral vascular disease with high mobility and mortality. CLI patients suffer from lower extremity rest pain, ulceration, and gangrene caused by insufficient blood and oxygen supply. Seeking for effective biomarkers and therapeutic targets is of great significance for improving the life quality of CLI patients. The circadian clock has been reported to be involved in the progression of kinds of cardiovascular diseases. Whether and how circadian genes play a role in CLI remains unknown. In this study, by collecting femoral artery and muscle specimens of CLI patients who underwent amputation, we confirmed that the circadian gene Bmal1 is downregulated in the CLI femoral artery and ischemic distal lower limb muscle. Furthermore, we verified that Bmal1 affects CLI by regulating lipid metabolism, inflammation, and angiogenesis. A hindlimb ischemia model performed in wild-type and Bmal1−/− mice confirmed that Bmal1 disruption would lead to impaired angiogenesis. In vitro experiments indicated that the decreased expression of Bmal1 would increase ox-LDL uptake and impair endothelial cell functions, including proliferation, migration, and tube formation. As for mechanisms, Bmal1 represses inflammation by inhibiting lipid uptake and by activating IL-10 transcription and promotes angiogenesis by transcriptionally regulating VEGF expression. In conclusion, we provide evidence that the circadian gene Bmal1 plays an important role in CLI by inhibiting inflammation and promoting angiogenesis. Thus, Bmal1 may be an effective biomarker and a potential therapeutic target in CLI.

Abstract Background Although the mononuclear cell (MNC) transplantation could theoretically induce therapeutic angiogenesis in the patients with no-option critical limb ischemia (NO-CLI), the clinical responses to this approach are inconsistent among different clinical trials. The purpose of this study was to identify the prognostic factors of responders and develop a predictive nomogram to guide patient selection. Methods We retrospectively reviewed a consecutive NO-CLI cohort who received peripheral blood-derived transplantation in our center. The patients who survived and achieved complete remission of CLI at 6 months post-transplantation were defined as responders. Logistic regression models were used to screen and identify the prognostic factors based on which predictive nomogram was developed. A receiver operating characteristic (ROC) curve and a calibration curve were drawn to determine the discrimination level and predictive accuracy. Results The study ultimately enrolled 103 patients, including 58 responders and 45 non-responders. Based on the multivariate regression analysis, age ≥ 50 years (odds ratio [OR] 0.201, P = 0.004), blood fibrinogen > 4 g/L (OR 0.176, P = 0.003), arterial occlusion above the knee/elbow (OR 0.232, P = 0.010), the transcutaneous pressure of oxygen (TcPO2) (OR 1.062, P = 0.006), and the Log total transplanted CD34+ cell count (OR 3.506, P = 0.046) were identified as independent prognostic factors of the responders in the nomogram. An area under the ROC curve of 0.851 indicated good discrimination, and the calibration curve of the predicted probability showed optimal agreement with that of the observed probability. Conclusions Age, blood fibrinogen, arterial occlusion level, TcPO2, and the total transplanted CD34+ cell count were independent prognostic factors of the responders. A nomogram with high discrimination and accuracy was developed to provide individualized predictions. Trail registration ChiCTR, ChiCTR1800019401. Registered 9 November 2018—Retrospectively registered

Background: Peripheral blood mononuclear cells (PBMNCs) and purified CD34+ cells (PCCs) are increasingly being used at treating no-option critical limb ischaemia (NO-CLI). We aimed to compare the efficacies and uncover the advantages associated with each treatment approach. Methods: A randomised single-blinded non-inferiority trial (Number: NCT 02089828) was performed. NO-CLI patients were 1:1 randomised to the PBMNCs and PCCs groups, and compared in relation to safety and efficacy outcomes. The primary efficacy outcomes included major amputation and total amputation over 12 months. The major amputation-free survival (MAFS) and total amputation-free survival (TAFS) rates were calculated. Findings: Fifty patients (25 per group, 47 with thromboangiitis obliterans and 3 with other angiitis) were enrolled, with a median follow-up period of 24.5 months (interquartile range: 17–34 months). One patient in the PCCs group was lost at 2 months and one major amputation occurred in the PBMNCs group at 3 months post-transplantation. The total amputation rates at 6 months post-transplantation were 28.0% in the PCCs group and 16.0% in the PBMNCs group (p = 0.343), and remained unchanged at 12 months. The groups did not differ regarding the MAFS and TAFS (Breslow-Wilcoxon test: p = 0.3014 and p = 0.3414). The PCCs group had a significantly higher probability of rest pain relief than the PBMNCs group (Breslow-Wilcoxon test: p = 0.0454). Interpretation: PCCs was not inferior to PBMNCs at limb salvage in the treatment of angiitis-induced NO-CLI and appeared to induce earlier ischaemia relief. Each cell type had specific advantages. These outcomes require verification from longer-term trials involving larger numbers of patients. Fund: Training program for outstanding academic leaders of Shanghai health and family planning system (Hundred Talent Program，Grant No. 2018BR40); China National Natural Science Funds (Grant No. 30801122); The excellent core member training programme at Zhongshan Hospital, Fudan University, China (Grant No. 2015ZSYXGG02); and Zhongshan Funds for the Institute of Vascular Surgery, Fudan University, China. Clinical trial registration: This study is registered with ClinicalTrials.gov (NCT 02089828). Keywords: Critical limb ischaemia, Cell therapy, Purified CD34+ cells, Peripheral blood mononuclear cells, Limb salvage

Mapping new and old buildings are of great significance for understanding socio-economic development in rural areas. In recent years, deep neural networks have achieved remarkable building segmentation results in high-resolution remote sensing images. However, the scarce training data and the varying geographical environments have posed challenges for scalable building segmentation. This study proposes a novel framework based on Mask R-CNN, named Histogram Thresholding Mask Region-Based Convolutional Neural Network (HTMask R-CNN), to extract new and old rural buildings even when the label is scarce. The framework adopts the result of single-object instance segmentation from the orthodox Mask R-CNN. Further, it classifies the rural buildings into new and old ones based on a dynamic grayscale threshold inferred from the result of a two-object instance segmentation task where training data is scarce. We found that the framework can extract more buildings and achieve a much higher mean Average Precision (mAP) than the orthodox Mask R-CNN model. We tested the novel framework’s performance with increasing training data and found that it converged even when the training samples were limited. This framework’s main contribution is to allow scalable segmentation by using significantly fewer training samples than traditional machine learning practices. That makes mapping China’s new and old rural buildings viable.

As new drugs for the treatment of malignant tumors, transforming growth factor-beta receptor 1 (TGFβR1) antagonists have attracted wide attention. Based on the crystal structure of TGFβR1-BMS22 complex, the pharmacophore model A02 with two hydrogen bond acceptors (HBAs) and four hydrophobic (HYD) properties was constructed. From the common features of active ligands reported in the literature, pharmacophore model B10 was also generated, which has two aromatic ring centers (RAs) and two HYD properties. The two models have high sensitivity and specificity to the training set, and they are highly consistent in spatial structure. Combining the two pharmacophore models, two novel skeleton structures with potential activity were selected by virtual screening from the DruglikeDiverse, MiniMaybridge, and ZINC Drug-Like databases. Four compounds (YXY01⁻YXY04) with potential anti-TGFβR1 activity were designed based on the new skeleton structures. In combination with Lipinski’s rules; absorption, distribution, metabolism, excretion, and toxicity (ADMET); and, toxicological properties predicted in the study, YXY01-03 with the novel skeleton, good drug-like properties, and potential activity were finally discovered and may have higher safety relative to BMS22, which may be valuable for further research.

To investigate the predictors and treatment of the 6-Fr Perclose Proglide-related complications (PRC) in percutaneous endovascular aortic repair (pEVAR).We retrospectively analyzed the PRC after pEVAR for the treatment of aortic aneurysm or dissection in our center from December 2012 to November 2013. Procedure success was defined as effective functioning of the two devices and local hemostasis. Access-related adverse events included vascular complications and device failures. Operative data and angiographic and computed tomography images were collected to assess the complications and treatment strategy.A total of 198 patients with 275 puncture sites underwent pEVAR with the 6-Fr Perclose Proglide. The procedure was successful in 178 patients (89.9%), whereas PRC occurred in 20 cases (10.1%), including 10 device failures and 10 vascular complications. An extra manual ancillary compression was conducted in 7 patients, one more device was used in 8 patients, and surgical repair of the femoral artery was performed in 5 patients. PRC had a tendency to occur in patients with body mass index (BMI)>30 kg/m2 (p = 0.021), thoracic stent grafts (p = 0.038), common femoral artery (CFA) calcification (p = 0.001), CFA depth>4 cm (p = 0.001), and sheath size>20Fr (p = 0.005). Device failure-related mortality was zero. None of the access sites had complications during the midterm follow-up.The pre-close technique with 6-Fr Perclose Proglide devices for pEVAR appears to be safe and effective with low technical failure and complication rates. Careful patient selection and proficiency in device manipulation might reduce the device related complications.