Intergrative metabolomic and transcriptomic analyses reveal the potential regulatory mechanism of unique dihydroxy fatty acid biosynthesis in the seeds of an industrial oilseed crop Orychophragmus violaceus.

BACKGROUND: Orychophragmus violaceus is a potentially important industrial oilseed crop due to the two 24-carbon dihydroxy fatty acids (diOH-FA) that was newly identified from its seed oil via a 'discontinuous elongation' process. Although many research efforts have focused on the diOH-FA biosynthesis mechanism and identified the potential co-expressed diacylglycerol acyltranferase (DGAT) gene associated with triacylglycerol (TAG)-polyestolides biosynthesis, the dynamics of metabolic changes during seed development of O. violaceus as well as its associated regulatory network changes are poorly understood. RESULTS: In this study, by combining metabolome and transcriptome analysis, we identified that 1,003 metabolites and 22,479 genes were active across four stages of seed development, which were further divided into three main clusters based on the patterns of metabolite accumulation and/or gene expression. Among which, cluster2 was mostly related to diOH-FA biosynthesis pathway. We thus further constructed transcription factor (TF)-structural genes regulatory map for the genes associated with the flavonoids, fatty acids and diOH-FA biosynthesis pathway in this cluster. In particular, several TF families such as bHLH, B3, HD-ZIP, MYB were found to potentially regulate the metabolism associated with the diOH-FA pathway. Among which, multiple candidate TFs with promising potential for increasing the diOH-FA content were identified, and we further traced the evolutionary history of these key genes among species of Brassicaceae. CONCLUSION: Taken together, our study provides new insight into the gene resources and potential relevant regulatory mechanisms of diOH-FA biosynthesis uniquely in seeds of O. violaceus, which will help to promote the downstream breeding efforts of this potential oilseed crop and advance the bio-lubricant industry.

Extracting causal impulse responses from baseband band-limited S-parameters of passive photonic integrated circuits for time-domain simulations.

The dispersive characteristics and wavelength-dependent behaviors of passive photonic integrated circuits (PICs) can be well described by S-parameters. However, circuit-level simulations of PICs that commonly consist of both passive and active components have to be conducted in the time domain. Thus, S-parameters need to be converted into a time-domain representation without losing accuracy and violating physical properties (e.g., causality). To address this issue, this paper proposes an approach for extracting causal impulse responses of passive PICs by extrapolating their baseband band-limited S-parameters. The method is efficient and robust for a wide range of passive PICs.

Sustained virologic response improved the long-term health-related quality of life in patients with chronic hepatitis C: a prospective national study in China.

BACKGROUND: To investigate the trends in health-related quality of life (HRQoL) among hepatitis C virus (HCV) patients and to assess the longitudinal impact of antiviral therapy on their well-being. METHODS: In this prospective multicenter observational study in adults with HCV infection, sociodemographic, clinical characteristics and EQ-5D questionnaires were collected. Generalized estimating equation (GEE) models were used to assess the associations between these variables and changes in HRQoL over time. RESULTS: 456 patients were included, with a median age of 46.5 (36.5-57.0) years, of which 262 (57.5%) were males and 44 (9.6%) had cirrhosis. 335 patients (73.5%) receiving antiviral therapy and 61.8% achieved sustained virologic response (SVR). The baseline EQ-5D utility and EQ-VAS were 0.916 ± 0.208 and 80.6 ± 13.0. In multivariable analysis of GEE estimation, achieving SVR24 was positively associated with EQ-5D utility (p = 0.000) and EQ-VAS (p = 0.000) over time. Age and income were shown to be significant predictors of EQ-5D utility, while gender, age and genotype were associated with EQ-VAS over time. CONCLUSIONS: SVR improved long-term HRQoL in HCV patients in the first few years following viral clearance. Certain sociodemographic factors, such as gender, age, income as well as genotype, significantly influenced long-term changes in patients' quality of life. TRIAL REGISTRATION: NCT01594554. Registration date: 09/05/2012.

Nylon Suture Loop for Tagging Lymphatic Channels during Lymphaticovenular Anastomosis.

Background Lymphaticovenular anastomosis (LVA) requires special supermicrosurgery techniques designed for vessels less than 0.8 mm in size. While preparing the field for LVA, it is often difficult to handle the lymphatic vessel directly without injuring it or fracturing it entirely. Method We propose a novel technique, which is used in LVA for tagging of lymphatic vessels, with the use of a nylon 6-0 suture and micro-ligaclip. Results We have successfully performed 78 LVAs in 26 cases with this method. The average lymphatic vessel size was 0.3 mm (0.15-0.8 mm). Conclusion This novel technique to implement the use of a nylon suture with a micro-ligaclip to use as a vessel loop for lymphatics has not been previously described in the literature. It is a useful technique that we find beneficial to lymphatic identification through tagging of the lymphatic channels, contributing to greater success in each anastomosis.

Synthesis of 3-Azabicyclo[3.1.0]hexane Derivates.

3-Azabicyclo[3.1.0]hexanes are an important class of nitrogen-containing heterocycles that have been found to be key structural features in a wide range of biologically active natural products, drugs, and agrochemicals. As a cutting-edge area, the synthesis of these derivatives has made spectacular progress in recent decades, with various transition-metal-catalyzed and transition-metal-free catalytic systems being developed. In this review, we provide an overview of recent advances in the efficient methods for the synthesis of 3-azabicyclo[3.1.0]hexane derivatives since 2010, emphasizing the scope of substrates and synthesis' applications, as well as the mechanisms of these reactions.

Value of T2-weighted-based radiomics model in distinguishing Warthin tumor from pleomorphic adenoma of the parotid.

OBJECTIVES: The differentiation of Warthin tumor and pleomorphic adenoma before treatment is crucial for clinical strategies. The aim of this study was to develop and test a T2-weighted-based radiomics model for differentiating pleomorphic adenoma from Warthin tumor of the parotid gland. METHODS: A total of 117 patients, including 61 cases of Warthin tumor and 56 cases of pleomorphic adenoma, were retrospectively enrolled from two centers between January 2010 and June 2022. The training set included 82 cases, and the validation set included 35 cases. From T2-weighted images, 971 radiomics features were extracted. Seven radiomics features remained after a two-step selection process. We used the seven radiomics features and clinical factors through multivariable logistic regression to build radiomics and clinical models, respectively. A radiomics-clinical model was also built that combined the independent clinical predictors with the radiomics features. Through ROC curves, the three models were evaluated and compared. RESULTS: In the radiomics model, AUCs were 0.826 and 0.796 in training and validation sets, respectively. In the clinical model, the AUCs were 0.923 and 0.926 in the training and validation sets, respectively. Decision curve analysis revealed that the radiomics-clinical model had the best diagnostic performance for distinguishing Warthin tumor from pleomorphic adenoma of the parotid gland (AUC = 0.962 and 0.934 for the training and validation sets, respectively). CONCLUSION: The radiomics-clinical model performed well in differentiating pleomorphic adenoma from Warthin tumor of the parotid gland. KEY POINTS: • The clinical model outperformed the radiomics model in distinguishing pleomorphic adenoma from Warthin tumor of the parotid gland. • The radiomics features extracted from T2-weighted images could help differentiate pleomorphic adenoma from Warthin tumor of the parotid gland. • The radiomics-clinical model was superior to the radiomics and the clinical models for differentiating pleomorphic adenoma from Warthin tumor of the parotid gland.

Electrochemical Synthesis of Polysubstituted Sulfonated Pyrazoles via Cascade Intermolecular Condensation, Radical-Radical Cross Coupling Sulfonylation, and Pyrazole Annulation.

Electrochemical synthesis of polysubstituted sulfonated pyrazoles from enaminones and sulfonyl hydrazides was established under metal-free, exogenous-oxidant-free, and mild conditions. By judicious choice of different electrochemical reaction conditions, NH2-functionalized enaminones or N,N-disubstituted enaminones can react with aryl/alkyl sulfonyl hydrazides to afford tetra- or trisubstituted sulfonated pyrazoles in moderate to good yields, respectively. The gram-scale electrochemical transformation demonstrated the efficiency and practicability of this synthetic strategy. In addition, the sulfonated NH-pyrazole can be obtained via the dissociation of the N-tosyl group. Mechanistic studies reveal that the electrochemical cascade reaction synthesis of polysubstituted sulfonated pyrazoles proceeded via the sequence of intermolecular condensation, radical-radical cross coupling sulfonylation, and pyrazole annulation.

I2-Promoted [4 + 2] cycloaddition of in situ generated azoalkenes with enaminones: facile and efficient synthesis of 1,4-dihydropyridazines and pyridazines.

A facile and efficient strategy for the synthesis of 1,4-dihydropyridazines and pyridazines through I2-promoted [4 + 2] cycloaddition of in situ generated azoalkenes with enaminones has been developed. The switch in selectivity is attributed to the judicious choice of different reaction temperatures. The key features of this work include controllable and selective synthesis, good functional group tolerance, good to excellent reaction yields, metal/base-free conditions, and also applicability to one-pot methodology.

Dissipation behavior, residue distribution and risk assessment of three fungicides in pears.

BACKGROUND: Fungicides are often applied to pears before they are kept in storage facilities. The scientific application of pesticides can reduce unnecessary exposure, which in turn could benefit both humans and the environment. RESULTS: We investigated dissipation behavior and residue distribution, and conducted risk assessments for prochloraz, pyraclostrobin, and tebuconazole in pears stored under different conditions using ultra-performance liquid chromatography (UPLC). The recoveries of the three fungicides ranged from 76.5% to 114.5%, and the coefficients of variation were 1.0%-8.5%. The half-life (t1/2 ) ranges for degradation of the three fungicides in Dangshan Su pear peel were 8.8-13.9 days after storage at 25 °C and 99.0-346.6 days after storage at 2 °C. Among the three fungicides, tebuconazole had the lowest residue concentration in pear pulp (maximum of 0.226 mg·kg-1 ) and the longest half-life (≥ 231.0 days). Accordingly, among these fungicides, tebuconazole is the most suitable for the preservation of Dangshan Su pears during storage. Finally, we analyzed samples of six pear varieties from markets in China and found that the residue concentrations of the three fungicides in pear pulp and fruit met Chinese standards. CONCLUSION: The results provide a scientific basis for rationalizing the use of prochloraz, pyraclostrobin, and tebuconazole, and improving the safety of pears for eating. © 2019 Society of Chemical Industry.

Solid-State Molecular Protonics Devices of Solid-Supported Biological Membranes Reveal the Mechanism of Long-Range Lateral Proton Transport.

Lateral proton transport (PT) on the surface of biological membranes is a fundamental biochemical process in the bioenergetics of living cells, but a lack of available experimental techniques has resulted in a limited understanding of its mechanism. Here, we present a molecular protonics experimental approach to investigate lateral PT across membranes by measuring long-range (70 µm) lateral proton conduction via a few layers of lipid bilayers in a solid-state-like environment, i.e., without having bulk water surrounding the membrane. This configuration enables us to focus on lateral proton conduction across the surface of the membrane while decoupling it from bulk water. Hence, by controlling the relative humidity of the environment, we can directly explore the role of water in the lateral PT process. We show that proton conduction is dependent on the number of water molecules and their structure and on membrane composition, where we explore the role of the headgroup, the tail saturation, the membrane phase, and membrane fluidity. The measured PT as a function of temperature shows an inverse temperature dependency, which we explain by the desorption and adsorption of water molecules into the solid membrane platform. We explain our findings by discussing the role of percolating hydrogen bonding within the membrane structure in a Grotthuss-like mechanism.

Wholly sustainable graft copolymers derived from cellulose, lignin, and hemicellulose for high-performance elastomers, adhesives, and UV-blocking materials.

Sustainable elastomers derived from renewable biobased resources with excellent mechanical properties and varied functions are highly pursued to substitute traditional petroleum-based polymers yet challenging due to their limited macroscopic performance. In this work, we designed a series of wholly biobased cellulose-graft-poly(vanillin acrylate-co-tetrahydrofurfuryl acrylate) (Cell-g-P(VA-co-THFA) copolymer elastomers with cellulose as the rigid backbone, sustainable VA derived from lignin and soft THFA derived from hemicellulose as the hard and soft segments in the rubbery side chains. Moreover, the grafted side chains can be cross-linked to introduce an additional dynamic network structure via Schiff-base chemistry between the aldehyde and amino groups. The mechanical properties of Cell-g-P(VA-co-THFA) copolymer elastomers, including tensile strength, extensibility, elasticity, and toughness can be facilely manipulated by the VA/THFA feed ratio, cellulose content, and cross-linking density. These Cell-g-P(VA-co-THFA) copolymer elastomers are thermally stable and possess outstanding adhesion behavior and prominent UV-shielding performance. Besides dramatically enhanced mechanical properties, the cross-linked Cell-g-P(VA-co-THFA) counterparts exhibit remarkable shape memory behavior. This work provides a robust and convenient strategy for developing strong and versatile sustainable elastomers with different application demands by integrating different biomass feedstocks via elaborate molecular design.

Breakdown of Ohm's Law in Molecular Junctions with Electrodes of Single-Layer Graphene.

For sufficiently low biases, Ohm's law, the cornerstone of electricity, stating that current I and voltage V are proportional, is satisfied at low biases for all known systems ranging from macroscopic conductors to nanojunctions. In this study, we predict theoretically and demonstrate experimentally that in single-molecule junctions fabricated with single-layer graphene as electrodes the current at low V scales as the cube of V, thereby invalidating Ohm's law. The absence of the ohmic regime is a direct consequence of the unique band structure of the single-layer graphene, whose vanishing density of states at the Dirac points precludes electron transfer from and to the electrodes at low biases.

Deep learning system for malignancy risk prediction in cystic renal lesions: a multicenter study.

OBJECTIVES: To develop an interactive, non-invasive artificial intelligence (AI) system for malignancy risk prediction in cystic renal lesions (CRLs). METHODS: In this retrospective, multicenter diagnostic study, we evaluated 715 patients. An interactive geodesic-based 3D segmentation model was created for CRLs segmentation. A CRLs classification model was developed using spatial encoder temporal decoder (SETD) architecture. The classification model combines a 3D-ResNet50 network for extracting spatial features and a gated recurrent unit (GRU) network for decoding temporal features from multi-phase CT images. We assessed the segmentation model using sensitivity (SEN), specificity (SPE), intersection over union (IOU), and dice similarity (Dice) metrics. The classification model's performance was evaluated using the area under the receiver operator characteristic curve (AUC), accuracy score (ACC), and decision curve analysis (DCA). RESULTS: From 2012 to 2023, we included 477 CRLs (median age, 57 [IQR: 48-65]; 173 men) in the training cohort, 226 CRLs (median age, 60 [IQR: 52-69]; 77 men) in the validation cohort, and 239 CRLs (median age, 59 [IQR: 53-69]; 95 men) in the testing cohort (external validation cohort 1, cohort 2, and cohort 3). The segmentation model and SETD classifier exhibited excellent performance in both validation (AUC = 0.973, ACC = 0.916, Dice = 0.847, IOU = 0.743, SEN = 0.840, SPE = 1.000) and testing datasets (AUC = 0.998, ACC = 0.988, Dice = 0.861, IOU = 0.762, SEN = 0.876, SPE = 1.000). CONCLUSION: The AI system demonstrated excellent benign-malignant discriminatory ability across both validation and testing datasets and illustrated improved clinical decision-making utility. CRITICAL RELEVANCE STATEMENT: In this era when incidental CRLs are prevalent, this interactive, non-invasive AI system will facilitate accurate diagnosis of CRLs, reducing excessive follow-up and overtreatment. KEY POINTS: The rising prevalence of CRLs necessitates better malignancy prediction strategies. The AI system demonstrated excellent diagnostic performance in identifying malignant CRL. The AI system illustrated improved clinical decision-making utility.

The super-pangenome of Populus unveils genomic facets for its adaptation and diversification in widespread forest trees.

Understanding the underlying mechanisms and links between genome evolution and adaptive innovations stands as a key goal in evolutionary studies. Poplars, among the world's most widely distributed and cultivated trees, exhibit extensive phenotypic diversity and environmental adaptability. In this study, we present a genus-level super-pangenome comprising 19 Populus genomes, revealing the likely pivotal role of private genes in facilitating local environmental and climate adaptation. Through the integration of pangenomes with transcriptomes, methylomes, and chromatin accessibility mapping, we unveil that the evolutionary trajectories of pangenes and duplicated genes are closely linked to local genomic landscapes of regulatory and epigenetic architectures, notably CG methylation in gene-body regions. Further comparative genomic analyses have enabled the identification of 142 202 structural variants across species that intersect with a significant number of genes and contribute substantially to both phenotypic and adaptive divergence. We have experimentally validated a ∼180-bp presence/absence variant affecting the expression of the CUC2 gene, crucial for leaf serration formation. Finally, we developed a user-friendly web-based tool encompassing the multi-omics resources associated with the Populus super-pangenome (http://www.populus-superpangenome.com). Together, the present pioneering super-pangenome resource in forest trees not only aids in the advancement of breeding efforts of this globally important tree genus but also offers valuable insights into potential avenues for comprehending tree biology.

Decellularized porcine saphenous artery for small-diameter tissue-engineered conduit graft.

Decellularized xenografts have been identified as potential scaffolds for small-diameter vascular substitutes. This study aimed to develop and investigate a biomechanically functional and biocompatible acellular conduit using decellularized porcine saphenous arteries (DPSAs), through a modified decellularization process using Triton X-100/NH4 OH solution and serum-containing medium. Histological and biochemical analysis indicated a high degree of cellular removal and preservation of the extracellular matrix. Bursting pressure tests showed that the DPSAs could withstand a pressure of 1854 ± 164 mm Hg. Assessment of in vitro cell adhesion and biocompatibility showed that porcine pulmonary artery endothelial cells were able to adhere and proliferate on DPSAs in static and rotational culture. After interposition into rabbit carotid arteries in vivo, DPSAs showed patency rates of 60% at 1 month and 50% at 3 months. No aneurysm and intimal hyperplasia were observed in any DPSAs. All patent grafts showed regeneration of vascular elements, and thrombotic occlusion was found to be the main cause of graft failure, probably due to remaining xenoantigens. In conclusion, this study showed the development and evaluation of a decellularization process with the potential to be used as small-diameter grafts.

Fully biobased sustainable elastomers derived from chitin, lignin, and plant oil via grafting strategy and Schiff-base chemistry.

With the dramatically increased environmental problems, the rational design of sustainable polymers from renewable feedstocks opens new avenues to reduce the huge pollution impact. The major challenge for sustainable polymers is the decreased mechanical performance compared to that of petroleum-based materials. In this work, fully biobased sustainable elastomers were developed by integrating renewable chitin, lignin, and plant oil into one macromolecule, in which chitin was chosen as the rigid backbone, while a lignin-derived monomer vanillin acrylate (VA) and a plant oil-based monomer lauryl acrylate (LA) were selected as the hard and soft segments for the grafted side chains. A series of Chitin-graft-poly(vanillin acrylate-co-lauryl acrylate) (Chitin-g-P(VA-co-LA)) copolymers with varied feed ratios and chitin contents were synthesized by using reversible addition-fragmentation chain transfer (RAFT) polymerization as an effective grafting strategy. In addition, a dynamic cross-linked network was incorporated via Schiff-base reaction to improve the macroscopic behavior of such kind of chitin graft elastomers. These sustainable elastomers are mechanically strong and show excellent reprocessablity, as well as outstanding UV-blocking property. This strategy is versatile and can inspire the further development of fully biobased sustainable materials from natural resources.

Deep learning and radiomic feature-based blending ensemble classifier for malignancy risk prediction in cystic renal lesions.

BACKGROUND: The rising prevalence of cystic renal lesions (CRLs) detected by computed tomography necessitates better identification of the malignant cystic renal neoplasms since a significant majority of CRLs are benign renal cysts. Using arterial phase CT scans combined with pathology diagnosis results, a fusion feature-based blending ensemble machine learning model was created to identify malignant renal neoplasms from cystic renal lesions (CRLs). Histopathology results were adopted as diagnosis standard. Pretrained 3D-ResNet50 network was selected for non-handcrafted features extraction and pyradiomics toolbox was selected for handcrafted features extraction. Tenfold cross validated least absolute shrinkage and selection operator regression methods were selected to identify the most discriminative candidate features in the development cohort. Feature's reproducibility was evaluated by intra-class correlation coefficients and inter-class correlation coefficients. Pearson correlation coefficients for normal distribution and Spearman's rank correlation coefficients for non-normal distribution were utilized to remove redundant features. After that, a blending ensemble machine learning model were developed in training cohort. Area under the receiver operator characteristic curve (AUC), accuracy score (ACC), and decision curve analysis (DCA) were employed to evaluate the performance of the final model in testing cohort. RESULTS: The fusion feature-based machine learning algorithm demonstrated excellent diagnostic performance in external validation dataset (AUC = 0.934, ACC = 0.905). Net benefits presented by DCA are higher than Bosniak-2019 version classification for stratifying patients with CRL to the appropriate surgery procedure. CONCLUSIONS: Fusion feature-based classifier accurately distinguished malignant and benign CRLs which outperformed the Bosniak-2019 version classification and illustrated improved clinical decision-making utility.

Association between Ki67 expression and therapeutic outcome in colon cancer.

Ki67 is a commonly used proliferation marker in pathological diagnosis of tumors; however, its prognostic value in colon cancer is controversial. A total of 312 consecutive patients with stage I-III colon cancer who underwent radical surgery with or without adjuvant chemotherapy were included in the present study. Ki67 expression was assessed using immunohistochemistry and was classified according to 25% intervals. The association between Ki67 expression and clinicopathological features was analyzed. Long-term postoperative survival, including disease-free survival (DFS) and overall survival, was calculated, and its association with Ki67 was analyzed. High Ki67 expression (>50%) was associated with improved DFS in patients treated with adjuvant chemotherapy postoperatively, but not in patients who received surgery alone (P=0.138). Ki67 expression was significantly associated with histological differentiation of the tumor (P=0.01), while it was not associated with other clinicopathological factors. Multivariate analysis demonstrated that pathological T and N stage were independent prognostic factors. In conclusion, high Ki67 expression was associated with a good therapeutic outcome in patients receiving adjuvant chemotherapy in colon cancer.

A case of cutaneous psoriasis vulgaris achieving complete remission post major breast reconstructive surgery.

Psoriasis is a debilitating chronic inflammatory systemic condition largely affecting the skin. Major surgery is relatively contraindicated due to the propensity for triggering psoriatic flares and koebnerization of the surgical scars. We detail an interesting case of complete psoriasis remission following a right nipple-sparing mastectomy with sentinel lymph node biopsy with vascular augmented pedicled transverse rectus abdominal myocutaneous (TRAM) flap in a patient with systemic psoriasis vulgaris and arthropathy. Intra-operatively, majority of the psoriatic plaques were excised or de-epithelized and used as part of the ipsilateral TRAM flap. Post-operatively, koebnerization did not occur and her psoriasis was cured completely even after cancer chemotherapy. One of several hypotheses include excision with de-epithelization of most of the psoriatic plaques reduces disease and inflammatory burden leading to complete remission. Perhaps, surgery could one day play a supporting role to existing treatment options to achieve psoriasis remission.