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Abstract Fatigue failure is invariably the most crucial failure mode for metallic structural components. Most microstructural strategies for enhancing fatigue resistance are effective in suppressing either crack initiation or propagation, but often do not work for both synergistically. Here, we demonstrate that this challenge can be overcome by architecting a gradient structure featuring a surface layer of nacre-like nanolaminates followed by multi-variant twinned structure in pure titanium. The polarized accommodation of highly regulated grain boundaries in the nanolaminated layer to cyclic loading enhances the structural stability against lamellar thickening and microstructure softening, thereby delaying surface roughening and thus crack nucleation. The decohesion of the nanolaminated grains along horizonal high-angle grain boundaries gives rise to an extraordinarily high frequency (≈1.7 × 103 times per mm) of fatigue crack deflection, effectively reducing fatigue crack propagation rate (by 2 orders of magnitude lower than the homogeneous coarse-grained counterpart). These intriguing features of the surface nanolaminates, along with the various toughening mechanisms activated in the subsurface twinned structure, result in a fatigue resistance that significantly exceeds those of the homogeneous and gradient structures with equiaxed grains. Our work on architecting the surface nanolaminates in gradient structure provides a scalable and sustainable strategy for designing more fatigue-resistant alloys.

C30H29MnN6 O7V2, triclinic, P 1‾ $\overline{1}$ (no. 2), a = 9.0806(3) Å, b = 11.1937(3) Å, c = 16.3585(5) Å, α = 102.2430(10)°, β = 100.090(1)°, γ = 97.7410(10)°, V = 1574.09(8) Å3, Z = 2, Rgt (F) = 0.0335, wRref (F 2) = 0.0886, T = 100 K.

Abstract Previous published data have confirmed that the addition of a citric acid meal improves the accuracy of the 13C-urea breath test (13C-UBT). However, some studies have suggested that a citric acid test meal may not be necessary. Thus, the aim of this study was to evaluate the combination of a 13C-UBT with a citric acid meal for the diagnosis of Helicobacter pylori (Hp) infection in a Chinese population, particularly for patients with results in the gray zone. In this paired self-controlled study, all subjects had previously undergone 13C-UBTs without citric acid meals and were randomly divided into two groups based on different doses of citric acid (a low-dose citric acid group and a high-dose citric acid group, comprising meals with 0.68 g and 3.84 g citric acid powder, respectively). Positive rapid urease test (CLO) test and histology results were considered the 'gold standard'. The mean delta over baseline (DOB) value, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were compared between the two groups, particularly for patients with results in the gray zone. In total, 285 patients were tested. Of these patients, 189 were included in the low-dose citric acid group, and 96 were included in the high-dose citric acid group. Among patients with a positive 13C-UBT result without citric acid [delta over baseline (DOB) value ≥ 4‰, n = 174] and a negative 13C-UBT result without citric acid (DOB value

Objective(s): Proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) contribute to hypoxia-induced pulmonary hypertension (HPH). The transcription factor Cbp/p300-interacting transactivator with Glu/Asp-rich carboxy-terminal domain 2 (Cited2) has been implicated in the control of tumor cells and mesenchymal stem cell (MSC) and cardiomyocyte growth or migration. Whether Cited2 is involved in the proliferation and migration of PASMCs and the underlying mechanisms deserve to be explored. Materials and Methods: Cited2 expression was detected in rat PASMCs under hypoxia conditions and HPH rat models. The effect of Cited2 on the proliferation and migration of PASMC was detected by overexpression or knockdown of the Cited2 gene. After PAMSCs were treated with recombinant TGF-β1 and the lentivirus vector overexpressing Cited2, expression of peroxisome proliferator-activated receptor gamma (PPARγ) was examined by western blotting.Results: We revealed that hypoxia down-regulated the expression of Cited2 in PASMCs and rat pulmonary arteries. Cited2 overexpression inhibited the proliferation and migration of PASMCs under hypoxia, while Cited2 knockdown induced the proliferation and migration of PASMCs. Cited2 inhibits the negative regulation of the TGF-β1 pathway on PPARγ to inhibit the proliferation and migration of PASMCs.Conclusion: These findings suggest that increased Cited2 expression contributes to the inhibition of PASMCs proliferation and migration by regulating TGF-β1-mediated target gene expression in HPH and provides a new target for molecular therapy of HPH.

Abstract High or medium- entropy alloys (HEAs/MEAs) are multi-principal element alloys with equal atomic elemental composition, some of which have shown record-breaking mechanical performance. However, the link between short-range order (SRO) and the exceptional mechanical properties of these alloys has remained elusive. The local destruction of SRO by dislocation glide has been predicted to lead to a rejuvenated state with increased entropy and free energy, creating softer zones within the matrix and planar fault boundaries that enhance the ductility, but this has not been verified. Here, we integrate in situ nanomechanical testing with energy-filtered four-dimensional scanning transmission electron microscopy (4D-STEM) and directly observe the rejuvenation during cyclic mechanical loading in single crystal CrCoNi at room temperature. Surprisingly, stacking faults (SFs) and twin boundaries (TBs) are reversible in initial cycles but become irreversible after a thousand cycles, indicating SF energy reduction and rejuvenation. Molecular dynamics (MD) simulation further reveals that the local breakdown of SRO in the MEA triggers these SF reversibility changes. As a result, the deformation features in HEAs/MEAs remain planar and highly localized to the rejuvenated planes, leading to the superior damage tolerance characteristic in this class of alloys.

It is still a challenging task to perform the semantic segmentation with high accuracy due to the complexity of real picture scenes. Many semantic segmentation methods based on traditional deep learning insufficiently captured the semantic and appearance information of images, which put limit on their generality and robustness for various application scenes. Thus, in this paper, we proposed a novel strategy that reformulated the popularly used convolution operation to multi-layer convolutional sparse coding block in semantic segmentation method to ease the aforementioned deficiency. To prove the effectiveness of our idea, we chose the widely used U-Net model for the demonstration purpose, and we designed CSC-Unet model series based on U-Net. Through extensive analysis and experiments, we provided credible evidence showing that the multi-layer convolutional sparse coding block enables semantic segmentation model to converge faster, extract finer semantic and appearance information of images, and improve the ability to recover spatial detail information. The best CSC-Unet model significantly outperforms the results of the original U-Net on three public datasets with different scenarios, i.e., 87.14% vs. 84.71% on DeepCrack dataset, 68.91% vs. 67.09% on Nuclei dataset, and 53.68% vs. 48.82% on CamVid dataset, respectively. In addition, the proposed strategy could be possibly used to significantly improve segmentation performance of any semantic segmentation model that involves convolution operations and the corresponding code is available at https://github.com/NZWANG/CSC-Unet.

Abstract Background Nebulized drug delivery is commonly used in pediatric clinical practice. The growing number of literatures have reported the application of nebulized ketamine in pediatric sedation in recent years. This meta-analysis of randomized controlled trials comparing the efficacy and safety of nebulized ketamine versus different pharmacological approaches was conducted to estimate the effects of this technique in pediatric sedation. Methods We searched PubMed, Embase, and Cochrane Library from inception to Feb 2023. All randomized controlled trials used nebulized ketamine as presurgical and pre-procedural sedatives in children were included. Sedative effects and various adverse events were considered as the outcomes. Results Ten studies with 727 pediatric patients were enrolled. Compared to nebulized dexmedetomidine, using of ketamine via nebulization showed similar sedation satisfaction (54.79% vs. 60.69%, RR = 0.88, with 95%CI [0.61, 1.27]), success rate of parental separation (57.27% vs. 73.64%, RR = 0.81, with 95%CI [0.61, 1.08]), and mask acceptability (37.27% vs. 52.73%, RR = 0.71, with 95%CI [0.45, 1.10]). However, the using of combination of two medications (nebulized ketamine plus nebulized dexmedetomidine) was associated with better sedative satisfaction (33.82% vs. 68.11%, RR = 0.50, with 95%CI [0.27, 0.92]) and more satisfactory mask acceptance (45.59% vs. 71.01%, RR = 0.69, with 95%CI [0.56, 0.86]). Compared with nebulized ketamine, using of nebulized dexmedetomidine was associated with less incidence of emergence agitation (18.18% vs. 3.33%, RR = 4.98, with 95%CI [1.88, 13.16]). Conclusions Based on current evidences, compared to nebulized dexmedetomidine, nebulized ketamine provides inconspicuous advantages in pediatric sedation, and it has a relatively high incidence of emergence agitation. Combination of nebulized ketamine and dexmedetomidine might be considered as one preferred option in pediatric sedation as it can provide more satisfactory sedative effects. However, there is insufficient evidence regarding nebulized ketamine versus ketamine administered through other routes and nebulized ketamine versus other sedatives. The overall low or moderate quality of evidence evaluated by the GRADE system also calls for more high-quality studies with larger sample sizes in future. Research registration The protocol of present study was registered with PROSPERO (CRD42023403226).

Abstract S1P, also referred to as sphingosine-1-phosphate, is a lipid molecule with bioactive properties involved in numerous cellular processes such as cell growth, movement, programmed cell death, self-degradation, cell specialization, aging, and immune system reactions. Autophagy is a meticulously controlled mechanism in which cells repurpose their elements to maintain cellular balance. There are five stages in autophagy: initiation, nucleation, elongation and maturation, fusion, and degradation. New research has provided insight into the complex connection between S1P and autophagy, uncovering their interaction in both normal and abnormal circumstances. Gaining knowledge about the regulatory mechanism of S1P signaling on autophagy can offer a valuable understanding of its function in well-being and illness, potentially leading to innovative therapeutic concepts for diverse ailments. Hence, this review analyzes the essential stages in mammalian autophagy, with a specific emphasis on recent research exploring the control of each stage by S1P. Additionally, it sheds light on the roles of S1P-induced autophagy in various disorders.

Abstract The objective of this study was to investigate the clinical significance and roles of tumor progression locus 2 (TPL2) and peptidyl-prolyl cis–trans isomerase 1 (Pin1) in the occurrence and development of breast invasive ductal carcinoma (IDC). Immunohistochemistry was used to detect the expression of TPL2 and Pin1 in human breast tissues, which included normal breast tissues (Normal), tissues with fibrocystic changes (FCC), ductal carcinoma in situ (DCIS), and IDC. The roles of TPL2 and Pin1 in the occurrence and development of IDC, as well as the correlation between their expression levels and clinicopathological parameters, were analyzed. Compared with Normal and FCC groups, the overexpression of TPL2 and Pin1 was significantly increased in DCIS and IDC groups (DCIS vs Normal: P = 0.002/P

Abstract Inflammatory Bowel Disease (IBD), a chronic nonspecific intestinal inflammatory disease, is comprised of Ulcerative Colitis (UC) and Crohn’s Disease (CD). IBD is closely related to a systemic inflammatory reaction and affects the progression of many intestinal and extraintestinal diseases. As one of the representative bacteria for probiotic-assisted therapy in IBD, multiple strains of Lactobacillus have been proven to alleviate intestinal damage and strengthen the intestinal immunological barrier, epithelial cell barrier, and mucus barrier. Lactobacillus also spares no effort in the alleviation of IBD-related diseases such as Colitis-associated Colorectal cancer (CAC), Alzheimer’s Disease (AD), Depression, Anxiety, Autoimmune Hepatitis (AIH), and so on via gut-brain axis and gut-liver axis. This article aims to discuss the role of Lactobacillus in IBD and IBD-related diseases, including its underlying mechanisms and related curative strategies from the present to the future.

Abstract Background Traditional radiotherapy and chemotherapy have been intensively studied for their role in the treatment of tumours. However, these therapies often cause side effects for patients, which calls for the development of novel treatment options for tumours. B-cell lymphoma-2 (Bcl-2)/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) reportedly apoptosis-inducing effects in tumour cells and is associated with the progression and treatment of multiple tumours. Nevertheless, little is known about its potential role in tumour diagnosis and targeted therapy. Findings The results of the study demonstrated that the interaction of BNIP3 with HDAC1 may affect the progression of breast invasive cancer (BRCA), sarcoma (SARC), kidney renal clear cell carcinoma (KIRC), and low-grade glioma (LGG). BNIP3 seemed to exert its effects in BRCA and SARC primarily through gene silencing and integrator complex, and in KIRC and LGG, mainly by affecting olfactory function, suggesting that targeted therapy can be developed based on the above signalling pathway and downstream molecules. Interpretation BNIP3 has emerged as a promising therapeutic and diagnostic target for BRCA, SARC, KIRC, and LGG, providing new insights into tumour molecular therapies in the clinic.

Abstract Endoscopic evaluation is the key to the management of ulcerative colitis (UC). However, there is interobserver variability in interpreting endoscopic images among gastroenterologists. Furthermore, it is time‐consuming. Convolutional neural networks (CNNs) can help overcome these obstacles and has yielded preliminary positive results. We aimed to develop a new CNN‐based algorithm to improve the performance for evaluation tasks of endoscopic images in patients with UC. A total of 12,163 endoscopic images from 308 patients with UC were collected from January 2014 to December 2021. The training set and test set images were randomly divided into 37,515 and 3191 after excluding possible interference and data augmentation. Mayo Endoscopic Subscores (MES) were predicted by different CNN‐based models with different loss functions. Their performances were evaluated by several metrics. After comparing the results of different CNN‐based models with different loss functions, High‐Resolution Network with Class‐Balanced Loss achieved the best performances in all MES classification subtasks. It was especially great at determining endoscopic remission in UC, which achieved a high accuracy of 95.07% and good performances in other evaluation metrics with sensitivity 92.87%, specificity 95.41%, kappa coefficient 0.8836, positive predictive value 93.44%, negative predictive value 95.00% and area value under the receiver operating characteristic curve 0.9834, respectively. In conclusion, we proposed a new CNN‐based algorithm, Class‐Balanced High‐Resolution Network (CB‐HRNet), to evaluate endoscopic activity of UC with excellent performance. Besides, we made an open‐source dataset and it can be a new benchmark in the task of MES classification.

Abstract Genomic structural variation (SV) has profound effects on organismal evolution; often serving as a source of novel genetic variation. Gene copy number variation (CNV), one type of SV, has repeatedly been associated with adaptive evolution in eukaryotes, especially with environmental stress. Resistance to the widely used herbicide, glyphosate, has evolved through target-site CNV in many weedy plant species, including the economically important grass, Eleusine indica (goosegrass); however, the origin and mechanism of these CNVs remain elusive in many weed species due to limited genetic and genomic resources. To study this CNV in goosegrass, we present high-quality reference genomes for glyphosate-susceptible and -resistant goosegrass lines and fine-assembles of the duplication of glyphosate’s target site gene 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS). We reveal a unique rearrangement of EPSPS involving chromosome subtelomeres. This discovery adds to the limited knowledge of the importance of subtelomeres as genetic variation generators and provides another unique example for herbicide resistance evolution.

Abstract Background Anti-programmed death 1/anti-programmed death ligand 1 (PD-1/PD-L1) combined with radiotherapy (RT) has a synergistic effect on systemic tumor control. A dissociated response (DR), characterized by some lesions shrinking and others growing, has been recognized with immune checkpoint inhibitor (ICI) monotherapy or combination therapy. The objective of this study was to assess the frequency and clinical benefit of DR in patients with advanced metastatic solid tumors receiving PD-1 inhibitors in combination with RT. Methods We conducted a single-center retrospective analysis of patients with advanced metastatic solid tumors receiving PD-1 inhibitor combined with RT at the Department of Radiotherapy & Oncology, The Second People’s Hospital Affiliated with Soochow University. Treatment response was assessed for each measurable lesion according to the Response Evaluation Criteria in Solid Tumours ( RECIST) v 1.1 guidelines. Patterns of response are divided into four groups: (1) DR, (2) uniform response, (3) uniform progression, and (4) only stable lesions. The overall survival (OS) of different groups was compared using Kaplan–Meier methods and log-rank tests. Results Between March 2019 and July 2022, 93 patients were included. The median follow-up was 10.5 months (95% CI 8.8–12.1). The most common tumor types were lung cancer (19.8%), colorectal adenocarcinoma (17.2%), and esophageal cancer (10.8%). DR was observed in 22 (23.7%) patients. The uniform progression and DR are two different patterns of progression. After confirming progression, the overall survival of patients with DR was significantly longer than that of patients with uniform progression (9.9 months (95%CI 5.7-14.1) vs. 4.2 months (95%CI 1.9-6.5), P = 0.028). Compared with DR patients who did not continue PD-1 inhibitor combined with RT or PD-1 inhibitor monotherapy (n = 12), DR patients who continued treatment (n = 10) had significantly longer OS (15.7 (95%CI 3.5-27.9) vs 8.2 (95%CI 5.6-10.8) months, P = 0.035). Conclusions DR is not uncommon (23.7%) in patients with advanced metastatic solid tumors treated with PD-1 inhibitors combined with RT and shows a relatively favorable prognosis. Some patients with DR may benefit from continued PD-1 inhibitor therapy in combination with RT or PD-1 inhibitor monotherapy and may have longer OS.

Following the Belt and Road, the Air Silk Road has also been proposed. The coordinated development of multiple transportation modes, including air, land, and water, will create a strong transportation force in node cities. However, the current insufficient supply of cargo in various regions and the lack of integration among different transportation modes result in low transportation efficiency, which in turn affects the further advancement of the Belt and Road. To investigate these issues and attempt to find a solution, we selected 44 candidate cities from the prefecture-level cities in China as nodes based on relevant government policies, and constructed an integrated transportation network. For each node city, we first calculated the values of six classical indicators and then used the CRITIC to assign weights to each indicator. Subsequently, we employed the TOPSIS method combined with Grey Relational Analysis (GRA) to compute the comprehensive score for each node city. Based on the spatial layout and government policies under the BRI, eight cities, including Wuhan, Chongqing, Tianjin, Shanghai, Guangzhou, Lianyungang, Hefei, and Dalian, were finally recommended as the consolidation centers of the integrated transportation network. It is hoped that the results of this analysis can provide some insights for the government to outline and build the consolidation centers of the integrated transportation network composed of railway, air, highway, and water routes, which in turn can offer insights for elevating the Belt and Road Initiative (BRI) to a new level.

Objective(s): Paraquat (PQ), a highly effective and rapidly non-selective herbicide, mainly targets the lungs and causes acute lung injury (ALI). So far, the scarcity of effective drug candidates against PQ-induced ALI remains a big challenge. Andrographolide (Andro), with its anti-inflammatory and antioxidant activities, has been demonstrated to alleviate ALI. Nevertheless, whether Andro could alleviate the PQ-mediated ALI remains unknown. Therefore, this study will explore the effects as well as the possible mechanism of Andro against ALI caused by PQ. Materials and Methods: C57BL/6J mice were injected with 20 mg/kg PQ intraperitoneally to establish an ALI model. PQ-treated MLE-12 cells were applied to a vitro model. Nuclear factor erythroid like-2 (Nrf2) was knocked out to explore the specific effects of the Nrf2/ Heme oxygenase-1 (OH-1) pathway in the protection of Andro against ALI caused by PQ.Results: Andro significantly reduced lung damage and the ratio of Wet/Dry (W/D) weight, decreased MDA, IL-6, IL-1β, and TNF-ɑ levels, reversed the decrease of CAT and SOD levels, and inhibited apoptosis caused by PQ. Andro obviously increased the ratio of Bcl-2/Bax while reducing caspase-3 and cleaved caspase-3 levels. Furthermore, Andro dramatically elevated the antioxidant proteins Nrf2, NQO-1, and HO-1 levels compared with the PQ group. This experiment demonstrated that Andro reduced ROS and inhibited apoptosis, induced by PQ in MLE-12 cells, by inducing Nrf2/HO-1 pathway activation.Conclusion: Andro effectively ameliorates oxidant stress and apoptosis in ALI caused by PQ, possibly through inducing Nrf2/HO-1 pathway activation.

Abstract Bioinspired nacre-like structures are effective in toughening materials, yet are difficult to construct in magnesium-ceramic systems. Here, a set of magnesium-MAX phase composites with nacre-like lamellar and brick-and-mortar architectures are fabricated by pressureless infiltration of the magnesium melt into ice-templated Ti3AlC2 ceramic scaffolds. The structure and mechanical properties of the composites are elucidated with a special focus on the effects of the types of architectures (lamellar or brick-and-mortar) and matrices (pure magnesium or AZ91D alloy) on the toughening mechanisms. The nacre-like architectures are found to play a role in blunting the cracks via plastic deformation and microcracking, and shielding the cracks from applied stress by promoting crack deflection and uncracked-ligament bridging mechanisms. These composites achieve a good combination of specific strength and fracture toughness, which are superior to many other reported magnesium-ceramic and nacre-like metal-ceramic composite materials.

Grain size and weight are key components of wheat yield. Exploitation of major underlying quantitative trait loci (QTL) can improve yield potential in wheat breeding. A recombinant inbred line (RIL) population was constructed to detect QTL for thousand-grain weight (TGW), grain length (GL) and grain width (GW) across eight environments. Genomic regions associated with grain size and grain weight were identified on chromosomes 4A and 6A using bulked segregant exome sequencing (BSE-Seq) analysis. After constructing genetic maps, six major QTL detected in at least four individual environments and in best linear unbiased estimator (BLUE) datasets, explained 7.50%–23.45% of the phenotypic variation. Except for QGl.cib-4A, the other five QTL were co-located in two regions, namely QTgw/Gw.cib-4A and QTgw/Gw/Gl.cib-6A. Interactions of these QTL were analyzed. Unlike QTgw/Gw/Gl.cib-6A, QTgw/Gw.cib-4A and QGl.cib-4A had no effect on grain number per spike (GNS). The QTL were validated in a second cross using Kompetitive Allele Specific PCR (KASP) markers. Since QTgw/Gw.cib-4A was probably a novel locus, it and the KASP markers reported here can be used in wheat breeding. TraesCS4A03G0191200 was predicted to be potential candidate gene for QTgw/Gw.cib-4A based on the sequence differences, spatiotemporal expression patterns, gene annotation and haplotype analysis. Our findings will be useful for fine mapping and for marker-assisted selection in wheat grain yield improvement.

Introduction: Current research has mostly simplified CFRP components as isotropic media or homogenized them as anisotropic media, which fails to present the actual acoustic propagation behavior inside the CFRP components and restricts the accuracy of decoupling sound line tracking results and defect feature information.Method: Based on clarifying the influence of fiber direction on the spatial distribution of CFRP elastic properties, this paper proposes an acoustic modeling method for CFRP multi-directional plates considering the coupling effect of multi-layer structure and elastic anisotropy.Results: There are two main innovations: 1. The model is optimized using the Voigt representation method, which can quantitatively characterize the elastic anisotropy of any homogeneous material with a 6 × 6 elastic stiffness matrix containing 21 independent elastic constants. In this paper, the elastic stiffness matrix only includes five independent elastic constants; 2. Finite element simulation is used to analyze the propagation rules of ultrasonic waves inside CFRP and compare the detection methods with or without sound coupling layer.Discussion: The acoustic characteristics of the sound coupling layer are changed to find the optimal coupling method, reduce the refraction of ultrasonic waves in the specimen layer, and make the sound line path more accurate.

C29H41N10O7V2, triclinic, P 1‾ $\overline{1}$ (no. 2), a = 11.3461(5) Å, b = 12.7013(5) Å, c = 14.0649(5) Å, α = 111.609(1)∘ $111.609{(1)}^{\circ }$ , β = 108.702(1)∘ $108.702{(1)}^{\circ }$ , γ = 93.957(2)∘ $93.957{(2)}^{\circ }$ , V = 1744.20(12) Å3, Z = 2, R gt(F) = 0.0439, wR ref(F 2) = 0.1160, T = 173 K.

Natural fish scales demonstrate outstanding mechanical efficiency owing to their elaborate architectures and thereby may serve as ideal prototypes for the architectural design of man-made materials. Here bioinspired magnesium composites with fish-scale-like orthogonal plywood and double-Bouligand architectures were developed by pressureless infiltration of a magnesium melt into the woven contextures of continuous titanium fibers. The composites exhibit enhanced strength and work-hardening ability compared to those estimated from a simple mixture of their constituents at ambient to elevated temperatures. In particular, the double-Bouligand architecture can effectively deflect cracking paths, alleviate strain localization, and adaptively reorient titanium fibers within the magnesium matrix during the deformation of the composite, representing a successful implementation of the property-optimizing mechanisms in fish scales. The strength of the composites, specifically the effect of their bioinspired architectures, was interpreted based on the adaptation of classical laminate theory. This study may offer a feasible approach for developing new bioinspired metal-matrix composites with improved performance and provide theoretical guidance for their architectural designs.

Corrosion is a ubiquitous failure mode in materials. Here the authors report a percolating 1D wormhole corrosion morphology using advanced electron microscopy and theoretical simulations. The work presents a vacancy mapping method with nm-resolution, identifying the incubation sites of the wormholes.

In complex environments of wireless communication, to improve the communication anti-interference performance, quasi-synchronous frequency-hopping (FH) communication system requires low-hit-zone (LHZ) FH sequence sets with optimal Hamming correlation (HC) properties and flexible parameters. In this paper, based upon cyclotomy theory, two classes of LHZ FH sequence sets with flexible parameters not included in the literatures are designed, and the periodic HC properties of which are analyzed. It turns out that the designed LHZ FH sequence sets are optimal on the maximum periodic HC. And thus the new constructions can be used to provide optimal FH sequence sets for quasi-synchronous FH communication system.

Colon cancer (COAD) is a common malignancy, yet its etiology is not fully elucidated. This study gathered endocytosis-related genes, using gene expression profiles from TCGA databases to categorize molecular subtypes of COAD into Cluster1 and Cluster2 based on genes related to endocytosis, and further explored the connection between the two molecular subtypes and prognostic characteristics. Differential expression analysis of the two subtypes revealed 3412 differentially expressed genes (DEGs), whose functions were remarkably enriched in the cellular metastasis and oxidative phosphorylation in Cluster1 by fGSEA. Additionally, Cluster1 exhibited higher expression levels of DEGs associated with immune infiltration and metabolism in comparison to Cluster2 by GSVA, and TIDE scores indicated patients with Cluster2 may benefit more from immunotherapy. Based on the DEGs, we utilized univariate Cox regression to identify 759 prognostic genes, which were then screened by three machine learning models (Lasso, RF, SVM-RFE) simultaneously, resulting in four feature genes: NEK4, MED13, OXSR1, and SLAIN2. Moreover, in Cluter1, these feature genes displayed consistent positive or negative correlations with immune escape-related and metabolic reprogramming-related pathways and genes in Pearson heatmap. There results suggesting that there are significant differences in immune escape and metabolic reprogramming between colon cancer subtypes Cluster1 and Cluster2 as determined by genes according to endocytosis.

The idea of a digital China was introduced at the 19th Party Congress, after which all regions of the nation launched to vigorously promote digital management, particularly in areas where population conflicts are more prevalent. This was done in order to improve governance capacity through the use of digital technology, which has since become the main goal of the current modernization of China’s overall governance system. The issues encountered are still rather noticeable as we work to improve the capability of digital governance. As an example of Meiyuan Xincun community’s attention on its digital governance capability to increase the difficulties encountered by the analysis, and so put up the corresponding ideal remedies, this article is primarily for the urban community digital governance status quo analysis

Six benzophenone derivatives, carneusones A-F (1–6), along with seven known compounds (7–13) were isolated from a strain of sponge-derived marine fungus Aspergillus carneus GXIMD00543. Their chemical structures were elucidated by detailed spectroscopic data and quantum chemical calculations. Compounds 5, 6, and 8 exhibited moderate anti-inflammatory activity on NO secretion using lipopolysaccharide (LPS)-induced RAW 264.7 cells with EC50 values of 34.6 ± 0.9, 20.2 ± 1.8, and 26.8 ± 1.7 μM, while 11 showed potent effect with an EC50 value of 2.9 ± 0.1 μM.

In this study, twelve polymorphic microsatellite loci were screened to evaluate the genetic diversity of five yellow drum (Nibea albiflora) populations in the Zhoushan Sea region of the East China Sea, including one wild population (WP), one artificially propagated population (common population, CP), and three breeding populations (parent population, F4; all-female population, AF; and neo-male population, NeoG). The results of genetic diversity analyses showed that all five yellow drum populations had relatively high genetic diversity, with the highest in WP and the lowest in NeoG. Genetic structure analyses showed that the level of genetic differentiation among populations was low, with that between CP and F4 being the largest, whereas that between CP and WP was the smallest. Mutation–drift equilibrium analysis showed that the five populations likely did not experience a recent bottleneck. Our results suggest the CP population was the most suitable for large-scale release for stock enhancement, and precautionary measures shall be taken for the AF population before it is used for cage culture to avoid potential genetic concerns of the wild population. Nevertheless, further genetic diversity monitoring is needed to evaluate genetic effects and avoid the negative impact of excessive genetic differentiation between breeding and wild populations.

C25H33N10O7V2, triclinic, P1‾ $P\overline{1}$ (no. 2), a = 10.3933(4) Å, b = 12.5655(5) Å, c = 14.1841(5) Å, α = 65.373(1)°, β = 70.351(1)∘ $70.351{(1)}^{\circ }$ , γ = 88.052(2)∘ $88.052{(2)}^{\circ }$ , V = 1573.62(11) Å3, Z = 2, R gt(F) = 0.0362, wR ref(F 2) = 0.0885, T = 173 K.

Cadmium (Cd) exposure is a risk factor for endothelial dysfunction and cardiovascular disease. Ferroptosis is a type of cell death that relies on lipid peroxidation. Whether ferroptosis acts in Cd-induced vascular endothelial damage and the underlying mechanisms remain unclear. Herein, we found that Cd resulted in ferroptosis of vascular endothelial cells (ECs) in vivo and in vitro. In the visualized zebrafish embryos, Cd accumulated in vascular ECs, ROS and lipid peroxidation levels were increased, and the oxidoreductase system was disturbed after exposure. Moreover, Cd decreased Gpx4 in ECs and caused smaller mitochondria with increased membrane density. Accompanied by ferroptosis, the number of ECs and the area of the caudal venous plexus in zebrafish embryos were reduced, and the survival rate of HUVECs decreased. These effects were partially reversed by ferrostatin-1 and aggravated by erastin. Mechanistically, an excessive increase in Heat Shock Protein 70 (Hsp70) was identified by transcriptomics after Cd exposure. Inhibition of Hsp70 by VER-155008 or siRNA ameliorated Cd-induced ferroptosis, thereby alleviating endothelial injury. Furthermore, Hsp70 regulated Cd-induced ferroptosis by targeting multiple targets, including Gpx4, Fth1, Nrf2 and Acsl4. Our findings provide a new approach to investigating the endothelial damage of Cd and indicate that regulation of Hsp70 is an important target for alleviating this process.

Voriconazole (VRZ) is a broad-spectrum antifungal medication widely used to treat invasive fungal infections (IFI). The administration dosage and blood concentration of VRZ are influenced by various factors, posing challenges for standardization and individualization of dose adjustments. On the one hand, VRZ is primarily metabolized by the liver, predominantly mediated by the cytochrome P450 (CYP) 2C19 enzyme. The genetic polymorphism of CYP2C19 significantly impacts the blood concentration of VRZ, particularly the trough concentration (Ctrough), thereby influencing the drug’s efficacy and potentially causing adverse drug reactions (ADRs). Recent research has demonstrated that pharmacogenomics-based VRZ dose adjustments offer more accurate and individualized treatment strategies for individuals with hepatic insufficiency, with the possibility to enhance therapeutic outcomes and reduce ADRs. On the other hand, the security, pharmacokinetics, and dosing of VRZ in individuals with hepatic insufficiency remain unclear, making it challenging to attain optimal Ctrough in individuals with both hepatic insufficiency and IFI, resulting in suboptimal drug efficacy and severe ADRs. Therefore, when using VRZ to treat IFI, drug dosage adjustment based on individuals’ genotypes and hepatic function is necessary. This review summarizes the research progress on the impact of genetic polymorphisms and hepatic insufficiency on VRZ dosage in IFI individuals, compares current international guidelines, elucidates the current application status of VRZ in individuals with hepatic insufficiency, and discusses the influence of CYP2C19, CYP3A4, CYP2C9, and ABCB1 genetic polymorphisms on VRZ dose adjustments and Ctrough at the pharmacogenomic level. Additionally, a comprehensive summary and analysis of existing studies’ recommendations on VRZ dose adjustments based on CYP2C19 genetic polymorphisms and hepatic insufficiency are provided, offering a more comprehensive reference for dose selection and adjustments of VRZ in this patient population.

ABSTRACT Tuberculosis (TB) is an important infectious disease suffered by many countries, including China. In this stage, accurate diagnosis and treatment are key measures for the prevention and control of TB. Stenotrophomonas maltophilia is a global emerging Gram-negative, multidrug-resistant (MDR) organism characterized by its high contribution to the increase in crude mortality rates. By single cell preparation and strain identification, we isolated S. maltophilia from stored cultures of Mycobacterium tuberculosis (Mtb). We found that S. maltophilia could not be removed from sputum by alkali treatment or inhibited by antibiotic mixture added to MGIT 960 indicator tubes. When co-cultured with Mtb on a Löwenstein-Jensen (L-J) slant, it could inhibit the growth of Mtb and liquefy the medium. More seriously, it was resistant to 10 of the 12 anti-TB drugs, including isoniazid and rifampin, and made the mixed samples display multidrug-resistant Mtb (MDR-TB) results in the drug sensitivity test, which might change a treatment regimen and increase disease burden. Following, we conducted a small-scale surveillance which showed that the isolation rate of S. maltophilia in TB patients was 6.74%, but these patients had no special characteristics and the presence of S. maltophilia was hidden. The effect of S. maltophilus on TB and its mechanism are unclear and require more attention. IMPORTANCE China is a high-burden country for tuberculosis (TB), multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB), and HIV-associated TB. Increasing the positive rate of culture and the accuracy of antibiotic susceptibility testing (AST) are important for diagnosis, treatment, and control of TB. In our study, we found that the isolation rate of Stenotrophomonas maltophilia in TB patients was not neglectable and that this bacterium affects the isolation and AST results of TB. Due to a lack of relevant research, the impact of S. maltophilia on the course and outcome of TB is unclear. However, the characteristics of S. maltophilia that increase disease mortality require attention. Therefore, in the clinical testing of TB, in addition to mycobacteria, it is recommended to increase the detection of co-infected bacteria and improve the awareness of TB clinicians of these bacteria.

As one of the clean energy sources, geothermal resources have no negative impact in changing the climate. However, the accurate assessment and precise identification of the potential geothermal resource is still complex and dynamic. In this paper, ~2,000 large-scale high-precision gravity survey points are conducted in the north of the Tianchi caldera, Changbaishan. Advanced data processing technologies can provide straightforward information on deep geothermal resources (Hot source, caprock, geothermal reservoir and geothermal migration pathway). Upwards continuation and the technologies decode two dome shaped low and gentle anomalies (−48 × 10−5 m/s2−65 m/s2) and a positive gravity gradient anomaly (0.4 × 10−7 m/s2−1.6 × 10−5 m/s2) in large-scale high-precision gravity planar. According to two point five dimensional man-machine interactive inversion technology and the research on petrophysical parameters, the density of the shied-forming basalts in the two orthogonal gravity sections is 2.58 g/cm3. The relatively intermediate to high density (2.60–2.75 g/cm3) represents geothermal reservoir, and low density (low to 2.58 g/cm3) is the geothermal migration pathway. In addition, large-scale high-precision gravity planar with a solution of about 1/50,000 indicate that the north of the Tianchi caldera exits the sedimentary basin and uplift mountain geothermal system.

With functional information of tea as the starting point, information visualization as the means and tea packaging as the medium, benefiting from the visual communication between tea and consumers realized by the joint forces of the three, this paper discusses the principles and methods of information visualization in tea packaging design, and transmits the relevant information of tea to consumers easily, quickly and effectively to achieve the purpose of promotion.

Abstract Magnolia sinostellata is one of the endangered species in China and largely suffers light deficiency stress in the understory of forest. However, the weak light response molecular mechanism remains unclear. More importantly, hub genes in the molecular network have not been pinpointed. To explore potential regulators in the mechanism, weighted gene co-expression network analysis (WGCNA) was performed to analysis the trancriptome data of M. sinostellata leaves subjected to weak light with different time points. Gene co-expression analysis illustrated that module 1, 2 and 3 were closely associated with light deficiency treatment, which. Gene ontology and KEGG analyses showed that genes in module 1 mainly participated in amino and nucleotide metabolism, module 2 mostly involved in carbon fixation and module 3 mostly regulated photosynthesis related pathways, among which 6, 7 and 8 hub genes were identified, respectively. Hub genes isoform_107196 in module 1 and isoform_55976 in module 2 were unique to M. sinostellata. This study found that light deficiency inhibited photosynthesis and stress tolerance, while improved carbon metabolism and flowering related pathways in M. sinostellata, which can impact its accumulation reserves of growth and reproduction in the next season. In addition, key shade response regulators identified in this study have laid a firm foundation for further investigation of shade response molecular mechanism and protection of other shade sensitive plants.

Abstract Background Many factors can affect the recurrence of endometriosis after surgery, however, whether endometriotic cyst fluid contributes to endometriosis recurrence after surgical excision of ovarian endometriomas remains unclear. The objective of this study was to determine the presence of endometrial cells in ovarian endometriosis cyst fluid and the potential differences between these cells and those in the cyst wall. Methods Samples of cyst fluid (n = 39) and drainage fluid (n = 14) were collected from patients with ovarian endometriomas undergoing laparoscopic surgery. Drainage fluid from 14 patients without endometriosis was used as a control. The presence of endometrial cells in cyst fluid and drainage fluid was determined by cell culture in vitro and immunostaining. In addition, cyst fluid endometrial fragments and viscosity were analysed by transcriptome sequencing analysis and apparent diffusion coefficients, respectively. An animal model was used to confirm the ability of endometrial cells in cyst fluid to form new lesions. Results We found endometrium-like tissues in 71.8% (28/39) of cyst fluid and 71.4% (10/14) of drainage fluid samples by histopathological examination, and the presence of endometrioid tissue in cyst fluid was related to the viscosity of the cyst fluid. The living endometrial cells in cyst fluid and drainage fluid were confirmed by cell culture in vitro and immunostaining. Moreover, the adhesion ability of endometrial fragments in cyst fluid was significantly higher than that of ectopic tissues in the cyst wall (P

A multifunctional microwave absorber with high thermal conductivity for 5G base station packaging comprising silylated GO/FeSiAl epoxy composites were fabricated by a simple solvent-handling method, and its microwave absorption properties and thermal conductivity were presented. It could act as an applicable microwave absorber for highly integrated 5G base station packaging with 5G antennas within a range of operating frequency of 2.575–2.645 GHz at a small thickness (2 mm), as evident from reflection loss with a maximum of −48.28 dB and an effective range of 3.6 GHz. Such a prominent microwave absorbing performance results from interfacial polarization resonance attributed to a nicely formed GO/FeSiAl interface through silylation. It also exhibits a significant enhanced thermal conductivity of 1.6 W/(mK) by constructing successive thermal channels.

Psoriasis is an inflammatory skin disease mediated by the immune system and characterized by an inflammatory ring, also known as an epithelial immune microenvironment (EIME). The interaction between the epithelial tissue of the skin and the immune system has a crucial role in the immune cycle of psoriasis. Although the formation of new blood vessels in skin lesions provides energy support for the proliferation of epidermal keratinocytes, the role of angiogenesis in psoriasis has not been extensively studied. Vascular endothelial growth factor A (VEGFA) is a key regulator of angiogenesis that has an important role in the development of psoriasis. VEGFA promotes angiogenesis and directly stimulates epidermal keratinocytes and infiltrating immune cells, thus contributing to the progression of psoriasis. Measuring VEGFA levels to identify angiogenic characteristics in psoriasis patients may be a predictive biomarker for disease severity and response to anti-angiogenic therapy. Clinical data have shown that anti-angiogenic therapy can improve skin lesions in psoriasis patients. Therefore, this study aimed to uncover the underestimated role of blood vessels in psoriasis, explore the relationship between VEGFA and keratinocytes in the EIME, and inspire innovative drug therapies for the treatment of psoriasis.

Depression is a mental disorder characterized by low mood, lack of motivation, negative cognitive outlook, and sleep problems. Suicide may occur in severe cases, although suicidal thoughts are not seen in all cases. Globally, an estimated 350 million individuals grapple with depression, as reported by the World Health Organization. At present, drug and psychological treatments are the main treatments, but they produce insufficient responses in many patients and fail to work at all in many others. Consequently, treating depression has long been an important topic in society. Given the escalating prevalence of depression, a comprehensive strategy for managing its symptoms and impacts has garnered significant attention. In this context, nutritional psychiatry emerges as a promising avenue. Extensive research has underscored the potential benefits of a well-rounded diet rich in fruits, vegetables, fish, and meat in alleviating depressive symptoms. However, the intricate mechanisms linking dietary interventions to brain function alterations remain largely unexplored. This review delves into the intricate relationship between dietary patterns and depression, while exploring the plausible mechanisms underlying the impact of dietary interventions on depression management. As we endeavor to unveil the pathways through which nutrition influences mental well-being, a holistic perspective that encompasses multidisciplinary strategies gains prominence, potentially reshaping how we approach and address depression.

The semi-continuous digestion experiment of food waste was carried out based on a solar-assisted heat anaerobic digestion reactor. The effects of organic load regulation (OLR of 2.0, 4.0, 6.0 and 7.0 kg m−3 d−1 VS (volatile solid)) on methane production, physical and chemical parameters, and microbial community structure were studied. The results showed that 6.0 kg m−3 d−1 VS could achieve the optimal methane production as the anaerobic digestion limit OLR of kitchen waste. At this stage, the accumulation of organic acids in the reactor led to a great fluctuation of pH. Artificial alkali regulation could restore the stable operation of the reactor, but the reactor could not withstand the OLR shock of 7.0 kg m−3 d−1 VS. In addition, Qualcomm sequencing results showed that microorganisms showed high functional concentration and poor community richness under low OLR, and increasing OLR could promote microbial richness. At the same time, the Methanosaeta of acetic acid methanogens was relatively abundant in the low OLR stage, while the hydrogen trophic methanogenic bacteria Methanoregula and Methanospirillum showed high activity in the high OLR stage, but the excessive reproduction of acidogenic bacteria in the digestive system would affect the stability of the archaea community when the OLR was too high. HIGHLIGHTS Electric energy was saved by the solar system with a slight decrease of methane yield.; A low organic loading rate suppresses the succession of microbial structure.; Unstability caused by organic acid can be restored by artificial control of pH.;

Activating Wireless Power Transfer (WPT) in Radio-Frequency (RF) to provide on-demand energy supply to widely deployed Internet of Everything devices is a key to the next-generation energy self-sustainable 6G network. However, Simultaneous Wireless Information and Power Transfer (SWIPT) in the same RF bands is challenging. The majority of previous studies compared SWIPT performance to Gaussian signaling with an infinite alphabet, which is impossible to implement in any realistic communication system. In contrast, we study the SWIPT system in a well-known Nakagami-m wireless fading channel using practical modulation techniques with finite alphabet. The attainable rate-energy-reliability tradeoff and the corresponding rationale are revealed for fixed modulation schemes. Furthermore, an adaptive modulation-based transceiver is provided for further expanding the attainable rate-energy-reliability region based on various SWIPT performances of different modulation schemes. The modulation switching thresholds and transmit power allocation at the SWIPT transmitter and the power splitting ratios at the SWIPT receiver are jointly optimized to maximize the attainable spectrum efficiency of wireless information transfer while satisfying the WPT requirement and the instantaneous and average BER constraints. Numerical results demonstrate the SWIPT performance of various fixed modulation schemes in different fading conditions. The advantage of the adaptive modulation-based SWIPT transceiver is validated.

Bioinspired architectures are desired to achieve improved mechanical properties, but challenging to achieve in metallic systems. Here the authors fabricate a Mg-Ti interpenetrating phase composite with brick-and-mortar, Bouligand, and crossed-lamellar architectures by pressureless infiltrating method.

Abstract Background A recent survey revealed that extensive off-label use of sugammadex in pediatric anesthesia deserved particular attention. The present study with trial sequential analysis (TSA) aimed to evaluate the effects of sugammadex for antagonizing neuromuscular blockade (NMB) in pediatric patients, and to investigate whether the findings achieved the required information size to draw conclusions. Methods PubMed, Embase, Cochrane Library and China National Knowledge Infrastructure (CNKI) were searched from inception to April 2021. All randomized controlled trials used sugammadex as reversal agent in pediatric patients were enrolled. Time from NMB reversal to recovery of the train-of-four ratio (TOFr) to 0.9 and extubation time were considered as co-primary outcomes, and incidences of adverse events were considered as secondary outcomes. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used to rate the quality of evidences. Results Data from 18 studies involving 1,065 pediatric patients were acquired. The results revealed that use of sugammadex was associated with shorter duration from administration of reversal agents to TOFr > 0.9 (MD = -14.42, with 95% CI [-17.08, -11.75]) and shorter interval from reversal from NMB to extubation (MD = -13.98, with 95% CI [-16.70, -11.26]) compared to control groups. TSA also indicated that the current sample sizes were sufficient with unnecessary further trials. Analysis of secondary outcomes indicated that administration of sugammadex was associated with less incidence of postoperative nausea and vomiting (PONV), bradycardia, and dry mouth compared to control groups. Conclusion Considering of satisfactory and rapid neuromuscular blockade reversal with low incidences of adverse events, sugammadex might be considered as the preferred option for children in clinical anesthesia practice compared to acetylcholinesterase inhibitors. However, overall low-quality evidences in present study rated by GRADE system indicated that superiority of sugammadex employed in pediatric patients needs to be confirmed by more studies with high quality and large sample size in future.

Abstract Sacubitril/valsartan, simultaneously inhibits neprilysin and angiotensin II receptor, showed an effect in reducing blood pressure (BP). The authors aimed to study whether it can be used as an antihypertensive agent in patients with refractory hypertension who have already been treated. A total of 66 Chinese patients with refractory hypertension were enrolled. Patients received sacubitril/valsartan 200 instead of angiotensin II receptor blocker or angiotensin converting enzyme inhibitor while other agents continued. If BP was uncontrolled after 4 weeks, sacubitril/valsartan was increased to 400 mg. The BP reduction was evaluated by office BP and ambulatory BP monitoring after 8‐week treatment. The baseline office BP and mean arterial pressure (MAP) were 150.0/95.0 mmHg and 113.3 mmHg. BP and MAP reduced to 130.6/83.2 mmHg and 99.0 mmHg at week 8. Office BP and MAP reductions were 19.4/11.8 mmHg and 14.3 mmHg at endpoint (all p

Abstract Cadmium (Cd) is a high‐risk pathogenic toxin for hepatic diseases. Excessive mitophagy is a hallmark in Cd‐induced hepatotoxicity. However, the underlying mechanism remains obscure. Mitochondrial calcium uniporter (MCU) is a key regulator for mitochondrial and cellular homeostasis. Here, Cd exposure upregulated MCU expression and increased mitochondrial Ca2+ uptake are found. MCU inhibition through siRNA or by Ru360 significantly attenuates Cd‐induced excessive mitophagy, thereby rescues mitochondrial dysfunction and increases hepatocyte viability. Heterozygous MCU knockout mice exhibit improved liver function, ameliorated pathological damage, less mitochondrial fragmentation, and mitophagy after Cd exposure. Mechanistically, Cd upregulates MCU expression through phosphorylation activation of cAMP‐response element binding protein at Ser133(CREBS133) and subsequent binding of MCU promoter at the TGAGGTCT, ACGTCA, and CTCCGTGATGTA regions, leading to increased MCU gene transcription. The upregulated MCU intensively interacts with voltage‐dependent anion‐selective channel protein 1 (VDAC1), enhances its dimerization and ubiquitination, resulting in excessive mitophagy. This study reveals a novel mechanism, through which Cd upregulates MCU to enhance mitophagy and hepatotoxicity.

PurposeNoninvasively assessing the tumor biology and microenvironment before treatment is greatly important, and glypican-3 (GPC-3) is a new-generation immunotherapy target for hepatocellular carcinoma (HCC). This study investigated the application value of a nomogram based on LI-RADS features, quantitative contrast-enhanced MRI parameters and clinical indicators in the noninvasive preoperative prediction of GPC-3 expression in HCC.Methods and materialsWe retrospectively reviewed 127 patients with pathologically confirmed solitary HCC who underwent Gd-EOB-DTPA MRI examinations and related laboratory tests. Quantitative contrast-enhanced MRI parameters and clinical indicators were collected by an abdominal radiologist, and LI-RADS features were independently assessed and recorded by three trained intermediate- and senior-level radiologists. The pathological and immunohistochemical results of HCC were determined by two senior pathologists. All patients were divided into a training cohort (88 cases) and validation cohort (39 cases). Univariate analysis and multivariate logistic regression were performed to identify independent predictors of GPC-3 expression in HCC, and a nomogram model was established in the training cohort. The performance of the nomogram was assessed by the area under the receiver operating characteristic curve (AUC) and the calibration curve in the training cohort and validation cohort, respectively.ResultsBlood products in mass, nodule-in-nodule architecture, mosaic architecture, contrast enhancement ratio (CER), transition phase lesion-liver parenchyma signal ratio (TP-LNR), and serum ferritin (Fer) were independent predictors of GPC-3 expression, with odds ratios (ORs) of 5.437, 10.682, 5.477, 11.788, 0.028, and 1.005, respectively. Nomogram based on LI-RADS features (blood products in mass, nodule-in-nodule architecture and mosaic architecture), quantitative contrast-enhanced MRI parameters (CER and TP-LNR) and clinical indicators (Fer) for predicting GPC-3 expression in HCC was established successfully. The nomogram showed good discrimination (AUC of 0.925 in the training cohort and 0.908 in the validation cohort) and favorable calibration. The diagnostic sensitivity and specificity were 76.9% and 92.3% in the training cohort, 76.8% and 93.8% in the validation cohort respectively.ConclusionThe nomogram constructed from LI-RADS features, quantitative contrast-enhanced MRI parameters and clinical indicators has high application value, can accurately predict GPC-3 expression in HCC and may help noninvasively identify potential patients for GPC-3 immunotherapy.

Abstract Background Traditional CRISPR/Cas9 systems that rely on U6 or U3 snRNA promoters (RNA polymerase III-dependent promoters) can only achieve constitutive gene editing in plants, hampering the functional analysis of specifically expressed genes. Ribozyme-mediated CRISPR/Cas9 systems increase the types of promoters which can be used to transcribe sgRNA. Therefore, such systems allow specific gene editing; for example, transcription of the artificial gene Ribozyme-sgRNA-Ribozyme (RGR) is initiated by an RNA polymerase II-dependent promoter. Genetic transformation is indispensable for editing plant genes. In certain plant species, including pyrethrum, genetic transformation remains challenging to do, limiting the functional verification of novel CRISPR/Cas9 systems. Thus, this study’s aim was to develop a simple Agrobacterium rhizogenes-mediated hairy root transformation system to analyze the function of a ribozyme-mediated CRISPR/Cas9 system in pyrethrum. Results A hairy root transformation system for pyrethrum is described, with a mean transformation frequency of 7%. Transgenic hairy roots transformed with the pBI121 vector exhibited significantly increased beta-glucuronidase staining as a visual marker of transgene expression. Further, a ribozyme-based CRISPR/Cas9 vector was constructed to edit the TcEbFS gene, which catalyzes synthesis of the defense-related compound (E)-β-farnesene in pyrethrum. The vector was transferred into the hairy roots of pyrethrum and two stably transformed hairy root transgenic lines obtained. Editing of the TcEbFS gene in the hairy roots was evaluated by gene sequencing, demonstrating that both hairy root transgenic lines had DNA base loss at the editing target site. Gas chromatography–mass spectrometry showed that the (E)-β-farnesene content was significantly decreased in both hairy root transgenic lines compared with the empty vector control group. Altogether, these results show that RGR can be driven by the CaMV35S promoter to realize TcEbFS gene editing in pyrethrum hairy roots. Conclusion An A. rhizogenes-mediated hairy root transformation and ribozyme-mediated CRISPR/Cas9 gene editing system in pyrethrum was established, thereby facilitating gene editing in specific organs or at a particular developmental stage in future pyrethrum research.

Abstract Background Recent studies show that human gut microbial composition can determine whether a patient is a responder or non-responder to immunotherapy but have not identified a common microbial signal shared by responding patients. The functional relationship between immunity, intestinal microbiota, and NSCLC response to immune checkpoint inhibitor/inhibition (ICI) in an American cohort remains unexplored. Methods RNAlater-preserved fecal samples were collected from 65 pre-treatment (baseline) and post-treatment stage III/IV NSCLC patients undergoing ICI therapy, categorized as responders or non-responders according to RECIST criteria. Pooled and individual responder and non-responder microbiota were transplanted into a gnotobiotic mouse model of lung cancer and treated with ICIs. 16S rDNA and RNA sequencing was performed on patient fecal samples, 16S rDNA sequencing on mouse fecal samples, and flow cytometric analysis on mouse tumor tissue. Results Responder patients have both a different microbial community structure than non-responders (P = 0.004) and a different bacterial transcriptome (PC2 = 0.03) at baseline. Taxa significantly enriched in responders include amplicon sequence variants (ASVs) belonging to the genera Ruminococcus, Akkermansia, and Faecalibacterium. Pooled and individual responder microbiota transplantation into gnotobiotic mice decreased tumor growth compared to non-responder colonized mice following ICI (P = 0.023, P = 0.019, P = 0.008, respectively). Responder tumors showed an increased anti-tumor cellular phenotype following ICI treatment. Responder mice are enriched with ASVs belonging to the genera Bacteroides, Blautia, Akkermansia, and Faecalibacterium. Overlapping taxa mapping between human and mouse cohorts correlated with tumor size and weight revealed a network highlighting responder-associated ASVs belonging to the genera Colidextribacter, Frisingicoccus, Marvinbryantia, and Blautia which have not yet been reported. Conclusions The role of isolate-specific function and bacterial gene expression in gut microbial-driven responsiveness to ICI has been underappreciated. This work supports further investigation using isolate-driven models to characterize the mechanisms underlying this phenomenon.

Non-small cell lung cancer (NSCLC) is one of the principal causes of death worldwide. The disease is often diagnosed late, at the stage of metastasis, which leads to a poor prognosis. With currently available treatment, most patients experience relapse and drug resistance. This study aimed to determine the potential role of insulin growth factor-like family member 1 (IGFL1) in lung adenocarcinoma (LUAD). We analyzed the expression of IGFL1 using TIMER, UALCAN, and GEPIA. The association of IGFL1 expression with symptoms and overall survival (OS) in LUAD patients was evaluated using a tissue microarray (TMA). Moreover, A549 and H1299 cells with selective IGFL1 knockdown were used to observe their proliferation and apoptosis in vitro. From the TIMER, UALCAN and GEPIA databases, we found that IGFL1 was upregulated in LUAD (p < 0.001). The level of promoter methylation in IGFL1 was significantly downregulated in LUAD and patient groups with different gender. Similar results were obtained in UALCAN. The semi-quantitative analysis revealed that IGFL1 expression is correlated with TNM stage (p < 0.001) and tumor size (p < 0.001) in TMA. High levels of IGFL1 expression were associated with poor OS (p < 0.05). Functional tests in A549 and H1299 cells showed that knocking down the expression of IGFL1 inhibited proliferation and enhanced apoptosis. Our study revealed the potential utility of IGFL1 as a predictive biomarker, which may play a biological role by regulating the proliferation and apoptosis of tumor cells.

Echinochloa is an important genus in the grass family as many of them are either problematic weeds or domesticated millets. Here, the authors assemble three polyploidy genomes in this genus using the diploid-assisted scaffolding method DipHic and provide genomic insights into the dual roles of some species as weeds and orphan crops.