Copper-Catalyzed Asymmetric [3 + 2] Cycloaddition of N-2,2,2-Trifluoroethylisatin Ketimines to Access Three Classes of Polyfunctionalized Spiro-Pyrrolidine-Oxindole Motifs.

A facile copper-catalyzed [3 + 2] cycloaddition of N-2,2,2-trifluoroethylisatin ketimines with various electron-deficient alkenes to access structurally polyfunctionalized spiro-pyrrolidine-oxindole motifs has been developed. Under the catalytic system, the N-2,2,2-trifluoroethylisatin ketimines could be utilized to react with a series of exocyclic alkenes, including 2-acylamino acrylates, 3-methylene-ß-lactams, and sterically hindered cycloalkenes represented by cyclobutenone, to obtain a variety of densely functionalized spiro-pyrrolidine frameworks bearing an α-amino acid ester, ß-lactam, and cyclobutanone, respectively, in generally good yields with excellent diastereo- and enantioselectivities.

Pharmacokinetics of trastuzumab and its efficacy and safety in HER2-positive cancer patients.

Trastuzumab is a potent targeted therapy drug for HER2-positive cancer patients. A comprehensive understanding of trastuzumab's mechanism of action, pharmacokinetic (PK) parameters, and steady-state exposure in different treatment regimens and administration routes is essential for a thorough evaluation of the drug's safety and effectiveness. Due to the distinctive pharmacokinetics, indications, and administration methods of trastuzumab, this understanding becomes crucial. Drug exposure can be assessed by measuring trastuzumab's peak concentration, trough concentration, or area under the curve through assays like enzyme-linked immunosorbent assay (ELISA) or liquid chromatography-tandem mass spectrometry (LC-MS/MS). The dose-response (D-R) and exposure-response (E-R) relationships establish the correlation between drug dosage/exposure and the therapeutic effect and safety. Additionally, various covariates such as body weight, aspartate transaminase, and albumin levels can influence drug exposure. This review provides a comprehensive overview of trastuzumab's mechanism of action, data on steady-state concentration and PK parameters under multiple administration routes and indications, discussions on factors influencing PK parameters, and evaluations of the effectiveness and safety of E-R and D-R in diverse HER2-positive cancer patients.

Comparative biomechanical analysis of four different tooth- and bone-borne frog appliances for molar distalization : A three-dimensional finite element study.

PURPOSE: The purpose of this study was to analyze the biomechanical effects of four different designs of frog appliances for molar distalization using finite element analysis. METHODS: A three-dimensional finite element model including complete dentition, periodontal ligament, palatine, and alveolar bone was established. Four types of frog appliances were designed to simulate maxillary molar distalization: tooth-button-borne (Type A), bone-borne (Type B), bone-button-borne (Type C), and tooth-bone-borne (Type D) frog appliances. A force of 10 N was applied simulating a screw in the anteroposterior direction. To assess the von Mises stress distribution and the resultant displacements in the teeth and periodontal tissues, geometric nonlinear theory was utilized. RESULTS: Compared to the conventional tooth-borne frog appliance (Type A), the bone-borne frog appliances showed increased first molar distalization with enhanced mesiolingual rotation and distal tipping, but the labial inclination and intrusion of the incisors were insignificant. When replacing the palatal acrylic button with miniscrews (Types B and D), more anchorage forces were transmitted from the first premolar to palatine bone, which was further dispersed by the assistance of a palatal acrylic button (Type C). CONCLUSIONS: Compared to tooth-borne frog appliances, the bone-borne variants demonstrated a clear advantage for en masse molar distalization. The combined anchorage system utilizing palatal acrylic buttons and miniscrews (Type C) offers the most efficient stress distribution, minimizing force concentration on the palatine bone.

SARS-CoV-2 N protein-induced Dicer, XPO5, SRSF3, and hnRNPA3 downregulation causes pneumonia.

Though RNAi and RNA-splicing machineries are involved in regulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication, their precise roles in coronavirus disease 2019 (COVID-19) pathogenesis remain unclear. Herein, we show that decreased RNAi component (Dicer and XPO5) and splicing factor (SRSF3 and hnRNPA3) expression correlate with increased COVID-19 severity. SARS-CoV-2 N protein induces the autophagic degradation of Dicer, XPO5, SRSF3, and hnRNPA3, inhibiting miRNA biogenesis and RNA splicing and triggering DNA damage, proteotoxic stress, and pneumonia. Dicer, XPO5, SRSF3, and hnRNPA3 knockdown increases, while their overexpression decreases, N protein-induced pneumonia's severity. Older mice show lower expression of Dicer, XPO5, SRSF3, and hnRNPA3 in their lung tissues and exhibit more severe N protein-induced pneumonia than younger mice. PJ34, a poly(ADP-ribose) polymerase inhibitor, or anastrozole, an aromatase inhibitor, ameliorates N protein- or SARS-CoV-2-induced pneumonia by restoring Dicer, XPO5, SRSF3, and hnRNPA3 expression. These findings will aid in developing improved treatments for SARS-CoV-2-associated pneumonia.

The policies on the use of large language models in radiological journals are lacking: a meta-research study.

OBJECTIVE: To evaluate whether and how the radiological journals present their policies on the use of large language models (LLMs), and identify the journal characteristic variables that are associated with the presence. METHODS: In this meta-research study, we screened Journals from the Radiology, Nuclear Medicine and Medical Imaging Category, 2022 Journal Citation Reports, excluding journals in non-English languages and relevant documents unavailable. We assessed their LLM use policies: (1) whether the policy is present; (2) whether the policy for the authors, the reviewers, and the editors is present; and (3) whether the policy asks the author to report the usage of LLMs, the name of LLMs, the section that used LLMs, the role of LLMs, the verification of LLMs, and the potential influence of LLMs. The association between the presence of policies and journal characteristic variables was evaluated. RESULTS: The LLM use policies were presented in 43.9% (83/189) of journals, and those for the authors, the reviewers, and the editor were presented in 43.4% (82/189), 29.6% (56/189) and 25.9% (49/189) of journals, respectively. Many journals mentioned the aspects of the usage (43.4%, 82/189), the name (34.9%, 66/189), the verification (33.3%, 63/189), and the role (31.7%, 60/189) of LLMs, while the potential influence of LLMs (4.2%, 8/189), and the section that used LLMs (1.6%, 3/189) were seldomly touched. The publisher is related to the presence of LLM use policies (p < 0.001). CONCLUSION: The presence of LLM use policies is suboptimal in radiological journals. A reporting guideline is encouraged to facilitate reporting quality and transparency. CRITICAL RELEVANCE STATEMENT: It may facilitate the quality and transparency of the use of LLMs in scientific writing if a shared complete reporting guideline is developed by stakeholders and then endorsed by journals. KEY POINTS: The policies on LLM use in radiological journals are unexplored. Some of the radiological journals presented policies on LLM use. A shared complete reporting guideline for LLM use is desired.

Inhalation of hydrogen gas protects against mitomycin-induced pulmonary veno-occlusive disease.

BACKGROUND: As a subtype of pulmonary hypertension (PH), pulmonary veno-occlusive disease (PVOD) is devastating and life-threatening disease without effective therapy. Hydrogen has been reported to exhibits antioxidant and anti-inflammatory effects in a rat model induced by monocrotaline of PH. In this study, we investigated the effects of inhaled hydrogen gas on the prevention and treatment of PVOD induced by mitomycin C (MMC) in rats. METHODS: PVOD was induced in female Sprague-Dawley rats through intraperitoneal injection of MMC at a concentration of 3 mg·kg- 1·wk- 1 for 2 weeks. Inhalation of hydrogen gas (H2) was administered through a designed rat cage concurrently or two weeks after MMC administration. The severity of PVOD was assessed by using hemodynamic measurements and histological analysis. The expression levels of general control nonderepressible 2 (GCN2), nuclear factor erythroid 2-related factor-2 (Nrf2), heme oxygenase-1 (HO-1) and endothelial-to-mesenchymal transition (EndoMT) related proteins in lung tissue were measured. Levels of lipid peroxidation pro-inflammatory cytokines in serum were determined. RESULTS: Inhaled H2 improved hemodynamics and right heart function, reversed right ventricular hypertrophy, and prevented pulmonary vessel reconstitution in both prevention and treatment approaches. It decreased malondialdehyde (MDA) levels in the serum and the expression of NADPH oxidase 1 (NOX-1) in lung tissue. It regulated Nrf2/HO-1 signaling pathway and anti-inflammatory factor GCN2 in lung tissue, accompanied by a decrease in macrophages and pro-inflammatory cytokines. Our data suggested that H2 inhalation effectively countered EndoMT induced by MMC, as evidenced by the detection of endothelial markers (e.g., VE-cadherin and CD31) and mesenchymal markers (e.g., vimentin and fibronectin). Further research revealed that H2 preserved p-Smad3 and induced p-Smad1/5/9. CONCLUSION: Inhalation of H2 effectively inhibits the pathogenesis of PVOD induced by MMC in rats. This inhibitory effect may be attributed to the antioxidant and anti-inflammatory properties of H2.

Robustness of radiomics among photon-counting detector CT and dual-energy CT systems: a texture phantom study.

OBJECTIVES: To evaluate the robustness of radiomics features among photon-counting detector CT (PCD-CT) and dual-energy CT (DECT) systems. METHODS: A texture phantom consisting of twenty-eight materials was scanned with one PCD-CT and four DECT systems (dual-source, rapid kV-switching, dual-layer, and sequential scanning) at three dose levels twice. Thirty sets of virtual monochromatic images at 70 keV were reconstructed. Regions of interest were delineated for each material with a rigid registration. Ninety-three radiomics were extracted per PyRadiomics. The test-retest repeatability between repeated scans was assessed by Bland-Altman analysis. The intra-system reproducibility between dose levels, and inter-system reproducibility within the same dose level, were evaluated by intraclass correlation coefficient (ICC) and concordance correlation coefficient (CCC). Inter-system variability among five scanners was assessed by coefficient of variation (CV) and quartile coefficient of dispersion (QCD). RESULTS: The test-retest repeatability analysis presented that 97.1% of features were repeatable between scan-rescans. The mean ± standard deviation ICC and CCC were 0.945 ± 0.079 and 0.945 ± 0.079 for intra-system reproducibility, respectively, and 86.0% and 85.7% of features were with ICC > 0.90 and CCC > 0.90, respectively, between different dose levels. The mean ± standard deviation ICC and CCC were 0.157 ± 0.174 and 0.157 ± 0.174 for inter-system reproducibility, respectively, and none of the features were with ICC > 0.90 or CCC > 0.90 within the same dose level. The inter-system variability suggested that 6.5% and 12.8% of features were with CV < 10% and QCD < 10%, respectively, among five CT systems. CONCLUSION: The radiomics features were non-reproducible with significant variability in values among different CT techniques. CLINICAL RELEVANCE STATEMENT: Radiomics features are non-reproducible with significant variability in values among photon-counting detector CT and dual-energy CT systems, necessitating careful attention to improve the cross-system generalizability of radiomic features before implementation of radiomics analysis in clinical routine. KEY POINTS: CT radiomics stability should be guaranteed before the implementation in the clinical routine. Radiomics robustness was on a low level among photon-counting detectors and dual-energy CT techniques. Limited inter-system robustness of radiomic features may impact the generalizability of models.

Magnesium alleviates growth inhibition under low potassium by enhancing photosynthesis and carbon-nitrogen metabolism in apple plants.

Potassium (K) and magnesium (Mg) play analogous roles in regulating plant photosynthesis and carbon and nitrogen (C-N) metabolism. Based on this consensus, we hypothesize that appropriate Mg supplementation may alleviate growth inhibition under low K stress. We monitored morphological, physiological, and molecular changes in G935 apple plants under different K (0.1 and 6 mmol L-1) and Mg supply (3 and 6 mmol L-1) conditions. Low K stress caused changes in root and leaf structure, inhibited photosynthesis, and limited the root growth of the apple rootstock. Further study on Mg supplementation showed that it could promote the uptake of K+ and NO3- by upregulating the expression of K+ transporter proteins such as Arabidopsis K+ transporter 1 (MdAKT1), high-affinity K+ transporter 1 (MdHKT1), and potassium transporter 5 (MdPT5) and nitrate transporters such as nitrate transporter 1.1/1.2/2.1/2.4 (MdNRT 1.1/1.2/2.1/2.4). Mg promoted the translocation of 15N from roots to leaves and enhanced photosynthetic N utilization efficiency (PNUE) by increasing the proportion of photosynthetic N and alleviating photosynthetic restrictions. Furthermore, Mg supplementation improved the synthesis of photosynthates by enhancing the activities of sugar-metabolizing enzymes (Rubisco, SS, SPS, S6PDH). Mg also facilitated the transport of sucrose and sorbitol from leaves to roots by upregulating the expression of sucrose transporter 1.1/1.2/4.1/4.2 (MdSUT 1.1/1.2/4.1/4.2) and sorbitol transporter 1.1/1.2 (MdSOT 1.1/1.2). Overall, Mg effectively alleviated growth inhibition in apple rootstock plants under low K stress by facilitating the uptake of N and K uptake, optimizing nitrogen partitioning, enhancing nitrogen use efficiency (NUE) and PNUE, and promoting the photosynthate synthesis and translocation.

Comparative effects of various dietary selenium sources on growth performance, meat quality, essential trace elements content, and antioxidant capacity in broilers.

This study aimed to compare the effects of various dietary selenium (Se) sources (0.5 mg/kg) on performance, meat quality, and antioxidant capacity in broilers as well as essential trace elements concentrations in their blood and tissues. A total of 360 one-day-old male yellow-feathered chickens (37.00 ± 0.17 g) were randomly allocated to 5 diet treatments: the basal diet (CON) and 4 diets supplemented with sodium selenite (SS), selenomethionine (SM), selenium-enriched yeast (SY), and nano-selenium (NS) for 56 d, respectively, with 6 replicates per treatment and 12 chickens per replicate. Dietary Se supplementation did not affect growth performance and carcass characteristics in broilers (P > 0.05). Supplemental SM enhanced the redness in the pectoral muscle compared to CON and NS (P < 0.05). Supplementation of SY and NS improved the concentrations of Se, copper, manganese, and zinc in the serum (P < 0.05). Supplemental SS also elevated the zinc content in the serum (P < 0.05). Broilers fed the SY diet showed increased Se content in the liver and pectoral muscle compared to those fed CON, SM, and NS diets (P < 0.05). Also, SY improved the pectoral muscle Se concentration compared to SS (P < 0.05). Besides, dietary Se supplementation increased the Se content in the thigh muscle (P < 0.05), with SY showing highest Se deposition. Dietary supplementation with SS, SM, and NS improved the activities of total superoxide dismutase and total antioxidant capacity (T-AOC) in the serum (P < 0.05). Supplemental SY also elevated the T-AOC in the serum (P < 0.05). Additionally, SS and SM enhanced the T-AOC in the liver (P < 0.05). In conclusion, supplemental SM affected meat color. Supplementing diets with various Se sources increased antioxidant capacity and Se content in the thigh muscle of broilers, with SY showing a more pronounced deposition efficiency. Besides, diets supplemented with different Se sources had variable effects on the concentrations of essential trace elements in the serum and tissues of broilers.

Nephrectomy and high-salt diet inducing pulmonary hypertension and kidney damage by increasing Ang II concentration in rats.

BACKGROUND: Chronic kidney disease (CKD) is a significant risk factor for pulmonary hypertension (PH), a complication that adversely affects patient prognosis. However, the mechanisms underlying this association remain poorly understood. A major obstacle to progress in this field is the lack of a reliable animal model replicating CKD-PH. METHODS: This study aimed to establish a stable rat model of CKD-PH. We employed a combined approach, inducing CKD through a 5/6 nephrectomy and concurrently exposing the rats to a high-salt diet. The model's hemodynamics were evaluated dynamically, alongside a comprehensive assessment of pathological changes in multiple organs. Lung tissues and serum samples were collected from the CKD-PH rats to analyze the expression of angiotensin-converting enzyme 2 (ACE2), evaluate the activity of key vascular components within the renin-angiotensin-aldosterone system (RAAS), and characterize alterations in the serum metabolic profile. RESULTS: At 14 weeks post-surgery, the CKD-PH rats displayed significant changes in hemodynamic parameters indicative of pulmonary arterial hypertension. Additionally, right ventricular hypertrophy was observed. Notably, no evidence of pulmonary vascular remodeling was found. Further analysis revealed RAAS dysregulation and downregulated ACE2 expression within the pulmonary vascular endothelium of CKD-PH rats. Moreover, the serum metabolic profile of these animals differed markedly from the sham surgery group. CONCLUSIONS: Our findings suggest that the development of pulmonary arterial hypertension in CKD-PH rats is likely a consequence of a combined effect: RAAS dysregulation, decreased ACE2 expression in pulmonary vascular endothelial cells, and metabolic disturbances.

Pathogen stimulations and immune cells synergistically affect the gene expression profile characteristics of porcine peripheral blood mononuclear cells.

BACKGROUND: Pigs serve as a crucial source of protein in the human diet and play a fundamental role in ensuring food security. However, infectious diseases caused by bacteria or viruses are a major threat to effective global pig farming, jeopardizing human health. Peripheral blood mononuclear cells (PBMCs) are a mixture of immune cells that play crucial roles in immunity and disease resistance in pigs. Previous studies on the gene expression regulation patterns of PBMCs have concentrated on a single immune stimulus or immune cell subpopulation, which has limited our comprehensive understanding of the mechanisms of the pig immune response. RESULTS: Here, we integrated and re-analyzed RNA-seq data published online for porcine PBMC stimulated by lipopolysaccharide (LPS), polyinosinic acid (PolyI:C), and various unknown microorganisms (EM). The results revealed that gene expression and its functional characterization are highly specific to the pathogen, identifying 603, 254, and 882 pathogen-specific genes and 38 shared genes, respectively. Notably, LPS and PolyI:C stimulation directly triggered inflammatory and immune-response pathways, while exposure to mixed microbes (EM) enhanced metabolic processes. These pathogen-specific genes were enriched in immune trait-associated quantitative trait loci (QTL) and eGenes in porcine immune tissues and were implicated in specific cell types. Furthermore, we discussed the roles of eQTLs rs3473322705 and rs1109431654 in regulating pathogen- and cell-specific genes CD300A and CD93, using cellular experiments. Additionally, by integrating genome-wide association studies datasets from 33 complex traits and diseases in humans, we found that pathogen-specific genes were significantly enriched for immune traits and metabolic diseases. CONCLUSIONS: We systematically analyzed the gene expression profiles of the three stimulations and demonstrated pathogen-specific and cell-specific gene regulation across different stimulations in porcine PBMCs. These findings enhance our understanding of shared and distinct regulatory mechanisms of genetic variants in pig immune traits.

Deep learning image reconstruction for low-kiloelectron volt virtual monoenergetic images in abdominal dual-energy CT: medium strength provides higher lesion conspicuity.

BACKGROUND: The best settings of deep learning image reconstruction (DLIR) algorithm for abdominal low-kiloelectron volt (keV) virtual monoenergetic imaging (VMI) have not been determined. PURPOSE: To determine the optimal settings of the DLIR algorithm for abdominal low-keV VMI. MATERIAL AND METHODS: The portal-venous phase computed tomography (CT) scans of 109 participants with 152 lesions were reconstructed into four image series: VMI at 50 keV using adaptive statistical iterative reconstruction (Asir-V) at 50% blending (AV-50); and VMI at 40 keV using AV-50 and DLIR at medium (DLIR-M) and high strength (DLIR-H). The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of nine anatomical sites were calculated. Noise power spectrum (NPS) using homogenous region of liver, and edge rise slope (ERS) at five edges were measured. Five radiologists rated image quality and diagnostic acceptability, and evaluated the lesion conspicuity. RESULTS: The SNR and CNR values, and noise and noise peak in NPS measurements, were significantly lower in DLIR images than AV-50 images in all anatomical sites (all P < 0.001). The ERS values were significantly higher in 40-keV images than 50-keV images at all edges (all P < 0.001). The differences of the peak and average spatial frequency among the four reconstruction algorithms were significant but relatively small. The 40-keV images were rated higher with DLIR-M than DLIR-H for diagnostic acceptance (P < 0.001) and lesion conspicuity (P = 0.010). CONCLUSION: DLIR provides lower noise, higher sharpness, and more natural texture to allow 40 keV to be a new standard for routine VMI reconstruction for the abdomen and DLIR-M gains higher diagnostic acceptance and lesion conspicuity rating than DLIR-H.

Electron bifurcation and fluoride efflux systems implicated in defluorination of perfluorinated unsaturated carboxylic acids by Acetobacterium spp.

Enzymatic cleavage of C─F bonds in per- and polyfluoroalkyl substances (PFAS) is largely unknown but avidly sought to promote systems biology for PFAS bioremediation. Here, we report the reductive defluorination of α, ß-unsaturated per- and polyfluorocarboxylic acids by Acetobacterium spp. The microbial defluorination products were structurally confirmed and showed regiospecificity and stereospecificity, consistent with their formation by enzymatic reactions. A comparison of defluorination activities among several Acetobacterium species indicated that a functional fluoride exporter was required for the detoxification of the released fluoride. Results from both in vivo inhibition tests and in silico enzyme modeling suggested the involvement of enzymes of the flavin-based electron-bifurcating caffeate reduction pathway [caffeoyl-CoA reductase (CarABCDE)] in the reductive defluorination. This is a report on specific microorganisms carrying out enzymatic reductive defluorination of PFAS, which could be linked to electron-bifurcating reductases that are environmentally widespread.

Comparison of chimney technique and single-branched stent graft in a cohort of patients with type B aortic dissections: a retrospective cohort study.

Background: Single-branched stent grafts and the chimney technique are widely used in the treatment of type B aortic dissection (TBAD). The main objective of this study was to compare the outcomes of single-branched stent grafts and the chimney technique in the treatment of TBAD. Methods: From January 2019 to December 2021, the retrospective cohort study contained a cohort of 91 patients with TBAD undergoing thoracic endovascular aortic repair (TEVAR) using single-branched stent grafts and the chimney technique. Group A included 55 patients treated with single-branched covered stents, and Group B included 36 patients treated with the chimney technique. We compared the effects of the procedures on peri-/post-operative outcomes between the two groups. The primary endpoint is clinical death, and the secondary endpoints include the patency of branch stents, the incidence of cerebral infarction, false lumen thrombosis, and the proportion of paraplegia. Results: For the baseline data, the two groups of patients show no differences in terms of age, gender, and associated symptoms. All procedures were successfully performed in both groups. The median follow-up period was 17.6 months (range, 10-34 months). During TEVAR, 5 (9.1%) type I endoleaks occurred in group A, and 11 (30.6%) occurred in group B (P<0.05). During follow-up, there were 2 cases (3.6%) of paraplegia and 1 case (1.8%) of cerebral infarction in Group A, while Group B had 1 case (2.8%) of paraplegia. Three patients in group B reported retrograde type A aortic dissection (RTAD), and 1 of them died (2.8%); however, there were no RTAD cases in group A. Complete thrombosis of the false lumen in the thoracic aorta was observed in 45.5% (25/55) of patients in group A and in 41.7% (15/36) in group B (P=0.72). No significant difference in the thrombosis-volume ratio in the whole false lumen was found during follow-up between group A (81.0%±2.9%) and group B (81.8%±2.6%; P=0.23). Conclusions: Branched stent grafts can be used in cases with insufficient proximal landing zones and reduce the occurrence of type 1 endoleak compared to the chimney technique. This may help to prevent RTAD. Further research, including more cases and longer follow-up periods, is needed to substantiate these results.

Deep learning image reconstruction generates thinner slice iodine maps with improved image quality to increase diagnostic acceptance and lesion conspicuity: a prospective study on abdominal dual-energy CT.

BACKGROUND: To assess the improvement of image quality and diagnostic acceptance of thinner slice iodine maps enabled by deep learning image reconstruction (DLIR) in abdominal dual-energy CT (DECT). METHODS: This study prospectively included 104 participants with 136 lesions. Four series of iodine maps were generated based on portal-venous scans of contrast-enhanced abdominal DECT: 5-mm and 1.25-mm using adaptive statistical iterative reconstruction-V (Asir-V) with 50% blending (AV-50), and 1.25-mm using DLIR with medium (DLIR-M), and high strength (DLIR-H). The iodine concentrations (IC) and their standard deviations of nine anatomical sites were measured, and the corresponding coefficient of variations (CV) were calculated. Noise-power-spectrum (NPS) and edge-rise-slope (ERS) were measured. Five radiologists rated image quality in terms of image noise, contrast, sharpness, texture, and small structure visibility, and evaluated overall diagnostic acceptability of images and lesion conspicuity. RESULTS: The four reconstructions maintained the IC values unchanged in nine anatomical sites (all p > 0.999). Compared to 1.25-mm AV-50, 1.25-mm DLIR-M and DLIR-H significantly reduced CV values (all p < 0.001) and presented lower noise and noise peak (both p < 0.001). Compared to 5-mm AV-50, 1.25-mm images had higher ERS (all p < 0.001). The difference of the peak and average spatial frequency among the four reconstructions was relatively small but statistically significant (both p < 0.001). The 1.25-mm DLIR-M images were rated higher than the 5-mm and 1.25-mm AV-50 images for diagnostic acceptability and lesion conspicuity (all P < 0.001). CONCLUSIONS: DLIR may facilitate the thinner slice thickness iodine maps in abdominal DECT for improvement of image quality, diagnostic acceptability, and lesion conspicuity.

Genome-wide association analysis and transgenic characterization for amylose content regulating gene in tuber of Dioscorea zingiberensis.

BACKGROUND: Amylose, a prebiotic found in yams is known to be beneficial for the gut microflora and is particularly advantageous for diabetic patients' diet. However, the genetic machinery underlying amylose production remains elusive. A comprehensive characterization of the genetic basis of amylose content in yam tubers is a prerequisite for accelerating the genetic engineering of yams with respect to amylose content variation. RESULTS: To uncover the genetic variants underlying variation in amylose content, we evaluated amylose content in freshly harvested tubers from 150 accessions of Dioscorea zingibensis. With 30,000 high-quality single nucleotide polymorphisms (SNP), we performed a genome-wide association analysis (GWAS). The population structure analysis classified the D. zingiberensis accessions into three groups. A total of 115 significant loci were detected on four chromosomes. Of these, 112 significant SNPs (log10(p) = 5, q-value < 0.004) were clustered in a narrow window on the chromosome 6 (chr6). The peak SNP at the position 75,609,202 on chr6 could explain 63.15% of amylose variation in the population and fell into the first exon of the ADP-glucose pyrophosphorylase (AGPase) small subunit gene, causing a non-synonymous modification of the resulting protein sequence. Allele segregation analysis showed that accessions with the rare G allele had a higher amylose content than those harboring the common A allele. However, AGPase, a key enzyme precursor of amylose biosynthesis, was not expressed differentially between accessions with A and G alleles. Overexpression of the two variants of AGPase in Arabidopsis thaliana resulted in a significantly higher amylose content in lines transformed with the AGPase-G allele. CONCLUSIONS: Overall, this study showed that a major genetic variant in AGPase probably enhances the enzyme activity leading to high amylose content in D. zingiberensis tuber. The results provide valuable insights for the development of amylose-enriched genotypes.

Transcutaneous auricular vagus nerve stimulation improves anxiety symptoms and cortical activity during verbal fluency task in Parkinson's disease with anxiety.

OBJECTIVE: To investigate the effect of 20/4Hz transcutaneous auricular vagus nerve stimulation (taVNS) on anxiety symptoms in Parkinson's disease (PD) and the potential neural mechanism. METHODS: In the current randomized, double-blind, sham-controlled trial, 30 PD patients with anxiety (PD-A), 30 PD patients without anxiety (PD-nA), and 30 healthy controls (HCs) were enrolled. PD-A patients were randomly (1:1) allotted to real taVNS stimulation group (RS) or sham stimulation group (SS) to explore the efficacy of a two-week treatment of taVNS to promote anxiety recovery. Simultaneously, all participants were measured activation in the bilateral prefrontal cortex during verbal fluency task (VFT) using functional near-infrared spectroscopy. RESULTS: PD-A patients showed significantly decreased oxyhemoglobin in the left triangle part of the inferior frontal gyrus (IFG) during VFT, which was negatively related to the severity of anxiety symptoms. After two-week treatment of taVNS, the interaction of group and time had significant effect on HAMA scores (F = 18.476, p < 0.001, η2 = 0.398). In RS group, compared with baseline, HAMA scores decreased significantly in the post-treatment and follow-up condition (both p < 0.001). Meanwhile, in RS group, HAMA scores were lower than those in SS group in the post-treatment and follow-up condition (p = 0.006, <0.001, respectively). Furthermore, the 20/4Hz taVNS remarkably ameliorated anxiety symptoms in PD patients, directly correlated with the increased activation of the left triangle part of the IFG during VFT in RS group. CONCLUSION: Our results depicted that taVNS could ameliorate the anxiety symptoms of PD-A patients and regulated the function of the left triangle part of the IFG.

Decreased IgA binding levels were accompanied by increased IgG sialylation in IgA nephropathy.

INTRODUCTION: IgA nephropathy (IgAN) is a kidney disorder characterized by the deposition of circulating immune complexes of IgG bound to galactose-deficient IgA1 (Gd-IgA1) in the mesangial glomeruli. However, limited research has been conducted on the levels of IgA binding in relation to the various sialylation profiles of IgG in IgAN. MATERIALS AND METHODS: Sialylated IgG (SA-IgG) and desialylated IgG (DSA-IgG) were isolated from IgAN patients. The IgG-IgA immune complex (IgG-IgA-IC) was detected using two customized commercial ELISA kits. Additionally, IgG was enzymatically digested with neuraminidase to produce DSA-IgG. Subsequently, the binding capacities of both intact IgG and the neuraminidase-digested DSA-IgG with Gd-IgA1 were determined using ELISA kits. RESULTS: Our research revealed that SA-IgG levels were negatively correlated with Gd-IgA1 (R = -0.16, p = 0.03) in IgAN patients. The optical density (OD) levels of IgG-IgA complexes in SA-IgG samples were significantly lower (0.58 ± 0.09) compared to those in DSA-IgG samples (0.78 ± 0.12) when using the Gd-IgA1 assay kit. These results were confirmed using an IgG assay kit, which showed that the SA-IgG groups had significantly lower IgA indices (0.31 ± 0.12) compared to the DSA-IgG groups (0.57 ± 0.19). Furthermore, we investigated the binding capacity of IgG with different sialic acid levels to Gd-IgA1. The results revealed that neuraminidase digestion of IgG increased its propensity to bind to Gd-IgA1. Additionally, we examined the binding capacity of both intact IgG and DSA-IgG to Gd-IgA1 at different mix ratios (IgG 1.5 µg and Gd-IgA1 1.5 µg, IgG 1.5 µg and Gd-IgA1 3 µg, IgG 3 µg and Gd-IgA1 1.5 µg). Interestingly, DSA-IgG demonstrated significantly higher binding capacity to Gd-IgA1 compared to intact IgG at all mix ratios tested. CONCLUSION: The preliminary findings from our present study indicate that the binding level of IgA in purified sialylated IgG is lower than that in desialylated IgG.