Serum Proteomics Identifies Biomarkers Associated With the Pathogenesis of Idiopathic Pulmonary Fibrosis.

The heterogeneity of idiopathic pulmonary fibrosis (IPF) limits its diagnosis and treatment. The association between the pathophysiological features and the serum protein signatures of IPF currently remains unclear. The present study analyzed the specific proteins and patterns associated with the clinical parameters of IPF based on a serum proteomic dataset by data-independent acquisition using MS. Differentiated proteins in sera distinguished patients with IPF into three subgroups in signal pathways and overall survival. Aging-associated signatures by weighted gene correlation network analysis coincidently provided clear and direct evidence that aging is a critical risk factor for IPF rather than a single biomarker. Expression of LDHA and CCT6A, which was associated with glucose metabolic reprogramming, was correlated with high serum lactic acid content in patients with IPF. Cross-model analysis and machine learning showed that a combinatorial biomarker accurately distinguished patients with IPF from healthy individuals with an area under the curve of 0.848 (95% CI = 0.684-0.941) and validated from another cohort and ELISA assay. This serum proteomic profile provides rigorous evidence that enables an understanding of the heterogeneity of IPF and protein alterations that could help in its diagnosis and treatment decisions.

A comparison of [18F]AlF- and 68Ga-labeled dual targeting heterodimer FAPI-RGD in malignant tumor: preclinical evaluation and pilot clinical PET/CT imaging.

Due to the heterogeneity of tumors, strategies to improve the effectiveness of dual-targeting tracers in tumor diagnostics have been intensively practiced. In this study, the radiolabeled [18F]AlF-NOTA-FAPI-RGD (denoted as [18F]AlF-LNC1007), a dual-targeting heterodimer tracer targeting both fibroblast activation protein (FAP) and integrin αvß3 to enhance specific tumor uptake and retention, was synthesized and evaluated. The tracer was compared with [68Ga]Ga-LNC1007 in preclinical and clinical settings. METHODS: The preparation of [18F]AlF- and 68Ga-labeled FAPI-RGD was carried out with an optimized protocol. The stability was tested in PBS and fetal bovine serum (FBS). Cellular uptake and in vivo distribution of the two products were compared and carried out on the U87MG cell line and its xenograft model. The safety and dosimetry of [18F]AlF-LNC1007 PET/CT scan were evaluated in six patients with malignant tumors. RESULTS: Two radiolabeling protocols of [18F]AlF-/[68Ga]Ga-LNC1007 were developed and optimized to give a high yield of tracers with good stability. In vivo microPET images showed that the two tracers exhibited comparable pharmacokinetic characteristics, with high tumor uptake and prolonged tumor retention. In vivo distribution data showed that the target-to-non-target ratios of [18F]AlF-LNC1007 were similar to[68Ga]Ga-LNC1007. A total of six patients underwent [18F]AlF-LNC1007 PET/CT evaluation while two had head-to-head [18F]FDG PET/CT scans. The total body effective dose was 9.94E-03 mSv/MBq. The biodistribution curve showed optimal normal organ uptake with high tumor uptake and long retention of up to 3h p.i., and notably, the tumor-to-background ratio increased over time. CONCLUSION: We successfully prepared an [18F]AlF-LNC1007 dual-targeting PET probe with comparable performances as [68Ga]Ga-LNC1007. With prolonged tumor retention and tumor specificity, it produced good imaging quality in preclinical and clinical translational studies, indicating that [18F]AlF-LNC1007 is a promising non-invasive tracer for detecting tumors expressing FAP and/or integrin avß3, with the prospect of clinical implementation.

Effects of PEGylation on Imaging Contrast of 68Ga-Labeled Bicyclic Peptide PET Probes Targeting Nectin-4.

Nectin cell adhesion molecule 4 (Nectin-4) is overexpressed in various malignant tumors and has emerged as a promising target for tumor imaging. Bicyclic peptides, known for their conformational rigidity, metabolic stability, and membrane permeability, are ideal tracers for positron emission tomography (PET) imaging. In this study, we evaluated the feasibility of visualizing Nectin-4-positive tumors using radiolabeled bicyclic peptide derivatives and optimized the pharmacokinetics of radiotracers by introducing PEG chains of different lengths. Five PEGylated radiotracers radiolabeled with 68Ga3+ exhibited high radiochemical purity and stability. As the chain length increased, the Log D values decreased from -2.32 ± 0.13 to -2.50 ± 0.16, indicating a gradual increase in the hydrophilicity of the radiotracers. In vitro cell-binding assay results showed that the PEGylated bicyclic peptide exhibits nanomolar affinity, and blocking experiments confirmed the specific binding of the tracers to the Nectin-4 receptor. In vivo PET imaging and biodistribution studies in SW780 and 5637 xenograft mice showed that [68Ga]Ga-NOTA-PEG12-BP demonstrated optimal pharmacokinetics, characterized by rapid and good tumor uptake, faster background clearance, and improved tumor-to-tissue contrast. Finally, compared with 18F-FDG, PET imaging, in vivo blocking assays of [68Ga]Ga-NOTA-PEG12-BP and histological staining confirmed that specific tumor uptake was mediated by Nectin-4 receptors. The results indicated that [68Ga]Ga-NOTA-PEG12-BP was a promising PET radiotracer for Nectin-4 targeting, with applications for clinical translation.

ABA functions in low phosphate-induced anthocyanin accumulation through the transcription factor ABI5 in Arabidopsis.

KEY MESSAGE: ABI5 functions in ABA-mediated anthocyanin accumulation in plant response to low phosphate. Low phosphate (LP)-induced anthocyanin biosynthesis and accumulation play an important role in plant adaptive response to phosphate starvation conditions. However, whether and how the stress phytohormone abscisic acid (ABA) participates in LP-induced anthocyanin accumulation remain elusive. Here, we report that ABA is required for LP-induced anthocyanin accumulation in Arabidopsis thaliana. Disrupting ABA DEFICIENT2 (ABA2), a key ABA-biosynthetic gene, or BETA-GLUCOSIDASE1 (BG1), a major gene implicated in converting conjugated ABA to active ABA, significantly impairs LP-induced anthocyanin accumulation, as LP-induced expression of the anthocyanin-biosynthetic genes Chalcone Synthase (CHS) is dampened in the aba2 and bg1 mutant. In addition, LP-induced anthocyanin accumulation is defective in the mutants of ABA signaling pathway, including ABA receptors, ABA Insensitive2, and the transcription factors ABA Insensitive5 (ABI5), suggesting a role of ABI5 in ABA-mediated upregulation of anthocyanin-biosynthetic genes in plant response to LP. Indeed, LP-induced expression of CHS is repressed in the abi5-7 mutant but further promoted in the ABI5-overexpressing plants compared to the wild-type. Moreover, ABI5 can bind to and transcriptionally activate CHS, and the defectiveness of LP-induced anthocyanin accumulation in abi5-7 can be restored by overexpressing CHS. Collectively, our findings illustrates that ABI5 functions in ABA-mediated LP-induced anthocyanin accumulation in Arabidopsis.

Perinatal outcome of emergency cesarean section under neuraxial anesthesia versus general anesthesia: a seven-year retrospective analysis.

OBJECTIVE: An emergency cesarean section (CS), which is extremely life-threatening to the mother or fetus, seems to be performed within an adequate time horizon to avoid negative fetal-maternal denouement. An effective and vigilant technique for anesthesia remains vital for emergency cesarean delivery. Therefore, this study aimed to validate the impact of various anesthesia tactics on maternal and neonatal outcomes. METHOD: This was a retrospective cohort study of parturient patients who were selected for emergency CS with the assistance of general or neuraxial anesthesia between January 2015 and July 2021 at our institution. The 5-min Apgar score was documented as the primary outcome. Secondary outcomes, including the 1 min Apgar score, decision-to-delivery interval (DDI), onset of anesthesia to incision interval (OAII), decision to incision interval (DII), duration of operation, length of hospitalization, height and weight of the newborn, use of vasopressors, blood loss, neonatal resuscitation rate, admission to neonatal intensive care unit (NICU), duration of NICU and complications, were also measured. RESULTS: Of the 539 patients included in the analysis, 337 CSs were performed under general anesthesia (GA), 137 under epidural anesthesia (EA) and 65 under combined spinal-epidural anesthesia (CSEA). The Apgar scores at 1 min and 5 min in newborns receiving GA were lower than those receiving intraspinal anesthesia, and no difference was found between those receiving EA and those receiving CSEA. The DDI of parturients under GA, EA, and CSE were 7[6,7], 6[6,7], and 14[11.5,20.5], respectively. The DDI and DII of GA and EA were shorter than those of CSE, and the DDI and DII were similar between GA and EA. Compared to that in the GA group, the OAII in the intraspinal anesthesia group was significantly greater. GA administration correlated with more frequent resuscitative interventions, increased admission rates to NICU, and a greater incidence of neonatal respiratory distress syndrome (NRDS). Nevertheless, the duration of NICU stay and the incidence rates of neonatal hypoxic ischemic encephalopathy (HIE) and pneumonia did not significantly differ based on the type of anesthesia performed. CONCLUSION: Compared with general anesthesia, epidural anesthesia may not be associated with a negative impact on neonatal or maternal outcomes and could be utilized as an alternative to general anesthesia in our selected patient population following emergency cesarean section; In addition, a comparably short DDI was achieved for emergency cesarean delivery under epidural anesthesia when compared to general anesthesia in our study. However, the possibility that selection bias related to the retrospective study design may have influenced the results cannot be excluded.

Single-Cell RNA Sequencing Provides New Insights into Therapeutic Roles of Thyroid Hormone in Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive fatal interstitial lung disease without an effective cure. Herein, we explore the role of 3,5,3'-triiodothyronine (T3) administration on lung alveolar regeneration and fibrosis at the single-cell level. T3 supplementation significantly altered the gene expression in fibrotic lung tissues. Immune cells were rapidly recruited into the lung after the injury; there were much more M2 macrophages than M1 macrophages in the lungs of bleomycin-treated mice; and M1 macrophages increased slightly, whereas M2 macrophages were significantly reduced after T3 treatment. T3 enhanced the resolution of pulmonary fibrosis by promoting the differentiation of Krt8+ transitional alveolar type II epithelial cells into alveolar type I epithelial cells and inhibiting fibroblast activation and extracellular matrix production potentially by regulation of Nr2f2. In addition, T3 regulated the crosstalk of macrophages with fibroblasts, and the Pros1-Axl signaling axis significantly facilitated the attenuation of fibrosis. The findings demonstrate that administration of a thyroid hormone promotes alveolar regeneration and resolves fibrosis mainly by regulation of the cellular state and cell-cell communication of alveolar epithelial cells, macrophages, and fibroblasts in mouse lungs in comprehensive ways.

Two transporters mobilize magnesium from vacuolar stores to enable plant acclimation to magnesium deficiency.

Magnesium (Mg) is an essential metal for chlorophyll biosynthesis and other metabolic processes in plant cells. Mg is largely stored in the vacuole of various cell types and remobilized to meet cytoplasmic demand. However, the transport proteins responsible for mobilizing vacuolar Mg2+ remain unknown. Here, we identified two Arabidopsis (Arabidopsis thaliana) Mg2+ transporters (MAGNESIUM TRANSPORTER 1 and 2; MGT1 and MGT2) that facilitate Mg2+ mobilization from the vacuole, especially when external Mg supply is limited. In addition to a high degree of sequence similarity, MGT1 and MGT2 exhibited overlapping expression patterns in Arabidopsis tissues, implying functional redundancy. Indeed, the mgt1 mgt2 double mutant, but not mgt1 and mgt2 single mutants, showed exaggerated growth defects as compared to the wild type under low-Mg conditions, in accord with higher expression levels of Mg-starvation gene markers in the double mutant. However, overall Mg level was also higher in mgt1 mgt2, suggesting a defect in Mg2+ remobilization in response to Mg deficiency. Consistently, MGT1 and MGT2 localized to the tonoplast and rescued the yeast (Saccharomyces cerevisiae) mnr2Δ (manganese resistance 2) mutant strain lacking the vacuolar Mg2+ efflux transporter. In addition, disruption of MGT1 and MGT2 suppressed high-Mg sensitivity of calcineurin B-like 2 and 3 (cbl2 cbl3), a mutant defective in vacuolar Mg2+ sequestration, suggesting that vacuolar Mg2+ influx and efflux processes are antagonistic in a physiological context. We further crossed mgt1 mgt2 with mgt6, which lacks a plasma membrane MGT member involved in Mg2+ uptake, and found that the triple mutant was more sensitive to low-Mg conditions than either mgt1 mgt2 or mgt6. Hence, Mg2+ uptake (via MGT6) and vacuolar remobilization (through MGT1 and MGT2) work synergistically to achieve Mg2+ homeostasis in plants, especially under low-Mg supply in the environment.

SIAH1 ubiquitination-modified HMGCR inhibits lung cancer progression and promotes drug sensitivity through cholesterol synthesis.

BACKGROUNDS: Lung cancer is one of the most frequently diagnosed cancers and the leading cause of cancer-related deaths worldwide. Deep understanding of chemoresistance will lead to remarkable progress in lung cancer treatment strategy. Cholesterol accumulation was associated with cisplatin resistance in lung cancer treatment. And we found the degree of cisplatin resistance was correlated with the expression of the cholesterol synthesis HMGCR. METHODS: We analyzed a group of 42 lung cancer patients who received cisplatin treatment after lung resection surgery. The expression of HMGCR and its correlation with cholesterol in lung cancer cell lines were determined by qRT-PCR and ELISA analyses. We focus on the function and mechanism of HMGCR in lung cancer and reveal that knockdown of HMGCR expression inhibits the proliferation, colony formation, and migration of lung cancer cell lines in vitro or in vivo and dramatically enhances the efficacy of cisplatin. RESULTS: Through mechanism studies, we illustrate that SIAH1, an E3 ubiquitin-protein ligase, ubiquitination modifies HMGCR and inhibits efflux protein activity via regulating cholesterol synthesis. In vivo experiments showed that SIAH1 overexpression or using HMGCR knockdown retard tumor growth and enhanced the efficacy of cisplatin. In summary, HMGCR affects cholesterol metabolism by regulating key enzymes in cholesterol synthesis, thereby reducing drug sensitivity. CONCLUSION: This study indicates that lung cancer patients with lower HMGCR levels may lead to a better prognosis and provide a potential treatment by SIAH1 overexpression for lung cancer patients with cisplatin resistance.

Predicting central lymph node metastasis in patients with papillary thyroid carcinoma based on ultrasound radiomic and morphological features analysis.

OBJECTIVES: To build a combined model based on the ultrasound radiomic and morphological features, and evaluate its diagnostic performance for preoperative prediction of central lymph node metastasis (CLNM) in patients with papillary thyroid carcinoma (PTC). METHOD: A total of 295 eligible patients, who underwent preoperative ultrasound scan and were pathologically diagnosed with unifocal PTC were included at our hospital from October 2019 to July 2022. According to ultrasound scanners, patients were divided into the training set (115 with CLNM; 97 without CLNM) and validation set (45 with CLNM; 38 without CLNM). Ultrasound radiomic, morphological, and combined models were constructed using multivariate logistic regression. The diagnostic performance was assessed by the area under the curve (AUC) of the receiver operating characteristic curve, accuracy, sensitivity, and specificity. RESULTS: A combined model was built based on the morphology, boundary, length diameter, and radiomic score. The AUC was 0.960 (95% CI, 0.924-0.982) and 0.966 (95% CI, 0.901-0.993) in the training and validation set, respectively. Calibration curves showed good consistency between prediction and observation, and DCA demonstrated the clinical benefit of the combined model. CONCLUSION: Based on ultrasound radiomic and morphological features, the combined model showed a good performance in predicting CLNM of patients with PTC preoperatively.

HbBIN2 Functions in Plant Cold Stress Resistance through Modulation of HbICE1 Transcriptional Activity and ROS Homeostasis in Hevea brasiliensis.

Cold stress poses significant limitations on the growth, latex yield, and ecological distribution of rubber trees (Hevea brasiliensis). The GSK3-like kinase plays a significant role in helping plants adapt to different biotic and abiotic stresses. However, the functions of GSK3-like kinase BR-INSENSITIVE 2 (BIN2) in Hevea brasiliensis remain elusive. Here, we identified HbBIN2s of Hevea brasiliensis and deciphered their roles in cold stress resistance. The transcript levels of HbBIN2s are upregulated by cold stress. In addition, HbBIN2s are present in both the nucleus and cytoplasm and have the ability to interact with the INDUCER OF CBF EXPRESSION1(HbICE1) transcription factor, a central component in cold signaling. HbBIN2 overexpression in Arabidopsis displays decreased tolerance to chilling stress with a lower survival rate and proline content but a higher level of electrolyte leakage (EL) and malondialdehyde (MDA) than wild type under cold stress. Meanwhile, HbBIN2 transgenic Arabidopsis treated with cold stress exhibits a significant increase in the accumulation of reactive oxygen species (ROS) and a decrease in the activity of antioxidant enzymes. Further investigation reveals that HbBIN2 inhibits the transcriptional activity of HbICE1, thereby attenuating the expression of C-REPEAT BINDING FACTOR (HbCBF1). Consistent with this, overexpression of HbBIN2 represses the expression of CBF pathway cold-regulated genes under cold stress. In conclusion, our findings indicate that HbBIN2 functions as a suppressor of cold stress resistance by modulating HbICE1 transcriptional activity and ROS homeostasis.

Injured Endothelial Cell: A Risk Factor for Pulmonary Fibrosis.

The pathological features of pulmonary fibrosis (PF) are the abnormal activation and proliferation of myofibroblasts and the extraordinary deposition of the extracellular matrix (ECM). However, the pathogenesis of PF is still indistinct. In recent years, many researchers have realized that endothelial cells had a crucial role in the development of PF. Studies have demonstrated that about 16% of the fibroblasts in the lung tissue of fibrotic mice were derived from endothelial cells. Endothelial cells transdifferentiated into mesenchymal cells via the endothelial-mesenchymal transition (E(nd)MT), leading to the excessive proliferation of endothelial-derived mesenchymal cells and the accumulation of fibroblasts and ECM. This suggested that endothelial cells, a significant component of the vascular barrier, played an essential role in PF. Herein, this review discusses E(nd)MT and its contribution to the activation of other cells in PF, which could provide new ideas for further understanding the source and activation mechanism of fibroblasts and the pathogenesis of PF.

The TiNI monolayer: a two-dimensional system with promising ferroelastic, topological, and thermoelectric properties.

We demonstrate using first-principles calculations that the TiNI monolayer simultaneously exhibits favorable ferroelastic, topological, and thermoelectric properties. Specifically, we discover a 90° lattice rotation with a moderate switching barrier of 56 meV per atom when a uniaxial tensile strain is applied to the system. Besides, the monolayer is found to be an intrinsic topological insulator with an inverted band structure, as characterized by the Z2 invariant of 1 and the presence of Dirac-like edge states at a critical width of 5.6 nm. Moreover, the thermoelectric ZT value of the system can reach as high as 1.4 at 600 K by fine tuning the carrier concentration. Collectively, these findings make the TiNI monolayer a promising multifunctional material to meet the various application requirements of nanoelectronic devices.

ß-Ketoenamine-linked covalent organic framework absorbent for online micro-solid phase extraction of trace levels bisphenols in plastic samples.

Covalent organic frameworks with tunable porous crystallinity and outstanding stability have exhibited fascinating pretreatment performance as ideal extraction media. Herein, the ß-ketoenamine-linked TpPa-1 synthesized by 1,3,5-triformylphloroglucinol and paraphenylenediamine was employed as the absorbent for online micro-solid phase extraction of trace bisphenols combined with high-performance liquid chromatography detection. A series of characterizations indicated that the TpPa-1 possessed large surface areas, high stability, and hydrophobicity. The main experimental parameters affecting the extraction efficiency were optimized in detail. Compared with four commercial sorbents, the TpPa-1 exhibited superior enrichment capacity for extracting bisphenols. Under the optimum conditions, the established method demonstrated a wide linear range and high sensitivity with the limit of detection ranging from 0.05-0.06 µg/L. Furthermore, the developed method was successfully applied to determine bisphenols in plastic samples. Bisphenol A was actually detected in a transparent box with a concentration of 0.31 µg/g, and the recoveries of the four bisphenols in the plastic samples were 80.5-116% with the relative standard deviation less than 9.2%. Such performance was attributed to recognition affinity, including the π-π affinity, hydrophobic effect, and hydrogen bond. These results demonstrated that TpPa-1 possessed great potential to be an excellent pretreatment medium for online separation and analysis of trace analytes in complex samples.

A comparative analysis of diagnostic values of high-frequency ultrasound and fiberoptic ductoscopy for pathologic nipple discharge.

BACKGROUND: This study aimed to compare the diagnostic accuracy of high-frequency ultrasound (HFUS) and fiberoptic ductoscopy (FDS) for pathologic nipple discharge (PND). METHODS: HFUS and FDS were conducted in 210 patients with PND (248 lesions) treated at our hospital. The diagnostic accuracy of these two methods was compared using pathological diagnosis as the standard. RESULTS: Among 248 lesions, 16 and 15 of 16 malignant lesions were accurately diagnosed by HFUS and FDS, respectively. Of 232 benign lesions, 183 and 196 cases were accurately diagnosed by HFUS and FDS, respectively. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of HFUS in diagnosis of intraductal lesions were 84.36% (95% CI 79.26-88.39%), 60% (95% CI 23.07-92.89%), 96.03% (95% CI 96.55-99.83%), and 7.31% (95% CI 2.52-19.4%) respectively. The sensitivity, specificity, PPV, and NPV of FDS in diagnosis of intraductal lesions were 86.83% (95% CI 82.00-90.52%), 100% (95% CI 56.55-100%), 100% (95% CI 98.21-100%), and 13.51% (95% CI 5.91-27.98%) respectively. Diagnostic accuracy rates of HFUS and FDS were 83.87% (208/248) and 85.08% (211/248), respectively, exhibiting no statistically differences (χ2 = 0.80, P > 0.05). The accuracy of HFUS combined with FDS was 93.14% (231/248), showing statistically differences (χ2 = 10.91, P < 0.05). CONCLUSIONS: Both HFUS and FDS demonstrated high diagnostic values for PND. HFUS has the advantage of non-invasive for nipple discharge with duct ectasia, exhibited good qualitative and localization diagnostic values. It is the preferred evaluation method for patients with nipple discharge. When HFUS cannot identify the cause of PND, FDS can be considered.

First Report of Fusarium Wilt of Industrial Hemp (Cannabis sativa L.) Caused by Fusarium oxysporum in the Northeast China.

Industrial hemp (Cannabis sativa L.) is an ancient and economically important crop used in food, medicine, textile, and paper industries (Chandra et al. 2017). In July 2021, an estimated 30% of the industrial hemp plants showed wilted leaves and root rot in the greenhouse at the Modern Agriculture Demonstration Area Management Center, Harbin City, Heilongjiang Province, China. Initially, the diseased plants exhibited green and reversible wilting of lower canopy leaves. Upon progression the plants showed irreversible wilting. The epidermal tissue of root and rhizome showed slight cracks and the vascular bundle exhibited light brown discoloration, and then died. Six randomly selected disease plants were collected. Small fragments (5 mm) were cut from the infected roots, surface-sterilized with 70% ethanol for 30s and 1% sodium hypochlorite for 5 min and rinsed three times in sterile H2O. Then the small pieces were embedded on potato dextrose agar at 25℃ for 4 days and sub-cultured by hyphal tipping to isolate the fungus. A single-spore culture was obtained by monosporic isolation. The colonies were characterized by an abundant white cottony mycelium, which became gray or purple with age. The macroconidia were transparent, short to medium in length, straight to slightly curved, septate 0 to 4, 16.8 to 26.6 µm long × 3.5 to 4.1 µm wide. The apical cells were long and tapering to a point and the basal cells were notched. Microconidia were elliptic or kidney-shaped, and septate 0 to 4. The conidia were 4.2 to 11.3 µm long × 3.5 to 5.5 µm wide (n = 50). The morphological characteristics were very similar to those of Fusarium oxysporum (Leslie and Summerell 2006). For molecular identification, the internal transcribed spacer (ITS), translation elongation factor 1-α (TEF1) and RNA polymerase II beta subunit (RPB2) genes were amplified and sequenced with the primers ITS1/ITS4, EF-1/EF-2 (Uwaremwe et al. 2020), and 5f2/7c (O'Donnell et al. 2010). The 520 bp (ITS), 948 bp (TEF1), and 861 bp (RPB2) sequences were deposited in GenBank with acce. nos. MZ722998, OK180473 and OK180474, respectively. NCBI BLAST analysis showed 98 to 100% similarity with the sequences of F. oxysporum. Moreover, the sequences alignment similarity for the six isolates were 100%. Based on the morphological and molecular characteristics, the isolates were identified as F. oxysporum. For the pathogenicity test, 20 seedlings were inoculated 30 ml of a conidial suspension (106 conidia/ml) using the root dip method. Another set of 20 seedlings were inoculated with the same quantity of sterile distilled water as the controls. After inoculation, all seedlings were maintained in a greenhouse at 25°C ± 2, with a relative humidity of 60 to 70% and a 16 h light/8 h dark cycle. This test was repeated twice. The leaves of the inoculated seedlings gradually became yellow and exhibited wilting within 15 to 20 days, the epidermal tissue of root showed light brown discoloration. Eventually the plants were dead within 40 to 50 days after inoculation. The control seedlings did not show any wilt symptoms. F. oxysporum was re-isolated from the infected root tissues to fulfill the Koch's postulates. In addition to F. oxysporum, F. brachygibbosum, Pythium aphanidermatum, F. solani, and F. equiseti have also been reported to cause wilt symptoms of industrial hemp (Zamir et al. 2018). To our knowledge, this is the first report of Fusarium wilt on C. sativa caused by F. oxysporum in the Northeast China.

Right Sinus of Valsalva Aneurysm and Dissection into the Interventricular Septum: A Case Report.

Sinus of Valsalva aneurysm (SVA) is considered to be an uncommon cardiac anomaly, carrying a very high rate of mortality. After treatment, the prognosis is excellent. Thus, it is important to make a timely diagnosis and clarify the anatomical details of the SVA. Here, we report a right SVA with dissection into the interventricular septum, with bulging and incomplete rupture into the left outflow tract. The SVA was evaluated using echocardiography (transoesophageal, transthoracic, and three-dimensional echocardiography) and cardiac computed tomography (CT), especially three-dimensional reconstruction, to help us plan the surgical approach. After surgery, the patient's recovery was favorable.

Assessment of early wound healing, pain intensity, quality of life and related influencing factors during periodontal surgery: a cross-sectional study.

BACKGROUND: This cross-sectional study assessed early wound healing, pain intensity, quality of life, surgical satisfaction, and related factors during periodontal surgery. METHODS: A total of 369 patients completed the questionnaire before undergoing periodontal surgery (baseline), immediately after the operation (phase I), on the day of suture removal (phase II), and one month later (phase III). The Early Wound Healing Score (EHS) was assessed, and the short-form McGill Pain Questionnaire (SF-MPQ), tooth hypersensitivity visual analog scale (VAS), oral health-related quality of life measure (OHQoL-UK), and surgical satisfaction VAS were administered and analysed. RESULTS: The EHS was 8.41 ± 2.74 and was influenced by disease severity and surgical factors. Scores on the SF-MPQ, pain intensity scores, and OHQoL-UK scores were significantly increased in phase I and decreased later. Tooth sensitivity decreased significantly one month after periodontal surgery. Psychological factors were positively related to SF-MPQ, pain intensity, OHQoL-UK and tooth sensitivity VAS scores in all phases, while disease severity and surgical factors were only related to these scores at baseline or in phases I/II/III. Surgical acceptance and reoperation willingness continuously decreased after surgery, and all these scores were related to surgical satisfaction. CONCLUSIONS: EHS, pain intensity and quality of life were closely related to disease severity, psychological factors and surgical factors in phase I (i.e., immediately after surgery). The findings suggest that surgical details should be enhanced and that behavioural and psychological interventions measures should be implemented to improve outcomes during periodontal operation and during the early postoperative period as well as to improve patient-oriented periodontal surgery experiences. Trial registration This cross-sectional study did not include interventions with human participants, and all the experimental procedures involving humans in this study were approved by the Ethics Committee of West China College of Stomatology, Sichuan University (WCHSIRB-D-2020-284).

Genome-wide identification and expression analysis of the WRKY transcription factor family in flax (Linum usitatissimum L.).

BACKGROUND: Members of the WRKY protein family, one of the largest transcription factor families in plants, are involved in plant growth and development, signal transduction, senescence, and stress resistance. However, little information is available about WRKY transcription factors in flax (Linum usitatissimum L.). RESULTS: In this study, comprehensive genome-wide characterization of the flax WRKY gene family was conducted that led to prediction of 102 LuWRKY genes. Based on bioinformatics-based predictions of structural and phylogenetic features of encoded LuWRKY proteins, 95 LuWRKYs were classified into three main groups (Group I, II, and III); Group II LuWRKYs were further assigned to five subgroups (IIa-e), while seven unique LuWRKYs (LuWRKYs 96-102) could not be assigned to any group. Most LuWRKY proteins within a given subgroup shared similar motif compositions, while a high degree of motif composition variability was apparent between subgroups. Using RNA-seq data, expression patterns of the 102 predicted LuWRKY genes were also investigated. Expression profiling data demonstrated that most genes associated with cellulose, hemicellulose, or lignin content were predominantly expressed in stems, roots, and less in leaves. However, most genes associated with stress responses were predominantly expressed in leaves and exhibited distinctly higher expression levels in developmental stages 1 and 8 than during other stages. CONCLUSIONS: Ultimately, the present study provides a comprehensive analysis of predicted flax WRKY family genes to guide future investigations to reveal functions of LuWRKY proteins during plant growth, development, and stress responses.

Brain CT registration using hybrid supervised convolutional neural network.

BACKGROUND: Image registration is an essential step in the automated interpretation of the brain computed tomography (CT) images of patients with acute cerebrovascular disease (ACVD). However, performing brain CT registration accurately and rapidly remains greatly challenging due to the large intersubject anatomical variations, low resolution of soft tissues, and heavy computation costs. To this end, the HSCN-Net, a hybrid supervised convolutional neural network, was developed for precise and fast brain CT registration. METHOD: HSCN-Net generated synthetic deformation fields using a simulator as one supervision for one reference-moving image pair to address the problem of lack of gold standards. Furthermore, the simulator was designed to generate multiscale affine and elastic deformation fields to overcome the registration challenge posed by large intersubject anatomical deformation. Finally, HSCN-Net adopted a hybrid loss function constituted by deformation field and image similarity to improve registration accuracy and generalization capability. In this work, 101 CT images of patients were collected for model construction (57), evaluation (14), and testing (30). HSCN-Net was compared with the classical Demons and VoxelMorph models. Qualitative analysis through the visual evaluation of critical brain tissues and quantitative analysis by determining the endpoint error (EPE) between the predicted sparse deformation vectors and gold-standard sparse deformation vectors, image normalized mutual information (NMI), and the Dice coefficient of the middle cerebral artery (MCA) blood supply area were carried out to assess model performance comprehensively. RESULTS: HSCN-Net and Demons had a better visual spatial matching performance than VoxelMorph, and HSCN-Net was more competent for smooth and large intersubject deformations than Demons. The mean EPE of HSCN-Net (3.29 mm) was less than that of Demons (3.47 mm) and VoxelMorph (5.12 mm); the mean Dice of HSCN-Net was 0.96, which was higher than that of Demons (0.90) and VoxelMorph (0.87); and the mean NMI of HSCN-Net (0.83) was slightly lower than that of Demons (0.84), but higher than that of VoxelMorph (0.81). Moreover, the mean registration time of HSCN-Net (17.86 s) was shorter than that of VoxelMorph (18.53 s) and Demons (147.21 s). CONCLUSION: The proposed HSCN-Net could achieve accurate and rapid intersubject brain CT registration.

HbSnRK2.6 Functions in ABA-Regulated Cold Stress Response by Promoting HbICE2 Transcriptional Activity in Hevea brasiliensis.

Low temperature remarkably limits rubber tree (Hevea brasiliensis Muell. Arg.) growth, latex production, and geographical distribution, but the underlying mechanisms of Hevea brasiliensis cold stress response remain elusive. Here, we identified HbSnRK2.6 as a key component in ABA signaling functions in phytohormone abscisic acid (ABA)-regulated cold stress response in Hevea brasiliensis. Exogenous application of ABA enhances Hevea brasiliensis cold tolerance. Cold-regulated (COR) genes in the CBF pathway are upregulated by ABA. Transcript levels of all five HbSnRK2.6 members are significantly induced by cold, while HbSnRK2.6A, HbSnRK2.6B, and HbSnRK2.6C can be further activated by ABA under cold conditions. Additionally, HbSnRK2.6s are localized in the cytoplasm and nucleus, and can physically interact with HbICE2, a crucial positive regulator in the cold signaling pathway. Overexpression of HbSnRK2.6A or HbSnRK2.6B in Arabidopsis extensively enhances plant responses to ABA and expression of COR genes, leading to increased cold stress tolerance. Furthermore, HbSnRK2.6A and HbSnRK2.6B can promote transcriptional activity of HbICE2, thus, increasing the expression of HbCBF1. Taken together, we demonstrate that HbSnRK2.6s are involved in ABA-regulated cold stress response in Hevea brasiliensis by regulating transcriptional activity of HbICE2.