TLTNet: A novel transscale cascade layered transformer network for enhanced retinal blood vessel segmentation.

Extracting global and local feature information is still challenging due to the problems of retinal blood vessel medical images like fuzzy edge features, noise, difficulty in distinguishing between lesion regions and background information, and loss of low-level feature information, which leads to insufficient extraction of feature information. To better solve these problems and fully extract the global and local feature information of the image, we propose a novel transscale cascade layered transformer network for enhanced retinal blood vessel segmentation, which consists of an encoder and a decoder and is connected between the encoder and decoder by a transscale transformer cascade module. Among them, the encoder consists of a local-global transscale transformer module, a multi-head layered transscale adaptive embedding module, and a local context(LCNet) module. The transscale transformer cascade module learns local and global feature information from the first three layers of the encoder, and multi-scale dependent features, fuses the hierarchical feature information from the skip connection block and the channel-token interaction fusion block, respectively, and inputs it to the decoder. The decoder includes a decoding module for the local context network and a transscale position transformer module to input the local and global feature information extracted from the encoder with retained key position information into the decoding module and the position embedding transformer module for recovery and output of the prediction results that are consistent with the input feature information. In addition, we propose an improved cross-entropy loss function based on the difference between the deterministic observation samples and the prediction results with the deviation distance, which is validated on the DRIVE and STARE datasets combined with the proposed network model based on the dual transformer structure in this paper, and the segmentation accuracies are 97.26% and 97.87%, respectively. Compared with other state-of-the-art networks, the results show that the proposed network model has a significant competitive advantage in improving the segmentation performance of retinal blood vessel images.

Identification of Autophagy-Related Genes Involved in Intervertebral Disc Degeneration by Microarray Data Analysis.

BACKGROUND: Nucleus pulposus cells survive in a hypoxic, acidic, nutrient-poor, and hypotonic microenvironment. Consequently, they maintain low proliferation and undergo autophagy to protect themselves from cellular stress. Therefore, we aimed to identify autophagy-related biomarkers involved in intervertebral disc degeneration pathogenesis. METHODS: Autophagy-related differentially expressed genes were derived from the intersection between the public GSE147383 microarray data set to identify differentially expressed genes and online databases to identify autophagy-related genes. Furthermore, we assessed their biological functions with gene annotation and enrichment analysis in the Metscape portal. Then, the STRING database and Cytoscape software allowed inferring a protein-protein interaction (PPI) network and identifying hub genes. In addition, to predict transcription factors that may regulate the hub genes, we used the GeneMANIA website. Finally, the competing endogenous RNA prediction tools and Cytoscape were also used to construct an mRNA-miRNA-lncRNA network. RESULTS: A total of 123 autophagy-related differentially expressed genes were identified, they were mainly involved in phosphoinositide 3-kinase-Akt signaling, autophagy animal, and apoptosis pathways. Nine were identified as hub genes (PTEN, MYC, CTNNB1, JUN, BECN1, ERBB2, FOXO3, ATM, and FN1) and 36 transcription factors were associated with them. Finally, an autophagy-associated competing endogenous RNA network was constructed based on the 9 hub genes. CONCLUSIONS: Nine hub genes were identified and a network of competing endogenous RNA associated with autophagy was established. They can be used as autophagy-related biomarkers of intervertebral disc degeneration and for further exploration.

siRNA incorporated in slow-release injectable hydrogel continuously silences DDIT4 and regulates nucleus pulposus cell pyroptosis through the ROS/TXNIP/NLRP3 axis to alleviate intervertebral disc degeneration.

Aims: In this investigation, we administered oxidative stress to nucleus pulposus cells (NPCs), recognized DNA-damage-inducible transcript 4 (DDIT4) as a component in intervertebral disc degeneration (IVDD), and devised a hydrogel capable of conveying small interfering RNA (siRNA) to IVDD. Methods: An in vitro model for oxidative stress-induced injury in NPCs was developed to elucidate the mechanisms underlying the upregulation of DDIT4 expression, activation of the reactive oxygen species (ROS)-thioredoxin-interacting protein (TXNIP)-NLRP3 signalling pathway, and nucleus pulposus pyroptosis. Furthermore, the mechanism of action of small interfering DDIT4 (siDDIT4) on NPCs in vitro was validated. A triplex hydrogel named siDDIT4@G5-P-HA was created by adsorbing siDDIT4 onto fifth-generation polyamidoamine (PAMAM) dendrimer using van der Waals interactions, and then coating it with hyaluronic acid (HA). In addition, we established a rat puncture IVDD model to decipher the hydrogel's mechanism in IVDD. Results: A correlation between DDIT4 expression levels and disc degeneration was shown with human nucleus pulposus and needle-punctured rat disc specimens. We confirmed that DDIT4 was responsible for activating the ROS-TXNIP-NLRP3 axis during oxidative stress-induced pyroptosis in rat nucleus pulposus in vitro. Mitochondria were damaged during oxidative stress, and DDIT4 contributed to mitochondrial damage and ROS production. In addition, siDDIT4@G5-P-HA hydrogels showed good delivery activity of siDDIT4 to NPCs. In vitro studies illustrated the potential of the siDDIT4@G5-P-HA hydrogel for alleviating IVDD in rats. Conclusion: DDIT4 is a key player in mediating pyroptosis and IVDD in NPCs through the ROS-TXNIP-NLRP3 axis. Additionally, siDDIT4@G5-P-HA hydrogel has been found to relieve IVDD in rats. Our research offers an innovative treatment option for IVDD.

Pretreatment mortality risk prediction model in patients with polymyositis/dermatomyositis-associated interstitial lung disease.

OBJECTIVES: Risk prediction for patients with polymyositis/dermatomyositis-associated interstitial lung disease (PM/DM-ILD) is challenging due to heterogeneity in the disease course. We aimed to develop a mortality risk prediction model for PM/DM-ILD. METHODS: This prognostic study analysed patients with PM/DM-ILD admitted to Nanjing Drum Hospital from 2016 to 2021. The primary outcome was mortality within 1 year. We used a least absolute shrinkage and selection operator (LASSO) logistic regression model to identify predictive laboratory indicators. These indicators were used to create a laboratory risk score, and we developed a mortality risk prediction model by incorporating clinical factors. The evaluation of model performance encompassed discrimination, calibration, clinical utility and practical application for risk prediction and prognosis. RESULTS: Overall, 418 patients with PM/DM-ILD were enrolled and randomly divided into development (n=282) and validation (n=136) cohorts. LASSO logistic regression identified four optimal features in the development cohort, forming a laboratory risk score: C reactive protein, lactate dehydrogenase, CD3+CD4+ T cell counts and PO2/FiO2. The final prediction model integrated age, arthralgia, anti-melanoma differentiation-associated gene 5 antibody status, high-resolution CT pattern and the laboratory risk score. The prediction model exhibited robust discrimination (area under the receiver operating characteristic: 0.869, 95% CI 0.811 to 0.910), excellent calibration and valuable clinical utility. Patients were categorised into three risk groups with distinct mortality rates. The internal validation, sensitivity analyses and comparative assessments against previous models further confirmed the robustness of the prediction model. CONCLUSIONS: We developed and validated an evidence-based mortality risk prediction model with simple, readily accessible clinical variables in patients with PM/DM-ILD, which may inform clinical decision-making.

Lanthanum Significantly Contributes to the Growth of the Fine Roots' Morphology and Phosphorus Uptake Efficiency by Increasing the Yield and Quality of Glycyrrhiza uralensis Taproots.

The occurrence of different degrees of phosphorus deficiency in the vast majority of G. uralensis cultivation regions worldwide is common. There is a pressing need within the cultivated G. uralensis industry to identify appropriate exogenous substances that can enhance the uptake of phosphorus and improve both the yield and quality of the taproots of G. uralensis. This study was conducted to investigate the fine root and taproot morphology, physiological characteristics, and secondary metabolite accumulation in response to the supply of varying concentrations of LaCl3 to G. uralensis, to determine the optimal concentration of LaCl3 that can effectively enhance the yield and quality of G. uralensis's taproots, while also alleviating its reliance on soil phosphate fertilizer. The findings indicate that the foliar application of lanthanum enhanced root activity and increased APase activity, eliciting alterations in the fine root morphology, leading to promoting the accumulation of biomass in grown G. uralensis when subjected to P-deficient conditions. Furthermore, it was observed that the nutrient uptake of G. uralensis was significantly improved when subjected to P-deficient conditions but treated with LaCl3. Additionally, the yield and quality of the medicinal organs of G. uralensis were significantly enhanced.

Exogenous betaine enhances salt tolerance of Glycyrrhiza uralensis through multiple pathways.

BACKGROUND: Glycyrrhiza uralensis Fisch., a valuable medicinal plant, shows contrasting salt tolerance between seedlings and perennial individuals, and salt tolerance at seedling stage is very weak. Understanding this difference is crucial for optimizing cultivation practices and maximizing the plant's economic potential. Salt stress resistance at the seedling stage is the key to the cultivation of the plant using salinized land. This study investigated the physiological mechanism of the application of glycine betaine (0, 10, 20, 40, 80 mM) to seedling stages of G. uralensis under salt stress (160 mM NaCl). RESULTS: G. uralensis seedlings' growth was severely inhibited under NaCl stress conditions, but the addition of GB effectively mitigated its effects, with 20 mM GB had showing most significant alleviating effect. The application of 20 mM GB under NaCl stress conditions significantly increased total root length (80.38%), total root surface area (93.28%), and total root volume (175.61%), and significantly increased the GB content in its roots, stems, and leaves by 36.88%, 107.05%, and 21.63%, respectively. The activity of betaine aldehyde dehydrogenase 2 (BADH2) was increased by 74.10%, 249.38%, and 150.60%, respectively. The 20 mM GB-addition treatment significantly increased content of osmoregulatory substances (the contents of soluble protein, soluble sugar and proline increased by 7.05%, 70.52% and 661.06% in roots, and also increased by 30.74%, 47.11% and 26.88% in leaves, respectively.). Furthermore, it markedly enhanced the activity of antioxidant enzymes and the content of antioxidants (SOD, CAT, POD, APX and activities and ASA contents were elevated by 59.55%, 413.07%, 225.91%, 300.00% and 73.33% in the root, and increased by 877.51%, 359.89%, 199.15%, 144.35%, and 108.11% in leaves, respectively.), and obviously promoted salt secretion capacity of the leaves, which especially promoted the secretion of Na+ (1.37 times). CONCLUSIONS: In summary, the exogenous addition of GB significantly enhances the salt tolerance of G. uralensis seedlings, promoting osmoregulatory substances, antioxidant enzyme activities, excess salt discharge especially the significant promotion of the secretion of Na+Future studies should aim to elucidate the molecular mechanisms that operate when GB regulates saline stress tolerance.

The structure of B-ARR reveals the molecular basis of transcriptional activation by cytokinin.

The phytohormone cytokinin has various roles in plant development, including meristem maintenance, vascular differentiation, leaf senescence, and regeneration. Prior investigations have revealed that cytokinin acts via a phosphorelay similar to the two-component system by which bacteria sense and respond to external stimuli. The eventual targets of this phosphorelay are type-B ARABIDOPSIS RESPONSE REGULATORS (B-ARRs), containing the conserved N-terminal receiver domain (RD), middle DNA binding domain (DBD), and C-terminal transactivation domain. While it has been established for two decades that the phosphoryl transfer from a specific histidyl residue in ARABIDOPSIS HIS PHOSPHOTRANSFER PROTEINS (AHPs) to an aspartyl residue in the RD of B-ARRs results in a rapid transcriptional response to cytokinin, the underlying molecular basis remains unclear. In this work, we determine the crystal structures of the RD-DBD of ARR1 (ARR1RD-DBD) as well as the ARR1DBD-DNA complex from Arabidopsis. Analyses of the ARR1DBD-DNA complex have revealed the structural basis for sequence-specific recognition of the GAT trinucleotide by ARR1. In particular, comparing the ARR1RD-DBD and ARR1DBD-DNA structures reveals that unphosphorylated ARR1RD-DBD exists in a closed conformation with extensive contacts between the RD and DBD. In vitro and vivo functional assays have further suggested that phosphorylation of the RD weakens its interaction with DBD, subsequently permits the DNA binding capacity of DBD, and promotes the transcriptional activity of ARR1. Our findings thus provide mechanistic insights into phosphorelay activation of gene transcription in response to cytokinin.

Maternal Effects of Habitats Induce Stronger Salt Tolerance in Early-Stage Offspring of Glycyrrhiza uralensis from Salinized Habitats Compared with Those from Non-Salinized Habitats.

(1) Wild Glycyrrhiza uralensis Fisch (licorice) seeds from different habitats are often mixed for cultivation. However, differences in the responses of seeds from different habitats to salt at the early-stage offspring stage are unclear. (2) Our objective was to evaluate the salt tolerance of G. uralensis germplasms by comparing differences in seed germination and seedling vigor in salinized (abandoned farmland and meadow) and non-salinized (corn farmland edge) soil habitats under different sodium chloride (NaCl) concentrations. (3) The germination rates and germination indexes of seeds from the two salinized habitats with 0-320 mmol·L-1 NaCl were higher and their germination initiation times were earlier. Only seeds from salinized habitats were able to elongate their germs at 240 mmol·L-1 NaCl. Seedlings from salinized habitats had higher fresh weights and relative water contents, while they exhibited lower accumulation of malondialdehyde and less cell electrolyte leakages. Under NaCl treatment, seedlings from the salinized habitats displayed higher superoxide dismutase, catalase, and peroxidase (SOD, CAT, and POD) activities and lower superoxide anion and hydrogen peroxide (O2- and H2O2) contents. Their comprehensive scores showed that the vigor of licorice seeds from salinized habitats was higher. (4) The salt tolerances of different wild G. uralensis seeds were different, and the offspring of licorice from salinized habitats had stronger early-stage salt tolerances.

Dracocephalum moldavica L.: An updated comprehensive review of its botany, traditional uses, phytochemistry, pharmacology, and application aspects.

Dracocephalum moldavica, known as Xiang-qing-lan (in Chinese), is a traditional folk medicine, which was commonly used by Mongolian and Xinjiang Uyghurs area. Dracocephalum moldavica has the effects of purging liver fire, clearing stomach heat, hemostasis. It is used for treating insufficient heart and blood, weakened brain function, weak feeling and spirit disease etc. This review aimed to summarize the botany, traditional uses, phytochemistry, pharmacology and application of Dracocephalum moldavica, which expected to provide theoretical support for future utilization and highlight the further investigation of this vital plant. In addition to the essential oil, approximately 154 compounds have been isolated and identified from aerial parts of the Dracocephalum moldavica, including flavonoids, terpenoids, lignans, phenylpropanoids, phenols, glycosides, polysaccharide and other compounds. Extensive pharmacological activities of the extracts or compounds of Dracocephalum moldavica in vivo and in vitro were confirmed including cardiovascular protection, antioxidative, antimicrobial, antifungal, anti-complementary and chronic mountain sickness. Moreover, Dracocephalum moldavica is used in a wide range of applications in food, biological pesticides and cosmetics. In the future, Dracocephalum moldavica needs further study, such as paying more attention to quality control, toxicity, pharmacological mechanism and pharmacokinetics.

ZLN005 improves the protective effect of mitochondrial function on alveolar epithelial cell aging by upregulating PGC-1α.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic and fatal pulmonary interstitial disease that usually occurs in the elderly. The senescence of alveolar epithelial cells (AECs) is an important mechanism of IPF. The AECs of patients with IPF have lower expression of peroxisome proliferator-activated receptor-γ coactivator-1 alpha (PGC-1α), which has been shown to play an important role in maintaining mitochondrial morphology and energy metabolism. This study sought to explore the mechanism by which ZLN005 improves mitochondrial function by upregulating PGC-1α to protect AECs from aging. Methods: Western blot was used to detect the expression of PGC-1α, mitochondrial synthesis protein nuclear respiratory factor-1 (NRF-1), and p21WAF1 in the lung tissue of the IPF patients and the mice with bleomycin (BLM)-induced pulmonary fibrosis. A549 cells and mice AEC2 cells were treated with hydrogen peroxide (H2O2) to construct cell senescence models. Cell senescence was detected by senescence-associated beta-galactosidase staining. The mitochondrial respiratory function was measured, including the adenosine triphosphate (ATP) generation, reactive oxygen species (ROS) level, changes in cell membrane potential, and energy metabolism. Using lentivirus as a vector and using gene editing technology to over express (upPGC-1α) and knockdown PGC-1α (shPGC-1α) in the A549 cells. The PGC-1α agonist ZLN005 was used to pretreat the A549 and shPGC-1α A549 cells, and cell aging and mitochondrial respiratory function were observed. Results: The Western blot and immunofluorescence assays showed that the expression of PGC-1α and NRF-1 was decreased in the lung tissues of the IPF patients and BLM-induced mice pulmonary fibrosis model, while the expression of p21WAF1 was increased. The results of the immunofluorescence and mitochondrial function experiments also indicated that the expression of PGC-1α and mitochondrial synthesis protein NRF-1 were decreased in the senescent cells. Further, the mitochondrial morphology was abnormal and the mitochondrial function was impaired. PGC-1α was involved in the AEC senescence by regulating mitochondrial morphology and function. Treatment with the agonist of PGC-1α (i.e., ZLN005) blocked the H2O2-induced cell senescence by enhancing the expression of PGC-1α. Conclusions: These results provide preliminary insights into the potential clinical application of ZLN005 as a novel therapeutic agent for the treatment of IPF.

Prenatal ultrasound diagnosis of congenital infantile fibrosarcoma and congenital hemangioma: Three case reports.

BACKGROUND: Congenital infantile fibrosarcoma (CIF) and congenital hemangioma (CH) have similarities on prenatal ultrasound and are rare. CASE SUMMARY: We report 3 cases of fetuses with superficial hypervascular tumors, confirmed by postnatal pathology as CIF (1 case) and CH (2 cases, including 1 in a twin fetus). In Case 1, a mass with a rich blood supply in the fetal axilla was discovered by prenatal ultrasound at 28+0 wk of gestation. The postpartum pathological diagnosis was CIF, the mass was surgically removed, and the prognosis of the child was good. In Case 2, at 23+1 wk of gestation, a mass was discovered at the base of the fetus's thigh on prenatal ultrasound. The postpartum pathological diagnosis was CH. After conservative treatment, the mass shrank significantly. Case 3 occurred in a twin fetus. At 30+0 wk of gestation, prenatal ultrasound revealed a bulging mass with a rich blood supply on the abdominal wall of one of the fetuses. Three weeks later, the affected fetus died, and the unaffected baby was successfully delivered by emergency cesarean section. The affected fetus was pathologically diagnosed with CH. CONCLUSION: Prenatal ultrasound can provide accurate information, such as the location, size and blood supply of a surface mass in a fetus. We found similarities between CIF and CH in prenatal ultrasound findings. Although it is difficult to distinguish these conditions by prenatal ultrasound alone, for superficial hypervascular tumors that rapidly increase in size in a short period, close ultrasound monitoring of the fetus is required to quickly address possible adverse outcomes.

Fast and Selective Luminescent Sensing by Langmuir-Schaeffer Films Based on Controlled Assembly of Perylene Bisimide Modified with A Cyclometalated AuIII Complex.

Condensed films of functional luminophores dominated by the magnitude and dimensionality of the intermolecular interactions play important roles in sensing performance. However, controlling the molecular assembly and regulating photophysical properties remain challenging. In this study, a new luminophore, ortho-PBI-Au, was synthesized by anchoring a cyclometalated alkynyl-gold(III) unit at the ortho-position of perylene bisimide. An unprecedented T-type packing model driven by weak Au-π interaction and Au-H bonds was observed, laying foundation for striking properties of the luminophore. Controlled assembly of ortho-PBI-Au at the air-water interface, realized using the classical Langmuir-Schaeffer technique, afforded the obtained luminescent films with different packing structures. With an optimized film, sensitive, selective, and rapid detection of a hazardous new psychoactive substance, phenylethylamine (PEA), was achieved. The detection limit, response time, and recovery time were <4 ppb, <1 s, and <5 s, respectively, surpassing the performance of the PEA sensors known thus far. The relationship between the characters of films and the sensing performance was systematically examined by grey relational analysis (GRA). The present study suggests that designing novel molecular aggregation with definite adlayer structure is a crucial strategy to enhance the sensing performance, which could be favorable for the film-based fluorescent sensors.

The Anxiolytic Effect of Polysaccharides from Stellariae Radix through Monoamine Neurotransmitters, HPA Axis, and ECS/ERK/CREB/BDNF Signaling Pathway in Stress-induced Male Rats.

BACKGROUND: Stellaria dichotoma L. var. lanceolata Bge. is renowned for its efficacy in "clearing deficiency heat" and represents a significant traditional Chinese medicine (TCM) resource. Modern pharmacology has demonstrated the anti-anxiety effects of Stellaria dichotoma L. var. lanceolata Bge. polysaccharides (SDPs). SDPs are one of the active constituents of Stellaria dichotoma L. var. lanceolata Bge. This study presents the first extraction of SDPs and investigates their potential molecular mechanisms and anxiolytic effects that are not previously reported. METHODS: First, SDPs were obtained by water extraction and alcohol precipitation and analyzed for their monosaccharide composition by high performance liquid chromatography (HPLC). Male SD rats were subjected to a two-week indeterminate empty bottle stress procedure and a three-day acute restraint stress procedure, during which diazepam (DZP) (1 mg/kg) and SDPs (50, 100 and 200 mg/kg, intragastrically) were administered. A number of behavioral tests, including the elevated plus maze test (EPM), the open field test (OFT) and the light/dark box test (LDB), were used to assess the anti-anxiety potential of SDPs. Serum levels of Corticosterone (CORT) and Adrenocorticotropic hormone (ACTH), as well as the levels of Dopamine (DA) and serotonin (5-HT) found in the hippocampus and frontal cortex, were quantified using commercially available enzyme-linked immunosorbent assay (ELISA) kits. In addition, protein levels of key proteins cAMP-response element binding protein (CREB), phospho-CREB (p-CREB), brain-derived neurotrophic factor (BDNF), ERK½, p-ERK½, and GAPDH expression in rat hippocampus were measured by Western blot analysis, and modulation of the endocannabinoid system was assessed by immunohistochemistry. RESULTS: Following administration of SDPs (50, 100, 200 mg/kg) and diazepam 1 mg/kg, anxiolytic activity was exhibited through an increase in the percentage of arm opening times and arm opening time of rats in the elevated plus maze. Additionally, there was an increase in the number of times and time spent in the open field center, percentage of time spent in the open box, and shuttle times in the LDB. Furthermore, tissue levels of DA and 5-HT were increased in the hippocampus and frontal cortex of rats after treatment with SDPs. In addition, SDPs significantly decreased serum levels of CORT and ACTH in rats. SDPs also effectively regulated the phosphorylation of the extracellular regulated protein kinases (ERK) and CREB-BDNF pathway in the hippocampus. Moreover, the expression levels of CB1 and CB2 proteins were heightened due to SDPs treatment in rats. CONCLUSIONS: The study verified that SDPs alleviate anxiety in the EBS and ARS. The neuroregulatory behavior is accomplished by regulating the Monoamine neurotransmitter, HPA axis, and ECB-ERK-CREB-BDNF signaling pathway.

Clinical significance of interleukin-6, total bilirubin, CD3 + CD4 + T cells counts in the acute exacerbation of connective tissue disease-associated interstitial lung disease: a cross-sectional study.

OBJECTIVE: Interstitial lung disease (ILD) is a severe complication of connective tissue disease (CTD) that can significantly impact patients' prognosis and quality of life. However, the current diagnostic arena lacks reliable biomarkers for detecting and monitoring the progression and exacerbation of CTD-ILD. This study aimed to investigate the clinical value of 12 serum cytokines in the diagnosis of CTD-ILD and prediction of the risk of acute exacerbation (AE) in this disease. METHODS: This study was a cross-sectional investigation. Ninety-one hospitalized CTD patients were allocated into two groups: CTD-ILD group (n = 61) and CTD-non-ILD group (n = 30), and 30 sex-age matched healthy volunteers were enrolled as controls. The serum concentrations of interferon (IFN)-α, IFN-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, and IL-1ß were measured by Luminex suspension arrays. Logistic regression was employed to determine the significance of variables in the occurrence of AE-CTD-ILD. A nomogram was constructed to visualize the independent variables. RESULTS: Elevated levels of IL-6, IL-8, and TNF-α were observed and compared in the CTD-ILD group with CTD-non-ILD (all P < 0.05). Similarly, the levels of IL-6, IL-8 and TNF-α were higher in the acute exacerbation (AE-CTD-ILD) group compared with stable CTD-ILD (S-CTD-ILD) (P < 0.001, P < 0.001, and P = 0.022). Significant correlations between serum IL-6 and PaO2/FiO2 ratio (r = - 0.463, P < 0.001), percent predicted forced vital capacity (FVC%; r = - 0.362, P < 0.05), and total ground-glass opacity (GGO) score (r = 0.439, P < 0.001) were observed in CTD-ILD patients. Multivariate logistic regression analysis revealed that elevated IL-6 levels, total bilirubin (TBil), and decreased CD3 + CD4 + T cells counts were independent risk factors for the occurrence of AE-CTD-ILD (OR = 1.121, P = 0.024; OR = 1.865, P = 0.047; OR = 0.983, P = 0.037, respectively). Furthermore, by employing these three variables in combination for the prediction of AE status, their collective impact surpasses the independent effects of any single biomarker. CONCLUSIONS: Elevated levels of serum IL-6, IL-8, and TNF-α were associated with the complication of ILD in CTD patients and the occurrence of AE in CTD-ILD patients. IL-6 could be a promising serum biomarker of severity and the occurrence of AE in CTD-ILD patients. The combination of the three variables (IL-6 level, TBil and CD3 + CD4 + T cells) predicted the AE-CTD-ILD better.

Comparative analysis of the effect of electromyogram to bispectral index and 95% spectral edge frequency under remimazolam and propofol anesthesia: a prospective, randomized, controlled clinical trial.

Background: Bispectral index (BIS), an index used to monitor the depth of anesthesia, can be interfered with by the electromyogram (EMG) signal. The 95% spectral edge frequency (SEF95) also can reflect the sedation depth. Remimazolam in monitored anesthesia care results in higher BIS values than propofol, though in the same sedation level assessed by Modified Observers Assessment of Alertness and Sedation (MOAA/S). Our study aims to illustrate whether EMG is involved in remimazolam causing higher BIS value than propofol preliminarily and to explore the correlations among BIS, EMG, and SEF95 under propofol and remimazolam anesthesia. Patients and methods: Twenty-eight patients were randomly divided into propofol (P) and remimazolam (RM) groups. Patients in the two groups received alfentanil 10 µg/kg, followed by propofol 2 mg/kg and remimazolam 0.15 mg/kg. Blood pressure (BP), heart rate (HR), and oxygen saturation (SpO2) were routinely monitored. The BIS, EMG, and SEF95 were obtained through BIS VISTATM. The primary outcomes were BIS, EMG, and the correlation between BIS and EMG in both groups. Other outcomes were SEF95, the correlation between BIS and SEF95, and the correlation between EMG and SEF95. And all the statistical and comparative analysis between these signals was conducted with SPSS 26.0 and GraphPad Prism 8. Results: BIS values, EMG, and SEF95 were significantly higher in the RM group than in the P group (all p < 0.001). There was a strong positive correlation between BIS and EMG in the RM group (r = 0.416). Nevertheless, the BIS in the P group showed a weak negative correlation with EMG (r = -0.219). Both P (r = 0.787) and RM group (r = 0.559) had a reasonably significant correlation coefficient between BIS and SEF95. SEF95 almost did not correlate with EMG in the RM group (r = 0.101). Conclusion: Bispectral index can be interfered with high EMG intensity under remimazolam anesthesia. However, EMG can hardly affect the accuracy of BIS under propofol anesthesia due to low EMG intensity and a weak negative correlation between EMG and BIS. Moreover, SEF95 may have a great application prospect in predicting the sedation condition of remimazolam.

CCNB1 is involved in bladder cancer pathogenesis and silencing CCNB1 decelerates tumor growth and improves prognosis of bladder cancer.

In search of an effective therapeutic target for bladder urothelial carcinoma (BLCA), the present study aimed to investigate the expression of cyclin B1 (CCNB1) and its putative mechanism in BLCA. BLCA sequencing data from Gene Expression Omnibus and The Cancer Genome Atlas were used to analyze expression of CCNB1 mRNA and high CCNB1 expression had a poorer prognosis compared with those with low expression. Immunohistochemistry (IHC) samples collected from the Human Protein Atlas database were analyzed for CCNB1 protein expression. Short hairpin (sh) CCNB1-transfected BLCA T24 and 5637 cells were used to investigate the effects of CCNB1 and inhibit the proliferation, migration and invasion of BLCA cells, affect the cell cycle distribution and promote apoptosis of 5637 cells. A sh-CCNB1 BLCA chicken embryo chorioallantoic membrane (CAM) transplantation model was established to observe the impacts of sh-CCNB1 on the tumorigenesis of BLCA in vivo. Analysis of sequencing data showed that CCNB1 mRNA was significantly elevated in tumor and BLCA compared with normal tissues [standardized mean difference (SMD)=1.21; 95% CI: 0.26-2.15; I²=95.9%]. IHC indicated that CCNB1 protein was localized in the nucleus and cytoplasm and was significantly increased in BLCA tumor tissues. The in vitro tests demonstrated that proliferation of T24 and 5637 cells transfected with sh-CCNB1 was significantly inhibited and cell migration and invasion ability were significantly decreased. sh-CCNB1 decreased the percentage of T24 cells in G0/G1, 5637 cells in the G0/G1 phase and S phase and increased percentage of 5637 cells in the G2/M phase and increased early apoptosis of 5637 cells. The in vivo experiments demonstrated that the mass of transplanted tumors was significantly decreased compared with the control group following silencing of CCNB1. The present results suggested that CCNB1 was involve in the development and prognosis of BLCA and silencing of CCNB1 may be a promising targeted therapy for BLCA.

Research progress and applications of colorful Brassica crops.

MAIN CONCLUSION: We review the application and the molecular regulation of anthocyanins in colorful Brassica crops, the creation of new germplasm resources, and the development and utilization of colorful Brassica crops. Brassica crops are widely cultivated: these include oilseed crops, such as rapeseed, mustards, and root, leaf, and stem vegetable types, such as turnips, cabbages, broccoli, and cauliflowers. Colorful variants exist of these crop species, and asides from increased aesthetic appeal, these may also offer advantages in terms of nutritional content and improved stress resistances. This review provides a comprehensive overview of pigmentation in Brassica as a reference for the selection and breeding of new colorful Brassica varieties for multiple end uses. We summarize the function and molecular regulation of anthocyanins in Brassica crops, the creation of new colorful germplasm resources via different breeding methods, and the development and multifunctional utilization of colorful Brassica crop types.

Bioinformatics Analysis of Programmed Cell Death in Spinal Cord Injury.

BACKGROUND: Programmed cell death (PCD) in the development of spinal cord injury (SCI) is complicated, including apoptosis, necroptosis, pyroptosis, ferroptosis, cuproptosis, and autophagy. It is necessary to make clear the expression levels of PCD and potential molecular targets after SCI for formulating relevant treatment strategies. METHODS: We downloaded the rats' SCI expression matrix GSE45006, and the ssGSEA method was used to analyze the PCD after SCI. Then the related differentially expressed genes (DEGs) were identified, and the gene ontology (GO) and pathway analysis, protein-protein interaction (PPI) network construction, and HUB genes were identified. Finally, the correlation between HUB genes and PCD was analyzed. RESULTS: Apoptosis, necroptosis, pyroptosis, ferroptosis, and autophagy increased significantly in acute SCI, and then decreased gradually in the subacute and chronic stages; cuproptosis in acute SCI decreased significantly, and then gradually increased. In addition, we also screened 116 DEGs during the development of SCI. GO and pathway analysis showed that DEGs was related to mitosis and cell cycle. The identified hub genes are closely related to cell apoptosis, necroptosis, pyroptosis, ferroptosis after injury, and autophagy. CONCLUSIONS: PCD occurs differently in different stages after SCI. To inhibit apoptosis, necroptosis, pyroptosis, and ferroptosis after injury and induce autophagy may be the therapeutic strategy. In addition, intervention therapy based on related HUB genes may be the therapeutic target of SCI.

Mapping and Identifying Candidate Genes Enabling Cadmium Accumulation in Brassica napus Revealed by Combined BSA-Seq and RNA-Seq Analysis.

Rapeseed has the ability to absorb cadmium in the roots and transfer it to aboveground organs, making it a potential species for remediating soil cadmium (Cd) pollution. However, the genetic and molecular mechanisms underlying this phenomenon in rapeseed are still unclear. In this study, a 'cadmium-enriched' parent, 'P1', with high cadmium transport and accumulation in the shoot (cadmium root: shoot transfer ratio of 153.75%), and a low-cadmium-accumulation parent, 'P2', (with a cadmium transfer ratio of 48.72%) were assessed for Cd concentration using inductively coupled plasma mass spectrometry (ICP-MS). An F2 genetic population was constructed by crossing 'P1' with 'P2' to map QTL intervals and underlying genes associated with cadmium enrichment. Fifty extremely cadmium-enriched F2 individuals and fifty extremely low-accumulation F2 individuals were selected based on cadmium content and cadmium transfer ratio and used for bulk segregant analysis (BSA) in combination with whole genome resequencing. This generated a total of 3,660,999 SNPs and 787,034 InDels between these two segregated phenotypic groups. Based on the delta SNP index (the difference in SNP frequency between the two bulked pools), nine candidate Quantitative trait loci (QTLs) from five chromosomes were identified, and four intervals were validated. RNA sequencing of 'P1' and 'P2' in response to cadmium was also performed and identified 3502 differentially expressed genes (DEGs) between 'P1' and 'P2' under Cd treatment. Finally, 32 candidate DEGs were identified within 9 significant mapping intervals, including genes encoding a glutathione S-transferase (GST), a molecular chaperone (DnaJ), and a phosphoglycerate kinase (PGK), among others. These genes are strong candidates for playing an active role in helping rapeseed cope with cadmium stress. Therefore, this study not only sheds new light on the molecular mechanisms of Cd accumulation in rapeseed but could also be useful for rapeseed breeding programs targeting this trait.

Genetic Diversity and Population Differentiation of a Chinese Endangered Plant Ammopiptanthus nanus (M. Pop.) Cheng f.

Ammopiptanthus nanus (M. Pop.) Cheng f. is a very important resource plant that integrates soil and water conservation, afforestation of barren mountains, and ornamental, medicinal, and scientific research functions and is also a critically endangered plant in China, remaining in only six small fragmented populations in the wild. These populations have been suffering from severe anthropomorphic disturbances, causing further losses in genetic diversity. However, its genetic diversity level and genetic differentiation degree among the fragmented populations are still unclear. Inthis study, DNA was extracted from fresh leaves from the remnant populations of A. nanus, and the inter-simple-sequence repeat (ISSR) molecular marker system was used to assess its level of genetic diversity and differentiation. The result was that its genetic diversity is low at both species and population levels, with only 51.70% and 26.84% polymorphic loci, respectively. The Akeqi population had the highest genetic diversity, whereas the Ohsalur and Xiaoerbulak populations had the lowest. There was significant genetic differentiation among the populations, and the value of the genetic differentiation coefficient (Gst) was as high as 0.73, while the gene flow value was as low as 0.19 owing to spatial fragmentation and a serious genetic exchange barrier among the populations. It is suggested that a nature reserve and germplasm banks should be established as soon as possible for elimination of the anthropomorphic disturbances, and mutual introductions between the populations and introduced patches of the species, such as with habitat corridors or stepping stones, should be performed simultaneously to improve the genetic diversity of the isolated populations for the conservation of this plant.