Characterization and transformation of TtMYB1 transcription factor from Tritipyrum to improve salt tolerance in wheat.

BACKGROUND: Common wheat (Triticum aestivum L.) is a worldwide cereal crop, which is an integral part of the diets of many countries. In addition, the MYB gene of wheat plays a role in the response to salt stress. RESULTS: "Y1805" is a Tritipyrum variety that is relatively tolerant to salt. We used transcriptome analysis to show that the "Y1805" MYB gene was both highly expressed and sensitive to salt stress. Compared with control roots, the level of MYB expression during salt stress was higher, which rapidly decreased to control levels during the recovery process. MYB gene relative expression showed the highest levels in "Y1805" roots during salt stress, with the stems and then leaves being the next highest stressed tissues. The novel MYB gene (TtMYB1) was successfully cloned from "Y1805". It showed a coding sequence length of 783 bp with 95.79% homology with Tel2E01G633100 from Thinopyrum elongatum. TtMYB1 and MYB from Th. elongatum were clustered in the same branch using phylogenetic analysis, which indicated high similarities. The TtMYB1 gene is located in the nucleus. The coleoptile method was employed when a TtMYB1 overexpression vector was used during transformation into "1718" (common wheat). Under high salt stress, TtMYB1 leaves of overexpression lines had decreased wilting, when compared with wild-type (WT) plants. During normal conditions, salt stress, and recovery, the lengths of the roots and the heights of seedlings from the overexpression lines were found to be significantly greater than roots and seedlings of WT plants. In addition, during high salt stress, the overexpression lines showed that proline and soluble sugar levels were higher than that of WT plants, but with lower malondialdehyde levels. Forty-three proteins that interacted with TtMYB1 were identified using the yeast two-hybrid assay. Protein-protein interaction analyses indicated that most were SANT domain-containing and Wd repeat region domain-containing proteins. Among these proteins, ribosomal proteins were the main node. Abiotic stress-related terms (such as "carbonate dehydratase activity", "protein targeting peroxisomes", and "glutathione peroxidase activity") were enriched in GO analysis. In KEGG analysis, "carbohydrate metabolism", "environmental information processing", "genetic information processing", "signaling and cell precursors", and "energy metabolism" pathways were enriched. CONCLUSION: The TtMYB1 gene might enhance salt tolerance by increasing proline and soluble sugar content and antioxidase activity in transgenic wheat. It therefore has the potential to enhance high salt tolerance in plants.

Genome-wide analysis of the Tritipyrum NAC gene family and the response of TtNAC477 in salt tolerance.

NAC transcription factors are widely distributed in the plant kingdom and play an important role in the response to various abiotic stresses in plant species. Tritipyrum, an octoploid derived from hybridization of Triticum aestivum (AABBDD) and Thinopyrum elongatum (EE), is an important genetic resource for integrating the desirable traits of Th. elongatum into wheat. In this study, we investigated the tissue distribution and expression of Tritipyrum NAC genes in the whole genomes of T. aestivum and Th. elongatum after obtaining their complete genome sequences. Based on phylogenetic relationships, conserved motifs, gene synthesis, evolutionary analysis, and expression patterns, we identified and characterized 732 Tritipyrum NAC genes. These genes were divided into six main groups (A, B, C, D, E, and G) based on phylogenetic relationships and evolutionary studies, with members of these groups sharing the same motif composition. The 732 TtNAC genes are widely distributed across 28 chromosomes and include 110 duplicated genes. Gene synthesis analysis indicated that the NAC gene family may have a common ancestor. Transcriptome data and quantitative polymerase chain reaction (qPCR) expression profiles showed 68 TtNAC genes to be highly expressed in response to various salt stress and recovery treatments. Tel3E01T644900 (TtNAC477) was particularly sensitive to salt stress and belongs to the same clade as the salt tolerance genes ANAC019 and ANAC055 in Arabidopsis. Pearson correlation analysis identified 751 genes that correlated positively with expression of TtNAC477, and these genes are enriched in metabolic activities, cellular processes, stimulus responses, and biological regulation. TtNAC477 was found to be highly expressed in roots, stems, and leaves in response to salt stress, as confirmed by real-time PCR. These findings suggest that TtNAC477 is associated with salt tolerance in plants and might serve as a valuable exogenous gene for enhancing salt tolerance in wheat.

Association between oxidative balance scores and severe abdominal aortic calcification in American adults: National health and nutrition examination survey.

BACKGROUND AND AIM: Abdominal aortic calcification (AAC) is a key predictor of cardiovascular diseases (CVDs). The Oxidative Balance Score (OBS) served as a tool to evaluate the systemic status of oxidative stress. However, evidence on the link between OBS and severe abdominal aortic calcification (SAAC) is currently inadequate. This study aims to establish this correlation in the US adult population, contributing valuable insights to the understanding of cardiovascular health. METHODS AND RESULTS: In our study with 2745 participants from the 2013-2014 National Health and Nutrition Examination Survey (NHANES), we analyzed both OBS and AAC score data. Logistic regression and smooth curve fitting were used to investigate the relationship between OBS and SAAC. The overall prevalence of severe abdominal aortic calcification disease was 9.1%. Multivariable logistic regression revealed that higher oxidative balance scores were associated with a lower risk of SAAC. After adjusting for potential confounders (model III), for every 1-point increase in oxidative balance scores, the odds of SAAC decreased by 3% [OR = 0.97, 95% CI= (0.95,0.99), P = 0.03]. The dose-response relationship demonstrated a negative correlation between oxidative balance scores and SAAC (p for nonlinear = 0.368). CONCLUSIONS: This study reveals a negative association between oxidative balance scores and severe abdominal aortic calcification in US adults. The implications of these findings merit careful consideration and should be taken into account in the formulation of clinical guidelines and updates.

Genome-wide analysis of the AP2/ERF gene family in Tritipyrum and the response of TtERF_B2-50 in salt-tolerance.

The AP2/ERF transcription factor is widely distributed across the plant kingdom and plays a crucial role in various abiotic stress responses in plants. Tritipyrum, an octoploid resulting from an intergeneric cross between Triticum aestivum (AABBDD) and Thinopyrum elongatum (EE), is a valuable source of germplasm for incorporating superior traits of Th. elongatum into T. aestivum. With the recent availability of whole -genome sequences for T. aestivum and Th. elongatum, we explored the organization and expression profiling of Tritipyrum AP2/ERF genes across the entire genome. Our investigation identified 543 Tritipyrum AP2/ERF genes, which evolutionary analysis categorized into four major groups (AP2, DREB, ERF, and RAV), whose members share a conserved motif composition. These 543 TtAP2/ERF genes were distributed throughout 28 chromosomes, with 132 duplications. Synteny analysis suggests that the AP2/ERF gene family may have a common ancestor. Transcriptome data and Real-Time PCR expression profiles revealed 43 TtAP2/ERF genes with high expression levels in response to various salt stressors and recovery regimens. Tel2E01T236300 (TtERF_B2-50) was particularly salt stress-sensitive and evolutionarily related to the salt-tolerant gene AtERF7 in A. thaliana. Pearson correlation analysis identified 689 genes positively correlated (R > 0.9) with TtERF_B2-50 expression, enriched in metabolic activities, cellular processes, stimulus response, and biological regulation. Real-time PCR showed that TtERF_B2-50 was highly expressed in roots, stems, and leaves under salt stress. These findings suggest that TtERF_B2-50 may be associated with salt stress tolerance and may serve as a valuable foreign gene for enhancing salt tolerance in wheat.

Transcriptome analysis of Auricularia fibrillifera fruit-body responses to drought stress and rehydration.

BACKGROUND: Drought stress severely restricts edible fungus production. The genus Auricularia has a rare drought tolerance, a rehydration capability, and is nutrient rich. RESULTS: The key genes and metabolic pathways involved in drought-stress and rehydration were investigated using a transcriptome analysis to clarify the relevant molecular mechanisms. In total, 173.93 Mb clean reads, 26.09 Gb of data bulk, and 52,954 unigenes were obtained. Under drought-stress and rehydration conditions, 14,235 and 8539 differentially expressed genes, respectively, were detected. 'Tyrosine metabolic', 'caffeine metabolism', 'ribosome', 'phagosome', and 'proline and arginine metabolism', as well as 'peroxisome' and 'mitogen-activated protein kinase signaling' pathways, had major roles in A. fibrillifera responses to drought stress. 'Tyrosine' and 'caffeine metabolism' might reveal unknown mechanisms for the antioxidation of A. fibrillifera under drought-stress conditions. During the rehydration process, 'diterpenoid biosynthesis', 'butanoate metabolism', 'C5-branched dibasic acid', and 'aflatoxin biosynthesis' pathways were significantly enriched. Gibberellins and γ-aminobutyric acid were important in the recovery of A. fibrillifera growth after rehydration. Many genes related to antibiotics, vitamins, and other health-related ingredients were found in A. fibrillifera. CONCLUSION: These findings suggested that the candidate genes and metabolites involved in crucial biological pathways might regulate the drought tolerance or rehydration of Auricularia, shedding light on the corresponding mechanisms and providing new potential targets for the breeding and cultivation of drought-tolerant fungi.

Whole-exome sequencing identified novel variants in three Chinese Leigh syndrome pedigrees.

Leigh syndrome (LS), the most common mitochondrial disease in early childhood, usually manifests variable neurodegenerative symptoms and typical brain magnetic resonance imaging (MRI) lesions. To date, pathogenic variants in more than 80 genes have been identified. However, there are still many cases without molecular diagnoses, and thus more disease-causing variants need to be unveiled. Here, we presented three clinically suspected LS patients manifesting neurological symptoms including developmental delay, hypotonia, and epilepsy during the first year of age, along with symmetric brain lesions on MRI. We explored disease-associated variants in patients and their nonconsanguineous parents by whole-exome sequencing and subsequent Sanger sequencing verification. Sequencing data revealed three pairs of disease-associated compound heterozygous variants: c.1A>G (p.Met1?) and 409G>C (p.Asp137His) in SDHA, c.1253G>A (p.Arg418His) and 1300C>T (p.Leu434Phe) in NARS2, and c.5C>T (p.Ala2Val) and 773T>G (p.Leu258Trp) in ECHS1. Among them, the likely pathogenic variants c.409G>C (p.Asp137His) in SDHA, c.1300C>T (p.Leu434Phe) in NARS2, and c.773T>G (p.Leu258Trp) in ECHS1 were newly identified. Segregation analysis indicated the possible disease-causing nature of the novel variants. In silico prediction and three-dimensional protein modeling further suggested the potential pathogenicity of these variants. Our discovery of novel variants expands the gene variant spectrum of LS and provides novel evidence for genetic counseling.

Efficacy and safety of triplet chemotherapy plus anti-EGFR agents in metastatic colorectal cancer: a systematic review and meta-analysis.

BACKGROUND: To date, the optimal treatment for potentially resectable metastatic colorectal cancer (mCRC) patients has yet to be determined. Encouraging results have been reported in studies exploring the efficacy of triplet chemotherapy plus anti-epidermal growth factor receptor (anti-EGFR) target agents. Thus, we conducted a meta-analysis to evaluate the efficacy and safety of triplet chemotherapy plus anti-EGFR target agents. METHODS: We systematically searched the PubMed, Embase, and Web of Science databases from December 2004 to October 2021 for studies examining the efficacy of triplet chemotherapy plus anti-EGFR target agents in mCRC patients. The primary outcomes were the objective response rate (ORR) and R0 resection rate (R0RR), and the secondary outcomes were median progression-free survival (mPFS), median overall survival (mOS), and toxicity. Data were analyzed with R software 4.1.2. RESULTS: Fourteen studies comprising 762 patients with mCRC were included in this meta-analysis. Analysis with a random effects model revealed that after treatment with triplet chemotherapy plus anti-EGFR target agents, the pooled ORR was 82% (95% CI= 76-88%, I2= 76%), and the pooled R0RR of colorectal liver metastasis (CLM) was 59% (95% CI= 49-68%, I2= 60%). The mPFS ranged from 9.5 to 17.8 months, and the mOS ranged from 24.7 to 62.5 months. A total of 648 grade 3 or 4 adverse events were reported; the most commonly reported events were diarrhea (174/648), neutropenia (157/648), and skin toxicity (95/648), which had pooled prevalence rates of 29% (95% CI= 20-39%, I2= 84%), 28% (95% CI= 20-37%, I2= 77%), and 17% (95% CI= 11-24%, I2= 66%), respectively. CONCLUSIONS: Triplet chemotherapy plus anti-EGFR agents therapy seems to be capable of increasing the ORR of mCRC patients and the R0RR of CLM patients. The toxicity of this treatment is manageable. High-quality randomized controlled trial (RCT) studies are required for further validation.

The IgE Blocking Activity Induced by Dermatophagoides pteronyssinus Subcutaneous Immunotherapy Does Not Correlate with Specific IgA but with IgG4 in both Serum and Saliva.

BACKGROUND: The role of salivary-specific IgG4 and IgA in subcutaneous immunotherapy (SCIT) is not well defined. We aimed to investigate the change of IgG4 and IgA in both serum and saliva and their correlations with IgE-blocking-factor (IgE-BF) during SCIT. METHOD: 307 Dermatophagoides pteronyssinus (DP) allergic rhinitis and/or asthma patients were recruited for this study. 286 patients received DP-SCIT for 1 year. Twenty-one patients received only symptomatic treatment. DP-, Der p 1-, and Der p 2-specific IgE in serum, specific-IgG4 and Der p 2-specific IgA1 and IgA2 in both serum and saliva were measured at timepoints 0, 4, and 12 months during DP-SCIT. Correlation between salivary and serological IgG4, IgA, and their correlation with DP-specific IgE-BF measured in serum was evaluated. RESULTS: During DP-SCIT, the allergen-specific IgG4 in both saliva and serum increased and correlated significantly, the correlation becomes stronger over the treatment time. DP-specific IgE-BF significantly correlated with DP-specific IgG4 in serum (p < 0.0001) at different timepoints and in saliva at 12 months of SCIT (p < 0.01). No change in Der p 2-specific IgA during DP-SCIT was observed, and the IgA in serum did not correlate with IgA in saliva. There was no correlation between DP IgE-BF and Der p 2-specific IgA in serum or saliva. The control group did not exhibit significant changes in any antibody level measured. CONCLUSION: The IgE blocking activity induced by DP-SCIT treatment correlated with specific IgG4 and not IgA. The IgG4 in saliva correlates with serum IgG4 and can be an alternative immunological marker beyond 1 year of SCIT treatment.

Common and distinctive electrocardiographic characteristics and effective catheter ablation of idiopathic ventricular arrhythmias originating from different areas of ventricular septum adjacent to atrioventricular annulus.

OBJECTIVE: To investigate electrocardiographic (ECG) characteristics and radiofrequency catheter ablation (RFCA) efficacy for premature ventricular complexes (PVCs) and idiopathic ventricular tachycardias (IVTs) originating from ventricular septum areas adjacent to atrioventricular annulus (VS-AVA). METHODS: Among 1,505 consecutive PVCs/IVTs cases, 106 (7.04%) were confirmed as origin of VS-AVA guided by both fluoroscopy and three-dimensional mapping system during RFCA. Characteristics of surface 12-lead ECG were analyzed. RESULTS: The overall success rate for RFCA of PVCs/IVTs originating from VS-AVA was 82.08% (87/106), common ECG characteristics were: mainly positive R wave on lead I; dominant-positive R on aVL (91/106, 85.85%) for most, r (1/106, 0.94%) or qr (14/106, 13.21%) in few; QS or qs on aVR; and decreasing R wave amplitude and increasing S wave depth on II, III, and aVF from superior to inferior septum; and S wave on at least one inferior lead (generally III). Distinctive ECG features were: precordial transition zone before or after V2 for septum adjacent to mitral (MA, 19/19, 100.0%) or tricuspid (TA, 74/87,85.05%) annulus origin; initial r wave and rS on V1 for superior septum near TA (above His bundle) origin (9/10, 90.0%) with no initial r wave for most other origins; and QS on V1 for mid-inferior septum near TA origin (73/77, 94.81%) and QR (Qr, qR or qr) on V1 for septum near MA origin (17/19, 89.47%). CONCLUSION: Distinctive ECG characteristics of PVCs/IVTs originating from VS-AVA aid in origin localization guiding effective RFCA.

Knowledge of cervical cancer and Pap smear among Uyghur women from Xinjiang, China.

BACKGROUND: Cervical cancer is a significant public health issue in Xinjiang China. In order to provide scientific basis for cervical cancer intervention in Xinjiang, women's knowledge of cervical cancer was investigated in this study. Besides, relations between Uyghur women's awareness and their age, educational background, yearly household were evaluated. METHODS: Questionnaire survey was conducted to 7100 Uyghur women from Karkax Hotan and Payzivat Kashgar during 2008 and 2009. Women aged 21 to 70 years, had sexual activity, no history of cervical lesion or cervical cancer were considered to be eligible to the study. Information include participants' socio-demographic background, personal data, awareness about Pap smear, about cervical cancer and HPV, sources of information acquisition was investigated. RESULTS: 65.1% of the 7100 respondents with primary education level, and 95.0% participants were farmers. Only 7.4% had undertaken Pap smears before, not aware of the importance of the test (97.4% of 7100) was the main reason for not performing Pap smears. 29.3% of total participants had heard about cervical cancer, and only 0.14% (10 out of 7100) had heard about HPV. Top three route of knowledge acquire were television advertises (39.1%), neighbors (21.0%) and health care providers (15.0%). Women younger than 40 years, with higher educational levels and higher income had better awareness of cervical cancer and more willing to accept regular Pap smears. CONCLUSIONS: Uyghur women in Xinjiang had poor knowledge of cervical cancer and HPV infection. Low awareness of women was associated with less household income and lower educational levels. TV shows and education from health care providers may increase women's participation in cervical cancer control and prevention.

Icariin Attenuates Human Renal Tubular Epithelial Cell Senescence by Targeting PAK2 via miR-23b-3p.

BACKGROUND: Renal tubular epithelial cells (RTECs) senescence is crucial in kidney diseases. Icariin is shown to have protective effects against renal fibrosis, acute kidney injury, and proteinuria. We aimed to explore the role of icariin in protecting RTECs from senescence and the underlying mechanism involved. METHODS: An in vitro model of RTEC senescence was established by incubating HK-2 cells with urine exosomes from patients with diabetic kidney disease. Stimulated cells were treated with icariin at various doses to evaluate the compound's therapeutic effects. After RNA transfection, cell cycle arrest and senescence, flow cytometry, and SA-ß-Gal staining were analyzed. At the same time, quantitative real-time PCR examined microRNA expression. Biochemical assays. RESULTS: Urine exosomes induced senescence and cell cycle arrest in the G1 stage in HK-2 cells, which were inhibited by icariin. Urine exosome stimulation up-regulated miR-23b-3p expression, which in turn suppressed PAK2 expression. Significantly, the induced and inhibited miR- 23b-3p expressions weakened and augmented the resistance of cells against urine exosome stimulation, respectively, while PAK2 overexpression provided additional protection. Icariin suppressed miR-23b-3p expression, and miR-23b-3p induction blocked the effects of icariin and promoted RTEC senescence. CONCLUSION: miR-23b-3p and PAK2 form a signaling axis that regulates RTEC senescence upon urine exosome stimulation. Icariin can increase the resistance of RTECs against senescence via miR-23b-3p/PAK2. Our findings shed light on the mechanism of the clinical effects of icariin on renal diseases, which can be exploited to develop effective drugs targeting RTEC senescence in the future.

ADAM9 deubiquitination induced by USP22 suppresses proliferation, migration, invasion, and epithelial-mesenchymal transition of trophoblast cells in preeclampsia.

INTRODUCTION: The dysregulation of deubiquitination has been shown to affect the development of pre-eclampsia (PE). A disintegrin and metalloprotease 9 (ADAM9) plays roles in diverse physiological contexts, including PE. Here, this study aimed to investigate whether ADAM9 regulated trophoblast cell dysfunction through ubiquitin-specific protease 22 (USP22) deubiquitinase-mediated deubiquitination during PE. METHODS: Levels of genes and proteins were tested via qRT-PCR and western blotting assays. Cell proliferation, migration, and invasion were detected using cell counting kit-8, 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, transwell and wound healing assays, respectively. Epithelial-mesenchymal transition related markers were assayed using western blotting. Proteins between USP22 and ADAM9 were identified by co-immunoprecipitation assay. RESULTS: ADAM9 was highly expressed in PE patients, functionally, ADAM9 overexpression weakened the proliferation, migration, invasion, and EMT progression in trophoblast cells. Mechanistically, the deubiquitinase USP22 removed ubiquitination on ADAM9 and maintained its stability. Forced expression of USP22 also suppressed the proliferation and mobility in trophoblast cells. Moreover, the regulatory effects of USP22 on trophoblast cells were reversed by ADAM9 silencing. In addition, USP22 interacted with ADAM9 to regulate the activation of Wnt/ß-catenin pathway. DISCUSSION: ADAM9 was deubiquitinated and stabilized by USP22 and then suppressed the proliferation, migration, invasion, and EMT progression in trophoblast cells, indicating a new pathway of USP10/RUNX1 axis in PE process.

Depression exacerbates myocardial ischemia-reperfusion injury in mice via CNR2 gene and MIF-AMPK signaling pathway.

BACKGROUND: Myocardial ischemia-reperfusion(I/R)injury constitute the fundamental pathophysiology of acute myocardial infarction (AMI). Ischemic heart releases macrophage migration inhibitory factor (MIF), which activates MIF- AMPK signaling pathway. Depression is a significant risk factor for AMI. In a state of depression, peripheral expression of cannabinoid receptor 2 (CNR2) genes was downregulated. AIMS: We investigated the mechanism by which depression exacerbates myocardial I/R injury through the CNR2 and MIF-AMPK signaling pathways. METHODS: We established mouse models of depression and myocardial I/R. Left ventricular function was assessed using cardiac ultrasound and TTC staining. The protein levels of myocardial CNR2, MIF, AMPK, and ACC were determined by Western blot, while the expression level of CNR2 was measured using RT-qPCR. Additionally, MIF content in peripheral blood was quantified using ELISA. RESULTS: After I/R, the expression level of CNR2 was found to be lower in the depression group, leading to a deterioration in left heart function. Depressed mice exhibited lower secretion of MIF, accompanied by a decrease in the activation of the MIF-AMPK signaling pathway. However, injection of CNR2 agonist JWH133 prior to ischemia increased the activation of the MIF-AMPK signaling pathway, while CNR2 inhibitor AM630 decreased the activation. LIMITATIONS: Further research is needed to investigate the specific neuroendocrine mechanism affecting myocardial CNR2 expression in depression. And these experimental conclusions require further verification at the cellular level. CONCLUSIONS: The activation of CNR2 in myocardium following I/R is impeded by depression, thereby exacerbating myocardial I/R injury through attenuation of the MIF-AMPK signaling pathway activation.

Resection of the tumor in the trigone of the lateral ventricle via the contralateral posterior interhemispheric transfalcine transprecuneus approach with multi-modern neurosurgery technology: a case report.

Choroid plexus papilloma (CPP) is a rare benign intracranial tumor origin that predominantly manifests in the lateral ventricle in children, accounting for 0.3%-0.6% of all primary intracranial tumors. It is extremely rare to have the CPP in the trigone of the lateral ventricle through the contralateral posterior interhemispheric transfalcine transprecuneus approach (PITTA). Herein, we report this rare case. A 7-year-old girl presented with headache. Magnetic resonance imaging of the brain showed periatrial lesions, and histopathological examination confirmed CPP (WHO grade I). The contralateral PITTA is a safe, effective, reasonable, and appropriate for some lesions in the trigone of the lateral ventricle. It provides a wider surgical angle (especially for the lateral extension) and reduces the risk of disturbance of the optic radiation compared with the conventional approaches. The use of multiple modern neurosurgical techniques, including interventional embolization, intraoperative navigation, microscope, and electrophysiological monitoring, make the procedure much easier and more accurate, and the neuroendoscope adds to the visualization of the microscope and can reduce surgical complications.

USP8 targeted by Mir-874-3p promotes trophoblastic cell invasion by stabilizing the expression of ENaC on trophoblast membrane.

The aim of this study was to investigate the role of ubiquitin-specific peptidase 8 (USP8) in human trophoblast cells and its molecular mechanism. Based on the GSE30186 dataset, USP8 was identified as a downregulated gene in pre-eclampsia (PE). Analysis of clinical samples also revealed that USP8 expression at both the mRNA and protein levels in placental tissue from patients with PE was significantly lower than that from healthy pregnant women. Plate clone formation, scratch-wound healing, Transwell, tubule formation, and western blot assays collectively revealed that USP8 overexpression promoted the proliferation, migration, invasion, and pro-angiogenesis function of trophoblast cells, while USP8 knockdown induced the opposite effects. Bioinformatics analysis and luciferase reporter assay results indicated that the 3' untranslated region of USP8 was targeted by miR-874-3p. USP8 expression in the placental tissue of patients with PE was significantly lower than that of healthy pregnant women. USP8 actively regulated the growth and invasion of human trophoblast cells and stabilized the epithelial sodium channel (ENaC) on the cell membrane. MiR-874 targeted USP8 in the trophoblast cells and upregulation of miR-874-3p resulted in a decrease in the proliferation, migration, invasion, and pro-angiogenesis ability of trophoblast cells. These results indicate that USP8 can reverse the above mentioned negative effects of miR-874-3p on trophoblast cells. USP8 targeted by miR-874-3p facilitates the invasion of trophoblastic cells by stabilizing the expression of the ENaC, which may be a possible therapeutic target for PE.

Characterization and transformation of the CabHLH18 gene from hot pepper to enhance waterlogging tolerance.

Basic helix-loop-helix (bHLH) proteins are important in abiotic stress control. Here, a specific bHLH transcription factor gene, CabHLH18, from a strong waterlogging-tolerant pepper cultivar, 'ZHC2', was successfully cloned. The CabHLH18 gene presented a coding sequence length of 1,056 bp, encoding 352 amino acids, and the protein was the closest to Capsicum annuum XM016694561.2 protein. The CabHLH18 protein was located in the nucleus. The transformation of the CabHLH18 overexpression vector into the plumules of hot peppers, 'DFZJ' and 'ZHC1', exhibited 21.37% and 22.20% efficiency, respectively. The root length, plant height, and fresh weight of the 'DFZJ' overexpression lines were greater than those of wild-type (WT) plants under waterlogging conditions. Compared with the WT plants, the overexpression lines generally showed greater contents of water, the amino acid, proline, soluble sugar, root viability, and superoxide dismutase activity, but lower malondialdehyde content under waterlogging conditions. Plant fresh weight, amino acids, proline, and soluble sugar levels of the overexpression lines were 39.17%, 45.03%, 60.67%, and 120.18% greater, respectively, compared with the WT plants at 24 h after waterlogging stress. Therefore, the CabHLH18 gene could be implicated in conferring waterlogging tolerance in hot peppers and holds promise for enhancing their overall waterlogging tolerance.

A prognostic nomogram for predicting overall survival in colorectal mucinous adenocarcinoma patients based on the SEER database.

A nomogram was constructed to predict the survival of patients with colorectal mucinous adenocarcinoma based on data extracted from the Surveillance, Epidemiology and End Result (SEER) database. Data collected between 2010 and 2018 were obtained from the SEER database. The log-rank test and multivariate Cox regression were performed to identify the independent prognostic factors for overall survival, which were further used to construct a nomogram model to predict 1-, 3-, and 5-year overall survival. In total, 10846 patients diagnosed with colorectal mucinous adenocarcinoma were enrolled in the study. The following 11 variables were associated with survival and were further incorporated into the nomogram: age at diagnosis, primary site, grade, tumour size, lymph node dissection, T stage, N stage, M stage, surgery for primary site, chemotherapy, and household income. The concordance index (C-index) value was 0.725 (95% confidence interval 0.716-0.734), and the receiver operating characteristic curves and calibration curves showed satisfactory predictive accuracy. Both the C-index and time-independent area under the curve values were greater than those of the American Joint Committee on Cancer 7th TNM classification system (both P < 0.001). In the validation group, the results were consistent with those of the training group, with a C-index value of 0.726 (95% confidence interval 0.713-0.739). This study constructed a practical nomogram to predict 1-, 3-, and 5-year OS for patients with colorectal colorectal mucinous adenocarcinoma based on SEER data.

Efficacy and Safety of Esketamine for Supplemental Analgesia During Elective Cesarean Delivery: A Randomized Clinical Trial.

Importance: Epidural anesthesia is a primary choice for cesarean delivery, but supplemental analgesics are often required to relieve pain during uterine traction. Objective: To investigate the sedative and analgesic effects of intravenous esketamine administered before childbirth via cesarean delivery with the patient under epidural anesthesia. Design, Setting, and Participants: This multicenter, double-blind randomized clinical trial assessed 903 women 18 years or older who had full-term single pregnancy and were scheduled for elective cesarean delivery with epidural anesthesia in 5 medical centers in China from September 18, 2021, to September 20, 2022. Intervention: Patients were randomized to receive intravenous injection of 0.25 mg/kg of esketamine or placebo before incision. Main Outcomes and Measures: The coprimary outcomes included scores on the numeric rating scale of pain (an 11-point scale, with 0 indicating no pain and 10 indicating the worst pain; a difference of ≥1.65 points was clinically meaningful) and Ramsay Sedation Scale (a 6-point scale, with 1 indicating restlessness and 6 indicating deep sleep without response; a difference of ≥2 points was clinically meaningful) immediately after fetal delivery. Secondary outcomes included neonatal Apgar score assessed at 1 and 5 minutes after birth. Results: A total of 600 women (mean [SD] age, 30.7 [4.3] years) were enrolled and randomized; all were included in the intention-to-treat analysis. Immediately after fetal delivery, the score on the numeric rating scale of pain was lower with esketamine (median [IQR], 0 [0-1]) than with placebo (median [IQR], 0 [0-2]; median difference, 0; 95% CI, 0-0; P = .001), but the difference was not clinically important. The Ramsay Sedation Scale scores were higher (sedation deeper) with esketamine (median [IQR], 4 [3-4]) than with placebo (median [IQR], 2 [2-2]; median difference, 2; 95% CI, 2-2; P < .001). The neonatal Apgar scores did not differ between the 2 groups at 1 minute (median difference, 0; 95% CI, 0-0; P = .98) and at 5 minutes (median difference, 0; 95% CI, 0-0; P = .27). Transient neurologic or mental symptoms were more common in patients given esketamine (97.7% [293 of 300]) than in those given placebo (4.7% [14 of 300]; P < .001). Conclusions and Relevance: For women undergoing cesarean delivery under epidural anesthesia, a subanesthetic dose of esketamine administered before incision produced transient analgesia and sedation but did not induce significant neonatal depression. Mental symptoms and nystagmus were common but transient. Indications and the optimal dose of esketamine in this patient population need further clarification, but study should be limited to those who require supplemental analgesia. Trial Registration: ClinicalTrials.gov Identifier: NCT04548973.

[Distribution of HLA-DRB1 allele polymorphism in the Uyghur women with family history of cervical cancer].

OBJECTIVE: To study the distribution of HLA-DRB1 allele polymorphism in Uyghur women with family history of cervical cancer, and provide theoretical evidence for detection and follow-up of high risk persons for cervical cancer by detection of HLA-DRB1 allele polymorphism. METHODS: The HLA-DRB1 13 alleles were detected in 1000 Uyghur women, all from Hotan Moyu county Karsay village by using polymerase chain reaction sequence-specific oligonucleotide (PCR-SSO) assay. RESULTS: The frequencies of HLA-DRB1*15 in women with family history of cervical cancer (17.3%), mother (18.0%) and other relatives except mother (17.0%) who had suffered from cervical cancer were significantly higher than that in the control group (9.7%, all P < 0.05). The frequencies of HLA-DRB1*04 in women with family history (16.8%) and other relatives except mother (20.7%) were significantly higher than that in the control group (12.7%, all P < 0.05). The frequencies of HLA-DRB1*03 in women with family history (2.6%) and other relatives except mother (1.1%) were significantly lower than that in the control group (6.3%, all P < 0.01). The frequencies of HLA-DRB1*12 in women with family history of cervical cancer (2.3%) and mother suffered from cervical cancer (1.5%) were significantly lower than that in the control group (5.7%, all P < 0.05). The frequencies of HLA-DRB1*14 in women with family history of cervical cancer (5.4%) and mother who suffered from cervical cancer (3.0%) were significantly lower than that in the control group (8.4%, all P < 0.05). CONCLUSIONS: There are similarity and difference in distribution of HLA-DRB1 allele polymorphisms between the Uyghur women with family history of cervical cancer from Hotan Moyu county and those from southern Xingjiang area. In general, the distribution of HLA-DRB1 allele polymorphism in women with family history of cervical cancer is similar to that reported in abroad. The results of this study support the role of susceptible and protective HLA gene detection in screening high risk persons for this cancer among Uyghur women from cervical cancer high risk areas in Xinjiang.

Progression-Free Survival of a Patient with Advanced Hepatocellular Carcinoma Treated with Adoptive Cell Therapy Using Natural Killer Cells: A Case Report.

Adoptive cell therapy (ACT) is a promising treatment that is considered safe and efficient. Natural killer (NK) cells play an important role in the innate immune system and destroy target cells such as tumor cells without prior sensitization. Here, we report a 59-year-old man with advanced diffuse hepatocellular carcinoma (HCC) who underwent 17 courses of NK cell treatment from March 2017 to July 2018. Although he presented with progressive disease, his hydrothorax and ascites decreased, and his state of mind, appetite and quality of life were markedly improved after treatment versus at admission. To date, his survival time is >48 months. Here, we provide evidence that NK cell adoptive therapy has no adverse effects, enhances immune function, and improves the quality of life of patients with HCC.