An integrated classification of tumor suppressor IKZF1 inactivation and oncogenic activation in Philadelphia chromosome-like acute lymphoblastic leukemia.

Philadelphia chromosome (Ph)-like acute lymphoblastic leukemia (ALL) is recognized for its genetic and clinical diversity. In this study, we identified a novel high-risk subset of Ph-like ALL, characterized by the activation of oncogenic signaling and the inactivation of the tumor suppressor gene IKZF1, resulting in a dismal outcome. The association between cytogenetic aberrations and clinical features was assessed on a cohort of 191 patients with Ph-like ALL. Our findings revealed that patients with inactivation of IKZF1 combined with activation of oncogenic signaling (CRLF2/EPOR/JAK2 rearrangements or p-CRKL/p-STAT5 high expression) had the worst outcome (3-year overall survival [OS] of 28.8% vs. 80.1% for others, p < 0.001; 2-year event-free survival [EFS] of 6.5% vs. 57.0% for others, p < 0.001). Multivariable analysis demonstrated that this high-risk feature was an independent inferior prognostic factor (adjusted hazard ratio for OS = 4.55, 95% confidence interval [CI]: 2.35-8.81, p < 0.001; adjusted hazard ratio for EFS = 3.27, 95% CI: 1.99-5.39, p < 0.001). Allogeneic hematopoietic stem cell transplantation was associated with improved prognoses in patients within the high-risk subgroup. In conclusion, this study identified a clinically distinct entity that possesses effective prognostic features and provides potential guidance for refining risk stratification in Ph-like ALL.

Analysis of tissue tropism of GCRV-II infection in grass carp using a VP35 monoclonal antibody.

Grass carp, one of the major freshwater aquaculture species in China, is susceptible to grass carp reovirus (GCRV). GCRV is a non-enveloped RNA virus and has a double-layered capsid, causing hemorrhagic disease and high mortalities in infected fish. However, the tropism of GCRV infection has not been investigated. In this study, monoclonal antibodies against recombinant VP35 protein were generated in mice and characterized. The antibodies exhibited specific binding to the N terminal region (1-155 aa) of the recombinant VP35 protein expressed in the HEK293 cells, and native VP35 protein in the GCRV-II infected CIK cells. Immunofluorescent staining revealed that viruses aggregated in the cytoplasm of infected cells. In vivo challenge experiments showed that high levels of GCRV-II viruses were present in the gills, intestine, spleen and liver, indicating that they are the major sites for virus infection. Our study showed that the VP35 antibodies generated in this study exhibited high specificity, and are valuable for the development of diagnostic tools for GCRV-II infection.

Magnetic beads and GO-assisted enzyme-free signal amplification fluorescent biosensors for disease diagnosis.

Cancer detection is still a major challenge in public health. Identification of oncogene is the first step toward solving this problem. Studies have revealed that various cancers are associated with miRNA expression. Therefore, the sensitive detection of miRNA is substantially important to solve the cancer problem. In this study, let-7a, a representative substance of miRNA, was selected as the detection target. With the assistance of magnetic beads commonly used in biosensors and self-synthesized graphene oxide materials, specificity and sensitivity detection of the target gene let-7a were achieved via protease-free signal amplification. The limit of detection (LOD) was as low as 15.015pM. The fluorescence signal intensity showed a good linear relationship with the logarithm of let-7a concentration. The biosensor could also detect let-7a in complex human serum samples. Overall, this fluorescent biosensor is not only simple to operate, but also strongly specificity to detect let-7a. Therefore, it has substantial potential for application in the early diagnosis of clinical medicine and biological research.

Transcutaneous auricular vagus nerve stimulation enhanced emotional inhibitory control via increasing intrinsic prefrontal couplings.

Background: Inhibitory control represents a core executive function that critically facilitates adaptive behavior and survival in an ever-changing environment. Non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) has been hypothesized to improve behavioral inhibition performance, however the neurocomputational mechanism of taVNS-induced neuroenhancement remains elusive. Method: In the current study, we investigated the efficacy of taVNS in a sham-controlled between-subject functional near infrared spectroscopy (fNIRS) experiment with an emotional face Go/No-Go paradigm in ninety healthy young adults. Results: After a data quality check, eighty-two subjects were included in the final data analysis. Behaviorally, the taVNS improved No-Go response accuracy, together with computational modeling using Hierarchical Bayesian estimation of the Drift Diffusion Model (HDDM) indicating that it specifically reduced the information accumulation rate for Go responses, and this was negatively associated with increased accuracy of No-Go responses. On the neural level, taVNS enhanced engagement of the bilateral inferior frontal gyrus (IFG) during inhibition of angry expression faces and modulated functional couplings (FCs) within the prefrontal inhibitory control network. Mediation models revealed that taVNS-induced facilitation of inhibitory control was critically mediated by a decreased information accumulation for Go responses and concomitantly enhanced neurofunctional coupling between the inferior and orbital frontal cortex. Discussion: Our findings demonstrate a potential for taVNS to improve emotional inhibitory control via reducing pre-potent responses and enhancing FCs within prefrontal inhibitory control networks, suggesting a promising therapeutic role in treating specific disorders characterized by inhibitory control deficits.

Oromucosal Administration of Oxytocin: The Development of 'Oxipops'.

The role of the hypothalamic neuropeptide oxytocin in influencing the brain and behavior has been the subject of widespread research over the last few decades due, most notably, to its reported involvement in promoting social cognition and motivation, reducing anxiety, and relieving pain. It is also increasingly being considered as an important therapeutic intervention in a variety of disorders with social dysfunction as a symptom. While, in recent years, studies in humans have administered oxytocin primarily via an intranasal route, since it may partly enter the brain directly this way via the olfactory and trigeminal nerves, there is increasing evidence that many of its functional effects can be peripherally mediated via increasing its concentration in the blood. This has opened up an oromucosal administration route as an alternative, which is beneficial since the oral consumption of peptides is problematic due to their rapid breakdown in the acidic environment of the gastrointestinal system. In this review we will discuss both the methodologies we have developed for administering oxytocin via lingual application and medicated lollipops, 'oxipops', in terms of increasing blood concentrations and the bioavailability of the peptide, and also their validation in terms of functional effects on the brain and behavior. While areas under the curve are significantly greater in terms of plasma oxytocin concentrations following intranasally relative to oromucosally administered oxytocin, with the estimated absolute bioavailability of the latter being around 4.4% compared with 11.1% for intranasal administration, the time to peak concentrations (around 30 min) and functional effects on the brain and behavior are broadly similar. We will also discuss potential therapeutic advantages of the oromucosal administration of oxytocin in different clinical contexts and its wider application for other peptides which are increasingly being developed for therapeutic use.

Paclitaxel mediates the PI3K/AKT/mTOR pathway to reduce proliferation of FLT3­ITD+ AML cells and promote apoptosis.

Acute myeloid leukemia (AML) with internal tandem duplication (ITD) mutations in the FLT3 tyrosine kinase tend to have a poor prognosis. FLT3-ITD can promote the progress of AML by activating the PI3K/AKT/mTOR pathway. Paclitaxel (PTX) is a natural anticancer drug that has been widely used in chemotherapy for multiple malignancies. The present study used the CCK-8 assay, flow cytometry, PCR and western blotting to explore the anti-leukemia effect and possible mechanisms of PTX on MV4-11 cells with the FLT3-ITD mutation and the underlying mechanism. As a result, it was found that PTX could inhibit proliferation of MV4-11 cells and promoted apoptosis by inhibiting the PI3K/AKT/mTOR pathway.

Mothers and fathers show different neural synchrony with their children during shared experiences.

Parent-child shared experiences has an important influence on social development in children although contributions of mothers and fathers may differ. Neural synchronicity occurs between mothers and fathers and their children during social interactions but it is unclear whether they differ in this respect. We used data from simultaneous fNIRS hyperscanning in mothers (n = 33) and fathers (n = 29) and their children (3-4 years) to determine different patterns and strengths of neural synchronization in the frontal cortex during co-viewing of videos or free-play. Mothers showed greater synchrony with child than fathers during passive viewing of videos and the synchronization was positively associated with video complexity and negatively associated with parental stress. During play interactions, mothers showed more controlling behaviors over their child and greater evidence for joint gaze and joint imitation play with child whereas fathers spent more time gazing at other things. In addition, different aspects of child communication promoted neural synchrony between mothers and fathers and child during active play interactions. Overall, our findings indicate greater neural and behavioral synchrony between mothers than fathers and young children during passive or active shared experiences, although for both it was weakened by parental distress and child difficulty.

Development of preimplantation genetic testing for monogenic reference materials using next-generation sequencing.

OBJECTIVE: Preimplantation genetic testing for monogenic disorders (PGT-M) has been used for over 20 years to detect many serious genetic conditions. However, there is still a lack of reference materials (RMs) to validate the test performance during the development and quality control of PGT-M. METHOD: Sixteen thalassemia cell lines from four thalassemia families were selected to establish the RMs. Each family consisted of parents with heterozygous mutations for α- and/or ß-thalassemia and two children, at least one of whom carried a homozygous thalassemia mutation (proband). The RM panel consisted of 12 DNA samples (parents and probands in 4 families) and 4 simulated embryos (cell lines constructed from blood samples from the four nonproband children). Four accredited genetics laboratories that offer verification of thalassemia samples were invited to evaluate the performance of the RM panel. Furthermore, the stability of the RMs was determined by testing after freeze‒thaw cycles and long-term storage. RESULTS: PGT-M reference materials containing 12 genome DNA (gDNA) reference materials and 4 simulated embryo reference materials for thalassemia testing were successfully established. Next-generation sequencing was performed on the samples. The genotypes and haplotypes of all 16 PGT-M reference materials were concordant across the four labs, which used various testing workflows. These well-characterized PGT-M reference materials retained their stability even after 3 years of storage. CONCLUSION: The establishment of PGT-M reference materials for thalassemia will help with the standardization and accuracy of PGT-M in clinical use.

Metastatic splenic angiosarcoma presenting with anemia and bone marrow fibrosis mimicking primary myelofibrosis: A case report and literature review.

Angiosarcomas, originating from endothelial cells, are infrequent soft tissue sarcomas characterized by a high propensity for metastasis and an unfavorable prognosis. Splenic angiosarcoma, an exceedingly rare and aggressive neoplasm, exhibits variable clinical manifestations. The present case report describes a patient initially exhibiting anemia and bone marrow fibrosis, mimicking primary myelofibrosis, ultimately diagnosed with splenic angiosarcoma. The findings of the present case report underscore the importance of considering splenectomy for histopathological confirmation. Employing a panel of vascular differentiation markers is invaluable for establishing the diagnosis of angiosarcoma.

Towards low carbon demand and highly efficient nutrient removal: Establishing denitrifying phosphorus removal in anaerobic/anoxic/oxic + nitrification system.

A two-sludge anaerobic/anoxic/oxic + nitrification system with simultaneous nitrogen and phosphorus removal was studied for enhanced low-strength wastewater treatment. After 158 days of operation, excellent NH4+-N, chemical oxygen demand (COD) and PO43--P removal (99.0 %, 90.0 % and 92.0 %, respectively) were attained under a low carbon/nitrogen ratio of 5, resulting in effluent NH4+-N, COD and PO43--P concentrations of 0.3, 30.0 and 0.5 mg/L, respectively. The results demonstrate that the anaerobic/anoxic/oxic sequencing batch reactor (A2-SBR) and nitrification sequencing batch reactor (N-SBR) had favorable denitrifying phosphorus removal and nitrification performance, respectively. High-throughput sequencing results indicate that the phosphate-accumulating organisms Dechloromonas (1.1 %) and Tetrasphaera (1.2 %) were enriched in the A2-SBR, while the ammonia-oxidizing bacteria Nitrosomonas (7.8 %) and the nitrite-oxidizing bacteria Nitrospira (18.1 %) showed excellent accumulation in the N-SBR. Further analysis via functional prediction revealed that denitrification is the primary pathway of nitrogen metabolism throughout the system. Overall, the system achieved low carbon and high efficiency nutrient removal.

Association between atherogenic index of plasma and asymptomatic intracranial arterial stenosis in middle-aged and elderly women: A cross-sectional study in Shandong, China.

BACKGROUND AND AIMS: The atherogenic index of plasma (AIP) is associated with progression of atherosclerosis and used to describe how pro- or anti-atherogenic components are balanced. However, the association of AIP with asymptomatic intracranial arterial stenosis (aICAS) is uncertain. The purpose of this study is to investigate the association between AIP and aICAS in rural China. METHODS AND RESULTS: A total of 1990 participants aged ≥40 years free of stroke or transient ischemic attack were enrolled in this study. The presence of aICAS was examined by Transcranial Doppler ultrasound and confirmed by magnetic resonance angiography. The adjusted AIP (aAIP) was calculated according to the ratio of TG and HDL-C and further separated into 4 quartiles. Multiple logistic regression was used to investigate the association between aAIP and aICAS, and the dose-response relationship was explored by restricted cubic spline. After adjusting for conventional confounders, aAIP was significantly higher in the aICAS group than that in the non-aICAS group. Furthermore, the common odds ratios for aICAS risk increased with increasing aAIP quartiles. Multivariate logistic regression revealed that aAIP was independently associated with aICAS in female or middle-aged and elderly (age ≥50 years), and superior to other lipid profiles. Multiple-adjusted spline regression showed the dose-response association between aAIP levels and aICAS prevalence. CONCLUSIONS: AIP might be independently and positively associated with the prevalence of aICAS in middle-aged and elderly women, which might be superior to traditional and nontraditional lipid profiles in rural China.

Sorafenib plus triplet therapy with venetoclax, azacitidine and homoharringtonine for refractory/relapsed acute myeloid leukemia with FLT3-ITD: A multicenter phase 2 study.

BACKGROUND: Patients with relapsed or refractory acute myeloid leukemia (R/R AML) and FLT3-internal tandem duplication (FLT3-ITD) respond infrequently to salvage chemotherapy. OBJECTIVE: To investigate the efficacy of sorafenib plus triplet therapy with venetoclax, azacitidine, and homoharringtonine (VAH) as a salvage therapy in this population. METHODS: This multicenter, single-arm, phase 2 study was conducted at 12 hospitals across China. Eligible patients had R/R AML with FLT3-ITD (aged 18-65 years) who were treated with VAH. The primary endpoint was composite complete remission (CRc) after two cycles. Secondary outcomes included the overall response rate (ORR), safety, and survival. RESULTS: Between July 9, 2020, and March 19, 2022, 58 patients were assessed for eligibility, 51 of whom were enrolled. The median patient age was 47 years (interquartile range [IQR] 31-57). CRc was 76.5% with ORR of 82.4%. At a median follow-up of 17.7 months (IQR, 8.7-24.7), the median duration of CRc was not reached (NR), overall survival was 18.1 months (95% confidence interval [CI], 11.8-NR) and event-free survival was 11.4 months (95% CI, 5.6-NR). Grade 3 or 4 adverse events occurring in ≥10% of patients included neutropenia in 47 (92.2%), thrombocytopenia in 41 (80.4%), anemia in 35 (68.6%), febrile neutropenia in 29 (56.9%), pneumonia in 13 (25.5%), and sepsis in 6 (11.8%) patients. Treatment-related death occurred in two (3.9%) patients. CONCLUSIONS: The sorafenib plus VAH regimen was well tolerated and highly active against R/R AML with FLT3-ITD. This regimen may be a suitable therapeutic option for this population, but larger population trials are needed to be explored. TRIAL REGISTRATION: Clinical Trials Registry: NCT04424147.

A retrospective observational study on maternal and neonatal outcomes of COVID-19: Does the mild SARS-CoV-2 infection affect the outcome?

Background: Currently, several SARS-CoV-2 variants, including Omicron, are still circulating globally. This underscores the necessity for a comprehensive understanding of their impact on obstetric and neonatal outcomes in pregnant women, even in cases of mild infection. Methods: We conducted a retrospective, single-center observational study to investigate the association between gestational SARS-CoV-2 infection and maternal-fetal outcomes in the Chinese population. The study enrolled 311 pregnant patients with SARS-CoV-2 infection (exposure group) and 205 uninfected pregnant patients (control group). We scrutinized the hospital records to collect data on demographics, clinical characteristics, and maternal and neonatal outcomes for subsequently comparison. Results: Similar characteristics were observed in both groups, including maternal age, height, BMI, gravidity, parity, and comorbidities (p > 0.05). A majority (97.4%) of pregnant women in the exposure group with COVID-19 experienced mild clinical symptoms, with fever (86.5%) and cough (74.3%) as the primary symptoms. The exposure group exhibited significantly higher incidences of cesarean section and fetal distress compared to the control group (p < 0.05). Furthermore, pregnant women in the exposure group showed reduced levels of hemoglobin and high-sensitivity C-reactive protein, while experiencing significantly increased levels of lymphocytes, prothrombin time, alanine aminotransferase, and aspartate aminotransferase (p < 0.05). Notably, recent SARS-CoV-2 infection prior to delivery appeared to have an adverse impact on liver function, blood and coagulation levels in pregnant women. When comparing the two groups, there were no significant differences in the postpartum hemorrhage rate, premature birth rate, birth weight, neonatal asphyxia rate, neonatal department transfer rate, and neonatal pneumonia incidence. Conclusions: Our study suggests that mild COVID-19 infection during pregnancy does not have detrimental effects on maternal and neonatal outcomes. However, the increased risks of events such as fetal distress and cesarean section, coupled with potential alterations in physical function, reveal the consequences of SARS-CoV-2 infection during pregnancy, even in mild cases. These findings emphasize the importance of proactive management and monitoring of pregnant individuals with COVID-19.

Clinical Characteristics and Prognosis of Acute Myeloid Leukemia Patients with Protein Tyrosine Phosphatase Non-Receptor Type 11 Gene Mutation.

Objective: The purpose of our study was to investigate the clinical characteristics, molecular biological characteristics and prognosis of acute myeloid leukemia (AML) patients with protein tyrosine phosphatase non-receptor type 11 (PTPN11) gene mutation. Methods: The clinical data of 30 newly diagnosed adult AML patients with PTPN11 gene mutation were analyzed retrospectively. Kaplan-Meier and Cox proportional risk regression model were examined for prognostic analysis and prognostic factor screening. Results: High-frequency mutation sites of PTPN11 gene are located in exon 3 of chromosome 12, which are D61 and A72 (16.7%), followed by E76 (13.3%). The median variant allele frequency (VAF) of PTPN11 mutant gene is 18.4%. The patients were divided into two groups according to PTPN11 VAF 35.3% (upper quartile). We observed that the peripheral blood leukocyte count in patients with VAF ≥35.3% was significantly higher than patients with VAF < 35.3% (p = 0.019) and also closely related to M5 (p = 0.016) and internal tandem duplication (ITD) of FMS-like tyrosine kinase 3 (FLT3) (FLT3-ITD) mutation (p = 0.048). Taking PTPN11 VAF 20% and 35.3% as the cutoff value, the patients were divided into two groups, and the overall survival and event-free survival (EFS) of the two groups were not significant. Multivariate analysis of Cox risk ratio model showed that white blood cell count and Eastern Cooperative Oncology Group (ECOG) physical status score were independent risk factors affecting the EFS. Conclusion: Our study observed that PTPN11 VAF may not be a prognostic factor in patients with PTPN11mut AML. Newly diagnosed high white blood cell count and poor performance status were independent risk factors for EFS in PTPN11mut AML.

A phase 1 open-label pilot study of low-dose interleukine-2 immunotherapy in patients with Alzheimer's disease.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05821153, Registered April 20 2023, Retrospectively registered, https://classic. CLINICALTRIALS: gov/ct2/show/NCT05821153.

Development of a separation platform comprising magnetic beads combined with the CRISPR/Cas12a system enabling ultrasensitive and rapid detection of miRNA-21.

A separation platform has been developed mediated by a combination of magnetic beads and the CRISPR/Cas12a system to achieve ultrasensitive and rapid detection of miRNA-21 at a low level. In this system, with the assistance of an auxiliary probe, the target miRNA-21 can be specifically combined with three-stranded probes to initiate the SDR reaction. Abundant aptamer A3 was added to the solution that can activate the CRISPR/Cas12a system and initiate the trans-cleavage reaction to recover the fluorescence signal. Using magnetic beads to mediate the separation considerably greatly improves the signal conversion efficiency and detection sensitivity. At the 492 nm excitation wavelength, and 502-650 nm scan range, through analyzing the fluorescence peak intensity at 520 nm, the biosensor's determination range and limit of detection is 8 fM-250 nM and 2.42 fM, respectively, and the RSD is 19.03-37.80. Compared with other biosensors, the biosensor developed exhibited superior performance and the signal recovered excellently in 1% human serum and the LOD is 12.12 fM. This method provides a novel highly sensitive scheme for detecting miRNA .

Association of plaque characteristics with long-term stroke recurrence in patients with intracranial atherosclerotic disease: a 3D high-resolution MRI-based cohort study.

OBJECTIVES: To evaluate the predictive ability of plaque characteristics for long-term stroke recurrence among patients with symptomatic intracranial atherosclerotic disease (ICAD). METHODS: This cohort study included 132 patients with acute ischemic stroke (AIS) attributed to ICAD who were recruited between July 2017 and December 2020 and followed until stroke recurrence or December 2021. Plaque surface irregularity, degree of stenosis, plaque burden, remodeling ratio, enhancement ratio, and intraplaque hemorrhage were assessed with 3-dimensional high-resolution magnetic resonance vessel wall imaging (3D HR-MRI). Data were analyzed using Cox models, receiver operating characteristic (ROC) curves, and Kaplan-Meier survival analysis. RESULTS: Of the 132 patients, during a median follow-up of 2.8 years, stroke recurrence occurred in 35 patients. The multivariable-adjusted hazard ratio (95% confidence interval) of stroke recurrence was 3.15 (1.34-7.42) per 10% increase in plaque burden and 2.17 (1.27-3.70) for enhancement ratio. The area under the curve (AUC) to predict stroke recurrence was 0.725 (95% CI 0.629-0.822) for plaque burden, 0.692 (95% CI 0.593-0.792) for enhancement ratio, and only 0.595 (95% CI 0.492-0.699) for the Essen stroke risk score. The Kaplan-Meier survival analysis further demonstrated significant differences in survival of free recurrent stroke between patients with plaque burden or enhancement ratio below and above the optimum cut-offs (both p < 0.001). CONCLUSION: Higher plaque burden and enhancement ratio are independent risk factors for long-term stroke recurrence among patients with symptomatic ICAD, and valuable imaging markers for predicting and stratifying risk of stroke recurrence. CLINICAL RELEVANCE STATEMENT: In patients with symptomatic ICAD, the results of this high-resolution magnetic resonance vessel wall imaging study have potential implications for optimal management of intracranial plaques and secondary prevention of stroke recurrence based on plaque burden and enhancement ratio. KEY POINTS: • Identification of intracranial plaque characteristics responsible for stroke recurrence is essential to preventing stroke recurrence in patients with symptomatic intracranial atherosclerotic disease. • Higher plaque burden and enhancement ratio are independent risk factors for stroke recurrence. • Plaque burden and enhancement ratio are valuable imaging markers in the prediction and stratification of the risk of stroke recurrence.

Abnormal multi-layered dynamic cortico-subcortical functional connectivity in major depressive disorder and generalized anxiety disorder.

Comorbidity has been frequently observed between generalized anxiety disorder (GAD) and major depressive disorder (MDD), however, common and distinguishable alterations in the topological organization of functional brain networks remain poorly understood. We sought to determine a robust and sensitive functional connectivity marker for diagnostic classification and symptom severity prediction. Multi-layered dynamic functional connectivity including whole brain, network-node and node-node layers via graph theory and gradient analyses were applied to functional MRI resting-state data obtained from 31 unmedicated GAD and 34 unmedicated MDD patients as well as 33 age and education matched healthy controls (HC). GAD and MDD symptoms were assessed using Penn State Worry Questionnaire and Beck Depression Inventory II, respectively. Three network measures including global properties (i.e., global efficiency, characteristic path length), regional nodal property (i.e., degree) and connectivity gradients were computed. Results showed that both patient groups exhibited abnormal dynamic cortico-subcortical topological organization compared to healthy controls, with MDD > GAD > HC in degree of randomization. Furthermore, our multi-layered dynamic functional connectivity network model reached 77% diagnostic accuracy between GAD and MDD and was highly predictive of symptom severity, respectively. Gradients of functional connectivity for superior frontal cortex-subcortical regions, middle temporal gyrus-subcortical regions and amygdala-cortical regions contributed more in this model compared to other gradients. We found shared and distinct cortico-subcortical connectivity features in dynamic functional brain networks between GAD and MDD, which together can promote the understanding of common and disorder-specific topological organization dysregulations and facilitate early neuroimaging-based diagnosis.

The Biological Functions and Intestinal Inflammation Regulation of IL-21 in Grass Carp (Ctenopharyngodon idella) during Infection with Aeromonas hydrophila.

Interleukin (IL) 21 is a pleiotropic cytokine that plays an important role in regulating innate and adaptive immune responses. In fish, the biological functions and cell source of IL-21 remain largely unknown. In this study, we performed qRT-PCR, Western blotting and immunofluorescent microscopy to examine the expression of IL-21 at the mRNA and protein levels. We found that il21 expression was induced in the primary head kidney leukocytes of grass carp (Ctenopharyngodon idella) by heat-inactivated Aeromonas hydrophila (A. hydrophila) and LPS and in tissues after infection with A. hydrophila. Recombinant IL-21 protein produced in the CHO-S cells was effective in elevating the expression of antibacterial genes, including ß-defensin and lysozyme, and, interestingly, inhibited the NF-κB signaling pathway. Furthermore, we investigated the response of the IL-21 expressing cells to A. hydrophila infection. Immunofluorescent assay showed that IL-21 protein was detected in the CD3γ/δ T cells and was markedly accumulated in the anterior, middle and posterior intestine. Collectively, the results indicate that IL-21 plays an important role in regulating the intestinal inflammation induced by bacterial infection in grass carp.

Association between the triglyceride to high-density lipoprotein cholesterol ratio and the risk of gestational diabetes mellitus: a second analysis based on data from a prospective cohort study.

Background: Although there is strong evidence linking triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio to insulin resistance and diabetes mellitus, its clinical importance in pregnant women has not been well determined. This study sought to determine the connection between the TG/HDL-C ratio in the first trimester and the eventual onset of gestational diabetes mellitus (GDM). Methods: We performed a secondary analysis of open-access data from a prospective cohort study. This present study included 590 singleton pregnant women at 10-14 weeks who visited the outpatient clinics for prenatal checks and were recorded at Incheon Seoul Women's Hospital and Seoul Metropolitan Government Seoul National University Boramae Medical Center in Korea. A binary logistic regression model, a series of sensitivity analyses, and subgroup analysis were used to examine the relationship between TG/HDL-C ratio and incident GDM. A receiver operating characteristic (ROC) analysis was also conducted to assess the ability of the TG/HDL-C ratio to predict GDM. Results: The mean age of the included individuals was 32.06 ± 3.80 years old. The mean TG/HDL-C ratio was 1.96 ± 1.09. The incidence rate of GDM was 6.27%. After adjustment for potentially confounding variables, TG/HDL-C ratio was positively associated with incident GDM (OR=1.77, 95%CI: 1.32-2.38, P=0.0001). Sensitivity analyses and subgroup analysis demonstrated the validity of the relationship between the TG/HDL-C ratio and GDM. The TG/HDL-C ratio was a good predictor of GDM, with an area under the ROC curve of 0.7863 (95% CI: 0.7090-0.8637). The optimal TG/HDL-C ratio cut-off value for detecting GDM was 2.2684, with a sensitivity of 72.97% and specificity of 75.05%. Conclusion: Our results demonstrate that the elevated TG/HDL-C ratio is related to incident GDM. The TG/HDL-C ratio at 10-14 weeks could help identify pregnant women at risk for GDM and may make it possible for them to receive early and effective treatment to improve their prognosis.