Irisin in thyroid diseases.

Irisin, a hormone-like adipo-myokine, has garnered considerable attention in recent years for its potential impact in metabolic diseases. Its physiological effects are similar to those of thyroid hormones, prompting numerous investigations into potential correlations and interactions between irisin and thyroid function through various in vitro and animal experiments. However, existing studies suggest that the relationship between irisin and thyroid diseases is highly complex and multifaceted. In this paper, we have summarized the research results on serum irisin and thyroid function, providing an overview of advancements and constraints in current research on irisin and thyroid hormones. The aim is to offer insights and directions for future clinical trials in this field.

Validation of full-length radiograph based musculoskeletal modeling method to estimate medial and lateral knee contact forces.

BACKGROUND: Anatomical parameters of the pelvis, femur, and tibia derived from the full-length radiograph can be used to create a more accurate musculoskeletal model compared to marker-based linear scaling method. However, whether this model leads to more accurate estimations of medial knee contact force (MCF) and lateral knee contact force (LCF) than marker-based linear scaling method is still unknown. RESEARCH QUESTION: This main purpose of this study was to determine whether musculoskeletal model generated from full-length radiograph improves the estimations of MCF and LCF. METHODS: An open-source dataset including marker trajectories, ground reaction forces, in vivo knee contact forces, and full-length radiograph was used to evaluate the accuracy of full-length radiograph musculoskeletal modeling method. Subject-specific musculoskeletal models were created using anatomical parameters derived from the full-length radiograph or marker-based linear scaling methods. MCF and LCF were estimated using musculoskeletal simulations of normal walking trails. The accuracy of modeling methods was determined by comparing the estimated and in vivo measured MCF and LCF. RESULTS: Compared to the marker-based linear scaling approach, the full-length radiograph musculoskeletal modeling method exhibited decreases of 38.3 % and 41.3 % in root mean square error for MCF and LCF respectively, as well as reductions of 50.0 % and 49.3 % in mean peak errors for MCF and LCF respectively. SIGNIFICANCE: The full-length radiograph musculoskeletal modeling method provides a more accurate way to estimate MCF and LCF compared to the traditional maker-based linear scaling approach, which may contribute to understand the initiation, progression, and treatment of OA.

Dapagliflozin suppressed gastric cancer growth via regulating OTUD5 mediated YAP1 deubiquitination.

Gastric cancer (GC) is a common malignant disease that has a fifth highest incidence and fourth highest mortality worldwide. The Warburg effect is a common phenomenon observed in tumors, which suggests that tumor cells would enhance glucose uptake by overexpressing multiple glucose transporters. Sodium glucose transporter 2 (SGLT2) is one of glucose transporters which highly expressed in several cancers, but its role in gastric cancer is still unclear. Our research found that there was a high expression level of SGLT2 in gastric cancer tissues. We found that Dapagliflozin (a SGLT2 inhibitor) could suppress gastric cancer cell proliferation and migration in vitro and tumor growth in vivo. In present study, we revealed how dapagliflozin would suppress gastric cancer progression in a novel mechanism. We proved that dapagliflozin decreased the expression level of OTU deubiquitinase 5 (OTUD5), which further increased the ubiquitination and degradation of YAP1. Overexpression of OTUD5 in gastric cancer cells partly reversed the anti-tumor effect of dapagliflozin. Our findings revealed a novel mechanism by which dapagliflozin has an antitumor effect on gastric cancer and proposed a beneficial strategy for the application of dapagliflozin in gastric cancer patients.

Epidemiological characterization of hand, foot, and mouth disease among hospitalized children from 2014 to 2023 in a hospital in Henan Province: Longitudinal surveillance study.

Hand, foot, and mouth disease (HFMD) is an acute infectious illness primarily caused by enteroviruses. The present study aimed to describe the epidemiological characteristics of hospitalized HFMD patients in a hospital in Henan Province (Zhengzhou, China), and to predict the future epidemiological parameters. In this study, we conducted a retrospective analysis of general demographic and clinical data on hospitalized children who were diagnosed with HFMD from 2014 to 2023. We used wavelet analysis to determine the periodicity of the disease. We also conducted an analysis of the impact of the COVID-19 epidemic on the detection ratio of severe illness. Additionally, we employed a Seasonal Difference Autoregressive Moving Average (SARIMA) model to forecast characteristics of future newly hospitalized HFMD children. A total of 19 487 HFMD cases were included in the dataset. Among these cases, 1515 (7.8%) were classified as severe. The peak incidence of HFMD typically fell between May and July, exhibiting pronounced seasonality. The emergence of COVID-19 pandemic changed the ratio of severe illness. In addition, the best-fitted seasonal ARIMA model was identified as (2,0,2)(1,0,1)12. The incidence of severe cases decreased significantly following the introduction of the vaccine to the market (χ2 = 109.9, p < 0.05). The number of hospitalized HFMD cases in Henan Province exhibited a seasonal and declining trend from 2014 to 2023. Non-pharmacological interventions implemented during the COVID-19 pandemic have led to a reduction in the incidence of severe illness.

Impact of the Peripheral Ligand Layer on the Excited-State Deactivation Mechanism of Au38S2(S-Adm)20 and Au30(S-Adm)18 (S-Adm = Adamantanethiolate) Clusters.

Gold nanoclusters are ideal fluorescent labels for biological imaging, disease diagnosis, and treatment. Understanding the origin of the photoluminescence phenomenon in ligand-protected gold nanoclusters is crucial for both basic science and practical applications. In this study, density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations were performed to study the mechanism of excited state deactivation of Au38S2(S-Adm)20 and Au30(S-Adm)18 (S-Adm = adamantanethiolate) clusters, which have similar sizes and compositions. The computational results indicate that the differences in structural symmetry and peripheral ligand layer lead to quite different excited state deactivation mechanisms and excited state lifetimes in Au38S2(S-Adm)20 and Au30(S-Adm)18. Specifically, the µ3-S atoms and bridging thiolate (SR) in the ligand layer of Au38S2(S-Adm)20 significantly suppress the structural relaxation of ligand motifs, resulting in a prolonged excited state lifetime and higher quantum yield. For the Au30(S-Adm)18, due to the symmetry forbidden and large structural relaxation of the ligand shell, a rapid nonradiative transition process resulted. This study provides new insights into how the photoluminescence of ligand-protected gold nanoclusters is influenced by their structure and symmetry.

Clinical Efficacy and Safety of transarterial chemoembolization Combined with Targeted Therapy for primary hepatocellular carcinoma.

Objective: To explore the clinical efficacy and safety of transarterial chemoembolization (TACE) combined with targeted therapy for primary hepatocellular carcinoma (PHC). Methods: This was a retrospective study. Retrospective selection of 150 PHC patients admitted to the Renmin Hospital, Hubei University of Medicine January 2019 and June 2021 were included. The patients were divided into the control group and the experimental group according to their treatment regimens. The control group received TACE treatment, while the experimental group received TACE combined with targeted therapy. We analyze the relevant data of two groups of patients and evaluate the clinical efficacy and safety of TACE combined with targeted therapy. Results: The tumor remission rate and control rate in the control group were 41.89% and 75.68%, respectively, while those in the experimental group were 77.63% and 90.79%, with statistically significant differences (p<0.05). The 1-year and 3-year recurrence rates in the control group were 52.71% and 98.65%, respectively, while those in the experimental group were 39.47% and 61.84%, with statistically significant differences (p<0.05). After treatment, the AFP, VEGF, ALT, and AST in the experimental group were significantly reduced compared to the control group (p<0.05). During the treatment period, the incidence and severity of nausea, vomiting, and fever in the experimental group were significantly lower than those in the control group (p<0.05). Conclusion: The clinical efficacy of TACE combined with targeted therapy for PHC is superior to that of TACE alone, with improved disease control rate, improved long-term survival rate, and good safety.

Constructing machine learning models based on non-contrast CT radiomics to predict hemorrhagic transformation after stoke: a two-center study.

Purpose: Machine learning (ML) models were constructed according to non-contrast computed tomography (NCCT) images as well as clinical and laboratory information to assess risk stratification for the occurrence of hemorrhagic transformation (HT) in acute ischemic stroke (AIS) patients. Methods: A retrospective cohort was constructed with 180 AIS patients who were diagnosed at two centers between January 2019 and October 2023 and were followed for HT outcomes. Patients were analyzed for clinical risk factors for developing HT, infarct texture features were extracted from NCCT images, and the radiomics score (Rad-score) was calculated. Then, five ML models were established and evaluated, and the optimal ML algorithm was used to construct the clinical, radiomics, and clinical-radiomics models. Receiver operating characteristic (ROC) curves were used to compare the performance of the three models in predicting HT. Results: Based on the outcomes of the AIS patients, 104 developed HT, and the remaining 76 had no HT. The HT group consisted of 27 hemorrhagic infarction (HI) and 77 parenchymal-hemorrhage (PH). Patients with HT had a greater neutrophil-to-lymphocyte ratio (NLR), baseline National Institutes of Health Stroke Scale (NIHSS) score, infarct volume, and Rad-score and lower Alberta stroke program early CT score (ASPECTS) (all p < 0.01) than patients without HT. The best ML algorithm for building the model was logistic regression. In the training and validation cohorts, the AUC values for the clinical, radiomics, and clinical-radiomics models for predicting HT were 0.829 and 0.876, 0.813 and 0.898, and 0.876 and 0.957, respectively. In subgroup analyses with different treatment modalities, different infarct sizes, and different stroke time windows, the assessment accuracy of the clinical-radiomics model was not statistically meaningful (all p > 0.05), with an overall accuracy of 79.5%. Moreover, this model performed reliably in predicting the PH and HI subcategories, with accuracies of 82.9 and 92.9%, respectively. Conclusion: ML models based on clinical and NCCT radiomics characteristics can be used for early risk evaluation of HT development in AIS patients and show great potential for clinical precision in treatment and prognostic assessment.

Prognostic nomogram for patients with advanced unresectable hepatocellular carcinoma treated with TAE combined with HAIC.

Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and often arises in the context of chronic liver disease, such as hepatitis B or C infection, and cirrhosis. Advanced unresectable HCC (uHCC) presents significant treatment challenges due to its advanced stage and inoperability. One efficient treatment method for advanced uHCC is the use of hepatic arterial infusion chemotherapy (HAIC) combined with transcatheter arterial embolization (TAE). Patients and Methods: In this study, we conducted a retrospective collection of clinical data, including basic information, radiological data, and blood test parameters, for patients with advanced uHCC who underwent TAE + HAIC treatment from August 2020 to February 2023. A total of 743 cases involving 262 patients were included. Ultimately, the covariates included in the analysis were the Child-Pugh score, extrahepatic metastasis, tumor number, tumor size, and treatment method. Results: In the study, we performed univariable and multivariable analysis on 23 clinical factors that were screened by LASSO regression, indicating that the five variables aforementionedly were identified as independent factors influencing patient prognosis. Then we developed a nomogram of the sensitive model and calculated concordance indices of prognostic survival models. Conclusion: Based on the uHCC patient cohort, we have developed a prognostic model for OS in patients who received TAE + HAIC treatment. This model can accurately predict OS and has the potential to assist in personalized clinical decision-making.

Large animal model species in pluripotent stem cell therapy research and development for retinal diseases: a systematic review.

Aim: Retinal cell therapy modalities, in the category of advanced therapy medicinal products (ATMPs), are being developed to target several retinal diseases. Testing in large animal models (LAMs) is a crucial step in translating retinal ATMPs into clinical practice. However, challenges including budgetary and infrastructure constraints can hinder LAM research design and execution. Here, to facilitate the comparison of the various LAMs in pluripotent retinal cell therapy research, we aimed to systematically evaluate the species distribution, reported scientific utility, and methodology of a range of LAMs. Methods: A systematic search using the words retina, stem cell, transplantation, large animal, pig, rabbit, dog, and nonhuman primate was conducted in the PubMed, Embase, Science Direct and GoogleScholar databases in February 2023. Results: We included 22 studies involving pluripotent stem cells (induced pluripotent stem cells or human embryonic stem cells) in LAMs, including non-human primates (NHP), pigs, dogs, and rabbits. Nearly half of the studies utilized wild-type animal models. In other studies, retinal degeneration features were simulated via laser, chemical, or genetic insult. Transplants were delivered subretinally, either as cell suspensions or pre-formed monolayers (with or without biodegradable scaffolding). The transplanted cells dose per eye varied widely (40,000 - 4,000,000 per dose). Cells were delivered via vitrectomy surgery in 15 studies and by an "ab externo" approach in one study. Structural outcomes were assessed using confocal scanning laser ophthalmoscopy imaging. Functional outcomes included multifocal electroretinogram and, in one case, a measure of visual acuity. Generally, cell suspension transplants exhibited low intraretinal incorporation, while monolayer transplants incorporated more efficiently. Immune responses posed challenges for allogeneic transplants, suggesting that autologous iPSC-derived transplants may be required to decrease the likelihood of rejection. Conclusion: The use of appropriate LAMs helps to advance the development of retinal ATMPs. The anatomical similarity of LAM and human eyes allows the implementation of clinically-relevant surgical techniques. While the FDA Modernization Act 2.0 has provided a framework to consider alternative methods including tissue-on-a-chip and human cell culture models for pharmacologic studies, LAM testing remains useful for cell and tissue replacement studies to inform the development of clinical trial protocols.

Zirconium-based nanoclusters as molecular robots for water decontamination.

Water contamination owing to anionic pollutants is a persisting and ubiquitous global threat. The current remediation technologies are mostly low in efficiency, expensive in materials and often associated with complicated processes. Herein, we report a characteristic zirconium-based nanocluster that can work as molecular robots for the efficient remediation of anions-contaminated water with great effectiveness and molecular-level accuracy. It exhibits a stimuli-responsive behavior to facilitate the water treatment process: dissolve in acidic aqueous solutions for molecular-level decontamination and quickly aggregate for post-remediation collection. It can precisely capture the representative anionic pollutants, whilst featuring satisfactory capacities (ca. 175 mg-arsenic/g, 60 mg-chromium/g, 45 mg-fluoride/g, 70 mg-phosphorus/g, respectively), super-fast kinetics (finishing uptake within seconds, which is two to four orders of magnitude faster than typical sorbents), as well as multi-cycle applications without appreciable loss of activity. The coexisting common ions show no effect on the target uptake. The responsible active site investigation shows that four active sites are responsible for the monovalent pollutant removal, and the active sites work in pairs to capture divalent chromate species. Cost analysis shows its economical applicability in practical applications. This work would lead to the development of effective water decontamination with higher effectiveness, more convenience, lower cost and more practical application value.

Expert consensus on the multidisciplinary diagnosis and treatment of multiple ground glass nodule-like lung cancer (2024 Edition).

ABSTRACT: This expert consensus reviews current literature and provides clinical practice guidelines for the diagnosis and treatment of multiple ground glass nodule-like lung cancer. The main contents of this review include the following: ① follow-up strategies, ② differential diagnosis, ③ diagnosis and staging, ④ treatment methods, and ⑤ post-treatment follow-up.

Analysis of genome-wide association studies of low-temperature germination in Xian and Geng rice.

Rice is the leading global staple crop. Low temperatures pose negative impacts on rice's optimal growth and development. Rice cultivars acclimating to low temperatures exhibited improved seedling emergence under direct-seeded sowing conditions, yet little is known about the genes that regulate germination at low temperatures (LTG). In this research investigation, we've performed whole genome sequencing for the 273 rice plant materials. Using the best linear unbiased prediction (BLUP) values for each rice material, we identified 7 LTG-related traits and performed the efficient genetic analysis and genome-wide association study (GWAS). As a result of this, 95 quantitative trait loci (QTLs) and 1001 candidate genes associated with LTG in rice were identified. Haplotype analysis and functional annotation of the candidate genes resulted in the identification of three promising candidate genes (LOC_Os08g30520 for regulating LTG4 and LTG5, LOC_Os10g02625 for regulating LTG6, LTg7 and LTG8, and LOC_Os12g31460 for regulating LTG7, LTg8 and LTG9) involving in the regulation of LTG in rice. This research provides a solid foundation for addressing the LTG issue in rice and will be valuable in future direct-seeded rice breeding programs.

[Retracted] MEG3/miR­21 axis affects cell mobility by suppressing epithelial­mesenchymal transition in gastric cancer.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the Transwell cell invasion assay data shown in Fig. 2B on p. 42 and the immunofluorescence data shown in Fig. 4D on p. 44 were strikingly similar to data appearing in other articles written by different authors at different research institutes that were submitted to different journals at around the same time. Moreover, a further investigation of this paper undertaken by the Editorial Office identified a large number of overlapping data panels comparing the Transwell cell migration and invasion assay data and the scratch­wound assay data both within and between Figs. 2 and 3, where data which were intended to have shown the results from differently performed experiments had apparently been derived from the same original source, including an overlapping section of data within the 'MEG3+mimic' panel in Fig. 3G that would be difficult to attribute to pure chance. Owing to the fact that the contentious data in the above article had already been submitted for publication at around the same time as its submission to Oncology Reports, and given an overall lack of confidence in the presented data, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 40: 39­48, 2018; DOI: 10.3892/or.2018.6424].

Granzyme B secreted by T cells is involved in anti-bacterial immune response of tilapia.

Secreted by natural killer cells and cytotoxic T lymphocytes, Granzyme B is involved in regulating the adaptive immune response in vertebrates and plays a pivotal role in resisting virus invasion and removing pathogens. Although it had been extensively studied in mammals, the involvement of Granzyme B in adaptive immune response of early vertebrates remained elusive. In this study, we investigated the Granzyme B in Oreochromis niloticus (OnGrB), found that its function domain was conserved. Additionally, OnGrB was widely expressed in various tissues and could respond to T-cell activation in vitro at the transcriptional level. Furthermore, we prepared the recombinant OnGrB (rOnGrB) as an immunogen to develop a mouse anti-OnGrB monoclonal antibody (mAb). Using this anti-OnGrB mAb as a tool, we explored the expression of OnGrB in the adaptive immune response of tilapia. Our findings revealed that T cell was a significant source of OnGrB production, the expression of OnGrB at the protein level and the proportion of OnGrB + T cells increased after both T cell activation in vitro and infection with Edwardsiella piscicida in vivo. More importantly, our findings also preliminarily illuminated that p65 could regulate the transcriptional activity of OnGrB. These results indicated that OnGrB was involved in the adaptive immunity of tilapia and played a critical role in T cell function in teleost. Our study provided theoretical support and new perspectives for understanding adaptive immunity in teleost.

Effects of an mHealth intervention on maternal and infant outcomes from pregnancy to early postpartum for women with overweight or obesity: A randomized controlled trial.

BACKGROUND: Women with overweight (OW) and those with obesity (OB) tend to gain excessive weight during pregnancy, often resulting in adverse outcomes. The long-term effects of mobile health (mHealth) interventions on maternal and infant outcomes remain unclear. AIMS: To examine the effects of an mHealth intervention on OW and OB from the course of their pregnancy to six months postpartum. METHODS: A randomized controlled trial was conducted in northern Taiwan. Ninety-two pregnant women with a body mass index (BMI)of ≥25 kg/m2 were recruited from prenatal clinics at <17 weeks of gestation. Prepregnancy weight was baseline maternal weight, with data collected subsequently at the last assessment before childbirth and six months postpartum. The intervention group (IG) received the mHealth intervention, while the control group (CG) received standard antenatal care. The trial was registered on ClinicalTrials.gov (identifier: NCT04553731) with the initial registration date of September 16, 2020. FINDINGS: The IG tended to have a lower mean body weight than the CG at the last assessment before childbirth (82.23 kg vs 84.35 kg) and at six months postpartum (72.55 Kg vs 72.58 Kg). IG's newborn birth weight was significantly lower than CG's (3074.8 vs. 3313.6 g; p = 0.009). Regression analysis revealed that OB in IG had a significant reduction in weight before childbirth (ß = -7.51, p = 0.005) compared to OB in CG. Compared to OW in CG, both OW in IG (ß = -243.59, p = 0.027) and OB in IG (ß = -324.59, p = 0.049) were associated with decreased newborn birth weight. CONCLUSIONS: mHealth helped women with obesity to successfully manage their GWG and body weight before childbirth and newborns' birth weight, despite this effect not persisting to reduce weight retention at six months postpartum.

Peri- and intra-nodular radiomic features based on 18F-FDG PET/CT to distinguish lung adenocarcinomas from pulmonary granulomas.

Objective: To compare the effectiveness of radiomic features based on 18F-FDG PET/CT images within (intranodular) and around (perinodular) lung nodules/masses in distinguishing between lung adenocarcinoma and pulmonary granulomas. Methods: For this retrospective study, 18F-FDG PET/CT images were collected for 228 patients. Patients diagnosed with lung adenocarcinoma (n = 156) or granulomas (n = 72) were randomly assigned to a training (n = 159) and validation (n = 69) groups. The volume of interest (VOI) of intranodular, perinodular (1-5 voxels, termed Lesion_margin1 to Lesion_margin5) and total area (intra- plus perinodular region, termed Lesion_total1 to Lesion_total5) on PET/CT images were delineated using PETtumor and Marge tool of segmentation editor. A total of 1,037 radiomic features were extracted separately from PET and CT images, and the optimal features were selected to develop radiomic models. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC). Results: Good and acceptable performance was, respectively, observed in the training (AUC = 0.868, p < 0.001) and validation (AUC = 0.715, p = 0.004) sets for the intranodular radiomic model. Among the perinodular models, the Lesion_margin2 model demonstrated the highest AUC in both sets (0.883 and 0.616, p < 0.001 and p = 0.122). Similarly, in terms of total models, Lesion_total2 model was found to outperform others in the training (AUC = 0.879, p < 0.001) and validation (AUC = 0.742, p = 0.001) sets, slightly surpassing the intranodular model. Conclusion: When intra- and perinodular radiomic features extracted from the immediate vicinity of the nodule/mass up to 2 voxels distance on 18F-FDG PET/CT imaging are combined, improved differential diagnostic performance in distinguishing between lung adenocarcinomas and granulomas is achieved compared to the intra- and perinodular radiomic features alone.

Stochastic lattice-based porous implant design for improving the stress transfer in unicompartmental knee arthroplasty.

BACKGROUND: Unicompartmental knee arthroplasty (UKA) has been proved to be a successful treatment for osteoarthritis patients. However, the stress shielding caused by mismatch in mechanical properties between human bones and artificial implants remains as a challenging issue. This study aimed to properly design a bionic porous tibial implant and evaluate its biomechanical effect in reconstructing stress transfer pathway after UKA surgery. METHODS: Voronoi structures with different strut sizes and porosities were designed and manufactured with Ti6Al4V through additive manufacturing and subjected to quasi-static compression tests. The Gibson-Ashby model was used to relate mechanical properties with design parameters. Subsequently, finite element models were developed for porous UKA, conventional UKA, and native knee to evaluate the biomechanical effect of tibial implant with designed structures during the stance phase. RESULTS: The internal stress distribution on the tibia plateau in the medial compartment of the porous UKA knee was found to closely resemble that of the native knee. Furthermore, the mean stress values in the medial regions of the tibial plateau of the porous UKA knee were at least 44.7% higher than that of the conventional UKA knee for all subjects during the most loading conditions. The strain shielding reduction effect of the porous UKA knee model was significant under the implant and near the load contact sites. For subject 1 to 3, the average percentages of nodes in bone preserving and building region (strain values range from 400 to 3000 µm/m) of the porous UKA knee model, ranging from 68.7 to 80.5%, were higher than that of the conventional UKA knee model, ranging from 61.6 to 68.6%. CONCLUSIONS: The comparison results indicated that the tibial implant with designed Voronoi structure offered better biomechanical functionality on the tibial plateau after UKA. Additionally, the model and associated analysis provide a well-defined design process and dependable selection criteria for design parameters of UKA implants with Voronoi structures.

CD122 is an activation marker ensuring proper proliferation of T cells in teleost.

As one of subunits for interleukin-2 receptor (IL-2R), CD122 can bind to IL-2 and then activate downstream signal transduction to participate in adaptive immune response. Although CD122 has been identified and investigated from several teleost species, studies on its function at T-cell level are still scarce for lack of specific antibodies. In this study, a typical CD122 in Nile tilapia (Oreochromis niloticus) was characterized by bioinformatics analysis, cloned to produce retrovirus infected NIH/3T3 cells for mouse immunization. After cell fusion and screening, we successfully developed a mouse anti-tilapia CD122 monoclonal antibody (mAb), which could specifically recognize CD122 and identify CD122-producing T cells of tilapia. Using the mAb to detect, CD122 was found to widely distribute in immune-related tissues, and significantly elevate post Edwardsiella piscicida infection or T-cell activation. More importantly, the expansion of CD122+ T cells and up-regulation of CD122 occurred both in total T cells and T-cell subsets during T-cell activation upon in vitro stimulation or in vivo infection. These results indicate that CD122 can be used as a T-cell activation marker in tilapia. Notably, CD122 mAb blocking blunted the activation of MAPK/Erk and mTORC1 pathways, and inhibited T-cell proliferation, suggesting a critical role of CD122 in ensuring proper proliferation of tilapia T cells. Therefore, this study enriches the knowledge of T-cell responses in fish and provides new evidence for understanding the evolution of lymphocyte-mediated adaptive immunity.

Cerastecin Inhibition of the Lipooligosaccharide Transporter MsbA to Combat Acinetobacter baumannii: From Screening Impurity to In Vivo Efficacy.

Acinetobacter baumannii, a commonly multidrug-resistant Gram-negative bacterium responsible for large numbers of bloodstream and lung infections worldwide, is increasingly difficult to treat and constitutes a growing threat to human health. Structurally novel antibacterial chemical matter that can evade existing resistance mechanisms is essential for addressing this critical medical need. Herein, we describe our efforts to inhibit the essential A. baumannii lipooligosaccharide (LOS) ATP-binding cassette (ABC) transporter MsbA. An unexpected impurity from a phenotypic screening was optimized as a series of dimeric compounds, culminating with 1 (cerastecin D), which exhibited antibacterial activity in the presence of human serum and a pharmacokinetic profile sufficient to achieve efficacy against A. baumannii in murine septicemia and lung infection models.