Clonal evolution dissection reveals that a high MSI2 level promotes chemoresistance in T-cell acute lymphoblastic leukemia.

ABSTRACT: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive cancer with resistant clonal propagation in recurrence. We performed high-throughput droplet-based 5' single-cell RNA with paired T-cell receptor (TCR) sequencing of paired diagnosis-relapse (Dx_Rel) T-ALL samples to dissect the clonal diversities. Two leukemic evolutionary patterns, "clonal shift" and "clonal drift" were unveiled. Targeted single-cell DNA sequencing of paired Dx_Rel T-ALL samples further corroborated the existence of the 2 contrasting clonal evolution patterns, revealing that dynamic transcriptional variation might cause the mutationally static clones to evolve chemotherapy resistance. Analysis of commonly enriched drifted gene signatures showed expression of the RNA-binding protein MSI2 was significantly upregulated in the persistent TCR clonotypes at relapse. Integrated in vitro and in vivo functional studies suggested that MSI2 contributed to the proliferation of T-ALL and promoted chemotherapy resistance through the posttranscriptional regulation of MYC, pinpointing MSI2 as an informative biomarker and novel therapeutic target in T-ALL.

Hydrogen-Bonded Organic Cocrystal-Encapsulated Perovskite Nanocrystals as Coreactant-Free Electrochemiluminescent Luminophore for the Detection of Uranium.

Lead halide perovskite nanocrystals with excellent photophysical properties are promising electrochemiluminescence (ECL) candidates, but their poor stability greatly restricts ECL applications. Herein, hydrogen-bonded cocrystal-encapsulated CsPbBr3 perovskite nanocrystals (PeNCs@NHS-M) were synthesized by using PeNCs as nuclei for inducing the crystallization of melamine (M) and N-hydroxysuccinimide (NHS). The as-synthesized composite exhibits multiplicative ECL efficiencies (up to 24-fold that of PeNCs) without exogenous coreactants and with excellent stability in the aqueous phase. The enhanced stability can be attributed to the well-designed heterostructure of the PeNCs@NHS-M composite, which benefits from both moiety passivation and protection of the peripheral cocrystal matrix. Moreover, the heterostructure with covalent linkage facilitates charge transfer between PeNCs and NHS-M cocrystals, realizing effective ECL emission. Meanwhile, the NHS and M components act as coreactants for PeNCs, shortening the electron-transport distance and resulting in a significant increase in the ECL signal. Furthermore, by taking advantage of the specific binding effect between NHS-M and uranyl (UO22+), an ECL system with both a low detection limit (1 nM) and high selectivity for monitoring UO22+ in mining wastewater is established. The presence of UO22+ disrupted the charge-transfer effect within PeNCs@NHS-M, weakening the ECL signals. This work provides an efficient design strategy for obtaining stable and efficient ECLs from perovskite nanocrystals, offering a new perspective for the discovery and application of perovskite-based ECL systems.

Hydrogen-Bonded Cocrystals Encapsulating CsPbBr3 Perovskite Nanocrystals with Enhancement of Charge Transport for Photocatalytic Reduction of Uranium.

At present, poor stability and carrier transfer efficiency are the main problems that limit the development of perovskite-based photoelectric technologies. In this work, hydrogen-bonded cocrystal-coated perovskite composite (PeNCs@NHS-M) is easily obtained by inducing rapid crystallization of melamine (M) and N-hydroxysuccinimide (NHS) with PeNCs as the nuclei. The outer NHS-M cocrystal passivates the undercoordinated lead atoms by forming covalent bonds, thereby greatly reducing the trap density while maintaining good structure stability for perovskite nanocrystals. Moreover, benefiting from the interfacial covalent band linkage and long-range ordered structures of cocrystals, the charge transfer efficiency is effectively enhanced and PeNCs@NHS-M displays superior photoelectric performance. Based on the excellent photoelectric performance and abundant active sites of PeNCs@NHS-M, photocatalytic reduction of uranium is realized. PeNCs@NHS-M exhibits U(VI) reduction removal capability of up to 810.1 mg g-1 in the presence of light. The strategy of cocrystals trapping perovskite nanocrystals provides a simple synthesis method for composites and opens up a new idea for simultaneously improving the stability and photovoltaic performance of perovskite.

Outcome of first or second transplantation using unrelated umbilical cord blood without ATG conditioning regimen for pediatric bone marrow failure disorders.

BACKGROUND: Unrelated umbilical cord blood transplantation (UCBT) for bone marrow failure (BMF) disorders using conditioning regimens without Anti-Thymocyte Globulin (ATG) has been used as an alternative transplantation for emerging patients without matched-sibling donors. Experience with this transplant modality in children is limited, especially as a secondary treatment for transplant failure patients. PROCEDURE: We retrospectively reviewed 17 consecutive bone marrow failure patients who underwent unrelated umbilical cord blood transplantation in our center and received conditioning regimens of Total Body Irradiation (TBI) or Busulfan (BU) + Fludarabine (FLU) + Cyclophosphamide (CY). RESULTS: Among the 17 BMF patients, 15 patients were treated with first cord blood transplantation and another 2 with secondary cord blood transplantation because of graft failure after first haploidentical stem cell transplantation at days +38 and +82. All patients engrafted with a median donor cell chimerism of 50 % at days +7 (range, 16 %-99.95 %) and finally rose to 100 % at days +30. Median time to neutrophil engraftment was 19 days (range, 12-30) and time to platelet engraftment was 32 days (range, 18-61). Pre-engraftment syndrome (PES) was found in 16 patients (94.11 %, 16/17). Cumulative incidence of grades II to IV acute GVHD was 58.8 % (95 % CI: 32.7-84.9 %), and 17.6 % (95 % CI: 2.6-37.9 %) of patients developed chronic GVHD. The 3-year overall survival (OS) and failure-free survival (FFS) rates were 92.86 ± 6.88 %. CONCLUSION: UCBT is an effective alternative treatment for bone marrow failure pediatric patients. TBI/BU + FLU + CY regimen ensure a high engraftment rate for unrelated umbilical cord blood transplantation, which overcomes the difficulty of graft failure. Secondary salvage use of cord blood transplantation may still be useful for patients who have failed after other transplantation.

Minimal residual disease monitoring in childhood Philadelphia chromosome-positive acute lymphoblastic leukemia: prognostic significance and correlation between multiparameter flow cytometry and real-time quantitative polymerase chain reaction

Not available.

Construction of a Bifunctional Redox-Site Conjugated Covalent-Organic Framework for Photoinduced Precision Trapping of Uranyl Ions.

The performance of covalent-organic frameworks (COFs) for the photocatalytic extraction of uranium is greatly limited by the number of adsorption sites. Herein, inspired by electronegative redox reactions, we designed a nitrogen-oxygen rich pyrazine connected COF (TQY-COF) with multiple redox sites as a platform for extracting uranium via combining superaffinity and enhanced photoinduction. The preorganized bisnitrogen-bisoxygen donor configuration on TQY-COF is entirely matched with the typical geometric coordination of hexavalent uranyl ions, which demonstrates high affinity (tetra-coordination). In addition, the presence of the carbonyl group and pyrazine ring effectively stores and controls electron flow, which efficaciously facilitates the separation of e-/h+ and enhances photocatalytic performance. The experimental results show that TQY-COF removes up to 99.8% of uranyl ions from actual uranium mine wastewater under the light conditions without a sacrificial agent, and the separation coefficient reaches 1.73 × 106 mL g-1 in the presence of multiple metal ions, which realizes the precise separation in the complex environment. Importantly, DFT calculations further elucidate the coordination mechanism of uranium and demonstrate the necessity of the presence of N/O atoms in the photocatalytic adsorption of uranium.

High-Resolution CT Patterns of Anti-PD1 Checkpoint Inhibitor-Related Pneumonitis in Patients With Lung Cancer.

BACKGROUND: Lung cancer has the highest morbidity and mortality in the world, and immunotherapies have been developed for this disease in recent years. However, activation of the immune system can cause immune-related adverse events (irAEs), and checkpoint inhibitor-related pneumonitis (CIP), can be the most severe and fatal. But few reports have systematically examined the spectrum of imaging findings of this condition. Therefore, the objective of this paper is to investigate the high-resolution computed tomography (HRCT) characteristics of CIP in patients with lung cancer. OBJECTIVE: To investigate the HRCT characteristics of CIP in patients with lung cancer. METHODS: HRCT patterns in 41 lung cancer patients who developed CIP after treatment with immune checkpoint inhibitors were retrospectively characterized by interstitial lung disease classification, and their severity was graded. Specific HRCT characteristics related to CIP were identified. RESULTS: There are 4 types of immunotherapy-induce pneumonitis patterns (organizing pneumonia OP 19 cases, nonspecific interstitial pneumonia NSIP 8 cases, acute interstitial pneumonia AIP 7 cases, 7 cases of undetermined type) and image grade (13 cases of grade 1, 17 cases of grade 2, 11 cases of grade 3, 0 cases of grade 4) were identified. Spatial distribution characteristics of these lesions were noted (17 cases predominantly distributed in tumor-containing lobes, 6 cases predominantly distributed in non-tumor-containing lobes, and no specific predilection in 18 cases). Specific CT imaging features found in CIP included, in the order of prevalence, the following: ground glass opacities (38 cases), subpleural/vertical line (37 cases), interstitial thickening around the bronchovascular bundles (36 cases), reticulation (34 cases), fine reticular shadow (31 cases), consolidation (31 cases), small cystic shadow (24 cases, may not having honeycombing), small nodules (17 cases), bronchiectasis (15 cases), honeycombing (11 cases), mosaic sign (11 cases), and pleural effusion (18 cases). CONCLUSION: HRCT of CIP predominantly manifests as ground glass opacities, reticulation, subpleural/vertical line, interstitial thickening around the bronchovascular bundle, and consolidation.

Prevalence and association of uncorrected refractive error among Chinese adolescents: a cross-sectional study.

BACKGROUND: Uncorrected refractive error (URE) is one of the main causes of visual impairments. URE may reduce interaction and learning in the classroom, leading to social isolation, irreversible amblyopia, lack of external knowledge, and restrictions on education and employment opportunities. Our aim was to investigate the prevalence and related factors of URE in adolescents using epidemiological surveys and questionnaire surveys related to lifestyle habits. METHODS: A cross-sectional school-based study was conducted in Nantong, China, including adolescents 12-19 years of age from 16 schools. URE was defined as presenting visual acuity worse than 6/12 and improving to ≥ 1 lines after correction in either eye. Univariate and multivariate logistic regression analyses were used to investigate specific correlations between URE and related lifestyle parameters. Non-cycloplegic autorefraction was assessed for each adolescent. RESULTS: A total of 2,910 adolescents were analyzed, of which 50.3% (n = 1,465) were male, and 49.7% (n = 1,445) were female. The mean age was 15.23 ± 1.77 years. The overall prevalence of URE was 23.7%. The total prevalence of REC and eREC was 85.1% and 71.7%, respectively, and both of them showed an increasing trend with age (Ptrend = 0.018 and Ptrend = 0.019, respectively). A higher prevalence of URE was related to myopia, anisometropia, and increased daily use of electronic products. Timely visual examination by medical institutions, more extracurricular homework, and older age were protective factors for URE. Among the 689 adolescents with URE, 362 (52.5%) did not receive any refractive correction, and 327 (47.5%) used corrected glasses. CONCLUSION: URE was highly prevalent among adolescents in China. Myopia was the most important risk factor for URE. The impact of anisometropia and increased daily use of electronic devices on URE was significant. Timely visual examinations by medical institutions served as an effective protective factor against URE. Further research on adjusting intervention strategies is therefore needed to eliminate preventable visual impairments.

Decapod iridescent virus 1 (DIV1) 168L can target cuticle protein 8 from Litopenaeus vannamei.

Decapod iridescent virus 1 (DIV1) stands as a significant pathogen affecting crustaceans, posing a grave threat to the shrimp industries in aquaculture dependent nations. Within the Iridoviridae family, the conserved envelope protein DIV1-168L plays a pivotal role in virion entry. Nonetheless, the host factors that interact with 168L remain unidentified. To address this gap, we established a cDNA library derived from Litopenaeus vannamei gill tissue and conducted yeast two-hybrid screening to identify host factors that interact with 168L. Additionally, we performed co-immunoprecipitation assays to verify the interaction between cuticle protein 8 (CP8) and 168L. Expression pattern analysis revealed the presence of CP8 transcripts in the gill and epidermis. Furthermore, immunohistochemistry results demonstrated the expression of CP8 in gill cells and its localization in the gill filament epithelium. Fluorescence analysis indicated that full-length CP8 colocalized with 168L in the cytoplasm of Sf9 cells. Removal of the signal peptide from the N-terminal of CP8 eliminated its concentration in the cytoplasm. Additionally, CP8 expression was significantly inhibited during DIV1 infection. Therefore, our research contributes to a better understanding of the entry mechanism of iridovirids. The GenBank accession number for the DIV1 sequence is MF197913.1.

Open-Circuit Fault Diagnosis of T-Type Three-Level Inverter Based on Knowledge Reduction.

Compared with traditional two-level inverters, multilevel inverters have many solid-state switches and complex composition methods. Therefore, diagnosing and treating inverter faults is a prerequisite for the reliable and efficient operation of the inverter. Based on the idea of intelligent complementary fusion, this paper combines the genetic algorithm-binary granulation matrix knowledge-reduction method with the extreme learning machine network to propose a fault-diagnosis method for multi-tube open-circuit faults in T-type three-level inverters. First, the fault characteristics of power devices at different locations of T-type three-level inverters are analyzed, and the inverter output power and its harmonic components are extracted as the basis for power device fault diagnosis. Second, the genetic algorithm-binary granularity matrix knowledge-reduction method is used for optimization to obtain the minimum attribute set required to distinguish the state transitions in various fault cases. Finally, the kernel attribute set is utilized to construct extreme learning machine subclassifiers with corresponding granularity. The experimental results show that the classification accuracy after attribute reduction is higher than that of all subclassifiers under different attribute sets, reflecting the advantages of attribute reduction and the complementarity of different intelligent diagnosis methods, which have stronger fault-diagnosis accuracy and generalization ability compared with the existing methods and provides a new way for hybrid intelligent diagnosis.

An SNR Enhancement Method for Φ-OTDR Vibration Signals Based on the PCA-VSS-NLMS Algorithm.

To improve the signal-to-noise ratio (SNR) of vibration signals in a phase-sensitive optical time-domain reflectometer (Φ-OTDR) system, a principal component analysis variable step-size normalized least mean square (PCA-VSS-NLMS) denoising method was proposed in this study. First, the mathematical principle of the PCA-VSS-NLMS algorithm was constructed. This algorithm can adjust the input signal to achieve the best filter effect. Second, the effectiveness of the algorithm was verified via simulation, and the simulation results show that compared with the wavelet denoising (WD), Wiener filtering, variational mode decomposition (VMD), and variable step-size normalized least mean square (VSS-NLMS) algorithms, the PCA-VSS-NLMS algorithm can improve the SNR to 30.68 dB when the initial SNR is -1.23 dB. Finally, the PCA-VSS-NLMS algorithm was embedded into the built Φ-OTDR system, an 11.22 km fiber was measured, and PZT was added at 10.19-10.24 km to impose multiple sets of fixed-frequency disturbances. The experimental results show that the SNR of the vibration signal is 8.77 dB at 100 Hz and 0.07 s, and the SNR is improved to 26.17 dB after PCA-VSS-NLMS filtering; thus, the SNR is improved by 17.40 dB. This method can improve the SNR of the system's position information without the need to change the existing hardware conditions, and it provides a new scheme for the detection and recognition of long-distance vibration signals.

In Situ Electrochemical Interfacial Polymerization for Covalent Organic Frameworks with Tunable Electrochromism.

A rapid in situ synthesis of electrochromic covalent organic frameworks (EC-COFs) was proposed by using green electrochemical interface polymerization of N,N,N',N'-tetrakis(4-aminophenyl)-1,4-benzenediamine (TPDA) and 2,5-dihydroxyterephthalaldehyde (DHBD). The synthetized TPDA-DHBD films exhibit stable polymorphic color variations under different applied potentials, which can be attributed to the redox state changes of bis(triphenylamine) and imine electroactive functional groups within the COFs skeleton. TPDA-DHBD represents markedly different electrochromisms from red to cyan due to the steric hindrance effect caused by the presence of UO2 2+, demonstrating the unique tunability of COFs materials. This work offers a new feasible idea for rapid EC-COFs synthesis and tunable EC-COFs realization.

Single-cell analysis highlights a population of Th17-polarized CD4+ naïve T cells showing IL6/JAK3/STAT3 activation in pediatric severe aplastic anemia.

Acquired aplastic anemia (AA) is recognized as an immune-mediated disorder resulting from active destruction of hematopoietic cells in bone marrow (BM) by effector T lymphocytes. Bulk genomic landscape analysis and transcriptomic profiling have contributed to a better understanding of the recurrent cytogenetic abnormalities and immunologic cues associated with the onset of hematopoietic destruction. However, the functional mechanistic determinants underlying the complexity of heterogeneous T lymphocyte populations as well as their correlation with clinical outcomes remain to be elucidated. To uncover dysfunctional mechanisms acting within the heterogeneous marrow-infiltrating immune environment and examine their pathogenic interplay with the hematopoietic stem/progenitor pool, we exploited single-cell mass cytometry for BM mononuclear cells of severe AA (SAA) patients pre- and post-immunosuppressive therapy, in contrast to those of healthy donors. Alignment of BM cellular composition with hematopoietic developmental trajectories revealed potential functional roles for non-canonically activated CD4+ naïve T cells in newly-diagnosed pediatric cases of SAA. Furthermore, single-cell transcriptomic profiling highlighted a population of Th17-polarized CD4+CAMK4+ naïve T cells showing activation of the IL-6/JAK3/STAT3 pathway, while gene signature dissection indicated a predisposition to proinflammatory pathogenesis. Retrospective validation from our SAA cohort of 231 patients revealed high plasma levels of IL-6 as an independent risk factor of delayed hematopoietic response to antithymocyte globulin-based immunosuppressive therapy. Thus, IL-6 warrants further investigation as a putative therapeutic target in SAA.

Effect of Gubenyiliu formula II and its disassembled prescriptions on cell autophagy in breast cancer through PI3K/AKT/mTOR pathway.

The aim of this study is to reveal the mechanism of Gubenyiliu II (GYII) inhibiting autophagy in breast cancer and the effect of its disassembled prescriptions, Quxie (QX) and Fuzheng (FZ), which cause autophagy difference on tumor growth. After a breast cancer in situ tumor model was established, mice were randomly distributed into different groups: model, GYII, QX, FZ and tamoxifen groups, and treated correspondingly. Then, the tumor volumes and weights were monitored. Immunohistochemistry detected the contents of microtubule-associated protein light chain 3 (LC3), phosphorylated phosphatidylinositol 3-kinase (p-PI3K), phosphorylated protein kinase B (p-AKT) and phosphorylated mammalian target of rapamycin (p-mTOR) in tumor tissues. Furthermore, 4T1 cells were administrated with the 20% contained serum. Cell proliferation, migration and invasion were measured using cell counting kit-8 and transwell assays. Electron microscopy and flow cytometry detected autophagy and apoptosis. The content of LC3 was measured by immunofluorescence. Western blot detected the protein levels of LC3, Beclin1, p-PI3K/PI3K, p-AKT/AKT and p-mTOR/mTOR in tumor tissues and 4T1 cells. GYII, QX and FZ treatment significantly reduced the tumor volumes and weights in breast cancer tumor-bearing mice. The cell proliferation, migration and invasion were restrained, and cell apoptosis and autophagy were promoted in GYII, QX and FZ groups. Moreover, GYII, QX and FZ increased the expression of LC3 in 4T1 cells and tumor tissues and decreased the phosphorylation levels of PI3K, AKT and mTOR in tumor tissues. The protein levels of LC3 and Beclin1 were upregulated, and p-PI3K/PI3K, p-AKT/AKT and p-mTOR/mTOR were downregulated in tumor tissues and 4T1 cells of treatment groups. Our study confirmed that GYII could treat breast cancer by restraining the PI3K/AKT/mTOR signaling pathway-mediated autophagy. While QX focuses on inhibiting tumor growth, FZ acts on inhibiting tumor metastasis.

CpG ODN 2102 promotes antibacterial immune responses and enhances vaccine-induced protection in golden pompano (Trachinotusovatus).

CpG oligodeoxynucleotides (ODNs) are oligodeoxynucleotides containing CpG motifs and can be recognized by toll-like receptor 9 (TLR9), activating the host's immune responses. In this study, ten different CpG ODNs were designed and synthesized to study the antibacterial immune responses of CpG ODNs in golden pompano (Trachinotus ovatus). Results showed that CpG ODN 2102 significantly improved the immunity of golden pompano against bacteria. Besides, CpG ODN 2102 promoted the proliferation of head kidney lymphocytes and activated the head kidney macrophages. When TLR9-specific small interfering RNA (siRNA) was used to interfere with TLR9 expression, the immune responses were decreased. Moreover, the expression levels of myeloid differentiation primary response 88 (Myd88), p65, tumor necrosis factor receptor-associated factor 6 (TRAF6), and tumor necrosis factor-alpha (TNF-α) in the TLR9-knockdown golden pompano kidney (GPK) cells were significantly reduced. The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) promoter activity of the TLR9-knockdown GPK cells was also significantly reduced. In vivo, the antibacterial immune effects induced by CpG ODN 2102 in golden pompano were mostly abolished when TLR9 expression was knocked down. These results suggested that TLR9 was involved in the immune responses induced by CpG ODN 2102. CpG ODN 2102 also enhanced the protective effect of the Vibrio harveyi vaccine pCTssJ, where the survival rate of golden pompano was significantly improved by 20%. In addition, CpG ODN 2102 enhanced the messenger RNA (mRNA) expression levels of TLR9, Myxovirus resistance (Mx), interferon γ (IFN-γ), TNF-α, interleukin (IL)-1ß, IL-8, major histocompatibility complex class (MHC) Iα, MHC IIα, Immunoglobulin D (IgD), and IgM. Therefore, TLR9 was involved in the antibacterial immune responses induced by CpG ODN 2102 and CpG ODN 2102 possessed adjuvant immune effects. These results enlarged our knowledge of the antibacterial immunity of fish TLRs signaling pathway and had important implications for exploring natural antibacterial molecules in fish and developing new vaccine adjuvants.

TroTNFSF6, a tumor necrosis factor ligand superfamily member, promotes antibacterial immune response of golden pompano, Trachinotus ovatus.

Tumor necrosis factor ligand superfamily member 6 (TNFSF6), also known as FasL/CD95L, is essential for maintaining the body's immune homeostasis. However, the current reports on TNFSF6 in fish are relatively scarce. In the present study, we conducted functional analyses of a TNFSF6 (TroTNFSF6) from the teleost fish golden pompano (Trachinotus ovatus). TroTNFSF6 is composed of 228 amino acids and has a low similarity with other species (9.65%-58.79%). TroTNFSF6 was expressed in the 11 tissues tested and was significantly up-regulated after Edwardsiella tarda infection. In vivo, overexpression of TroTNFSF6 effectively stimulated the AKP and ACP activities, and reduced bacterial infection in fish tissues. Correspondingly, knockdown of TroTNFSF6 expression resulted in increasing bacterial dissemination and colonization in fish tissues. In vitro, recombinant TroTNFSF6 protein promoted the proliferation of T. ovatus head kidney lymphocytes (HKLs), and promoted the apoptosis of murine liver cancer cells (Hepa1-6). The results indicated that TroTNFSF6 plays an important role in the T. ovatus antibacterial immunity. These observations will facilitate the future in-depth study of teleost TNFSF6.

CpG ODN 1668 as TLR9 agonist mediates humpback grouper (Cromileptes altivelis) antibacterial immune responses.

Cromileptes altivelis (humpback grouper) is the main farmed species in the southern coastal area of China owing to its important economic value. Toll-like receptor 9 (TLR9) belongs to the toll-like receptor (TLR) family and functions as a pattern recognition receptor, recognising unmethylated oligodeoxynucleotides containing the CpG motif (CpG ODNs) in bacterial and viral genomes, thereby activating host immune response. In this study, the C. altivelis TLR9 (CaTLR9) ligand CpG ODN 1668 was screened and found to significantly enhance the antibacterial immunity of humpback grouper in vivo and head kidney lymphocytes (HKLs) in vitro. In addition, CpG ODN 1668 also promoted the cell proliferation and immune gene expression of HKLs and strengthened the phagocytosis activity of head kidney macrophages. However, when the CaTLR9 expression was knocked down in the humpback group, the expression levels of TLR9, myeloid differentiation factor 88 (Myd88), tumour necrosis factor-α (TNF-α), interferon γ (IFN-γ), interleukin-1ß (IL-1ß), IL-6, and IL-8 were significantly reduced, and the antibacterial immune effects induced by CpG ODN 1668 were mostly abolished. Therefore, CpG ODN 1668 induced antibacterial immune responses in a CaTLR9-dependent pathway. These results enhance the knowledge of the antibacterial immunity of fish TLR signalling pathways and have important implications for exploring natural antibacterial molecules in fish.

Incremental predictive value of platelet parameters for preeclampsia: results from a large prospective cohort study.

BACKGROUND: Platelet parameters during pregnancy were associated with the risk of preeclampsia (PE), but the predictive value of these parameters for PE remained unclear. Our aim was to clarify the individual and incremental predictive value of platelet parameters, including platelet count (PC), mean platelet volume (MPV), plateletcrit (PCT), and platelet distribution width (PDW) for PE. METHODS: This study was based on the Born in Guangzhou Cohort Study in China. Data on platelet parameters were extracted from medical records of routine prenatal examinations. Receiver operating characteristic (ROC) curve was performed to analyze the predictive ability of platelet parameters for PE. Maternal characteristic factors proposed by NICE and ACOG were used to develop the base model. Detection rate (DR), integrated discrimination improvement (IDI) and continuous net reclassification improvement (NRI) were calculated compared with the base model to assess the incremental predictive value of platelet parameters. RESULTS: A total of 30,401 pregnancies were included in this study, of which 376 (1.24%) were diagnosed with PE. Higher levels of PC and PCT were observed at 12-19 gestational weeks in women who developed PE later. However, no platelet parameters before 20 weeks of gestation reliably distinguished between PE complicated pregnancy and non-PE complicated pregnancy, with all values of the areas under the ROC curves (AUC) below 0.70. The addition of platelet parameters at 16-19 gestational weeks to the base model increased the DR for preterm PE from 22.9 to 31.4% at a fixed false positive rate of 5%, improved the AUC from 0.775 to 0.849 (p = 0.015), and yielded a NRI of 0.793 (p < 0.001), and an IDI of 0.0069 (p = 0.035). Less but significant improvement in prediction performance was also observed for term PE and total PE when all the four platelet parameters were added to the base model. CONCLUSIONS: Although no single platelet parameter at the early stage of pregnancy identified PE with high accuracy, the addition of platelet parameters to known independent risk factors could improve the prediction of PE.

Meta-analysis of correlation between sleep duration and gender difference in adults with type 2 diabetes.

OBJECTIVE: To explore the correlation between sleep duration and type II diabetes in adults. METHOD: Computer databases searches were carried out through October 1, 2022, including PubMed, Cochrane Library, Embase, and Web of Science. Relevant literature was collected, and the Newcastle-Ottawa Scale (NOS) and extracted data were used to exclude studies and evaluate quality on the basis of inclusion and exclusion criteria. Meta-analysis was conducted using RevMan 5.4.1 software with random/fixed effects models. RESULTS: A total of 5 studies with 74,226 subjects (31,611 in the male study group, 42,615 in the female study group) were included. The meta-analysis revealed that women with long sleep duration (LSD) have a higher risk for developing type II diabetes than men, OR = 0.70; 95% CI 0.59-0.84, Z = 4.00 and P < 0.001. Men with short sleep duration (SSD) tended to have a higher risk in developing type II diabetes than women though the difference between men and women did not reach statistical significance, OR = 1.09, 95% CI 0.73-1.62, Z = 0.42 and P = 0.68. Further subgroup analysis by regional populations suggested that men in Europe and America with SSD had a higher risk of type II diabetes OR = 1.52, 95% CI 1.04-2.21, Z = 2.18 and P = 0.03. CONCLUSION: Women with LSD may have a higher risk for type II diabetes, and men in Europe and America with SSD may have a higher risk for type II diabetes than men of other regions.

Mechanism of forkhead transcription factors binding to a novel palindromic DNA site.

Forkhead transcription factors bind a canonical consensus DNA motif, RYAAAYA (R = A/G, Y = C/T), as a monomer. However, the molecular mechanisms by which forkhead transcription factors bind DNA as a dimer are not well understood. In this study, we show that FOXO1 recognizes a palindromic DNA element DIV2, and mediates transcriptional regulation. The crystal structure of FOXO1/DIV2 reveals that the FOXO1 DNA binding domain (DBD) binds the DIV2 site as a homodimer. The wing1 region of FOXO1 mediates the dimerization, which enhances FOXO1 DNA binding affinity and complex stability. Further biochemical assays show that FOXO3, FOXM1 and FOXI1 also bind the DIV2 site as homodimer, while FOXC2 can only bind this site as a monomer. Our structural, biochemical and bioinformatics analyses not only provide a novel mechanism by which FOXO1 binds DNA as a homodimer, but also shed light on the target selection of forkhead transcription factors.