Thoughts on the research of African swine fever live-attenuated vaccines.

African swine fever (ASF) is a contagious and fatal disease caused by the African swine fever virus (ASFV), which can infect pigs of all breeds and ages. Most infected pigs have poor prognosis, leading to substantial economic losses for the global pig industry. Therefore, it is imperative to develop a safe and efficient commercial vaccine against ASF. The development of ASF vaccine can be traced back to 1960. However, because of its large genome, numerous encoded proteins, and complex virus particle structure, currently, no effective commercial vaccine is available. Several strategies have been applied in vaccine design, some of which are potential candidates for vaccine development. This review provides a comprehensive analysis on the safety and effectiveness, suboptimal immunization effects at high doses, absence of standardized evaluation criteria, notable variations among strains of the same genotype, and the substantial impact of animal health on the protective efficacy against viral challenge. All the information will be helpful to the ASF vaccine development.

Relay Annulation of Ammonium Ylides with Oxindole-Derived α,ß-Unsaturated Ketimines: Catalytic Construction of Spiro-polycyclic Oxindoles.

An ammonium ylide-based relay annulation was disclosed, which uses DABCO as the catalyst and oxindole-derived α,ß-unsaturated ketimines and γ-bromo-crotonates as the starting materials. This method enables the rapid assembly of a series of structurally novel spiro-polycyclic oxindoles containing a bicyclo[4.1.0]heptane moiety through simultaneous generation of three new bonds and two rings in one step under mild reaction conditions.

YTHDC1 inhibits autophagy-dependent NF-κB signaling by stabilizing Beclin1 mRNA in macrophages.

BACKGROUND: YTHDC1, a key m(6)A nuclear reader, plays a crucial role in regulating mRNA splicing, export, and stability. However, the functional significance and regulatory mechanisms of YTHDC1 in inflammatory bowel disease (IBD) remain to be explored. METHODS: We established a dextran sulfate sodium (DSS)-induced murine colitis model in vivo and LPS/IFN-γ-stimulated macrophage inflammation in vitro. The expression of YTHDC1 was determined. Colocalization of YTHDC1 and macrophages was assayed by immunofluorescence staining. LV-YTHDC1 or shYTHDC1 lentiviruses were applied for YTHDC1 overexpression or inhibition. For NF-κB inhibition, JSH-23 was utilized. The interaction of YTHDC1 and Beclin1 mRNA was determined by RIP, and the m6A modification of Beclin1 was confirmed by MeRIP. RESULTS: In DSS-induced colitis and LPS/IFN-γ-treated RAW264.7 macrophages, we observed a significant downregulation of YTHDC1. Overexpression of YTHDC1 resulted in decreased levels of iNOS, CD86, and IL-6 mRNA, along with inhibited NF-κB activation in LPS/IFN-γ-treated RAW264.7 cells. Conversely, downregulation of YTHDC1 promoted iNOS expression and inhibited autophagy. Additionally, the effect of YTHDC1 knockdown on CD86 and IL-6 mRNA induced by LPS/IFN-γ was abolished by the NF-κB inhibitor JSH-23. Mechanistically, YTHDC1 interacted with Beclin1 mRNA, thereby stabilizing Beclin1 mRNA and enhancing Beclin1 expression and autophagy. These effects ultimately led to the inhibition of NF-κB signaling in LPS/IFN-γ-challenged macrophages. CONCLUSIONS: YTHDC1 inhibited the macrophage-mediated inflammatory response by stabilizing Beclin1 mRNA, which may be a potential therapeutic target for the treatment of IBD.

Clinical comprehensive treatment protocol for managing diabetic foot ulcers: A retrospective cohort study.

BACKGROUND: Diabetic foot ulcers (DFUs) are a common complication of diabetes, often leading to severe infections, amputations, and reduced quality of life. The current standard treatment protocols for DFUs have limitations in promoting efficient wound healing and preventing complications. A comprehensive treatment approach targeting multiple aspects of wound care may offer improved outcomes for patients with DFUs. The hypothesis of this study is that a comprehensive treatment protocol for DFUs will result in faster wound healing, reduced amputation rates, and improved overall patient outcomes compared to standard treatment protocols. AIM: To compare the efficacy and safety of a comprehensive treatment protocol for DFUs with those of the standard treatment protocol. METHODS: This retrospective study included 62 patients with DFUs, enrolled between January 2022 and January 2024, randomly assigned to the experimental (n = 32) or control (n = 30) group. The experimental group received a comprehensive treatment comprising blood circulation improvement, debridement, vacuum sealing drainage, recombinant human epidermal growth factor and anti-inflammatory dressing, and skin grafting. The control group received standard treatment, which included wound cleaning and dressing, antibiotics administration, and surgical debridement or amputation, if necessary. Time taken to reduce the white blood cell count, number of dressing changes, wound healing rate and time, and amputation rate were assessed. RESULTS: The experimental group exhibited significantly better outcomes than those of the control group in terms of the wound healing rate, wound healing time, and amputation rate. Additionally, the comprehensive treatment protocol was safe and well tolerated by the patients. CONCLUSION: Comprehensive treatment for DFUs is more effective than standard treatment, promoting granulation tissue growth, shortening hospitalization time, reducing pain and amputation rate, improving wound healing, and enhancing quality of life.

Study of the mechanism by which Xiaoyan decoction combined with E7449 regulates tumorigenesis in lung adenocarcinoma.

TNKS is a new target for the treatment of lung adenocarcinoma, the synergistic effects of the TCM compound Xiaoyan decoction and the TNKS inhibitor E7449 in the intervention on TNKS were investigated, and the possible underlying mechanisms involved were clarified. Immunohistochemistry was used to analyse TNKS expression in tumour tissues. The impact of targeting TNKS on cell growth, invasion, apoptosis, key genes and signalling pathways was investigated in tumour cells by Western blotting, rescue experiments, colony formation assays, flow cytometry and label-free experiments. Tumour xenografts with A549 cells were then transplanted for in vivo study. We found that TNKS high expression was closely related to the advanced tumour stage and tumour size in lung adenocarcinom. After TNKS was knocked down in vitro, the growth, proliferation, migration and invasion were markedly reduced in A549 and H1975 cells. We subsequently applied the Xiaoyan decoction and TNKS inhibitors to intervene in lung adenocarcinoma. Xiaoyan decoction and E7449 suppressed TNKS expression and inhibited adenocarcinoma cell proliferation, migration, invasion and apoptosis in vitro. Proteomic analysis revealed that E7449 treatment may be most closely associated with the classic Wnt/ß-catenin pathway, whereas Xiaoyan decoction treatment may be related to the WNT/PLAN pathway. Xenograft studies confirmed that E7449 or Xiaoyan decoction inhibited lung tumour growth in vivo and attenuated the Wnt signalling pathway in adenocarcinoma. These findings suggest that TNKS is a novel therapeutic target. TCM preparations and small molecule inhibitors are expected to constitute an effective combination strategy.

TYG Index as a Novel Predictor of Clinical Outcomes in Advanced Chronic Heart Failure with Renal Dysfunction Patients.

Background: The triglyceride-glucose (TYG) index is a novel and reliable marker reflecting insulin resistance. Its predictive ability for cardiovascular disease onset and prognosis has been confirmed. However, for advanced chronic heart failure (acHF) patients, the prognostic value of TYG is challenged due to the often accompanying renal dysfunction (RD). Therefore, this study focuses on patients with aHF accompanied by RD to investigate the predictive value of the TYG index for their prognosis. Methods and Results: 717 acHF with RD patients were included. The acHF diagnosis was based on the 2021 ESC criteria for acHF. RD was defined as the eGFR < 90 mL/(min/1.73 m2). Patients were divided into two groups based on their TYG index values. The primary endpoint was major adverse cardiovascular events (MACEs), and the secondary endpoints is all-cause mortality (ACM). The follow-up duration was 21.58 (17.98-25.39) months. The optimal cutoff values for predicting MACEs and ACM were determined using ROC curves. Hazard factors for MACEs and ACM were revealed through univariate and multivariate COX regression analyses. According to the univariate COX regression analysis, high TyG index was identified as a risk factor for MACEs (hazard ratio = 5.198; 95% confidence interval [CI], 3.702-7.298; P < 0.001) and ACM (hazard ratio = 4.461; 95% CI, 2.962-6.718; P < 0.001). The multivariate COX regression analysis showed that patients in the high TyG group experienced 440.2% MACEs risk increase (95% CI, 3.771-7.739; P < 0.001) and 406.2% ACM risk increase (95% CI, 3.268-7.839; P < 0.001). Kaplan-Meier survival analysis revealed that patients with high TyG index levels had an elevated risk of experiencing MACEs and ACM within 30 months. Conclusion: This study found that patients with high TYG index had an increased risk of MACEs and ACM, and the TYG index can serve as an independent predictor for prognosis.

Ordering Bimetallic Cu-Pd Catalysts onto Orderly Mesoporous SrTiO3-Crystal Nanotubular Networks for Efficient Carbon Dioxide Photoreduction.

Artificial photosynthesis of fuels has garnered significant attention, with SrTiO3 emerging as a potential candidate for photocatalysis due to its exceptional physicochemical properties. However, selectively converting CO2 into fuels with desired reaction products remains a grand challenge. Herein, we design an updated method via an aging strategy based on the electrospinning technique to synthesize a single-crystalline Al-doped SrTiO3 nanotubular networks with self-assembled orderly mesopores, further modified by Cu-Pd alloy. It exhibits both high crystallinity and superior cross-linked mesoporous structures, effectively facilitating charge carrier transfer, photon utilization, and mass transfer, with a remarkable enhancement from 0.025 mmol·h-1·m-2 to 1.090 mmol·h-1·m-2 in the CO production rate. Meanwhile, the ordered arrangement of Cu and Pd atoms on the (111) surface can promote the rate-determining step (*CO2 to *COOH), which is also responsible for its good activity. The presence of CuO in the reaction confers a significant advantage for CO desorption, leading to a remarkable CO selectivity of 95.54%. This work highlights new insights into developing advanced heterogeneous photocatalysts.

ZIF-8/g-C3N4 photocatalysts: enhancing CO2 reduction through improved adsorption and photocatalytic performance.

Nowadays, the widespread concern over controlling CO2 emissions and mitigating the adverse effects of greenhouse gases on global climate has attracted significant attention. In this study, g-C3N4 was synthesized by thermopolymerizing urea. Subsequently, ZIF-8 was combined with g-C3N4 using an in situ deposition method, resulting in the fabrication of ZIF-8/g-C3N4 composite photocatalysts at various molar ratios. Effective incorporation of ZIF-8 into g-C3N4 suppressed the recombination of photogenerated electrons and holes, thereby enhancing CO2 capture capacity and preserving light absorption capabilities. The ZIF-8/g-C3N4 composite demonstrates excellent photocatalytic performance for CO2 reduction, where the optimized material exhibited a CO2 adsorption capacity 1.52 times that of pure g-C3N4 and increased the conversion of CO2 to CH4 by more than sevenfold. This study harnesses the superior CO2 adsorption properties of metal-organic frameworks to develop more efficient photocatalysts, enhancing CO2 conversion efficacy and offering insights for developing efficient photocatalysts that utilize CO2.

1,5-Hydrogen atom transfer of α-iminyl radical cations: a new platform for relay annulation for pyridine derivatives and axially chiral heterobiaryls.

The exploitation of new reactive species and novel transformation modes for their synthetic applications have significantly promoted the development of synthetic organic methodology, drug discovery, and advanced functional materials. α-Iminyl radical cations, a class of distonic ions, exhibit great synthetic potential for the synthesis of valuable molecules. For their generation, radical conjugate addition to α,ß-unsaturated iminium ions represents a concise yet highly challenging route, because the in situ generated species are short-lived and highly reactive and they have a high tendency to cause radical elimination (ß-scission) to regenerate the more stable iminium ions. Herein, we report a new transformation mode of the α-iminyl radical cation, that is to say, 1,5-hydrogen atom transfer (1,5-HAT). Such a strategy can generate a species bearing multiple reactive sites, which serves as a platform to realize (asymmetric) relay annulations. The present iron/secondary amine synergistic catalysis causes a modular assembly of a broad spectrum of new structurally fused pyridines including axially chiral heterobiaryls, and exhibits good functional group tolerance. A series of mechanistic experiments support the α-iminyl radical cation-induced 1,5-HAT, and the formation of several radical species in the relay annulations. Various synthetic transformations of the reaction products demonstrate the usefulness of this relay annulation protocol for the synthesis of significant molecules.

Iodine intercalation-assisted alkali activation constructs coal-based porous carbon for high-performance supercapacitors.

Supercapacitors have the advantages of fast charging and discharging speeds, high power density, long cycle life, and wide operating temperature range. They are widely used in portable electronic equipment, rail transit, industry, military, aerospace, and other fields. The design and preparation of low-cost, high-performance electrode materials still pose a bottleneck that hinders the development of supercapacitors. In this paper, coal was used as the raw material, and the coal-based porous carbon electrode material was constructed using the iodine intercalation-assisted activation method and used for supercapacitors. The CK-700 electrode exhibits excellent charge storage performance in a 6 M potassium hydroxide (KOH) electrolyte, with a maximum specific capacitance of 350 F/g at a current density of 0.5 A/g. In addition, it has an excellent rate performance (310 F/g at 1 A/g) and cycle stability (capacitance retention up to 91.7 % after 30000 cycles). This work provides a method for realizing high-quality, high-yield and low-cost preparation of coal-based porous carbon, and an idea for improving the performance of supercapacitors.

A CT based radiomics analysis to predict the CN0 status of thyroid papillary carcinoma: a two- center study.

OBJECTIVES: To develop and validate radiomics model based on computed tomography (CT) for preoperative prediction of CN0 status in patients with papillary thyroid carcinoma (PTC). METHODS: A total of 548 pathologically confirmed LNs (243 non-metastatic and 305 metastatic) two distinct hospitals were retrospectively assessed. A total of 396 radiomics features were extracted from arterial-phase CT images, where the strongest features containing the most predictive potential were further selected using the least absolute shrinkage and selection operator (LASSO) regression method. Delong test was used to compare the AUC values of training set, test sets and cN0 group. RESULTS: The Rad-score showed good discriminating performance with Area Under the ROC Curve (AUC) of 0.917(95% CI, 0.884 to 0.950), 0.892 (95% CI, 0.833 to 0.950) and 0.921 (95% CI, 868 to 0.973) in the training, internal validation cohort and external validation cohort, respectively. The test group of CN0 with a AUC of 0.892 (95% CI, 0.805 to 0.979). The accuracy was 85.4% (sensitivity = 81.3%; specificity = 88.9%) in the training cohort, 82.9% (sensitivity = 79.0%; specificity = 88.7%) in the internal validation cohort, 85.4% (sensitivity = 89.7%; specificity = 83.8%) in the external validation cohort, 86.7% (sensitivity = 83.8%; specificity = 91.3%) in the CN0 test group.The calibration curve demonstrated a significant Rad-score (P-value in H-L test > 0.05). The decision curve analysis indicated that the rad-score was clinically useful. CONCLUSIONS: Radiomics has shown great diagnostic potential to preoperatively predict the status of cN0 in PTC.

Solution-Processed One-Dimensional Photonic Crystals Based on Hollow Silica Exhibiting High Refractive Index Contrast.

Poor interfacial quality and low refractive index contrast (Δn) are critical challenges for the development of high-performance one-dimensional photonic crystals (1DPhCs) via solution methods that impede their optical efficiency. Herein, we introduce an innovative approach by hybridizing hollow SiO2 with poly(vinyl alcohol), referred to as PHS, followed by alternate assembly with TiO2 via spin-coating, achieving a 1DPhC with Δn = 0.76 at the wavelength of 550 nm. This method circumvents the need for high-temperature treatment and complex curing conditions, resulting in a 1DPhC with superior interfacial and optical characteristics. By adjusting the thickness of the PHS layers, we can finely tune the reflectance spectrum, attaining over 99% reflectance at the photonic band gap. Furthermore, 1DPhC demonstrates excellent adhesion to polycarbonate substrates and retains its optimal optical performance even after rigorous environmental testing, including hygrothermal cycles, exposure to hot water, friction, and solvent sonication. This research paves the way for the facile fabrication of high-performance 1DPhCs under mild conditions, offering new perspectives for photonic material processing.

Tunable Optical Anisotropy in Rare-Earth Borates with Flexible [BO3] Clusters.

Borates have garnered a lot of attention in the realm of solid-state chemistry due to their remarkable characteristics, in which the synthesis of borates with isolated [BO3] by adding rare-earth elements is one of the main areas of structural design study. Five new mixed-metal Y-based rare-earth borates, Ba2ZnY2(BO3)4, KNa2Y(BO3)2, Li2CsY4(BO3)5, LiRb2Y(BO3)2, and RbCaY(BO3)2, have been discovered using the high-temperature solution approach. Isolated [BO3] clusters arranged in various configurations comprise their entire anionic framework, allowing for optical anisotropy tuning between 0.024 and 0.081 under 1064 nm. In this study, we characterize the relative placements of their [BO3] groups and examine how their structure affects their characteristics. The origin of their considerable optical anisotropy has been proven theoretically. This study unequivocally demonstrates that even a slight alteration to borates' anionic structure can result in a significant improvement in performance.

Enhancement of PLA crystallization, transparency, and strength by adding the long aliphatic chains grafted CNC.

The combination of crystallization, transparency, and strength is still a challenge for broadening the application of polylactic acid (PLA) films, while it is also difficult to balance. In this work, the long aliphatic chains of octadecylamine (ODA) were grafted onto the surface of cellulose nanocrystal (CNC) by tannic acid oxidation self-polymerization and Michael addition/Schiff base reaction between polytannic acid and ODA. Furthermore, the ODA grafted CNC (g-CNC) was used as green reinforcement for the PLA matrix and a series of PLA/g-CNC nanocomposite films were prepared by the casting method. The DSC, WAXD, POM, UV-vis and stretching test were employed to examine the effect of g-CNC on the properties of the as-prepared PLA/g-CNC nanocomposite films. It shows that the g-CNC is effective to improve the melt crystallization rate of PLA from 11 min to 7.3 min. Most importantly, the crystal size of the PLA spherulites was significantly reduced due to the well dispersion in the amorphous PLA matrix, which would effectively improve the transmittance of the PLA films and synchronously realize the combination of crystallization (62 %) and transparency (80.6 %). Moreover, the improved crystallization could also enhance the heat deformation performance of the PLA films since the heat resistance is closely associated with the crystallinity. Besides, the grafted ODA long chains improve the compatibility between CNC and PLA, leading to the reinforcement of PLA matrix, where the tensile strength reaches 65.05 MPa from 44.31 MPa. Compared with the pristine CNC, the addition of g-CNC makes more comprehensive improvement in the properties of the PLA films.

Complete mitochondrial genome sequence and phylogenetic analysis of Tylopilus brunneirubens (Boletales, Basidiomycota).

Tylopilus brunneirubens is a common species in southern China. It is known for brown to dark brown pileus, white context turning reddish brown or rust brown when touched and distinct reticulation on the upper stem. However, little is known about its mitochondrial genome and its relationship with other boletes. Our analysis revealed that the mitochondrial genome of this species is a circular DNA molecule that spans 32,389 bp. It contains 15 core protein-coding genes, 24 transfer RNA genes, and two ribosomal RNA genes. The base composition of the mitochondrial genome is as follows: A (37.20%), C (11.32%), G (12.48%), and T (39.00%), with a GC content of 23.80%. Furthermore, a phylogenetic tree based on 24 mitochondrial genomes provided valuable insights into the phylogenetic relationships of Tylopilus brunneirubens with other boletes for the first time.

Clinical Analysis of Risk Factors and Perinatal Outcomes in Recurrent Pre-Eclampsia with Severe Features.

To analyze the differences in risk factors and pregnancy outcomes between recurrent and initial pre-eclampsia(PE) with severe features. Data from recurrent (n = 128) and initial (n = 904) PE with severe features who terminated their pregnancy or gave birth at 20 weeks of gestation or later at the tertiary teaching hospital (Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital) from January 2016 to December 2022 were collected. Risk factors for recurrent PE with severe features and differences in pregnancy outcomes between the two groups were assessed using the chi-square test, student t-test, or nonparametric test. Independent risk factors for recurrent PE with severe features were further analyzed by logistic regression. (1) Logistic regression analysis identified 3 independent risk factors for recurrent PE with severe features: history of cesarean section, rural residence and chronic hypertension. In addition, assisted reproductive technology (ART) is an independent risk factor for initial PE with severe features; (2) The incidence of oligohydramnios, chorioamnionitis, preterm birth, stillbirth, fetal growth restriction (FGR) and abnormal umbilical blood flow was higher in the recurrent PE with severe features group than in the initial PE with severe features group(P < 0.05). In contrast, the incidence of premature rupture of membrane (PROM) and postpartum hemorrhage (PPH) was higher in the group of initial PE with severe features(P < 0.05); (3) In the recurrent PE with severe features group, gestational age(GA) of birth and birth weight were lower than those in the initial PE with severe features group(P < 0.05). Also, the incidence of mild asphyxia, the rate of neonatal intensive care unit (NICU) hospitalization, length of stay in NICU, and the rate of abandoning treatment in the recurrent PE with severe features group were higher than those in the initial PE with severe features group(P < 0.05). 3 independent risk factors was identified for recurrent PE with severe features: history of cesarean section, rural residence and chronic hypertension. Women with recurrent PE with severe features are more likely to have adverse perinatal outcomes than those with initial PE with severe features.

Synthesis, Characterization, and Antifungal Activity of Benzimidazole-Grafted Chitosan against Aspergillus flavus.

Aspergillus flavus contamination in agriculture and food industries poses threats to human health, leading to a requirement of a safe and effective method to control fungal contamination. Chitosan-based nitrogen-containing derivatives have attracted much attention due to their safety and enhanced antimicrobial applications. Herein, a new benzimidazole-grafted chitosan (BAC) was synthesized by linking the chitosan (CS) with a simple benzimidazole compound, 2-benzimidazolepropionic acid (BA). The characterization of BAC was confirmed by Fourier transform infrared (FTIR) spectroscopy and nuclear magnetic resonance spectroscopy (1H and 13C NMR). Then, the efficiency of BAC against A. flavus ACCC 32656 was investigated in terms of spore germination, mycelial growth, and aflatoxin production. BAC showed a much better antifungal effect than CS and BA. The minimum inhibitory concentration (MIC) value was 1.25 mg/mL for BAC, while the highest solubility of CS (16.0 mg/mL) or BA (4.0 mg/mL) could not completely inhibit the growth of A. flavus. Furthermore, results showed that BAC inhibited spore germination and elongation by affecting ergosterol biosynthesis and the cell membrane integrity, leading to the permeabilization of the plasma membrane and leakage of intracellular content. The production of aflatoxin was also inhibited when treated with BAC. These findings indicate that benzimidazole-derived natural CS has the potential to be used as an ideal antifungal agent for food preservation.

A Multiplex Fluorescence of Loop Primer Upon Self-Dequenching Loop-Mediated Isothermal Amplification Assay for the Detection of Epstein-Barr Virus and Human Parvovirus B19 in Clinical Transplant Samples.

Viral infections are major causes of mortality in solid-organ and hematopoietic stem cell transplant recipients. Epstein-Barr virus (EBV) and Parvovirus B19 (B19V) are among the common viral infections after transplantation and were recommended for increased screening in relevant guidelines. Therefore, the development of rapid, specific, and cost-effective diagnostic methods for EBV and B19V is of paramount importance. We applied Fluorescence of Loop Primer Upon Self-Dequenching Loop-mediated Isothermal Amplification (FLOS-LAMP) for the first time to develop a novel multiplex assay for the detection of EBV and B19V; the fluorophore attached to the probe are self-quenched in unbound state. After binding to the dumbbell-shaped DNA target, the fluorophore is dequenched, resulting in fluorescence development. The novel multiplex FLOS-LAMP assay was optimized by testing various ratios of primer sets. This novel assay, with great specificity, did not cross-react with the common virus. For the detection of EBV and B19V, the limits of detection could reach 969 and 798 copies/µL, respectively, and the assay could be completed within 25 min. Applying this novel assay to detect 200 clinical transplant individuals indicated that the novel assay had high specificity and good sensitivity. We developed multiplex FLOS-LAMP assay for the detection of EBV and B19V, which has the potential to become an important tool for clinical transplant patient screening.

Long non-coding RNA NORAD regulates megakaryocyte differentiation and proplatelet formation via the DUSP6/ERK signaling pathway.

Megakaryopoiesis and platelet production is a complex process that is underpotential regulation at multiple stages. Many long non-coding RNAs (lncRNAs) are distributed in hematopoietic stem cells and platelets. lncRNAs may play important roles as key epigenetic regulators in megakaryocyte differentiation and proplatelet formation. lncRNA NORAD can affect cell ploidy by sequestering PUMILIO proteins, although its direct effect on megakaryocyte differentiation and thrombopoiesis is still unknown. In this study, we demonstrate NORAD RNA is highly expressed in the cytoplasm during megakaryocyte differentiation. Interestingly, we identified for the first time that NORAD has a strong inhibitory effect on megakaryocyte differentiation and proplatelet formation from cultured megakaryocytes. DUSP6/ERK1/2 pathway is activated in response to NORAD knockdown during megakaryocytopoiesis, which is achieved by sequestering PUM2 proteins. Finally, compared with the wild-type control mice, NORAD knockout mice show a faster platelet recovery after severe thrombocytopenia induced by 6 Gy total body irradiation. These findings demonstrate lncRNA NORAD has a key role in regulating megakaryocyte differentiation and thrombopoiesis, which provides a promising molecular target for the treatment of platelet-related diseases such as severe thrombocytopenia.

FNIRS based study of brain network characteristics in children with cerebral palsy during bilateral lower limb movement.

BACKGROUND: Motor dysfunctions in children with cerebral palsy (CP) are caused by nonprogressive brain damage. Understanding the functional characteristics of the brain is important for rehabilitation. PURPOSE: This paper aimed to study the brain networks of children with CP during bilateral lower limb movement using functional near-infrared spectroscopy (fNIRS) and to explore effective fNIRS indices for reflecting functional brain activity. METHODS: Using fNIRS, cerebral oxygenation signals in the bilateral prefrontal cortex (LPFC/RPFC) and motor cortex (LMC/RMC) were recorded from fifteen children with spastic CP and seventeen children with typical development (CTDs) in the resting state and during bilateral lower limb movement. Functional connectivity matrices based on phase-locking values (PLVs) were calculated using Hilbert transformation, and binary networks were constructed at different sparsity levels. Network metrics such as the clustering coefficient, global efficiency, local efficiency, and transitivity were calculated. Furthermore, the time-varying curves of network metrics during movement were obtained by dividing the time window and using sparse inverse covariance matrices. Finally, conditional Granger causality (GC) was used to explore the causal relationships between different brain regions. RESULTS: Compared to CTDs, the connectivity between RMC-RPFC (p = 0.017) and RMC-LMC (p = 0.002) in the brain network was decreased in children with CP, and the clustering coefficient (p = 0.003), global efficiency (p = 0.034), local efficiency (p = 0.015), and transitivity (p = 0.009) were significantly lower. The standard deviation of the changes in global efficiency of children with CP during motion was also greater than that of CTDs. Using GC, it was found that there was a significant increase in causal strength from the RMC to the RPFC (p = 0.04) and from the RMC to the LMC (p = 0.042) in children with CP during motion. Additionally, there were significant negative correlations between the PLV of LMC-RMC (p = 0.002) and the Gross Motor Function Classification System (GMFCS) and between the GMFCS and the clustering coefficient (p = 0.01). CONCLUSIONS: During rehabilitation training of the lower limbs, there were significant differences in brain network indices between children with CP and CTDs. The indicators proposed in this paper are effective at evaluating motor function and the real-time impact of rehabilitation training on the brain network and have great potential for application in guiding clinical motor function assessment and planning rehabilitation strategies.