Genome variations in sea cucumbers: Insights from genome survey sequencing and comparative analysis of mitochondrial genomes.

Sea cucumbers, marine benthic invertebrates, play crucial roles in maintaining the stability of marine ecosystems and hold key evolutionary positions. However, information regarding their genomes remains limited. Here, we conducted genome survey analyses on seven species from four orders. Results indicated that Colochirus anceps, Colochirus quadrangularis, and Pseudocolochirus violaceus within the order Dendrochirotida have significantly larger genomes (2238-3754 Mbp) compared to conventional sea cucumber genomes, accompanied by a very high proportion of repeat sequences (69.39-72.52 %). While Holothuria edulis and Holothuria atra exhibited similar genome sizes comparable to those of other species within the order Holothuriida, heterozygosity and repeat content varied among all the six species in this order. The representative species Apostichopus californicus of the order Synallactida possesses the smallest genome size (573.45Mbp) within its order, but its heterozygosity (2.24 %) is significantly higher than that of other species. The representative species Synapta maculata of the order Apodida exhibited a normal genome size (900.97 Mbp), lower proportion of repeat sequences (42.19 %), and lower heterozygosity (0.84 %), making it the species with the least challenges for genome sequencing and assembly in the future among all surveyed species. Subsequently, we compiled genomic information from a total of 19 sea cucumber genomes, both newly sequenced and previously reported, revealing a significant linear relationship (P = 0.0001) between genome size and the proportion of repeat sequences in sea cucumbers. Additionally, phylogenetic and comparative analysis of mitochondrial genomes among them indicated extensive rearrangements within the order Apodida, leading to significant discrepancies between mitochondrial and nuclear genome phylogenies.

Formation of thermal-induced microgels from soy protein hydrolysates: Effects of selective proteolysis on glycinin/ß-conglycinin.

This study explored the impact of selective proteolysis on the formation of thermally induced soy protein microgels. Glycinin hydrolysate (GH) and ß-conglycinin hydrolysate (CH) were obtained by subjecting soy protein isolate to selective proteolysis for different hydrolysis time (10-90 min), as confirmed by SDS-PAGE. In the early stages of hydrolysis, free sulfhydryl, surface hydrophobicity, storage modulus (G') and loss modulus (G″) of GH and CH increased, which enhanced their gelling potential. However, as hydrolysis time increased, the gel properties of the hydrolysates progressively weakened. Structural characterization of microgels revealed that GH yielded microgels with smaller particle sizes and coarser and relatively dispersed granular structures, while CH resulted in microgels with lower potential values, smoother surfaces, and lumps resembling strand-like formations. Analysis of the structure and intermolecular force of microgels showed that the microgel formed by the GH gradually tended to be disordered, whereas the secondary structure of microgels formed by CH showed lower random coil content, resulting in a dense gel network aggregated through disulfide bonding, hydrophobic interactions and hydrogen bonding as demonstrated by frequency-dependent storage moduli measurements. Overall, this study presents a thorough characterization of microgels and shows that they can be tailored by selective proteolysis, which enables controlling the ß-conglycinin/glycinin ratio of soy protein.

Characterization of volatile organic compounds in walnut oil with various oxidation levels using olfactory analysis and HS-SPME-GC/MS.

Walnut oil oxidizes and becomes rancid during storage, that could be significantly affecting flavor and quality. This study aimed to monitor the volatile compounds present in walnut oil during storage, identify the characteristic markers of walnut oil at different oxidation levels, and establish a correlation network analysis based on the relationship between the olfactory analyzer and the characteristic markers to understand their correlation. The results indicated that the oxidation level of walnut oil had a positive correlation with the response of the olfactory analyzer. 219 volatile compounds were identified in walnut oil, with 89 identified as key volatile compounds (VIP >1). Among these, compounds such as (E, E)-2,4-decadienal (6.10%-23.04%)，(E, E)-2,4-heptadienal (2.23%-13.61%)，(E)-2-octenal (0.95%-11.71%)， hexanoic acid (1.63%-4.30%)，1-octen-3-ol (2.53%-19.01%)，(Z)-2-heptenal (5.95%-25.01%)，2,3-dihydro-furan (1.08%-3.20%)，2-pentyl-furan (0.13%-0.54%), pyrazine (0.33%-1.32%), hexanal (24.52%-1.33%)，3-hethylbutylacetate (12.44%-1.29%)， 2-methyl butyl acetate (7.74%-1.56%) and ethenyl hexanoate (4.39%-0.41%) were found to be characteristic volatile compounds in the oxidation process of walnut oil. Furthermore, the correlation network analysis revealed a strong correlation between the olfactory analyzer sensors and the characteristic volatile compounds. The findings of this study can provide valuable data for the development of rapid determination of the oxidation level of walnut oil.

Development and validation of a prognostic nomogram to predict the recurrence of AFP-negative and DCP-positive hepatocellular carcinoma after curative resection.

Purpose: Approximately one-third of hepatocellular carcinoma (HCC) cases are characterized by alpha-fetoprotein (AFP) negativity (AFP-NHCC. Among these patients, around 60% exhibit des-gamma-carboxyprothrombin (DCP) positivity, and DCP-positive patients have a poorer prognosis. As a curative treatment, recurrence after liver resection poses significant challenges to the prognosis of HCC patients. Therefore, it is necessary to determine the relevant risk factors of these patients and provide timely treatment options. Methods: This study included 540 patients who underwent resection at Beijing You'an Hospital. 292 patients from 2014 to 2018 constituted the training cohort, while 248 patients from 2018 to 2020 constituted the validation cohort. All patients underwent routine follow-ups until December 2023. Variables were identified through Cox regression, and a nomogram was developed. The nomogram was evaluated using time-dependent receiver operating characteristic curves (ROC), calibration curves, Decision curve analysis (DCA), and Kaplan-Meier (KM) curve analysis. Results: We found that age, tumor number, tumor size, γ-glutamyl transpeptidase (γ-GT), and prothrombin time (PT) are independent risk factors for HCC recurrence, and a nomogram was developed and validated based on this result to predict recurrence-free survival (RFS) at 1, 2, and 3 years. The performance of the nomogram was further confirmed by the ROC curve, calibration curve, and DCA, all of which showed favorable results. The KM curve analysis clearly distinguishes between two groups of people with different risks in terms of prognosis in both the training and validation sets. Conclusion: In summary, we established and validated a novel nomogram by multivariate Cox regression analysis to predict recurrence in DCP-positive patients with AFP-NHCC after resection. The nomogram, including age, tumor number, tumor size, γ-GT, and PT, demonstrates better predictive ability for AFP-NHCC patients with DCP positive.

Novel 4-chlorophenoxyacetate dioxygenase-mediated phenoxyalkanoic acid herbicides initial catabolism in Cupriavidus sp. DL-D2.

Microbial metabolism is an important driving force for the elimination of 4-chlorophenoxyacetic acid residues in the environment. The α-Ketoglutarate-dependent dioxygenase (TfdA) or 2,4-D oxygenase (CadAB) catalyzes the cleavage of the aryl ether bond of 4-chlorophenoxyacetic acid to 4-chlorophenol, which is one of the important pathways for the initial metabolism of 4-chlorophenoxyacetic acid by microorganisms. However, strain Cupriavidus sp. DL-D2 could utilize 4-chlorophenoxyacetic acid but not 4-chlorophenol for growth. This scarcely studied degradation pathway may involve novel enzymes that has not yet been characterized. Here, a gene cluster (designated cpd) responsible for the catabolism of 4-chlorophenoxyacetic acid in strain DL-D2 was cloned and identified, and the dioxygenase CpdA/CpdB responsible for the initial degradation of 4-chlorophenoxyacetic acid was successfully expressed, which could catalyze the conversion of 4-chlorphenoxyacetic acid to 4-chlorocatechol. Then, an aromatic cleavage enzyme CpdC further converts 4-chlorocatechol into 3-chloromuconate. The results of substrate degradation experiments showed that CpdA/CpdB could also degrade 3-chlorophenoxyacetic acid and phenoxyacetic acid, and homologous cpd gene clusters were widely discovered in microbial genomes. Our findings revealed a novel degradation mechanism of 4-chlorophenoxyacetic acid at the molecular level.

Vitamin D level as a predictor of dysmobility syndrome with type 2 diabetes.

Dysmobility Syndrome (DMS), is a combination, that is analogous to the approach taken with metabolic syndrome, The diagnosis of DMS is complex. So this study aimed to explore the relationship between 25-(OH) Vit D with Dysmobility Syndrome (DMS)in type 2 diabetes mellitus(T2DM) patients. This is a cross-sectional study, including 330 patients (67.0 ± 8.8 years old) with T2DM who were admitted to the Qinhuangdao First Hospital from October 2020 to February 2022. Selected independent variables include grip strength, six-meter gait speed, level of 25-(OH) vitamin D, and bone mineral density (BMD) measured by Dual-energy X-ray (DXA). DMS includes six conditions: osteoporosis, low muscle mass, low muscle strength, slow gait speed, occurrences of falls in the past year ≥ 1, and obesity, having three or more of these conditions were diagnosed with DMS. Patients were classified based on DMS. The detection rate of DMS in patients with T2DM was 25.5%. The proportion of vitamin deficiency is 67.9% in patients with T2DM. The 25-(OH) Vit D deficiency was defined based on the 25th percentile into two groups; < 36.2 nmol/L. The vitamin D levels in Group DMS were significantly lower than that in Group Non-DMS (41.74 ± 14.60 vs. 47.19 ± 13.01, P < 0.05). After adjusting confounder factors including sex, age, vitamin D levels, HbA1c, ALB, HDLC, eGFR, diabetes microvascular complications and macrovascular, there was an independent association between risk of DMS and age (OR value = 1.160, 95% CI 1.091-1.234, P = 0.000), HbA1c(OR value = 1.262, 95% CI 1.046-1.532, P = 0.015), and vitamin D deficiency (< 36.2 nmol/L) (OR value = 2.990, 95% CI 1.284-6.964, P = 0.011). Our findings suggest that low levels of vitamin D are a predictor of DMS in middle-aged and elderly patients with poor control of type 2 diabetes.

Development of Reliable Male-Specific Molecular Markers for Genetic Sex Identification in Sea Cucumber Apostichopus japonicus.

Apostichopus japonicus is an important marine aquaculture species in China, with high nutritional and economic value. In A. japonicus, there is no obvious sexual dimorphism in external appearance, and sex differentiation primarily relies on the observation of mature gonads after dissection, which leads to difficulties in sex identification. The confusion in sex identification greatly reduces breeding efficiency in the sea cucumber industry. Therefore, developing a reliable sex-specific marker is crucial. In this study, we identified 586 male-specific sequences through whole-genome assembly and sequence alignment, but did not identify any female-specific sequences, inferring an XY-type sex determination system in sea cucumbers. We developed a set of male-specific molecular markers to establish an accurate, stable, and widely adaptable genetic sex identification technique for A. japonicus. The male-specific molecular markers were validated with 100% accuracy in sea cucumber populations from six different geographical regions in China. In conclusion, this study provides further evidence for the XY-type sex determination system in A. japonicus and establishes an effective genetic sex identification method for multi-geographic populations, which benefits future study on reproductive biology and has significant implications in sea cucumber aquaculture industry.

Ozone rectal insufflation mitigates chronic rapid eye movement sleep deprivation-induced cognitive impairment through inflammation alleviation and gut microbiota regulation in mice.

A range of sleep disorders has the potential to adversely affect cognitive function. This study was undertaken with the objective of investigating the effects of ozone rectal insufflation (O3-RI) on cognitive dysfunction induced by chronic REM sleep deprivation, as well as elucidating possible underlying mechanisms. O3-RI ameliorated cognitive dysfunction in chronic REM sleep deprived mice, improved the neuronal damage in the hippocampus region and decreased neuronal loss. Administration of O3-RI may protect against chronic REM sleep deprivation induced cognitive dysfunction by reversing the abnormal expression of Occludin and leucine-rich repeat and pyrin domain-containing protein 3 inflammasome as well as interleukin-1ß in the hippocampus and colon tissues. Moreover, the microbiota diversity and composition of sleep deprivation mice were significantly affected by O3-RI intervention, as evidenced by the reversal of the Firmicutes/Bacteroidetes abundance ratio and the relative abundance of the Bacteroides genus. In particular, the relative abundance of the Bacteroides genus demonstrated a pronounced correlation with cognitive impairment and inflammation. Our findings suggested that O3-RI can improve cognitive dysfunction in sleep deprivation mice, and its mechanisms may be related to regulating gut microbiota and alleviating inflammation and damage in the hippocampus and colon.

Effects of dietary arginine supplementation on muscle structure, meat characteristics and lipid oxidation products in lambs and its potential mechanisms of action.

This study aimed to assess the effect of dietary arginine supplementation on muscle structure and meat characteristics of lambs also considering lipid oxidation products and to contribute to reveal its mechanisms of action using tandem mass tagging (TMT) proteomics. Eighteen lambs were allocated to two dietary treatment groups: control diet or control diet with the addition of 1% L-arginine. The results revealed that dietary arginine supplementation increased muscle fibre diameter and cross-sectional area (P < 0.05), which was attributable to protein deposition, as evidenced by increased RNA content, RNA/DNA ratio, inhibition of apoptotic enzyme activity, and alterations in the IGF-1/Akt signaling pathway (P < 0.05). In addition, dietary arginine elevated pH24h, a* values, and IMF content, decreased shear force value and backfat thickness (P < 0.05), as well as decreased the formation of lipid oxidation products involved in meat flavor including hexanal, heptanal, octanal, nonanal and 1-octen-3-ol by increasing the antioxidant capacity of the muscle (P < 0.05). The proteomics results suggested that seven enrichment pathways may be potential mechanisms by which arginine affected the muscle structure and meat characteristics of lambs. In summary, arginine supplementation in lamb diets provides a safe and effective way to improve meat quality, and antioxidant capacity of muscle of lamb.

Mechanistic analysis of the hardening process of the thorns on stems of Bougainvillea glabra "Elizabeth Angus".

Introduction: Bougainvillea glabra "Elizabeth Angus" is a thorny woody vine or shrub. However, the hard thorns are considered a deficiency in its ornamental value. Methods: To find the genes and pathways related to the hardening process of the thorns on the stems of B. glabra, the eukaryotic unreferenced transcriptome sequencing analysis was conducted to explore the 3 stages of the thorn-hardening process. Total RNA was extracted from thorns and stems, and transcriptome libraries were constructed and sequenced using unreferenced Illumina sequencing. Results: Gene function annotation was performed using various databases, resulting in 8937 co-annotated genes. The density distribution of Fragments Per Kilobase of transcript per Million mapped reads (FPKM) depicted the overall gene expression patterns. The study found that stage 2 as the period of highest gene expression activity during the thorns hardening process in B. glabra. Differential expression analysis revealed that during thorn-hardening, 1045 genes up-regulated and 391 genes down-regulated significantly in thorns at stage 2 compared to stage 1 (early stage of thorns formation). Meanwhile, 938 genes up-regulated and 784 genes down-regulated significantly in stems. At stage 3, as thorns became harder, 63 genes exhibited notable expression increase and 98 genes' expression decreased obviously within thorns, and 46 genes up-regulated and 29 genes down-regulated in stems, compared to stage 2. Phenylpropanoid biosynthesis was the key step in the hardening process of the thorns of B. glabra. The formation and hardening of thorns on the stem of B. glabra was a process in which lignin gradually accumulated in the thorns, and several genes were involved in this process. They include PAL (EC:4.3.1.24), CYP73A (EC:1.14.14.91), 4CL (EC:6.2.1.12), CCR (EC:1.2.1.44), CAD (EC:1.1.1.195) and POX (EC:1.11.1.7). Discussion: This transcriptome analysis offers insights into the molecular mechanisms underlying thorns development in this plant species.

Med1 controls thymic T-cell migration into lymph node through enhancer-based Foxo1-Klf2 transcription program.

The migration is the key step for thymic T cells to enter circulation and then lymph nodes (LNs), essential for future immune surveillance. Although promoter-based transcriptional regulation through Foxo1, Klf2, Ccr7, and Sell regulates T-cell migration, it remains largely unexplored whether and how enhancers are involved in this process. Here we found that the conditional deletion of Med1, a component of the mediator complex and a mediator between enhancers and RNA polymerase II, caused a reduction of both CD4+ and CD8+ T cells in LNs, as well as a decrease of CD8+ T cells in the spleen. Importantly, Med1 deletion hindered the migration of thymic αßT cells into the circulation and then into LNs, accompanied by the downregulation of KLF2, CCR7, and CD62L. Mechanistically, Med1 promotes Klf2 transcription by facilitating Foxo1 binding to the Klf2 enhancer. Furthermore, forced expression of Klf2 rescued Ccr7 and Sell expression, as well as αßT-cell migration into LNs. Collectively, our study unveils a crucial role for Med1 in regulating the enhancer-based Foxo1-Klf2 transcriptional program and the migration of αßT cells into LNs, providing valuable insights into the molecular mechanisms underlying T-cell migration.

Deficiency of m 6 A RNA methylation promotes ZBP1-mediated cell death.

m 6 A RNA methylation suppresses the immunostimulatory potential of endogenous RNA. Deficiency of m 6 A provokes inflammatory responses and cell death, but the underlying mechanisms remain elusive. Here we showed that the noncoding RNA 7SK gains immunostimulatory potential upon m 6 A depletion and subsequently activates the RIG-I/MAVS axis to spark interferon (IFN) signaling cascades. Concomitant excess of IFN and m 6 A deficiency synergistically facilitate the formation of RNA G-quadruplexes (rG4) to promote ZBP1-mediated necroptotic cell death. Collectively, our findings delineate a hitherto uncharacterized mechanism that links m 6 A dysregulation with ZBP1 activity in triggering inflammatory cell death.

Ecotoxicity of thallium to two soil animal species with different niches and modification by organic materials.

Soil thallium (Tl) contamination is of major public concern but little is known about soil Tl ecological toxicity or potential ecological remediation strategies. Here, two soil animal species with different ecological niches, Folsomia candida and Enchytraeus crypticus, were used to test Tl toxicity and modification by exogenous organic materials (i.e. maize straw and biochar). The endpoints of Tl ecotoxicity to F. candida and E. crypticus were studied at two biological levels, i.e., the individual (body Tl concentrations) and the population (survival, reproduction, and growth). Thallium concentrations in F. candida and E. crypticus increased with increasing soil Tl concentration, and their survival and reproduction rates decreased with increasing soil Tl concentration. The LC50 value of Tl effects on F. candida mortality (28 d) was 24.0 mg kg-1 and the EC50 value of reproduction inhibition was 6.51 mg kg-1. The corresponding values were 4.15 mg kg-1 and 2.31 mg kg-1 respectively for E. crypticus showing higher sensitivity to soil Tl than F. candida. These effective values are comparable to or much lower than the environmental Tl concentrations in field soils, suggesting high potential ecological risk. Both biochar and straw can decrease animal body Tl concentrations in different ways, i.e. reducing Tl availability or offering clean food sources, and addition of exogenous organic materials clearly mitigated Tl ecotoxicity in highly polluted soil. The results highlight the potential Tl ecological risk to soil animals and the potential use of organic materials to control the toxicity.

A "Dual-Key-and-Lock" MRI Contrast Agent with T1-T2 Switchable Function for Accurate Diagnosis of Tumors.

Extremely small iron oxide nanoparticle (ESIONP)-based stimuli-responsive switchable MRI contrast agents (CAs) show great promise for accurate detection of tumors due to their outstanding advantages of high specificity and low background signal. However, currently developed ESIONP-based switchable CAs often suffer single-biomarker-induced responses, which lack absolute specificity to pathological tissues, potentially diminishing diagnostic accuracy. In this study, weak acidity and hypoxia, two of the most remarkable characteristics of tumors, are introduced as dual biomarker stimuli to construct an ESIONP-based switchable MRI CA (DKL-CA), with its signal switch controlled by a "dual-key-and-lock" strategy. Only when DKL-CA is exposed to a coexisting weakly acidic and hypoxic environment can monodispersed ESIONPs form nanoclusters, thereby realizing a switch from the T1 to T2 contrast. Moreover, DKL-CA exhibits favorable biosafety and the capacity for precise tumor diagnosis in tumor-bearing mice. Overall, DKL-CA paves the way for designing highly accurate ESIONP-based MRI CAs for tumor diagnosis.

Construction of a Novel Vanillin-Induced Autoregulating Bidirectional Transport System in a Vanillin-Producing E. coli Cell Factory.

Vanillin is one of the world's most extensively used flavoring agents with high application value. However, the yield of vanillin biosynthesis remains limited due to the low efficiency of substrate uptake and the inhibitory effect on cell growth caused by vanillin. Here, we screened high-efficiency ferulic acid importer TodX and vanillin exporters PP_0178 and PP_0179 by overexpressing genes encoding candidate transporters in a vanillin-producing engineered Escherichia coli strain VA and further constructed an autoregulatory bidirectional transport system by coexpressing TodX and PP_0178/PP_0179 with a vanillin self-inducible promoter ADH7. Compared with strain VA, strain VA-TodX-PP_0179 can efficiently transport ferulic acid across the cell membrane and convert it to vanillin, which significantly increases the substrate utilization rate efficiency (14.86%) and vanillin titer (51.07%). This study demonstrated that the autoregulatory bidirectional transport system significantly enhances the substrate uptake efficiency while alleviating the vanillin toxicity issue, providing a promising viable route for vanillin biosynthesis.

Targeting a disintegrin and metalloprotease (ADAM) 17-CD122 axis enhances CD8+ T cell effector differentiation and anti-tumor immunity.

CD8+ T cell immune responses are regulated by multi-layer networks, while the post-translational regulation remains largely unknown. Transmembrane ectodomain shedding is an important post-translational process orchestrating receptor expression and signal transduction through proteolytic cleavage of membrane proteins. Here, by targeting the sheddase A Disintegrin and Metalloprotease (ADAM)17, we defined a post-translational regulatory mechanism mediated by the ectodomain shedding in CD8+ T cells. Transcriptomic and proteomic analysis revealed the involvement of post-translational regulation in CD8+ T cells. T cell-specific deletion of ADAM17 led to a dramatic increase in effector CD8+ T cell differentiation and enhanced cytolytic effects to eliminate pathogens and tumors. Mechanistically, ADAM17 regulated CD8+ T cells through cleavage of membrane CD122. ADAM17 inhibition led to elevated CD122 expression and enhanced response to IL-2 and IL-15 stimulation in both mouse and human CD8+ T cells. Intriguingly, inhibition of ADAM17 in CD8+ T cells improved the efficacy of chimeric antigen receptor (CAR) T cells in solid tumors. Our findings reveal a critical post-translational regulation in CD8+ T cells, providing a potential therapeutic strategy of targeting ADAM17 for effective anti-tumor immunity.

CircRNA8388 functions as the sponge for miR-2392 during intestinal regeneration in sea cucumber Apostichopus japonicus.

The sea cucumber Apostichopus japonicus can expel internal organs under stress and regenerate them subsequently. However, growth is delayed during regeneration, significantly impacting the industry. Circular RNAs (circRNAs) are single-stranded circular RNA molecules produced through alternative splicing of mRNA precursors. They play crucial roles in regulating gene expression via the ceRNA mechanism. In this study, circRNA profiles of control and regenerated intestines were constructed. A total of 15,874 circRNAs were identified, with a length of 300-350 nucleotides (nt) being the most abundant. Sanger sequencing confirmed the circular structure of circRNA398. Compared with the normal intestine, 50 and 83 differentially expressed circRNAs (DE-circRNAs) were identified in the regenerated intestine at 1 and 3 days post evisceration (dpe), respectively. Gene ontology (GO) terms for signal transduction and development regulation were most significantly enriched in 1dpeVScon and 3dpeVScon treatments, respectively. The dual-luciferase assay revealed that circRNA8388 functions as a sponge for miR-2392, participating in the remodeling of the extracellular matrix (ECM). In conclusion, these findings will contribute to the enhancement of the non-coding RNA database for echinoderms and lay the groundwork for future investigations into circRNA regulation during intestinal regeneration.

A Novel Frameshift Variant of the ELF4 Gene in a Patient with Autoinflammatory Disease: Clinical Features, Transcriptomic Profiling and Functional Studies.

We described the diagnosis and treatment of a patient with autoinflammatory disease, named "Deficiency in ELF4, X-linked (DEX)". A novel ELF4 variant was discovered and its pathogenic mechanism was elucidated. The data about clinical, laboratory and endoscopic features, treatment, and follow-up of a patient with DEX were analyzed. Whole exome sequencing and Sanger sequencing were performed to identify potential pathogenic variants. The mRNA and protein levels of ELF4 were analyzed by qPCR and Western blotting, respectively. The association of ELF4 frameshift variant with nonsense-mediated mRNA decay (NMD) in the pathogenesis DEX was examined. Moreover, RNA-seq was performed to identify the key molecular events triggered by ELF4 variant. The relationship between ELF4 and IFN-ß activity was validated using a dual-luciferase reporter assay and a ChIP-qPCR assay. An 11-year-old boy presented with a Behçet's-like phenotype. The laboratory abnormality was the most obvious in elevated inflammatory indicators. Endoscopy revealed multiple ileocecal ulcers. Intestinal histopathology showed inflammatory cell infiltrations. The patient was treated with long-term immunosuppressant and TNF-α blocker (adalimumab), which reaped an excellent response over 16 months of follow-up. Genetic analysis identified a maternal hemizygote frameshift variant (c.1022del, p.Q341Rfs*30) in ELF4 gene in the proband. The novel variant decreased the mRNA level of ELF4 via the NMD pathway. Mechanistically, insufficient expression of ELF4 disturbed the immune system, leading to immunological disorders and pathogen susceptibility, and disrupted ELF4-activating IFN-ß responses. This analysis detailed the clinical characteristics of a Chinese patient with DEX who harbored a novel ELF4 frameshift variant. For the first time, we used patient-derived cells and carried out transcriptomic analysis to delve into the mechanism of ELF4 variant in DEX.

An Engineered Nanoplatform with Tropism Toward Irradiated Glioblastoma Augments Its Radioimmunotherapy Efficacy.

Combining radiotherapy with immune checkpoint blockade therapy offers a promising approach to treat glioblastoma multiforme (GBM), yet challenges such as limited effectiveness and immune-related adverse events (irAEs) persist. These issues are largely due to the failure in targeting immunomodulators directly to the tumor microenvironment. To address this, a biomimetic nanoplatform that combines a genetically modified mesenchymal stem cell (MSC) membrane with a bioactive nanoparticle core for chemokine-directed radioimmunotherapy of GBM is developed. The CC chemokine receptor 2 (CCR2)-overexpressing MSC membrane acts as a tactical tentacle to achieve radiation-induced tropism toward the abundant chemokine (CC motif) ligand 2 (CCL2) in irradiated gliomas. The nanoparticle core, comprising diselenide-bridged mesoporous silica nanoparticles (MSNs) and PD-L1 antibodies (αPD-L1), enables X-ray-responsive drug release and radiosensitization. In two murine models with orthotopic GBM tumors, this nanoplatform reinvigorated immunogenic cell death, and augmented the efficacy and specificity of GBM radioimmunotherapy, with reduced occurrence of irAEs. This study suggests a promising radiation-induced tropism strategy for targeted drug delivery, and presents a potent nanoplatform that enhances the efficacy and safety of radio-immunotherapy.

Investigation of Nasal Mucosal IgA Responses in the Population Following COVID-19 Pandemic - China, September 2022-August 2023.

What is already known about this topic?: Mucosal IgA plays a crucial role in host immunity against respiratory viruses. Recent studies suggest that it has the potential to mitigate the transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant. However, a comprehensive population-based analysis examining mucosal IgA levels following the winter 2022 wave of the coronavirus disease 2019 (COVID-19) pandemic is yet to be conducted. What is added by this report?: In our study involving 3,421 participants, we documented IgA responses subsequent to SARS-CoV-2 infection. A significant proportion of individuals sustained increased levels of IgA for over six months. These levels were also observed in individuals with prior infections who underwent asymptomatic reinfections, indicating an active production of IgA antibodies. Further, individuals with multiple vaccinations or severe symptoms tended to display elevated IgA levels after recovery. What are the implications for public health practice?: IgA in the nasal mucosa is crucial for defense against SARS-CoV-2 infection. These insights can enhance our knowledge of immune responses following infection and have provided certain reference values for disease prevention and control strategies.