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Oral mucositis (OM) is a severe side effect of anti‐cancer therapy, with limited available treatments. Mesenchymal stem cells (MSCs) and their secreted extracellular vesicles (EVs) have demonstrated effective protection against OM. However, the underlying mechanism remains elusive. In the current study, we purified EVs secreted by human umbilical cord MSCs (hUC‐MSC‐EVs) and investigated their role in lipopolysaccharide (LPS)‐induced human oral keratinocytes (HOKs). We observed that treatment with hUC‐MSC‐EVs significantly reduced the inflammatory response of HOKs to LPS induction. Through small RNA‐seq using miRNAs extracted from hUC‐MSC‐EVs, we identified hsa‐let‐7e‐5p as one of the most highly expressed miRNAs. Bioinformatic analysis data indicated that hsa‐let‐7e‐5p may inhibit the NF‐κB signalling pathway by targeting TAB2. Overexpression of the hsa‐let‐7e‐5p inhibitor significantly attenuated the anti‐inflammatory effect of hUC‐MSC‐EVs in LPS‐induced HOKs, which could be reversed by the knockdown of TAB2. In addition, we administered hUC‐MSC‐EVs in a hamster model for OM and observed that these EVs alleviated OM phenotypes. Taken together, our observations suggest that hsa‐let‐7e‐5p in hUC‐MSC‐EVs could protect the oral mucosa from OM by repressing TAB2 expression. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigated the relationship between specific gene polymorphisms (TRAF2, TAB2, IKBKB) and protein levels and pituitary adenomas (PAs). The research included 459 participants, divided into a control group and a PA group. The key findings include significant differences in TRAF2 genotypes between the groups, with the G allele being less common in the PA group. The presence of the G allele and GG genotype were linked to a reduced risk of developing PAs, particularly microadenomas and macroadenomas. These results indicate a protective effect of the TRAF2 G allele against pituitary tumors. Aim: The aim of this study was to determine associations of TRAF2 (rs867186), TAB2 (rs237025), IKBKB (rs13278372) gene polymorphisms and TRAF2, TAB2, IKBKB protein levels with clinical and morphological features of pituitary adenomas (PAs). Methods: This case–control study included 459 individuals divided into two groups: a control group (n = 320) and a group of individuals with PAs (n = 139). DNA from peripheral blood leukocytes was isolated using salt precipitation and column method. Real-time PCR was used for TRAF2 (rs867186), TAB2 (rs237025), and IKBKB (rs13278372) SNP genotyping, and TRAF2, TAB2, IKBKB protein concentration measurements were performed by immunoenzymatic analysis tests using a commercial ELISA kit according to the manufacturer's recommendations. The labeling index Ki-67 was determined by immunohistochemical analysis using a monoclonal antibody (clone SP6; Spring Bioscience Corporation). Statistical data analysis was performed using the programs "IMB SPSS Statistics 29.0". Results: We found significant differences in TRAF2 (rs867186) genotypes (AA, AG, GG) between groups: 79.1%, 17.3%, 3.6% vs. 55.3%, 20.9%, 23.8% (p < 0.001). The G allele was less frequent in the PA group than in controls (12.2% vs. 34.2%, p < 0.001). The AG and GG genotypes reduced PA occurrence by 1.74-fold and 9.43-fold, respectively, compared to AA (p < 0.001). In the dominant model, GG and AG genotypes reduced PA odds by 3.07-fold, while in the recessive model, the GG genotype reduced PA odds by 8.33-fold (p < 0.001). Each G allele decreased PA odds by 2.49-fold in the additive model (p < 0.001). Microadenomas had significant genotype differences compared to controls: 81.3%, 18.8%, 0.0% vs. 55.3%, 20.9%, 23.8% (p < 0.001), with the G allele being less frequent (9.4% vs. 34.2%, p < 0.001). In macroadenomas, genotype differences were 78%, 16.5%, 5.5% vs. 55.3%, 20.9%, 23.8% (p < 0.001), and the G allele was less common (13.7% vs. 34.2%, p < 0.001). The dominant model showed that GG and AG genotypes reduced microadenoma odds by 3.5-fold (p = 0.001), and each G allele reduced microadenoma odds by 3.1-fold (p < 0.001). For macroadenomas, the GG genotype reduced odds by 6.1-fold in the codominant model (p < 0.001) and by 2.9-fold in GG and AG genotypes combined compared to AA (p < 0.001). The recessive model indicated the GG genotype reduced macroadenoma odds by 5.3-fold (p < 0.001), and each G allele reduced odds by 2.2-fold in the additive model (p < 0.001). Conclusions: The TRAF2 (rs867186) G allele and GG genotype are significantly associated with reduced odds of pituitary adenomas, including both microadenomas and macroadenomas, compared to the AA genotype. These findings suggest a protective role of the G allele against the occurrence of these tumors. [ABSTRACT FROM AUTHOR]

In this study, TaB 2 -20 vol% SiC composites with and without rare-earth oxides (RE 2 O 3 , RE = Y and La) were fabricated via hot pressing at or above 1800 °C. 3 vol% RE 2 O 3 additions improved the sinterability of TaB 2 -SiC composite and resulted in a finer microstructure in addition to the crystalline RE 2 Si 2 O 7 grain-boundary phase. The shear and Young's moduli as well as hardness of the composites decreased with RE 2 O 3 additives. Conversely, the fracture toughness of the composites increased with RE 2 O 3 additives and the toughening effect was better for La 2 O 3 than for Y 2 O 3. On the other hand, the additions of RE 2 O 3 substantially enhanced the flexural strength and the strengthening effect was significantly stronger for Y 2 O 3 than for La 2 O 3 , the strengthening was ineffective at or above 1400 °C, however. Additionally, the temperature dependence of strengths varied with and without RE 2 O 3 additions, as a result of the difference in the chemistry of the intergranular phases. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to determine associations of TRAF2 (rs867186), TAB2 (rs237025), IKBKB (rs13278372) gene polymorphisms and TRAF2, TAB2, IKBKB protein levels with clinical and morphological features of pituitary adenomas (PAs). Methods: This case–control study included 459 individuals divided into two groups: a control group (n = 320) and a group of individuals with PAs (n = 139). DNA from peripheral blood leukocytes was isolated using salt precipitation and column method. Real-time PCR was used for TRAF2 (rs867186), TAB2 (rs237025), and IKBKB (rs13278372) SNP genotyping, and TRAF2, TAB2, IKBKB protein concentration measurements were performed by immunoenzymatic analysis tests using a commercial ELISA kit according to the manufacturer’s recommendations. The labeling index Ki-67 was determined by immunohistochemical analysis using a monoclonal antibody (clone SP6; Spring Bioscience Corporation). Statistical data analysis was performed using the programs "IMB SPSS Statistics 29.0". Results: We found significant differences in TRAF2 (rs867186) genotypes (AA, AG, GG) between groups: 79.1%, 17.3%, 3.6% vs. 55.3%, 20.9%, 23.8% (p < 0.001). The G allele was less frequent in the PA group than in controls (12.2% vs. 34.2%, p < 0.001). The AG and GG genotypes reduced PA occurrence by 1.74-fold and 9.43-fold, respectively, compared to AA (p < 0.001). In the dominant model, GG and AG genotypes reduced PA odds by 3.07-fold, while in the recessive model, the GG genotype reduced PA odds by 8.33-fold (p < 0.001). Each G allele decreased PA odds by 2.49-fold in the additive model (p < 0.001). Microadenomas had significant genotype differences compared to controls: 81.3%, 18.8%, 0.0% vs. 55.3%, 20.9%, 23.8% (p < 0.001), with the G allele being less frequent (9.4% vs. 34.2%, p < 0.001). In macroadenomas, genotype differences were 78%, 16.5%, 5.5% vs. 55.3%, 20.9%, 23.8% (p < 0.001), and the G allele was less common (13.7% vs. 34.2%, p < 0.001). The dominant model showed that GG and AG genotypes reduced microadenoma odds by 3.5-fold (p = 0.001), and each G allele reduced microadenoma odds by 3.1-fold (p < 0.001). For macroadenomas, the GG genotype reduced odds by 6.1-fold in the codominant model (p < 0.001) and by 2.9-fold in GG and AG genotypes combined compared to AA (p < 0.001). The recessive model indicated the GG genotype reduced macroadenoma odds by 5.3-fold (p < 0.001), and each G allele reduced odds by 2.2-fold in the additive model (p < 0.001). Conclusions: The TRAF2 (rs867186) G allele and GG genotype are significantly associated with reduced odds of pituitary adenomas, including both microadenomas and macroadenomas, compared to the AA genotype. These findings suggest a protective role of the G allele against the occurrence of these tumors.

TGF-β-activated kinase 1 binding protein 2 (TAB2) is an intermediate protein that connects TNFR1 and other receptor signals to the TGF-β-activated kinase 1 (TAK1) signaling complex. TAB2 has been proved clinically relevant to congenital heart defects (CHD) and cardiomyopathy. In this study, we created a TAB2 knockout human embryonic stem cell line by CRISPR/Cas9 technology. The WAe009-A-Z cell line displayed stem cell morphology, pluripotency and normal karyotype, which could develop into three germ layers in vitro.

Transforming growth factor-β (TGF-β) activated kinase 1 (TAK1), also named mitogen-activated protein kinase 7 (MAPK7), forms a pivotal signaling complex with TAK1-binding proteins (TAB1, TAB2, and TAB3), orchestrating critical biological processes, including immune responses, cell growth, apoptosis, and stress responses. Activation of TAK1 by stimuli, such as tumor necrosis factor α (TNFα), interleukin-1β (IL-1β), and Toll-like receptors (TLRs), underscores its central role in cellular signaling. Given the critical role of the TAK1-binding protein (TAK1–TAB) complex in cellular signaling and its impact on various biological processes, this review seeks to understand how ubiquitination thoroughly regulates the TAK1–TAB complex. This understanding is vital for developing targeted therapies for diseases where this signaling pathway is dysregulated. The exploration is significant as it unveils new insights into the activity, stability, and assembly of the complex, underscoring its therapeutic potential in disease modulation.

HfB 2 -MoSi 2 -based ultra-high temperature ceramic (UHTC) coatings have shown remarkable antioxidant effects owing to the formation of silicate glass layers with low oxygen permeability in high-temperature environments, which shows great potential in the antioxidation of carbon structural materials. To further enhance the oxidation resistance of the HfB 2 -MoSi 2 -based coating in a wide temperature region, the influence of volume ratio between HfB 2 and TaB 2 on the antioxidant capacity of the HfB 2 -MoSi 2 -TaB 2 coatings was investigated. The addition of 15 vol% TaB 2 in the 60HfB 2 -40MoSi 2 coating delays the initial oxidation temperature of the 60HfB 2 -40MoSi 2 sample from 300 °C to 500 °C, which decreased the oxidation loss by 75.85% during dynamic oxidation. In oxidation process at 900 °C and 1700 °C, the weight gains of the 45HfB 2 -40MoSi 2 –15TaB 2 coating reduced by 78.56% and 63.14%, respectively. Due to the coexistence of 45 vol%HfB 2 and 15 vol%TaB 2 , the suitable Ta5+ promoted the homogenization and dispersion of Hf/Ta-oxides, which forms the coral-like Hf/Ta oxides skeleton in the glass layer, thus preventing the oxygen penetration and decreasing the inert factor of the HfB 2 -MoSi 2 coating at 1700 °C by 51.19%. However, excessive TaB 2 weakened the self-healing ability of the Ta-Hf-Si-O glass layer and inhibited the oxygen barrier effect of the HfB 2 -MoSi 2 -TaB 2 coating. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) has become the most prevalent chronic liver disease worldwide, without any Food and Drug Administration-approved pharmacological intervention in clinic. Trim38, as an important member of the TRIM (tripartite motif-containing) family, was largely reported to be involved in the regulation of innate immune and inflammatory responses. However, the functional roles of TRIM38 in NAFLD remain largely unknown. Here, the expression of TRIM38 was first detected in liver samples of both NAFLD mice model and patients diagnosed with NAFLD. We found that TRIM38 expression was downregulated in NAFLD liver tissues compared with normal liver tissues. Genetic Trim38-KO in vivo showed that TRIM38 depletion deteriorated the high-fat diet and high fat and high cholesterol diet-induced hepatic steatosis and high fat and high cholesterol diet-induced liver inflammation and fibrosis. In particular, we found that the effects of hepatocellular lipid accumulation and inflammation induced by palmitic acid and oleic acid were aggravated by TRIM38 depletion but mitigated by TRIM38 overexpression in vitro. Mechanically, RNA-Seq analysis demonstrated that TRIM38 ameliorated nonalcoholic steatohepatitis progression by attenuating the activation of MAPK signaling pathway. We further found that TRIM38 interacted with transforming growth factor-β-activated kinase 1 binding protein 2 and promoted its protein degradation, thus inhibiting the transforming growth factor-β-activated kinase 1-MAPK signal cascades. In summary, our study revealed that TRIM38 could suppress hepatic steatosis, inflammatory, and fibrosis in NAFLD via promoting transforming growth factor-β-activated kinase 1 binding protein 2 degradation. TRIM38 could be a potential target for NAFLD treatment.

To solve the problem of silicide coatings on tantalum substrates failing due to elemental diffusion under high-temperature oxidation environments and to find diffusion barrier materials with excellent effects of impeding Si elemental spreading, TaB2 and TaC coatings were prepared on tantalum substrates by the encapsulation and infiltration methods, respectively. Through orthogonal experimental analysis of the raw material powder ratio and pack cementation temperature, the best experimental parameters for the preparation of TaB2 coatings were selected: powder ratio (NaF:B:Al2O3 = 2.5:1:96.5 (wt.%)) and pack cementation temperature (1050 °C). After diffusion treatment at 1200 °C for 2 h, the thickness change rate of the Si diffusion layer prepared using this process was 30.48%, which is lower than that of non-diffusion coating (36.39%). In addition, the physical and tissue morphological changes of TaC and TaB2 coatings after siliconizing treatment and thermal diffusion treatment were compared. The results prove that TaB2 is a more suitable candidate material for the diffusion barrier layer of silicide coatings on tantalum substrates. [ABSTRACT FROM AUTHOR]

Epidemiological evidence has shown that fine particulate matter (PM2.5)-triggered inflammatory cascades are pivotal causes of chronic obstructive pulmonary disease (COPD). However, the specific molecular mechanism involved in PM2.5-induced COPD has not been clarified. Herein, we found that PM2.5 significantly downregulated miR-149-5p and activated the mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways and generated the inflammatory response in COPD mice and in human bronchial epithelial (BEAS-2B) cells. We determined that increased expression of interleukin-1β (IL-1β), IL-6, IL-8, and tumor necrosis factor-α (TNF-α) induced by PM2.5 was associated with decreased expression of miR-149-5p. The loss- and gain-of-function approach further confirmed that miR-149-5p could inhibit PM2.5-induced cell inflammation in BEAS-2B cells. The double luciferase reporter assay showed that miR-149-5p directly targeted TGF-beta-activated kinase 1 binding protein 2 (TAB2), which regulates the MAPK and NF-κB signaling pathways. We showed that miR-149-5p mediated the inflammatory response by targeting the 3′-UTR sequence of TAB2 and that it subsequently weakened the TAB2 promotor effect via the MAPK and NF-κB signaling pathways in BEAS-2B cells exposed to PM2.5. Thus, miR-149-5p may be a key factor in PM2.5-induced COPD. This study improves our understanding of the molecular mechanism of COPD. [ABSTRACT FROM AUTHOR]

The search for new low-cost co-catalysts that can replace precious metals is highly desirable and challenging. Transition metal diboride can be ideal candidates due to their excellent electrical conductivity and suitable work function. In this work, a novel TaB 2 @TiO 2 heterostructure has been successfully constructed by a facile sol-gel method. The results show that TaB 2 has a suitable work function and B–O bonds are formed at the interface of the TaB 2 @TiO 2 heterojunction, which makes it easier for the photogenerated electrons of TiO 2 to migrate to the surface of TaB 2 and promotes the effective separation of photogenerated carriers. In addition, the metallic nanocrystalline TaB 2 also significantly increases the specific surface area of the heterojunction. The above two points lead to more hydroxyl radicals and superoxide radicals production, thus substantially improving the photocatalytic degradation performance. Therefore, the 3 wt% TaB 2 (TT3) catalyst degraded rhodamine B (RhB, 20 mg/L) with an efficiency of 100% under 90 min irradiation, which is much higher than pristine TiO 2 ∼92% and commercial TiO 2 (P25)∼64%. Furthermore, its photocatalytic rate is about 1.73 times and 3.77 times of pristine TiO 2 and commercial TiO 2 (P25), respectively. This finding can provide new insights for the replacement of photocatalytic noble metal co-catalysts. [ABSTRACT FROM AUTHOR]

Haplo‐insufficiency of the TGFβ‐activated kinase 1 binding protein 2 (TAB2) gene is associated with short stature, facial dysmorphisms, connective tissue abnormalities, hearing loss, and cardiac disease. Skeletal dysplasia and sacral dimples are also found in a minority of patients. Here, we describe a 3‐generation family with caudal appendage, other sacral anomalies, and skeletal abnormalities including hypoplasia of the iliac wings and scapulae, fusion of the carpal bones and stenosis of the spinal canal, as well as a remarkable course of prenatally‐detected cardiomyopathy with characteristics changing over time. Genetic analysis showed a heterozygous nonsense variant in the TAB2 gene. [ABSTRACT FROM AUTHOR]

TAB2 is a gene located on chromosome 6q25.1 and plays a key role in development of the heart. Existing literature describes congenital heart disease as a common recognized phenotype of TAB2 gene variants, with evidence of a distinct syndromic phenotype also existing beyond this. Here we describe 14 newly identified individuals with nine novel, pathogenic TAB2 variants. The majority of individuals were identified through the Deciphering Developmental Disorders study through trio whole exome sequencing. Eight individuals had de novo variants, the other six individuals were found to have maternally inherited, or likely maternally inherited, variants. Five individuals from the same family were identified following cardiac disease gene panel in the proband and subsequent targeted familial gene sequencing. The clinical features of this cohort were compared to the existing literature. Common clinical features include distinctive facial features, growth abnormalities, joint hypermobility, hypotonia, and developmental delay. Newly identified features included feeding difficulties, sleep problems, visual problems, genitourinary abnormality, and other anatomical variations. Here we report 14 new individuals, including novel TAB2 variants, in order to expand the emerging syndromic clinical phenotype and provide further genotype–phenotype correlation. [ABSTRACT FROM AUTHOR]

To suppress the oxidation of TaB 2 -SiC coatings, the effects of pre-oxidation temperature on the oxygen hindering properties of TaB 2 -SiC coatings were investigated to prepare TaB 2 -SiC coatings with enhanced oxidation behavior. The addition of 40 wt% TaB 2 made the oxygen permeability of the coating decrease by 62.16%. However, excessive TaB 2 weakened the oxygen hindering ability of the coating due to the large ion complex ability of Ta5+. The pre-oxidation temperature at 1500 °C led to a homogeneous dispersion of Ta-oxide nanocrystal particles in the Ta-B-Si-O complex-phase glass layer. In contrast with the untreated samples, the active factor and inert factor values of the TaB 2 -SiC coating after pre-oxidation treatment at 1500 °C decreased by 43.12% and 17.33%, respectively, which improved the dynamic stability of the coating during oxidation. [ABSTRACT FROM AUTHOR]

The effects of TaB 2 addition on the Nb-16Si-22Ti-3Al alloy were investigated in this study. The results showed that the Nb-16Si-22Ti-3Al alloy consisted of the Nbss phase, α-Nb 5 Si 3 phase, Nb 3 Si phase, and Tiss phase. With the addition of TaB 2 increased from 0 to 0.25 at. %, the Nb 3 Si disappeared and the eutectic transformation reaction occurred (Nb 3 Si → Nbss + α-Nb 5 Si 3), which made the volume fraction of the Nbss phase increased from 38.6% to 50.3%. With the TaB 2 addition further increasing to 2.0 at. %, the α-Nb 5 Si 3 became the primary phase, and the microstructure transformed from the Nbss + α-Nb 5 Si 3 eutectic structure to the primary α-Nb 5 Si 3 and (Nbss + γ-Nb 5 Si 3) hypereutectic structure. The alloy with 0.25 at. % TaB 2 addition had the highest fracture toughness of 10.2 MPa•m1/2 due to the refinement of microstructure and the increment of ductile Nbss. The maximum compressive strength of TaB 2 added alloy at room temperature reached 2587.25 MPa in 2.0TaB 2 specimen, owing to the solid solution strengthening of Ta and B, and the increment of the silicides content. Additionally, by comparing the fracture toughness of alloys with TaB 2 addition obtained by three-point bending (SENBs) and indentation methods, respectively, the feasibility of estimating the fracture toughness of Nb Si based alloys by the indentation method is demonstrated with an error of below 20%, which provided a basis for subsequent rapid performance characterization. • TaB 2 promoted the eutectic transformation of Nb 3 Si. • Microstructure morphology and Nbss volume fraction influence fracture toughness. • Indentation method rapidly assesses the fracture toughness of Nb Si based alloys. • Solid solution and fine-grain strengthening are the reinforcing mechanisms in Nb Si based alloy. [ABSTRACT FROM AUTHOR]

Transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1), TAK1-binding protein 1 (TAB1) and TAB2 are components of the mitogen-activated protein kinase (MAPK) pathway. In this study, TAK1, TAB1 and TAB2 were characterized from golden pompano (Trachinotus ovatus), a marine fish of great economic value, and named as trTAK1, trTAB1 and trTAB2, respectively. The lengths of the cDNA sequences of the three genes were 2429 bp, 2068 bp and 4229 bp and encoded 575, 506 and 759 amino acids, respectively. The trTAK1, trTAB1 and trTAB2 genes shared high sequence identities and were well clustered with their counterparts from other fish species. Real-time qPCR analysis showed that the three genes were constitutively expressed in all the selected tissues of healthy pompano, and the expression levels of the three genes were significantly up-regulated in head kidney and spleen following Vibrio alginolyticus, lipolysaccharide (LPS) and polyinosinic polycytidylic acid (poly I:C) challenge, indicating their roles in the immune response against pathogens in golden pompano. Our results provide a basis for further study of the functions of these genes in golden pompano. [ABSTRACT FROM AUTHOR]

Ticks are blood-sucking parasites that are harmful to humans and animals. MicroRNAs are a class of conserved small noncoding RNAs that play regulatory roles in the expression of many genes at the posttranscriptional level. Here, a novel miRNA (nov-miR-17) was identified from a small RNA data library of Hyalomma asiaticum by next-generation sequencing. PCR was used to obtain precursor nov-miR-17 by RACE using mature loop primers. The secondary structure was predicted with UNAFold. The interaction of nov-miR-17 with its target gene TAB2 was predicted using RNAhybrid software and identified in vitro by luciferase assays. Moreover, the interaction was confirmed in vivo by phenotype rescue experiments in which dsTAB2 was used for RNA interference (RNAi) and an antagomir of nov-miR-17 was used for miRNA silencing. The expression levels of nov-miR-17 and TAB2 in ticks at different developmental stages and the expression of nov-miR-17 in different tissues were analyzed by real-time qPCR. All data were analyzed using GraphPad Prism version 5. Results: The results showed that TAB2 was a target gene of nov-miR-17. When the blood-sucking process of larval, nymph and adult ticks was prolonged, the expression of nov-miR-17 was decreased, and TAB2 expression was increased. However, the level of nov-miR-17 in the midgut of engorged ticks was highest at all stages. Therefore, nov-miR-17 plays an important role in the blood-sucking process. The overexpression of nov-miR-17 indicated that this miRNA affected the engorged weight (P < 0.001) and spawn rate (P < 0.001) of female ticks. RNAi of TAB2 also had the same effect. dsRNA not only impacted the weight (P < 0.01) but also reduced the spawn rate (P < 0.001) of the ticks. Furthermore, significant recovery was observed in nov-miR- 17-silenced ticks after TAB2 silencing by RNAi. nov-miR-17 silencing by antagomir not only impacted the engorged weight of the female ticks (P < 0.001) but also the number of days that the females needed to progress from engorgement to spawning (P < 0.001). The study showed that nov-miR-17, as a new miRNA, plays an important role along with its target gene TAB2 in the blood-sucking and spawning processes in female ticks. [ABSTRACT FROM AUTHOR]

In this study, we explored to detect the effects and mechanism of bone‐marrow‐derived mesenchymal stem cells (BMSCs) on ventilator‐induced lung injury (VILI). We transplanted BMSCs in mice and then induced VILI using mechanical ventilation (MV) treatment. The pathological changes, the content of PaO2 and PaCO2, wet/dry weight ratio (W/D) of the lung, levels of tumor necrosis factor‐α and interleukin‐6 in bronchoalveolar lavage fluid, and apoptosis were detected. The autophagy‐associated factor p62, LC3, and Beclin‐1 expression were analyzed by western blot. The quantitative polymerase chain reaction was applied to detect abnormally expressed microRNAs, including miR‐155‐5p. Subsequently, we overexpressed miR‐155‐5p in VILI mice to detect the effects of miR‐155‐5p on MV‐induced lung injury. Then, we carried out bioinformatics analysis to verify the BMSCs‐regulated miR‐155‐5p that target messenger RNA. It was observed that BMSCs transplantation mitigated the severity of VILI in mice. BMSCs transplantation reduced lung inflammation, strengthened the arterial oxygen partial pressure, and reduced apoptosis and the W/D of the lung. BMSCs promoted autophagy of pulmonary endothelial cells accompanied by decreased p62 and increased LC3 II/I and Beclin‐1. BMSCs increased the levels of miR‐155‐5p in VILI mice. Overexpression of miR‐155‐5p alleviated lung injury in VILI mice following reduced apoptosis and increased autophagy. Finally, TAB2 was identified as a downstream target of miR‐155‐5p and regulated by miR‐155‐5p. BMSCs may protect lung tissues from MV‐induced injury, inhibit lung inflammation, promote autophagy through upregulating of miR‐155‐5p. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment is a severe complication of acute respiratory distress syndrome (ARDS). Emerging studies have revealed the effects of pyrrolidine dithiocarbamate (PDTC) on improving surgery-induced cognitive impairment. The major aim of the study was to investigate whether PDTC protected against ARDS-induced cognitive dysfunction and to identify the underlying mechanisms involved., Methods: The rat model of ARDS was established by intratracheal instillation of lipopolysaccharide (LPS), followed by treatment with PDTC. The cognitive function of rats was analyzed by the Morris Water Maze, and pro-inflammatory cytokines were assessed by quantitative real-time PCR, enzyme-linked immunosorbent assay, and western blot assays. A dual-luciferase reporter gene assay was performed to identify the relationship between miR-181c and its target gene, TAK1 binding protein 2 (TAB2) ., Results: The results showed that PDTC improved cognitive impairment and alleviated neuroinflammation in the hippocampus in LPS-induced ARDS model. Furthermore, we demonstrated that miR-181c expression was downregulated in the hippocampus of the ARDS rats, which was restored by PDTC treatment. In vitro studies showed that miR-181c alleviated LPS-induced pro-inflammatory response by inhibiting TAB2, a critical molecule in the nuclear factor (NF)-κB signaling pathway., Conclusion: PDTC improves cognitive impairment in LPS-induced ARDS by regulating miR-181c/NF-κB axis-mediated neuroinflammation, providing a potential opportunity for the treatment of this disease.

The Drosophila Imd pathways are well-known mechanisms involved in innate immunity responsible for Gram-negative (G-) bacterial infection. The intensity and durability of immunity need to be finely regulated to keep sufficient immune activation meanwhile avoid excessive immune response. In this study, we firstly demonstrated that miR-190 can downregulate the expression levels of antimicrobial peptides (AMPs) in the Imd immune pathway after Escherichia coli infection using the miR-190 overexpression flies and the miR-190KO/+ flies. Secondly, miR-190 overexpression significantly reduces while miR-190 KO increases Drosophila survival rates upon lethal Enterobacter cloacae infection. Thirdly, we further demonstrated that miR-190 negatively regulates innate immune responses by directly targeting both RA/RB and RC isoforms of Tab2. In addition, the dynamic expression pattern of AMPs (Dpt, AttA, CecA1), miR-190 and Tab2 in the wild-type flies reveals that miR-190 play an important role in Drosophila immune homeostasis restoration at the late stage of E. coli infection. Collectively, our study reveals that miR-190 can downregulate the expression of AMPs by targeting Tab2 and promote immune homeostasis restoration in Drosophila Imd pathway. Our study provides new insights into the regulatory mechanism of animal innate immune homeostasis., Competing Interests: Declaration of competing interest The authors have no financial conflicts of interest., (Copyright © 2024. Published by Elsevier Masson SAS.)

To solve the problem of silicide coatings on tantalum substrates failing due to elemental diffusion under high-temperature oxidation environments and to find diffusion barrier materials with excellent effects of impeding Si elemental spreading, TaB2 and TaC coatings were prepared on tantalum substrates by the encapsulation and infiltration methods, respectively. Through orthogonal experimental analysis of the raw material powder ratio and pack cementation temperature, the best experimental parameters for the preparation of TaB2 coatings were selected: powder ratio (NaF:B:Al2O3 = 2.5:1:96.5 (wt.%)) and pack cementation temperature (1050 °C). After diffusion treatment at 1200 °C for 2 h, the thickness change rate of the Si diffusion layer prepared using this process was 30.48%, which is lower than that of non-diffusion coating (36.39%). In addition, the physical and tissue morphological changes of TaC and TaB2 coatings after siliconizing treatment and thermal diffusion treatment were compared. The results prove that TaB2 is a more suitable candidate material for the diffusion barrier layer of silicide coatings on tantalum substrates.

The influence of two different spark plasma sintering (SPS)-based processing routes (i.e., reactive SPS [RSPS] and nonreactive SPS) on the properties of TaB2-TaC composites was investigated. Ta2O5 and B4C powders were used as starting materials in the RSPS method, and synthesis and densification of TaB2-TaC composites were accomplished in a facile single step. The effect of sintering temperature and time on the microstructure and densification of the in-situ RSPS were investigated. The obtained results were compared with nonreactive spark plasma sintered TaB2-TaC composites. The highest densification (~99.5%) was achieved for the TaB2-TaC composite with 6.64 vol.% TaC after reactive sintering at 1550° C under 40 MPa with a 5 min holding time. Although lower SPS temperature was used in the RSPS method, better densification and higher Vickers hardness were obtained compared to the nonreactive SPS. While platelet-shaped TaC formation was observed in both processes, the average grain size was smaller in the RSPS method. On the other hand, no significant difference was detected in the oxidation behavior of the composites produced by RSPS and nonreactive SPS. [ABSTRACT FROM AUTHOR]

Summary: Selective autophagy is a catabolic route that turns over specific cellular material for degradation by lysosomes, and whose role in the regulation of innate immunity is largely unexplored. Here, we show that the apical kinase of the Drosophila immune deficiency (IMD) pathway Tak1, as well as its co-activator Tab2, are both selective autophagy substrates that interact with the autophagy protein Atg8a. We also present a role for the Atg8a-interacting protein Sh3px1 in the downregulation of the IMD pathway, by facilitating targeting of the Tak1/Tab2 complex to the autophagy platform through its interaction with Tab2. Our findings show the Tak1/Tab2/Sh3px1 interactions with Atg8a mediate the removal of the Tak1/Tab2 signaling complex by selective autophagy. This in turn prevents constitutive activation of the IMD pathway in Drosophila. This study provides mechanistic insight on the regulation of innate immune responses by selective autophagy.

Objective: Mycoplasma gallisepticum (MG), a notorious avian pathogen, leads to considerable economic losses in the poultry industry. MG infection is characterized by severe, uncontrollable inflammation and host DNA damage. Micro ribonucleic acids (miRNAs) have emerged as important regulators in microbial pathogenesis. However, the role of miRNAs in MG infection is poorly characterized. In this study, we validated the functional roles of gga-miR-142-3p. Methods: The relative expression of gga-miR-142-3p in the lungs of the MG-infected chicken embryos and the MG-infected chicken embryonic fibroblast cell line (DF-1) was determined by reverse transcription quantitative real-time PCR analysis. Bioinformatics database was used to analysis the target gene of gga-miR-142-3p. The luciferase reporter assay as well as gene expression analysis were conducted to validate the target gene. To further explore the biological functions of gga-miR-142-3p upon MG infection, the cell proliferation was quantified using Cell Counting Kit-8 (CCK-8). Meanwhile, cell cycle analysis and apoptosis were measured using a flow cytometer. Results: gga-miR-142-3p was significantly upregulated in both MG-infected chicken-embryo lungs and the DF-1 cells. gga-miR-142-3p over expression significantly downregulated the expression of pro-inflammatory cytokines, including interleukin-1β, interleukin-6 and tumor necrosis factor alpha after MG infection. Meanwhile, gga-miR-142-3p enhanced the host defense against MG infection by facilitating cell proliferation, promoting cell progression and inhibiting cell apoptosis. Interestingly, TAB2 knockdown groups show similar results, whereas, TAB2 over-expression groups and gga-miR-142-3p inhibitor groups had thoroughly opposite results. The expression of p-p65 in nuclear factor kappa B (NF-κB) and p-p38 in the mitogen-activated protein kinase (MAPK) pathway was decreased when gga-miR-142-3p was over-expressed. Conclusion: Upon MG infection, upregulation of gga-miR-142-3p alleviates inflammation by negatively regulating the signaling pathways of NF-κB and MAPKs by targeting TAB2 and facilitates cell proliferation by inhibiting cell apoptosis and promoting cell cycle progression to defend against MG infection. [ABSTRACT FROM AUTHOR]

Background: Cachexia is a frequent syndrome in pancreatic and non-small cell lung (NSCL) cancer patients. The storm of cancer-induced inflammatory cytokines, in particular TNF-α, is a crucial pathogenic mechanism. Among the molecular alterations accused of cancer-induced cachexia, TNF-α 308 G/A (rs1800629) and −1031T/C (rs1799964) are single-nucleotide polymorphisms (SNPs) within the gene encoding this pro-inflammatory cytokine. Recent studies have demonstrated the crucial role of non-coding microRNAs (miRNAs) in pathogenesis of different diseases including cachexia. Moreover, the mechanistic cytokine signaling pathway of miR-155 , as a TNF-α regulator, supports the involvement of SOCS1, TAB2, and Foxp3, which are direct targets of TNF-α gene. Aim: A case–control study (NCT04131478) was conducted primarily to determine the incidence of TNF-α 308 G/A (rs1800629) and −1031T/C (rs1799964) gene polymorphisms in adult Egyptian patients with local/advanced or metastatic pancreatic or NSCL cancer and investigate both as cachexia risk factors. The association of gene polymorphism with cachexia severity and the expression of miR-155 in cachectic patients were analyzed. A mechanistic investigation of the cytokine signaling pathway, involving SOCS1, TAB2, and Foxp3, was also performed. Results: In both pancreatic and NSCL cancer cohorts, the mutant TNF-α variant of 308 G/A was positively associated with cachexia; on the contrary, that of 1031T/C was negatively associated with cachexia in the NSCL cancer patients. MiR-155 was higher in cachexia and in alignment with its severity in the cachectic group as compared with the non-cachectic group in both the pancreatic and NSCL cancer patients. Though TAB2 did not change to any significant extent in cachectic patients, the levels of SOCS1 and Foxp3 were significantly lower in the cachectic group as compared with the non-cachectic group. Conclusion: Carriers of the A allele 308 G/A gene and high miR-155 are at greater risk of cachexia in both the pancreatic and NSCL cancer patients; however, the mutant variant of 1031T/C gene is protective against cachexia in the NSCL cancer patients. Finally, high levels of miR-155 in the cachectic group lead to negative feedback inhibition of both SOCS1 and Foxp3 in both the pancreatic and NSCL cancer patients. [ABSTRACT FROM AUTHOR]

Circular RNA is a newly discovered member of non-coding RNA (ncRNA) and regulates the target gene by acting as a micro-RNA sponge. It plays vital roles in various diseases. However, the functions of circular RNA in non-small cell lung cancer (NSCLC) remain still unclear. Our data showed that circ-WHSC1 was highly expressed in NSCLC cells and tissues. Both in vitro and in vivo experiments showed that circ-WHSC1 promoted NSCLC proliferation. circ-WHSC1 also promoted the migration and invasion of lung cancer cells. Through bioinformatic analysis and functional experiments, we showed that circ-WHSC1 could act as a sponge for micro-RNA-7 (miR-7) and regulate the expression of TAB2 (TGF-beta activated kinase one binding protein two). Inhibition of the circ-WHSC1/miR-7/TAB2 pathway could effectively attenuate lung cancer progression. In summary, this study confirmed the existence and oncogenic function of circ-WHSC1 in NSCLC. The research suggests that the circ-WHSC1/miR-7/TAB2 axis might be a potential target for NSCLC therapy. [ABSTRACT FROM AUTHOR]

Abstract Background TAB2 is an activator of MAP 3 K7/TAK1, which is required for the IL-1 induced signal pathway. Microdeletions encompassing TAB2 have been detected in various patients with congenital heart defects (CHD), indicating that haploinsufficiency of TAB2 causes CHD. To date, seven variants within TAB2 were reported associated with CHD, only two of them are nonsense mutations. Case presentation Here we describe a three-generation Chinese family that included five CHD patients with heart valvular defects, such as mitral or tricuspid valves prolapse or regurgitation, and aortic valve stenosis or regurgitation. Our proband was a pregnant woman presenting with mitral, tricuspid, and aortic defects; her first child experienced sudden cardiac death at the age of 2 years. Whole-exome sequencing of the proband revealed a novel nonsense variant in TAB2 (c.C446G, p.S149X), which results in the elimination of the majority of C-terminal amino acids of TAB2, including the critical TAK1-binding domain. The variant was identified in five affected patients but not in the eight unaffected family members using Sanger sequencing and was classified as “pathogenic” according to the latest recommendation on sequence variants laid out by the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Conclusion We described a family with CHD caused by a novel TAB2 nonsense mutation. Our study broadens the mutation spectrum of TAB2; to the best of our knowledge, this is the first report of a pathogenic mutation within TAB2 in a Chinese population.

Transforming growth factor-β (TGF-β) activated kinase 1 (TAK1), also named mitogen-activated protein kinase 7 (MAPK7), forms a pivotal signaling complex with TAK1-binding proteins (TAB1, TAB2, and TAB3), orchestrating critical biological processes, including immune responses, cell growth, apoptosis, and stress responses. Activation of TAK1 by stimuli, such as tumor necrosis factor α (TNFα), interleukin-1β (IL-1β), and Toll-like receptors (TLRs), underscores its central role in cellular signaling. Given the critical role of the TAK1-binding protein (TAK1-TAB) complex in cellular signaling and its impact on various biological processes, this review seeks to understand how ubiquitination thoroughly regulates the TAK1-TAB complex. This understanding is vital for developing targeted therapies for diseases where this signaling pathway is dysregulated. The exploration is significant as it unveils new insights into the activity, stability, and assembly of the complex, underscoring its therapeutic potential in disease modulation., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

• Fractal-modified Petite Ensemble Model predicts the combustion front propagation in good correlation with experiments. • Ab-initio and thermodynamic modeling suggest that B 2 O 3 and B 6 O are the main volatile boron oxides in the system. • Combustion of Zr-Ta-Si-B mixtures forms intermediate Ta 5 Si 3 phase, consumed later in the secondary phase formation zone. • Repeated release of elemental Si and Zr in the combustion front results in formation of circular microgradient structures. • As compared to (Zr,Ta)B 2 , TaSi 2 -rich compositions have lower mechanical properties and oxidation resistance under plasma torch. The macrokinetic features and phase and structure formation mechanisms are investigated in the Zr-Ta-Si-B system in the framework of the fractal theory of combustion. The reaction mechanisms are explored using ab initio grand potential modeling and Ellingham diagrams and then verified via direct in situ time-resolved XRD and quenching of combustion fronts in a copper block. The tendency of the Zr-TaSi-B system to form tantalum boride Ta 3 B 4 and a transient tantalum silicide Ta 5 Si 3 and release elemental Si and Zr in the combustion front is suggested based on the developed models and verified using a quenched combustion front and timeresolved XRD analysis. Investigation of hot-pressed combustion products shows that despite slightly higher relative density, TaSi 2 -rich ceramics have relatively lower mechanical properties and oxidation resistance under plasma torch as compared to single-phase (Zr,Ta)B 2 solid solution. [ABSTRACT FROM AUTHOR]

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Transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1), TAK1-binding protein 1 (TAB1) and TAB2 are components of the mitogen-activated protein kinase (MAPK) pathway. In this study, TAK1, TAB1 and TAB2 were characterized from golden pompano (Trachinotus ovatus), a marine fish of great economic value, and named as trTAK1, trTAB1 and trTAB2, respectively. The lengths of the cDNA sequences of the three genes were 2429 bp, 2068 bp and 4229 bp and encoded 575, 506 and 759 amino acids, respectively. The trTAK1, trTAB1 and trTAB2 genes shared high sequence identities and were well clustered with their counterparts from other fish species. Real-time qPCR analysis showed that the three genes were constitutively expressed in all the selected tissues of healthy pompano, and the expression levels of the three genes were significantly up-regulated in head kidney and spleen following Vibrio alginolyticus, lipolysaccharide (LPS) and polyinosinic polycytidylic acid (poly I:C) challenge, indicating their roles in the immune response against pathogens in golden pompano. Our results provide a basis for further study of the functions of these genes in golden pompano.

• A TAB2 knockout hESC cell line have been generated. • The established ESC line has been confirmed the stable expression of pluripotent markers. • This new ESC line provides a model for studying disease mechanisms and drug screening. TGF-β-activated kinase 1 binding protein 2 (TAB2) is an intermediate protein that connects TNFR1 and other receptor signals to the TGF-β-activated kinase 1 (TAK1) signaling complex. TAB2 has been proved clinically relevant to congenital heart defects (CHD) and cardiomyopathy. In this study, we created a TAB2 knockout human embryonic stem cell line by CRISPR/Cas9 technology. The WAe009-A-Z cell line displayed stem cell morphology, pluripotency and normal karyotype, which could develop into three germ layers in vitro. [ABSTRACT FROM AUTHOR]

The development of invariant natural killer T (iNKT) cells requires a well-attuned set of transcription factors, but how these factors are regulated and coordinated remains poorly understood. MicroRNA-155 (miR-155) is a key regulator of numerous cellular processes that affects cell development and homeostasis. Here, we found that miR-155 was highly expressed in early iNKT cells upon thymic selection, and then its expression is gradually downregulated during iNKT cell development. However, the mice with miR-155 germline deletion had normal iNKT cell development. To address if downregulated miR-155 is required for iNKT cell development, we made a CD4Cre.miR-155 knock-in (KI) mouse model with miR-155 conditional overexpression in the T cell lineage. Upregulated miR-155 led to interruption of iNKT cell development, diminished iNKT17 and iNKT1 cells, augmented iNKT2 cells, and these defects were cell intrinsic. Furthermore, defective iNKT cells in miR-155KI mice resulted in the secondary innate-like CD8 T cell development. Mechanistically, miR-155 modulated multiple targets and signaling pathways to fine tune iNKT cell development. MiR-155 modulated Jarid2, a critical component of a histone modification complex, and Tab2, the upstream activation kinase complex component of NF-κB, which function additively in iNKT development and in promoting balanced iNKT1/iNKT2 differentiation. In addition, miR-155 also targeted Rictor, a signature component of mTORC2 that controls iNKT17 differentiation. Taken together, our results indicate that miR-155 serves as a key epigenetic regulator, coordinating multiple signaling pathways and transcriptional programs to precisely regulate iNKT cell development and functional lineage, as well as secondary innate CD8 T cell development.

Traumatic brain injury (TBI) triggers the activation of the endogenous coagulation mechanism, and a large amount of thrombin is released to curb uncontrollable bleeding through thrombin receptors, also known as protease-activated receptors (PARs). However, thrombin is one of the most critical factors in secondary brain injury. Thus, the PARs may be effective targets against hemorrhagic brain injury. Since the PAR1 antagonist has an increased bleeding risk in clinical practice, PAR4 blockade has been suggested as a more promising treatment. Here, we explored the expression pattern of PAR4 in the brain of mice after TBI, and explored the effect and possible mechanism of BMS-986120 (BMS), a novel selective and reversible PAR4 antagonist on secondary brain injury. Treatment with BMS protected against TBI in mice. mRNA-seq analysis, Western blot, and qRT-PCR verification in vitro showed that BMS significantly inhibited thrombin-induced inflammation in astrocytes, and suggested that the Tab2/ERK/NF-κB signaling pathway plays a key role in this process. Our findings provide reliable evidence that blocking PAR4 is a safe and effective intervention for TBI, and suggest that BMS has a potential clinical application in the management of TBI. [ABSTRACT FROM AUTHOR]

Background: TAB2 is an activator of MAP 3 K7/TAK1, which is required for the IL-1 induced signal pathway. Microdeletions encompassing TAB2 have been detected in various patients with congenital heart defects (CHD), indicating that haploinsufficiency of TAB2 causes CHD. To date, seven variants within TAB2 were reported associated with CHD, only two of them are nonsense mutations.Case Presentation: Here we describe a three-generation Chinese family that included five CHD patients with heart valvular defects, such as mitral or tricuspid valves prolapse or regurgitation, and aortic valve stenosis or regurgitation. Our proband was a pregnant woman presenting with mitral, tricuspid, and aortic defects; her first child experienced sudden cardiac death at the age of 2 years. Whole-exome sequencing of the proband revealed a novel nonsense variant in TAB2 (c.C446G, p.S149X), which results in the elimination of the majority of C-terminal amino acids of TAB2, including the critical TAK1-binding domain. The variant was identified in five affected patients but not in the eight unaffected family members using Sanger sequencing and was classified as "pathogenic" according to the latest recommendation on sequence variants laid out by the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.Conclusion: We described a family with CHD caused by a novel TAB2 nonsense mutation. Our study broadens the mutation spectrum of TAB2; to the best of our knowledge, this is the first report of a pathogenic mutation within TAB2 in a Chinese population. [ABSTRACT FROM AUTHOR]

To investigate the formation mechanism of the dendrites glass-ceramics and the effect of TaB 2 modifier on the oxidation-inhibition ability of Si-based coatings in aerobic environment with broad temperature region for carbon materials, the Si-based coatings modified with different TaB 2 content were fabricated by the liquid phase sintering method. The fabricated coatings and its corresponding composite powders were investigated in dynamic TG aerobic environments up to 1500 ℃. The initial oxidation temperatures of Si-based coatings modified with TaB 2 powders are almost completely suppressed to 800 ℃. With the increase of TaB 2 phase content, the relative oxygen permeability of the Si-based coatings is significantly reduced, which can be interpreted as the generation of liquid boride, silicide and Ta-Si-B-O compound glass ceramics those can improve the stability of the coating. The formation mechanism of the dendrites glass-ceramics was illustrated. [ABSTRACT FROM AUTHOR]

Liquid-phase-sintered SiC ceramics (LPS-SiC) with the sintering additives of Y 2 O 3 –Al 2 O 3 and Y 2 O 3 –Al 2 O 3 –TaB 2 were prepared. The oxidation behaviours of these sintered SiC ceramics were studied after oxidation test at 1300 °C in air. In comparison with SiC ceramicwith Y 2 O 3 –Al 2 O 3 , the addition of TaB 2 inhibited the formation of the secondary phase of Y 3 Al 5 O 12 (YAG) and homogeneous distribution of Al element in the SiC matrix was evidenced. After oxidation at 1300 °C, SiC ceramic without TaB 2 additive was found to possess a two-layer structure within the oxidation region. In contrast, SiC ceramic with TaB 2 additive demonstrated the three-layer structure consisting of a dense intermediate layer of SiO 2 , which could protect the SiC matrix from further oxidation. [ABSTRACT FROM AUTHOR]

Abstract Background Nutrient deprivation causes significant stress to the unicellular microalga, Chlamydomonas reinhardtii, which responds by significantly altering its metabolic program. Following N deprivation, the accumulation of starch and triacylglycerols (TAGs) is significantly altered following massive reprogramming of cellular metabolism. One protein that was found to change dramatically and early to this stress was TAB2, a photosystem I (PSI) translation initiation factor, whose transcript and protein levels increased significantly after only 30 min of N deprivation. A detailed physiological and omics-based analysis of an insertional mutant of Chlamydomonas with reduced TAB2 function was conducted to determine what role the functional PSI plays in regulating the cellular response to N deprivation. Results The tab2 mutant displayed increased acetate assimilation and elevated starch levels during the first 6 h of N deprivation, followed by a shift toward altered amino acid synthesis, reduced TAG content and altered fatty acid profiles. These results suggested a central role for PSI in controlling cellular metabolism and its implication in regulation of lipid/starch partitioning. Time course analyses of the tab2 mutant versus wild type under N-deprived versus N replete conditions revealed changes in the ATP/NADPH ratio and suggested that TAG biosynthesis may be associated with maintaining the redox state of the cell during N deprivation. The loss of ability to accumulate TAG in the tab2 mutant co-occurred with an up-regulation of photo-protective mechanisms, suggesting that the synthesis of TAG in the wild type occurs not only as a temporal energy sink, but also as a protective electron sink. Conclusions By exploiting the tab2 mutation in the cells of C. reinhardtii cultured under autotrophic, mixotrophic, and heterotrophic conditions during nitrogen replete growth and for the first 8 days of nitrogen deprivation, we showed that TAG accumulation and lipid/starch partitioning are dynamically regulated by alterations in PSI function, which concomitantly alters the immediate ATP/NADPH demand. This occurs even without removal of nitrogen from the medium, but sufficient external carbon must nevertheless be available. Efforts to increase lipid accumulation in algae such as Chlamydomonas need to consider carefully how the energy balance of the cell is involved in or affected by such efforts and that numerous layers of metabolic and genetic regulatory control are likely to interfere with such efforts to control oil biosynthesis. Such knowledge will enable synthetic biology approaches to alter the response to the N depletion stress, leading to rewiring of the regulatory networks so that lipid accumulation could be turned on in the absence of N deprivation, allowing for the development of algal production strains with highly enhanced lipid accumulation profiles.

The zoonotic pathogen Salmonella not only reduces the production performance in ducks, but also poses a serious threat to human health through eggs and pollutes water bodies through feces. SipC, an effector protein of type III secretion systems (T3SS) in Salmonella, mediates translocation of effectors into the eukaryotic host. However, the precise role of SipC effectors remains unknown in ducks. In this study, the SipC from duck granulosa cells (dGCs) was selected as bait, and the SipC-interacting proteins in Salmonella enteritidis (SE) were screened using Gal4 yeast two-hybrid system in duck. Twelve SipC-interacting proteins were identified. Among those, the p53-effector related to PMP-22 (PERP) and TGF-β activated kinase 1-binding protein 2 (TAB2) were selected to further confirm the function by GST pull-down in vitro. Over-expression of PERP resulted in not only increasing SE adhesion and invasion but also triggering the production of IL-1β and IFN-α in SE infected dGCs, while knock-down PERP showed the opposite tendency (P

Abstract (Hf,Ta)B 2 -based ceramics were produced by hot pressing (HP) and spark plasma sintering of powders obtained by combustion synthesis in Hf-Ta-B system. The dense ceramics possess exceptionally high hardness (60–70 GPa) and Young's modulus (584 GPa). The thermal conductivity is 30.3–52.9 W/m K depending on the phase composition. Plasma torch testing of the single- and two-phase (Hf,Ta)B 2 -based ceramics at 1500–2500 °C demonstrated the formation of a protective multi-layer oxide film with good adhesion to the ceramic, which increases the enthalpy of decomposition of ceramics up to 390 kJ/g. [ABSTRACT FROM AUTHOR]

Abstract Macrokinetic features of the combustion in Hf-Ta-B system were studied. Thermodynamic analysis and measured effective activation energies (Еа = 200 kJ/mol and 230 kJ/mol) suggest that chemical reactions which occur through gas and liquid phase play a crucial role in the combustion process. The sequence of the structure formation in the combustion wave of investigated mixtures was studied. The feature of this system is a narrow post-combustion zone, caused by high heat losses. The composition of synthesized phases does not change from the combustion zone to the zone of final products, leading to the chemical inhomogeneity and existence of intermediate phases. SHS without applied pressure leads to the formation of solid solutions on the base of (Hf,Ta)B2. Porous combustion products were used to prepare powders with particles size < 30 µm (median size 5 µm) for further sintering of bulk ceramics. [ABSTRACT FROM AUTHOR]

Abstract Two schemes for fabricating the composite powder ZrB 2 –TaB 2 –TaSi 2 by SHS are discussed in this study: (1) elemental synthesis in the Zr–Ta–B and Ta–Si mixtures followed by mixing of the combustion products, and (2) elemental synthesis in the Zr–Ta–Si–B mixture. The macrokinetic features of combustion of the Zr–Ta–Si–B mixtures, the mechanism of structure and phase formation in the combustion wave, and the structure and properties of the combustion products were studied. Primary crystals of tantalum and zirconium diborides were formed in the preheating zone as a result of gas-phase mass transfer of boron onto the surface of metal particles. In the combustion zone, melting of Si–B eutectic and Zr particles took place, followed by the formation of borides and silicides of tantalum and zirconium. In the zones of post-combustion and secondary structure formation, zirconium diboride partially interacted with tantalum diboride and formed solid solution (Ta,Zr)B 2. Hot pressing of SHS powders produced bulk ceramics with the relative density of 95–98%. Structure and mechanical properties of the hot pressed ceramics depend significantly on the selected scheme of powder synthesis. The ceramics fabricated using scheme 2 have a specific microgradient grain structure and significantly higher hardness and crack resistance (HV 10 =19.2 GPa; K 1c =3.5 MPa * m1/2) as compared to the similar composite prepared using scheme 1 (13.9 GPa and 2.4 MPa m1/2). Graphical abstract fx1 [ABSTRACT FROM AUTHOR]

Abstract The autophagy pathway has been suggested to influence skeletal structure by modulating bone metabolism. Recent findings suggest that microRNAs (miR) play a critical role in autophagy. We hypothesized that inflammation induces miR-155, which enhances autophagy in osteoclasts (OC), leading to inflammatory bone loss. The expression of miR-155 was elevated in tibiae from LPS-injected mice and in OC stimulated by lipopolysaccharide (LPS) compared with vehicle treatment. Overexpression of miR-155 enhanced autophagy as well as differentiation in OC, whereas inhibition of endogenous miR-155 decreased both. Transforming growth factor β-activated kinase 1-binding protein 2 (TAB2) was identified as a target gene of miR-155 via binding to the 3′-UTR of TAB2, which directly interacts with BECLIN1. BECLIN1 was dissociated from TAB2, which started to associate with TAK1 when autophagy was induced. Our data demonstrate that LPS-induced miR-155 promoted autophagy to increase OC formation via decreased TAB2. Graphical abstract Unlabelled Image Highlights • Micro RNA (miR-155) was induced by lipopolysaccharide. • MiR-155 enhanced autophagy as well as differentiation and activity in osteoclasts. • Transforming growth factor β-activated kinase 1-binding protein 2 (TAB2) was identified to be a target gene of miR-155. • MiR-155 bound to the 3'-UTR of TAB2 that interacted with BECLIN1, resulting in release of BECLIN 1 to induce autophagy. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) has become the most prevalent chronic liver disease worldwide, without any Food and Drug Administration-approved pharmacological intervention in clinic. Trim38, as an important member of the TRIM (tripartite motif-containing) family, was largely reported to be involved in the regulation of innate immune and inflammatory responses. However, the functional roles of TRIM38 in NAFLD remain largely unknown. Here, the expression of TRIM38 was first detected in liver samples of both NAFLD mice model and patients diagnosed with NAFLD. We found that TRIM38 expression was downregulated in NAFLD liver tissues compared with normal liver tissues. Genetic Trim38-KO in vivo showed that TRIM38 depletion deteriorated the high-fat diet and high fat and high cholesterol diet-induced hepatic steatosis and high fat and high cholesterol diet-induced liver inflammation and fibrosis. In particular, we found that the effects of hepatocellular lipid accumulation and inflammation induced by palmitic acid and oleic acid were aggravated by TRIM38 depletion but mitigated by TRIM38 overexpression in vitro. Mechanically, RNA-Seq analysis demonstrated that TRIM38 ameliorated nonalcoholic steatohepatitis progression by attenuating the activation of MAPK signaling pathway. We further found that TRIM38 interacted with transforming growth factor-β-activated kinase 1 binding protein 2 and promoted its protein degradation, thus inhibiting the transforming growth factor-β-activated kinase 1-MAPK signal cascades. In summary, our study revealed that TRIM38 could suppress hepatic steatosis, inflammatory, and fibrosis in NAFLD via promoting transforming growth factor-β-activated kinase 1 binding protein 2 degradation. TRIM38 could be a potential target for NAFLD treatment., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)