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Abstract As a chromatin remodelling factor, high mobility group A1 (HMGA1) plays various roles in both physiological and pathological conditions. However, its role in DNA damage response and DNA damage‐based chemotherapy remains largely unexplored. In this study, we report the poly ADP‐ribosylation (PARylation) of HMGA1 during DNA damage, leading to desensitization of esophageal squamous cell carcinoma (ESCC) cells to the poly(ADP‐ribose) polymerase 1 (PARP1) inhibitor, olaparib. We found that HMGA1 accumulates at sites of DNA damage, where it interacts with PARP1 and undergoes PARylation at residues E47 and E50 in its conserved AT‐hook domain. This modification enhances the accumulation of Ku70/Ku80 at the site of DNA damage and activates the DNA‐dependent protein kinase catalytic subunit, facilitating nonhomologous end‐joining repair. In both subcutaneous tumour models and genetically engineered mouse models of in situ esophageal cancer, HMGA1 interference increased tumour sensitivity to olaparib. Moreover, HMGA1 was highly expressed in ESCC tissues and positively correlated with PARP1 levels as well as poor prognosis in ESCC patients. Taken together, these findings reveal a mechanistic link between HMGA1 and PARP1 in regulating cell responses to DNA damage and suggest that targeting HMGA1 could be a promising strategy to increase cancer cell sensitivity to olaparib.

Abstract Background The aim of this study was to investigate the imaging features, lymph node metastasis, and genetic mutations in micropapillary lung adenocarcinoma (imaging with mixed ground‐glass nodules) ≤2 cm, to provide a more precise and refined basis for the selection of lung segment resection. Methods A retrospective analysis of 162 patients with surgically resected pathologically confirmed cancers ≤2.0 cm in diameter (50 cases of micropapillary mixed ground‐glass nodules [mGGNs], 50 cases of nonmicropapillary mGGNs, and 62 cases of micropapillary SNs [solid nodules]) was performed. mGGNs were classified into five categories according to imaging features. The distribution of these five morphologies in micropapillary with mGGN and nonmicropapillary with mGGN was analyzed. The postoperative pathology and prognosis of lymph node metastasis were also compared between micropapillary mGGNs and micropapillary with SNs. After searching the TCGA database, we demonstrated heterogeneity, high malignancy and high risk of microcapillary lung cancer cancers. Results Different pathological subtypes of mGGN differed in morphological features (p

Essential oils are potential alternatives to antibiotics for preventing Candida albicans (C. albicans) infection which is responsible for economic losses in the pigeon industry. Cymbopogon martini essential oil (EO) can inhibit pathogens, particularly fungal pathogens but its potential beneficial effects on C. albicans-infected pigeons remain unclear. Therefore, we investigated the impact of C. martini EO on antioxidant activity, immune response, intestinal barrier function, and intestinal microbiota in C. albicans-infected pigeons. The pigeons were divided into four groups as follows: (1) NC group: C. albicans uninfected/C. martini EO untreated group; (2) PC group: C. albicans infected/C. martini EO untreated group; (3) LPA group: C. albicans infected/1% C. martini EO treated group; and (4) HPA group: C. albicans infected/2% C. martini EO treated group. The pigeons were infected with C. albicans from day of age 35 to 41 and treated with C. martini EO from day of age 42 to 44, with samples collected on day of age 45 for analysis. The results demonstrated that C. martini EO prevented the reduction in the antioxidant enzymes SOD and GSH-Px causes by C. albicans challenge in pigeons. Furthermore, C. martini EO could decrease the relative expression of IL-1β, TGF-β, and IL-8 in the ileum, as well as IL-1β and IL-8 in the crop, while increasing the relative expression of Claudin-1 in the ileum and the crop and Occludin in the ileum in infected pigeons. Although the gut microbiota composition was not significantly affected by C. martini EO, 2% C. martini EO increased the abundance of Alistipes and Pedobacter. In conclusion, the application of 2% C. martini EO not only enhanced the level of antioxidant activity and the expression of genes related to intestinal barrier function but also inhibited inflammatory genes in C. albicans-infected pigeons and increased the abundance of gut bacteria that are resistant to C. albicans.

For solving the problems of poor structural stability and machining difficulties of non-metallic insulating rings in space conductive slip rings, Al2O3 ceramic coatings were deposited on 2A12 aluminum alloy substrate by atmospheric plasma spraying technology to replace non-metallic insulating materials, and the phase composition, microscopic morphology, microhardness, bonding strength, and insulation performance of the coating were studied. Results showed that the main phase of Al2O3 spherical powder prepared by agglomeration sintering of original nanoparticles was α-Al2O3. After spraying, Al2O3 in the coating existed as α phase and γ phase, and the coating bonded well with the substrate, and the porosity of the coating was relatively lower. Moreover, the as-prepared coating had a uniform and dense microstructure, with no obvious macroscopic cracks or large pores inside the coating. Although no sealing treatment was used, the coating still presented high insulation performance in insulation resistance tests with a DC voltage of 1 000 V in atmospheric environments, which could meet the service requirements of space conductive slip ring insulating rings.

As a chromatin remodelling factor, high mobility group A1 (HMGA1) plays various roles in both physiological and pathological conditions. However, its role in DNA damage response and DNA damage‐based chemotherapy remains largely unexplored. In this study, we report the poly ADP‐ribosylation (PARylation) of HMGA1 during DNA damage, leading to desensitization of esophageal squamous cell carcinoma (ESCC) cells to the poly(ADP‐ribose) polymerase 1 (PARP1) inhibitor, olaparib. We found that HMGA1 accumulates at sites of DNA damage, where it interacts with PARP1 and undergoes PARylation at residues E47 and E50 in its conserved AT‐hook domain. This modification enhances the accumulation of Ku70/Ku80 at the site of DNA damage and activates the DNA‐dependent protein kinase catalytic subunit, facilitating nonhomologous end‐joining repair. In both subcutaneous tumour models and genetically engineered mouse models of in situ esophageal cancer, HMGA1 interference increased tumour sensitivity to olaparib. Moreover, HMGA1 was highly expressed in ESCC tissues and positively correlated with PARP1 levels as well as poor prognosis in ESCC patients. Taken together, these findings reveal a mechanistic link between HMGA1 and PARP1 in regulating cell responses to DNA damage and suggest that targeting HMGA1 could be a promising strategy to increase cancer cell sensitivity to olaparib. [ABSTRACT FROM AUTHOR]

BackgroundThere is an urgent need to find an effective and accurate method for triaging coronavirus disease 2019 (COVID-19) patients from millions or billions of people. Therefore, this study aimed to develop a novel deep-learning approach for COVID-19 triage based on chest computed tomography (CT) images, including normal, pneumonia, and COVID-19 cases.MethodsA total of 2,809 chest CT scans (1,105 COVID-19, 854 normal, and 850 non-3COVID-19 pneumonia cases) were acquired for this study and classified into the training set (n = 2,329) and test set (n = 480). A U-net-based convolutional neural network was used for lung segmentation, and a mask-weighted global average pooling (GAP) method was proposed for the deep neural network to improve the performance of COVID-19 classification between COVID-19 and normal or common pneumonia cases.ResultsThe results for lung segmentation reached a dice value of 96.5% on 30 independent CT scans. The performance of the mask-weighted GAP method achieved the COVID-19 triage with a sensitivity of 96.5% and specificity of 87.8% using the testing dataset. The mask-weighted GAP method demonstrated 0.9% and 2% improvements in sensitivity and specificity, respectively, compared with the normal GAP. In addition, fusion images between the CT images and the highlighted area from the deep learning model using the Grad-CAM method, indicating the lesion region detected using the deep learning method, were drawn and could also be confirmed by radiologists.ConclusionsThis study proposed a mask-weighted GAP-based deep learning method and obtained promising results for COVID-19 triage based on chest CT images. Furthermore, it can be considered a convenient tool to assist doctors in diagnosing COVID-19.

Triboelectric nanogenerators (TENGs) provide promising power supply solutions by transforming mechanical energy into electrical energy. However, enhancing electrical performance of TENGs is essential for their widespread practical applications and commercialization. In this study, we fabricated TENGs in vertical contact‐separation mode using a tribopositive material—polyvinyl alcohol (PVA) slime—which is biocompatible, flexible, and wearable, decorated with graphene nanoplatelets (GnPs), and paired with tribonegative silicone. We analyzed the correlation between the electrical performance of the TENGs and the inherent triboelectric properties of the constituent material, including the evaluation of surface roughness, the measurement of the contact potential difference (CPD), and the material's dielectric constant. The incorporation of GnPs increased the dielectric constant of the composite material and its electron‐donating tendency, thus, increasing the contact potential difference. The GnPs concentration of 1 wt% was identified as the optimal value, resulting in a 42% increase in power density. The 1 wt% GnPs@PVA&Silicone TENG exhibited an open‐circuit voltage of 718 V and a peak power density of 15.3 W/m2. This study sheds light on enhancing the energy harvesting efficiency of TENGs through the utilization of biocompatible tribopositive and tribonegative materials. [ABSTRACT FROM AUTHOR]

Thermochromic polymers with tunable thermochromism, high stretchability and mechanical strength are of interests for optical information storage and encryption. In this work, we demonstrate a new design of thermo-fluorochromic carboxylated nitrile butadiene rubber (XNBR) elastomer cross-linked by Eu3+-COOH dynamic coordination with deprotonated imidazole (DPIm) as the ancillary ligand. The presence of DPIm not only improves the mechanical strength and stretchability, but also dramatically intensifies the fluorescence emission and lifetime of the Eu-containing elastomer. The elastomer behaves reversible thermo-fluorochromism with easily tunable transition temperature and emission intensity by the simple change of the deprotonation degree of imidazole. The facile tunable thermo-fluorochromism, exceptional mechanical strength, and high stretchability (up to about 5000%) enable the Eu-containing XNBR elastomer with potential applications in soft electronics where optical information storage and encryption are required. [ABSTRACT FROM AUTHOR]

Abstract Background LPIN1-related acute recurrent rhabdomyolysis (RM), first reported in 2008, is an autosomal recessive inherited metabolic disease. In recent years, LPIN1 gene variants have been identified as one of the main causes of severe RM in children in Western countries. The disease is extremely rare in China, and we report a case of acute recurrent RM caused by a novel compound heterozygous LPIN1 variant. Case presentation A 15-year-old Chinese boy presented with myalgia after strenuous exercise, accompanied by transient increases in serum creatine kinase and myoglobin and persistent hyperuricaemia and hyperbilirubinaemia. Genetic analysis using high-throughput genomic sequencing and Sanger sequencing revealed that there was a compound heterozygous variant in the LPIN1 gene of the proband: the paternal c.2047A > G(p.I683V) was an unreported missense variant, and the maternal c.2107_2108 insAGG(p.Q703delin sQE) was an unreported in-frame variant. Conclusions In children with RM, LPIN1 variants should always be considered in the differential diagnosis. The clinical features of our case are atypical, which highlights the importance of an accurate diagnosis by genetic testing. If detected early, the condition may be controlled, and the prognosis may be improved.