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Atopic dermatitis (AD) is one of the most common inflammatory skin diseases with complex pathogenesis involving epidermal barrier dysfunction, skin microbiome abnormalities and type-2-skewed immune dysregulation. Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that plays critical roles in various biological processes. However, the role of STAT3 in epidermal keratinocytes in AD remains unclear. In this study, we generated an epidermal keratinocyte-specific Stat3-deficient mouse strain (termed Stat3 cKO mice). After topical 2,4-dinitrochlorobenzene (DNCB) treatment, Stat3 cKO mice developed worsened AD-like skin inflammation with increased Ki67+ cells, decreased filaggrin and loricrin expression, and downregulated S100A9 and LL37. The dominant microbial population in Stat3 cKO mice changed from Ralstonia to Staphylococcus. DNCB-treated Stat3 cKO mice displayed more infiltrating type-2 inflammatory cells, including mast cells, eosinophils, and CD4+T cells, accompanied by increased skin IL-4 and serum IgE levels. Moreover, thymic stromal lymphopoietin (TSLP), mainly produced by keratinocytes, was highly expressed in the ear skin of Stat3 cKO mice and chemoattracted more TSLPR+ cells. TSLP blockade significantly alleviated DNCB-induced AD-like skin inflammation in Stat3 cKO mice. Thus, epidermal keratinocyte-specific STAT3 deficiency can aggravate AD-like skin inflammation in mice, possibly through TSLP dysregulation.

In January 2022, we received ant specimens collected from three field colonies from Shantou City, Guangdong Province, China. They were identified as the little fire ant, Wasmannia auropunctata, through morphological and molecular analyses. Wasmannia auropunctata is listed as one of the 100 most dangerous invasive species by the International Union for Conservation of Nature (IUCN) and has spread from its native range in South America to every continent except Antarctica. DNA analysis of mitochondrial cytochrome c oxidase subunit I (COI) in nine specimens of W. auropunctata found that they had a close genetic relationship with specimens from Argentina. This study represents the first formal record of the establishment of W. auropunctata outdoor in Chinese mainland. However, the invasion stage and occurrence degree of W. auropunctata in China are not clear to date. The implementation of quarantine measures, investigation of the occurrence and distribution, and development of monitoring and control strategies are needed to actively respond to the threat posed by this highly invasive ant.

ABSTRACT Gut symbiotic bacteria are known to be closely related to insect development, nutrient metabolism, and disease resistance traits, but the most important factors leading to changes in these communities have not been well clarified. To address this, we examined the associations between the gut symbiotic bacteria and the host genotype and geographical distribution of Solenopsis invicta in China, where it is invasive and has spread primarily by human-mediated dispersal. Thirty-two phyla were detected in the gut symbiotic bacteria of S. invicta. Proteobacteria were the most dominant group among the gut symbiotic bacteria. Furthermore, the Bray-Curtis dissimilarity matrices of the gut symbiotic bacteria were significantly positively correlated with the geographical distance between the host ant colonies, but this relationship was affected by the social form. The distance between monogyne colonies had a significant effect on the Bray-Curtis dissimilarity matrices of gut symbiotic bacteria, but the distance between polygyne colonies did not. Moreover, the Bray-Curtis dissimilarity matrices were positively correlated with Nei’s genetic distance of the host but were not correlated with the COI-based genetic distance. This study provides a scientific basis for further understanding the ecological adaptability of red imported fire ants during invasion and dispersal. IMPORTANCE We demonstrated that gut microbiota composition and diversity varied among populations. These among-population differences were associated with host genotype and geographical distribution. Our results suggested that population-level differences in S. invicta gut microbiota may depend more on environmental factors than on host genotype.

Radiation therapy is a standard treatment for head and neck tumors. However, patients often exhibit cognitive impairments following radiation therapy. Previous studies have revealed that hippocampal dysfunction, specifically abnormal hippocampal neurogenesis or neuroinflammation, plays a key role in radiation-induced cognitive impairment. However, the long-term effects of radiation with respect to the electrophysiological adaptation of hippocampal neurons remain poorly characterized. We found that mice exhibited cognitive impairment 3 months after undergoing 10 minutes of cranial irradiation at a dose rate of 3 Gy/min. Furthermore, we observed a remarkable reduction in spike firing and excitatory synaptic input, as well as greatly enhanced inhibitory inputs, in hippocampal CA1 pyramidal neurons. Corresponding to the electrophysiological adaptation, we found reduced expression of synaptic plasticity marker VGLUT1 and increased expression of VGAT. Furthermore, in irradiated mice, long-term potentiation in the hippocampus was weakened and GluR1 expression was inhibited. These findings suggest that radiation can impair intrinsic excitability and synaptic plasticity in hippocampal CA1 pyramidal neurons.

BackgroundTreatment for pediatric psoriasis is challenging because of the lack of real-world evidence, especially for biological therapies.ObjectivesThis study evaluated the efficacy and safety of biologics in children with psoriasis based on real-world evidence.MethodsPediatric psoriasis patients aged

The sulfate anion (SO42–) is known as an end metabolite of cysteine and methionine, and its proper concentration is associated with the expression of key functions in the physiological system. Thus, maintaining sulfate concentration at a precise level is of great significance for biology, environments, and industrial productions. Fundamental research for sulfate anion chemistry can help understand sulfate-associated physiological processes and related applications, for example, remediation. In this minireview, we summarized recent research progresses in sulfate recognition and separation using crystallization and liquid–liquid extraction. We focused on the studies wherein molecular recognition is the key element and is considered the driving force for selective sulfate separations from aqueous solution.

Abstract Background The enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase and induces the trimethylation of histone H3 lysine 27 (H3K27me3) in the promoter of many key genes; EZH2 acts as a transcriptional repressor and is an epigenetic regulator for several cancers. However, the role of EZH2 in nonneoplastic diseases, such as kidney diseases, is unknown and has been investigated. Materials and method NRK-52E cells were treated with DZNep, a potent inhibitor of EZH2, with different concentrations and for different times to evaluate the apoptosis level of NRK-52E cells by Western blot and Flow cytometry analysis. The binding of EZH2 to the Deptor promoter was determined by ChIP assay. Results The inhibition of EZH2 with 3-deazaneplanocin A (DZNep), a specific inhibitor of EZH2, led to the apoptosis of NRK-52E cells and the inhibition of mTORC1 and mTORC2 activity. A ChIP assay demonstrated that EZH2 bound the promoter region of Deptor, an endogenous inhibitor of mTORC1 and mTORC2, and regulated the transcription of Deptor by modulating H3K27me3 in its promoter region. Further experiments were performed to examine the effects of EZH2 inhibition on cisplatin-induced injured cells. Cisplatin induced the activation of mTORC1 and mTORC2 and apoptosis in NRK-52E cells, and DZNep inhibited mTORC1 and mTORC2 activity and aggravated cell apoptosis. Conclusions These data suggested that EZH2 inhibition increased the transcription of Deptor by modifying H3K27me3 in its promoter region, subsequently inhibited mTORC1 and mTORC2 activities, downregulated the expression of apoptosis suppressor genes, and finally led to apoptosis in renal tubular cells. The inhibition of EZH2 aggravated the cisplatin-induced injury in renal tubular cells by inactivating the mTOR complexes. The present study provides new insight into renal protection and suggests that EZH2 might be a target.

Cracks are the main form of tunnel complications and have drawn much attention in current tunnel safety monitoring. However, automatic crack detection cannot accurately extract cracks from tunnel concrete lining surfaces because of the inference of noises like lining seams, which have similar gray values and textures to cracks, and increase the topological complexity of cracks. In this paper, we proposed a novel method for eliminating lining seams in tunnel concrete crack images, to address the above-mentioned issues. Our contributions are shown as follows: 1) classified arbitrary line segments to better distinguish the edges on the cracks and the seams, and proposed uniform k-divided angle model to get accurate classification and 2) introduced two new principles to help effectively eliminate lining seams through the information of translation direction and expansion width of all line segments. The experimental results proved the superior precision and efficiency of our method compared with the existing methods.

Interferon-stimulated gene 15 (ISG15) is known to be involved in tumor progression. We previously reported that ISG15 expressed on nasopharyngeal carcinoma (NPC) cells and related to poor prognosis of patients with NPC. We further observed that ISG15 can be secreted by NPC cell and expressed on the macrophages in situ. However, the role of ISG15 in tumor-associated macrophages (TAMs) remains poorly understood. In the present study, we found that ISG15 treatment induces macrophages with M2-like phenotype, and the enhancement of NPC cell migration and tumorigenicity. Mechanically, ISG15-induced M2-like phenotype is dependent on the interaction with its receptor, LFA-1, and engagement of SRC family kinase (SFK) signal, and the subsequent secretion of CCL18. Blocking LFA-1, or SRC signal with small molecular inhibitors, or neutralizing with anti-CCL18 antibody can impede the activation of LFA-1-SFK-CCL18 axis in ISG15-treated macrophages. Clinically, ISG15+ CD163+ TAMs related to impaired survival of patients and advanced tumor stage of NPC. Furthermore, we found ISG15+ CD163+ macrophages inhibited antitumor CD8+ cells responses in NPC. Together, our findings suggested tumor cell-secreted ISG15, which acted as a tumor microenvironmental factor, induces M2-like phenotype, promoting tumor progression and suppression of cytotoxic T lymphocyte response.

Aedes mosquitoes can transmit dengue and several other severe vector-borne viral diseases, thereby influencing millions of people worldwide. Insects primarily control and clear the viral infections via their innate immune systems. Mitogen-Activated Protein Kinases (MAPKs) and antimicrobial peptides (AMPs) are both evolutionarily conserved components of the innate immune systems. In this study, we investigated the role of MAPKs in Aedes mosquitoes following DENV infection by using genetic and pharmacological approaches. We demonstrated that knockdown of ERK, but not of JNK or p38, significantly enhances the viral replication in Aedes mosquito cells. The Ras/ERK signaling is activated in both the cells and midguts of Aedes mosquitoes following DENV infection, and thus plays a role in restricting the viral infection, as both genetic and pharmacological activation of the Ras/ERK pathway significantly decreases the viral titers. In contrast, inhibition of the Ras/ERK pathway enhances DENV infection. In addition, we identified a signaling crosstalk between the Ras/ERK pathway and DENV-induced AMPs in which defensin C participates in restricting DENV infection in Aedes mosquitoes. Our results reveal that the Ras/ERK signaling pathway couples AMPs to mediate the resistance of Aedes mosquitoes to DENV infection, which provides a new insight into understanding the crosstalk between MAPKs and AMPs in the innate immunity of mosquito vectors during the viral infection.

The traditional image mosaic result based on SIFT feature points extraction, to some extent, has distortion errors: the larger the input image set, the greater the spliced panoramic distortion. To achieve the goal of creating a high-quality panorama, a new and improved algorithm based on the A-KAZE feature is proposed in this paper. This includes changing the way reference image are selected and putting forward a method for selecting a reference image based on the binary tree model, which takes the input image set as the leaf node set of a binary tree and uses the bottom-up approach to construct a complete binary tree. The root node image of the binary tree is the ultimate panorama obtained by stitching. Compared with the traditional way, the novel method improves the accuracy of feature points detection and enhances the stitching quality of the panorama. Additionally, the improved method proposes an automatic image straightening model to rectify the panorama, which further improves the panoramic distortion. The experimental results show that the proposed method cannot only enhance the efficiency of image stitching processing, but also reduce the panoramic distortion errors and obtain a better quality panoramic result.

The pullulanase gene (pulPL), encoding a novel type I pullulanase (PulPL), was obtained from a Paenibacillus lautus DSM3035 isolate. The gene has an open reading frame of 2355 bp, After optimizing induction conditions in Escherichia coli, we overexpressed recombinant PulPL, purified this enzyme, and assayed its function. The level of functional PulPL-like protein reached its maximum (about 0.28 mg/mL, 15% of total protein) after induction for 16 h at 20°C. Under these optimized harvesting conditions, PulPL activity was 11.1U/mL. The purified recombinant enzyme with an apparent molecular mass of about 87.9 kDa was able to specifically attack the a-1,6 linkages in pullulan to generate maltotriose as the major product. The purified PulPL exhibited optimal activity at pH 7.0 and 40°C. The PulPL hydrolyzed pullulan, amylopectin, starch, and glycogen, but not amylose. Substrate specificity observations and reaction products identifications indicate that the purified pullulanase from P. lautus DSM3035 is a type I pullulanase. The present report, to our knowledge, the first to identify type I pullulanase in P.lautus, and detail the enzymatic properties of this enzyme after heterologous expression. [ABSTRACT FROM AUTHOR]

Background: Brain-expressed X-linked (BEX) 4 is a member of BEX family. The functional role of BEX4 in oral squamous cell carcinoma (OSCC) remains unknown. Methods: Expression level of BEX family members (BEX1-5) in OSCC tissues and the paired normal epithelial were examined. Functions of epigenetic changes (DNA methylation and histone modifications) on BEX4 suppression in OSCC were examined by zebularine and trichostatin A (TSA) treatment on OSCC cell lines. Lentivector containing full-length BEX4 was used to generate OSCC cell lines with stable BEX4 expression. Effects of BEX4 expression on OSCC proliferation were monitored with xCELLigence RTCA real-time cell analyzer. BEX4-overexpressing CAL27 was implanted into nude mice to evaluate the effects on tumor growth in vivo. The signaling pathways regulated by BEX4 in OSCC was explored using human whole-transcript expression microarray. Results: Among the 5 BEX family members, BEX1 and BEX4 showed significant down-regulation in OSCC (P < 0.001). BEX3, in comparison, was overexpressed in the primary tumor. BEX4 expression in OSCC cell lines was re-activated after zebularine and TSA treatment. High BEX4 expression could suppress proliferation of OSCC in vitro. Subcutaneous tumor volume of BEX4-overexpressing CAL27 was remarkably reduced in nude mice. Microarray experiment showed that S100A family members (S100A7, S100A7A, S100A8, S100A9 & S100A12) might be the downstream targets of BEX4 in OSCC. Conclusions: BEX4 functions as tumor suppressor by inhibiting proliferation and growth of oral cancer. Decreased BEX4 contributes to the increased proliferative propensity of OSCC. [ABSTRACT FROM AUTHOR]

Background: Pullulanase is an important debranching enzyme and has been widely utilized to hydrolyse the α-1,6 glucosidic linkages in starch/sugar industry. Selecting new bacterial strains or improving bacterial strains is a prerequisite and effective solution in industrial applications. Although many pullulanase genes have been cloned and sequenced, there is no report of P. polymyxa type I pullulanase gene or the recombinant strain. Meanwhile most of the type I pullulanase investigated exhibit thermophilic or mesophilic properties. There are just few reports of cold-adapted pullulanases, which have optimum activity at moderate temperature and exhibit rather high catalytic activity at cold. Previously, six strains showing distinct pullulan degradation ability were isolated using enrichment procedures. As containing novel bacterium resource and significant pullulanase activity, strain Nws-pp2 was selected for in-depth study. Methods: In this study, a type I pullulanase gene (pulN) was obtained from the strain P. polymyxa Nws-pp2 by degenerate primers. Through optimization of induced conditions, the recombinant PulN achieved functional soluble expression by low temperature induction. The enzyme characterizations including the enzyme activity/stability, optimum temperature, optimum pH and substrate specificity were also described through protein purification. Results: The pullulanase gene (named pulN), encoding a novel cold-adapted type I pullulanase (named PulN), was obtained from isolated strain Paenibacillus polymyxa Nws-pp2. The gene had an open reading frame of 2532-bp and was functionally expressed in Escherichia coli through optimization of induced conditions. The level of functional PulN-like protein reached the maximum after induction for 16 h at 20 °C and reached about 0.34 mg/ml (about 20 % of total protein) with an activity of 6.49 U/ml. The purified recombinant enzyme with an apparent molecular mass of about 96 kDa was able to attack specifically the α-1,6 linkages in pullulan to generate maltotriose as the major product. The purified PulN showed optimal activity at pH 6.0 and 35 °C, and retained more than 40 % of the maximum activity at 10 °C (showing cold-adapted). The pullulanase activity was significantly enhanced by Co2+ and Mn2+, meanwhile Cu2+ and SDS inhibited pullulanase activity completely. The Km and Vmax values of purified PulN were 15.25 mg/ml and 20.1 U/mg, respectively. The PulN hydrolyzed pullulan, amylopectin, starch, and glycogen, but not amylose. Substrate specificity and products analysis proved that the purified pullulanase from Paenibacillus polymyxa Nws-pp2 belong to a type I pullulanase. Conclusions: This report of the novel type I pullulanase in Paenibacillus polymyxa would contribute to pullulanase research from Paenibacillus spp. significantly. Also, the cold-adapted pullulanase produced in recombinant strain shows the potential application. [ABSTRACT FROM AUTHOR]