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Tertiary lymphoid structure (TLS) is an ectopic lymphocyte aggregate formed in peripheral non-lymphoid tissues, including inflamed or cancerous tissue. Tumorassociated TLS serves as a prominent center of antigen presentation and adaptive immune activation within the periphery, which has exhibited positive prognostic value in various cancers. In recent years, the concept of maturity regarding TLS has been proposed and mature TLS, characterized by well-developed germinal centers, exhibits a more potent tumor-suppressive capacity with stronger significance. Meanwhile, more and more evidence showed that TLS can be induced by therapeutic interventions during cancer treatments. Thus, the evaluation of TLS maturity and the therapeutic interventions that induce its formation are critical issues in current TLS research. In this review, we aim to provide a comprehensive summary of the existing classifications for TLS maturity and therapeutic strategies capable of inducing its formation in tumors. [ABSTRACT FROM AUTHOR]

Background: Extramammary Paget's disease (EMPD) is a rare cutaneous malignancy, commonly affecting the external genitalia and perianal area of the elderly with unclear pathogenesis. Metabolomics provides a novel perspective for uncovering the metabolic mechanisms of a verity of cancers. Materials and methods: Here, we explored the metabolome of EMPD using an untargeted strategy. In order to further investigate the potential relationship between metabolites and gene expression, we re-analyzed the gene expression microarray data (GSE117285) using differential expression analysis and functional enrichment analyses. Results: Results showed that a total of 896 metabolites were identified and 87 metabolites including 37 upregulated and 50 downregulated significantly in EMPD were sought out. In the following feature selection analyses, four metabolites, namely, cyclopentyl fentanyl-d5, LPI 17:0, guanosine-3',5'-cyclic monophosphate, kynurenine (KYN, high in EMPD) were identified by both random forest and support vector machine analyses. We then identified 1,079 dysfunctional genes: 646 upregulated and 433 downregulated in EMPD. Specifically, the tryptophan-degrading enzyme including indoleamine-2,3- dioxygenase-1 (IDO1) and tryptophan 2,3-dioxygenase (TDO2) were also increased. Generally, cancers exhibit a high expression of IDO1 and TDO2 to catabolize tryptophan, generating abundant KYN. Moreover, we also noticed the abnormal activation of sustaining proliferative signaling in EMPD. Conclusion: In conclusion, this study was the first to reveal the metabolome profile of EMPD. Our results demonstrate that IDO1/TDO2-initialized KYN metabolic pathway may play a vital role in the development and progression of EMPD, which may serve as a potential therapeutic target for treating EMPD. [ABSTRACT FROM AUTHOR]

To explore the design of the virtual reality (VR) augmented reality (AR) mobile platform and game decision model based on deep learning (DL), the gesture-based interaction of VR games based on Leap Motion is researched. Based on the interactive features of gestures, a set of general gesture interaction rules in VR games is established. In the meantime, according to the theoretical basis and the characteristics of VR, a set of general models of VR gesture interaction is designed, the factors affecting the efficiency of VR gesture interaction are studied, and reasonable interaction feedback is designed. By using the computer vision and image processing technology, gesture-based interaction can collect natural gestures, extract gesture features, recognize gesture indications, and respond to the user demands. Also, it can extract the basic gestures from gesture-based interaction in VR, analyze the basic features of gestures and gesturebased interaction in VR games, and describes the gesture features by mathematical vectors and sets. The research results show that the application of gesture feature design method in the game can analyze the factors affecting the interaction efficiency. Also, the usability of the gesture-based interaction designed by the gesture design method is verified by tests. Therefore, the AR&DL platform of "ARþDL" establishes a learning platform supported by DL and AR technology. The game decision model is used to describe the process of gesture-based interaction in the game, and the factors affecting the interaction efficiency are reduced, which has certain reference and guidance for VR applications using gesture-based interaction. [ABSTRACT FROM AUTHOR]

Background: The immune microenvironment plays a critical role in maintaining skin homeostasis, which is closely related to the dysfunction in photoaged skin such as autoimmunity and tumorigenesis. Several recent studies have demonstrated the efficacy of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in alleviating photoaging and skin cancer. However, the underlying immune mechanisms and the immune microenvironment change by ALA-PDT remain largely unknown. Methods: To illustrate the effects of ALA-PDT on immune microenvironment in photoaged skin, single cell RNA sequencing (scRNA-seq) analysis of photoaged skin on the extensor side of the human forearm before and after ALA-PDT was performed. R-packages of Seurat, clusterProfiler, Monocle, CellChat were used for cell clustering, differentially expressed genes analysis, functional annotation, pseudotime analysis and cell-cell communication analysis. The gene sets related to specific functions were extracted from the MSigDB database, which were used to score the functions of immune cells in different states. We also compared our result with published scRNA-seq data of photoaged skin of the eyelids. Results: The increase score of cellular senescence, hypoxia and reactive oxygen species pathway in immune cells and the decrease of immune receptor activity function and proportion of naive T cells were found in skin photoaging. Moreover, the function of T cell ribosomal synthesis was also impaired or down regulated and function of G2M checkpoint was up regulated. However, ALA-PDT showed promising results in reversing these effects, as it improved the above functions of T cells. The ratio of M1/M2 and percentage of Langerhans cells also decreased with photoaging and increased after ALA-PDT. Additionally, ALA-PDT restored the antigen presentation and migration function of dendritic cells and enhanced cell-cell communication among immune cells. These effects were observed to last for 6 months. Conclusion: ALA-PDT has potential to rejuvenate immune cells, partially reversed immunosenescence and improved the immunosuppressive state, ultimately remodelling the immune microenvironment in photoaged skin. These results provide an important immunological basis for further exploring strategies to reverse skin photoaging, chronological aging and potentially systemic aging. [ABSTRACT FROM AUTHOR]

Background: We previously found that modified 5-aminolevulinic acid photodynamic therapy (M-PDT) is painless and effective in cutaneous squamous cell carcinoma (cSCC) treatment, however, the regulatory mechanism of M-PDT in cSCC is still unclear. Objective: To clarify the effect and relevant regulatory mechanism of M-PDT in cSCC. Methods: The cSCC apoptosis was examined by flow cytometry, TUNEL staining and Cleaved-caspase-3 immunofluorescence, respectively. The autophagyrelated characterization was detected by monodansylcadaverine (MDC) staining, transmission electron microscopy (TEM), GFP-LC3B autophagic vacuoles localization and mRFP-EGFP tandem fluorescence-tagged LC3B construct, respectively. The expression of autophagy-related proteins and Akt/mTOR signaling molecules were examined by Western blot. ROS generation was measured by DCFH-DA probe. Results: We found that M-PDT induced cSCC apoptosis in a dose-dependent manner, and this result was related to autophagic flux blockage. The phenomenon is confirmed by the results that M-PDT could induce autophagosomes accumulation and upregulate LC3-II and p62 expression. M-PDT elevated colocalization of RFP and GFP tandem-tagged LC3B puncta in cSCC cell, reflecting autophagic flux blockage, and this was confirmed by transmission electron microscopy. Furthermore, we noticed that M-PDT induced accumulated autophagosomes-dependent apoptosis via targeting ROS-mediated Akt/mTOR signaling. Suppression of Akt potentiated M-PDT-induced upregulation of LC3-II and p62 levels, whereas Akt activation and ROS inhibition rendered resistance to these events. In addition, we observed that lysosomal dysfunction was involved in M-PDT-triggered accumulated autophagosomes-dependent cSCC apoptosis. Conclusion: Our data demonstrates that M-PDT inhibits cSCC through blocking Akt/mTOR-mediated autophagic flux. [ABSTRACT FROM AUTHOR]

Congenital poikiloderma is an extremely rare autosomal dominant genetic syndrome, characterized by a combination of early onset poikiloderma, telangiectasia, and epidermal atrophy. FAM111B gene with multiple mutations has been identified as a potential causative gene for congenital poikiloderma. In this report, we described a boy with congenital poikiloderma confirmed by clinical manifestations. Next-generation sequencing based on a gene probe panel consisting of 541 genetic loci of genodermatoses, was used to screen mutations of the proband and his parents. Results showed that a missense mutation in the FAM111B gene c.1883G>A (rs587777238) was identified in the proband, but absent in his parents, indicating the mutation is de novo. In conclusion, a new case of congenital poikiloderma in China was reported, and the hotspot mutations in codon 628 of FAM111B gene was reviewed, as well as authenticating the uncertain association between genotypes and phenotypes in this rare disease. [ABSTRACT FROM AUTHOR]

Immune checkpoint blockade (ICB) is a powerful oncologic treatment modality for a wide variety of human malignancies, but the patient response rate to this treatment remains low, especially in patients with cutaneous squamous cell carcinoma (cSCC). 5-Aminoleuvulinic acid-photodynamic therapy (ALAPDT) is widely used to treat cancerous and precancerous skin diseases, but the value of ALA-PDT in the treatment of invasive cSCC is debatable. Our previous studies have shown that ALA-PDT can induce antitumor immune responses by promoting the immunogenic death of tumor cells. However, it is unclear whether ALA-PDT exerts synergistic effects with ICB in cSCC. Here, we report that PD-L1 blockade potentiates the antitumor effects of ALA-PDT both on primary and distant tumors, and optimizes the tumor microenvironment in cSCC. In this study, we first detected PD-L1 expression in patients with different grades of cSCC. Then we found the combination of anti-PD-L1 monoclonal antibody (mAb) and ALA-PDT killed tumor cells by apoptosis- and/or ferroptosis-mediated immunogenic cell death (ICD) and stimulated systemic immune response, as well as building the immunological memory response to prevent tumor recurrence. Furthermore, we found that combination therapy can be used to recruit tertiary lymphoid structure (TLS)-like intratumoral lymphoid aggregates, which may promote tumorinfiltrating lymphocyte (TIL)-mediated antitumor immunity. In summary, our work demonstrates that ICB treatment with an anti-PD-L1 antibody is a promising strategy that may potentiate the antitumor effects of ALA-PDT in cSCC. [ABSTRACT FROM AUTHOR]

The objective of the experiment was to evaluate a commercial Saccharomyces cerevisiae fermentation product (SCFP; NaturSafe, Dimond V, Cedar Rapids, IA) on performance, plasma metabolites, rumen parameters, and fecal pathogen shedding in feedlot steers. Crossbred steers (n = 61; 271 ± 48.1 kg) were sourced from 3 different research units at Oklahoma State University and assigned to 1 of 3 experimental treatments in a randomized complete block design. Steers were group housed in pens equipped with an automated individual feed intake system. Treatments consisted of a negative control (CON), CON with tylosin phosphate (TYL; 9.9 mg ⋅ kg-1 of diet DM), or CON with SCFP (1.63 g ⋅ kg-1 of diet DM). Body weight and feed efficiency did not differ among treatments (P ≥ 0.12). However, steers fed SCFP tended to have greater ADG from d 35 to 56 (P = 0.10). In addition, steers fed SCFP exhibited increased DMI from d 56 to 112 (P = 0.03), a tendency for increased DMI from d 112 to final (P = 0.07), and increased DMI overall (P = 0.05). There was no treatment x time interaction for pH, pH change, or lactate concentrations in rumen fluid (P ≥ 0.11), but all were impacted by time (P < 0.01). A treatment x time interaction (P < 0.01) was detected for fecal pH and fecal pH change, with the pH being greater in TYL fed steers on d 56 and in CON fed steers on the final day. Steers that consumed CON had a reduced fecal pH (P < 0.01) and steers consuming SCFP tended to have a reduced fecal pH (P = 0.08) from d 35 to 56 compared with TYL fed steers, while both CON and SCFP fed steers experienced an increase in fecal pH from d 56 to 112 (P < 0.01). A time effect was detected (P ≤ 0.04) for plasma glucose, lactate, urea nitrogen, and non-esterified fatty acid concentrations among treatment groups. A treatment x time interaction was observed (P < 0.02) for stx2 genes of Shiga toxin producing Escherichia coli (STEC) in individual fecal samples where SCFP and TYL fed steers tended to exhibit an increased concentration compared with CON fed steers on d 14, while on d 190 CON and SCFP fed steers exhibited an increased concentration compared with TYL fed steers. Overall, STEC, E. coli O157:H7, and Salmonella concentrations were all impacted by time (P < 0.001). This experiment suggests that SCFP could be utilized as a potential alternative to TYL in feedlot cattle without adversely affecting cattle performance. However, SCFP did not impact pathogen shedding. In addition, CON fed steers performed similarly to both SCFP and TYL fed steers. [ABSTRACT FROM AUTHOR]

A rise in antimicrobial resistance demands novel alternatives to antimicrobials for disease control and prevention. As an important component of innate immunity, host defense peptides (HDPs) are capable of killing a broad spectrum of pathogens and modulating a range of host immune responses. Enhancing the synthesis of endogenous HDPs has emerged as a novel host-directed antimicrobial therapeutic strategy. To facilitate the identification of natural products with a strong capacity to induce HDP synthesis, a stable macrophage cell line expressing a luciferase reporter gene driven by a 2-Kb avian β-defensin 9 (AvBD9) gene promoter was constructed through lentiviral transduction and puromycin selection. A high throughput screening assay was subsequently developed using the stable reporter cell line to screen a library of 584 natural products. A total of 21 compounds with a minimum Z-score of 2.0 were identified. Secondary screening in chicken HTC macrophages and jejunal explants further validated most compounds with a potent HDP-inducing activity in a dose-dependent manner. A follow-up oral administration of a lead natural compound, wortmannin, confirmed its capacity to enhance the AvBD9 gene expression in the duodenum of chickens. Besides AvBD9, most other chicken HDP genes were also induced by wortmannin. Additionally, butyrate was also found to synergize with wortmannin and several other newly-identified compounds in AvBD9 induction in HTC cells. Furthermore, wortmannin acted synergistically with butyrate in augmenting the antibacterial activity of chicken monocytes. Therefore, these natural HDP-inducing products may have the potential to be developed individually or in combinations as novel antibiotic alternatives for disease control and prevention in poultry and possibly other animal species including humans. [ABSTRACT FROM AUTHOR]

Branched chain amino acids (BCAAs), including leucine (Leu), isoleucine (Ile), and valine (Val), play critical roles in the regulation of energy homeostasis, nutrition metabolism, gut health, immunity and disease in humans and animals. As the most abundant of essential amino acids (EAAs), BCAAs are not only the substrates for synthesis of nitrogenous compounds, they also serve as signaling molecules regulating metabolism of glucose, lipid, and protein synthesis, intestinal health, and immunity via special signaling network, especially phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signal pathway. Current evidence supports BCAAs and their derivatives as the potential biomarkers of diseases such as insulin resistance (IR), type 2 diabetes mellitus (T2DM), cancer, and cardiovascular diseases (CVDs). These diseases are closely associated with catabolism and balance of BCAAs. Hence, optimizing dietary BCAA levels should have a positive effect on the parameters associated with health and diseases. This review focuses on recent findings of BCAAs in metabolic pathways and regulation, and underlying the relationship of BCAAs to related disease processes. [ABSTRACT FROM AUTHOR]

Dust emissions refer to the spatial displacement of dust particles from wind forcing, which is a key component of dust circulation. It plays an important role in the energy, hydrological, and carbon cycles of the Earth's systems. However, most dust emission schemes only consider natural dust, neglecting anthropogenic dust induced by human activities, which led to large uncertainties in quantitative estimations of dust emissions in numerical modeling. To fully consider the mechanisms of anthropogenic dust emissions, both indirect and direct anthropogenic dust emission schemes were constructed and developed in the study. Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) retrievals were used to constrain the simulations at global scale. The results showed that the schemes reasonably reproduced the spatio-temporal distributions of anthropogenic dust from 2007 to 2010. The high centers of anthropogenic dust emission flux appeared in India, eastern China, North America, and Africa range from 0.9 to 11 μg m-2 s-1. Compared with natural dust emissions, indirect anthropogenic dust emissions have indistinctive seasonal variation, with differences less than 3.2 μg m-2 s-1. Pasturelands contribute higher anthropogenic dust emissions than croplands, with emissions of approximately 6.8 μg m-2 s-1, accounting for 60% of indirect anthropogenic dust emissions. Moreover, average anthropogenic dust emissions in urban areas have a value of 13.5 μg m-2 s-1, which is higher than those in rural areas (7.9 μg m-2 s-1). This study demonstrates that the environmental problems caused by anthropogenic dust in urban areas cannot be ignored. [ABSTRACT FROM AUTHOR]

We conducted a comprehensive field campaign to explore the optical characteristics of mineral dust in Dunhuang farmland near the Gobi Desert of northwest China during spring of 2012. The day-to-day and diurnal variations of dust aerosol showed prominent features throughout the experiment, primarily attributable to frequent dust events and local anthropogenic emissions. The overall average mass concentrations of the particulate matter with an aerodynamic diameter less than 10 μm (PM10), light scattering coefficient (±sp;670/, absorption coefficient (σsp,670), and single-scattering albedo (SSA670) were 113±169 μg m-3, 53.3±74.8M m-1, 3.2±2.4M m-1, and 0.913±0.05, respectively, which were comparable to the background levels in the southern United States but smaller than those in the eastern and other northwestern Chinese cities. The anthropogenic dust produced by agricultural cultivations (e.g., land planning, plowing, and disking) exerted a significant superimposed effect on high dust concentrations in Dunhuang farmland prior to the growing season (i.e., from 1 April to 10 May). Strong south valley wind and vertical mixing in daytime scavenged the pollution, and the weak northeast mountain wind and stable inversion layer at night favorably accumulated the air pollutants near the surface. In the afternoon (13:00-18:00 LT, local time), mean SSA670 was 0.945±0.04 predominantly from dust particles, whereas finer particles and lower SSA670 values (±0.90-0.92) were measured at night, suggesting the potential influence by the mixed dust pollutants. During a typical biomass burning event on 4 April 2012, ±ap;670 increased from ~2.0 to 4.75M m-1 and SSA670 changed from ~0.90 to ~0.83, implying remarkable modification of aerosol absorptive properties induced by human activities. The findings of this study would help to advance an in-depth understanding of the interaction among dust aerosol, atmospheric chemistry, and climate change in a desert source region. [ABSTRACT FROM AUTHOR]

Background: Since the domestication of the red jungle fowls (Gallus gallus; dating back to ~10 000 B.P.) in Asia, domestic chickens (Gallus gallus domesticus) have been subjected to the combined effects of natural selection and human-driven artificial selection; this has resulted in marked phenotypic diversity in a number of traits, including behavior, body composition, egg production, and skin color. Population genomic variations through diversifying selection have not been fully investigated. Findings: The whole genomes of 78 domestic chickens were sequenced to an average of 18-fold coverage for each bird. By combining this data with publicly available genomes of five wild red jungle fowls and eight Xishuangbanna game fowls, we conducted a comprehensive comparative genomics analysis of 91 chickens from 17 populations. After aligning ~21.30 gigabases (Gb) of high-quality data from each individual to the reference chicken genome, we identified ~6.44 million (M) single nucleotide polymorphisms (SNPs) for each population. These SNPs included 1.10 M novel SNPs in 17 populations that were absent in the current chicken dbSNP (Build 145) entries. Conclusions: The current data is important for population genetics and further studies in chickens and will serve as a valuable resource for investigating diversifying selection and candidate genes for selective breeding in chickens. [ABSTRACT FROM AUTHOR]

Modulation of the synthesis of endogenous host defense peptides (HDPs) by probiotics represents a novel antimicrobial approach for disease control and prevention, particularly against antibiotic-resistant infections in human and animals. However, the extent of HDP modulation by probiotics is species dependent and strain specific. In the present study, The porcine small intestinal epithelial cell line (IPEC-J2) cells and neonatal piglets were used as in-vitro and in-vivo models to test whether Lactobacillus reuteri I5007 could modulate intestinal HDP expression. Gene expressions of HDPs, toll-like receptors, and fatty acid receptors were determined, as well as colonic short chain fatty acid concentrations and microbiota. Exposure to 108 colony forming units (CFU)/mL of L. reuteri I5007 for 6 h significantly increased the expression of porcine β-Defensin2 (PBD2), pBD3, pBD114, pBD129, and protegrins (PG) 1-5 in IPEC-J2 cells. Similarly, L. reuteri I5007 administration significantly increased the expression of jejunal pBD2 as well as colonic pBD2, pBD3, pBD114, and pBD129 in neonatal piglets (p < 0.05). This was probably associated with the increase in colonic butyric acid concentration and up-regulating expression of Peroxisome Proliferator-Activated Receptor-γ (PPAR-γ) and G Protein-Coupled Receptor 41 (GPR41) (p < 0.05), but not with stimulation of Pattern-Recognition Receptors. Additionally, supplementation with L. reuteri I5007 in the piglets did not affect the colonic microbiota structure. Our findings suggested that L. reuteri I5007 could modulate intestinal HDP expression and improve the gut health of neonatal piglets, probably through the increase in colonic butyric acid concentration and the up-regulation of the downstream molecules of butyric acid, PPAR-γ and GPR41, but not through modifying gut microbiota structure. [ABSTRACT FROM AUTHOR]

Dyschromatosis symmetrica hereditaria (DSH) is a rare type of pigmentary genodermatosis, which is autosomal dominantly inherited with high penetrance. The onset of DSH is typically during infancy or childhood. Cases of patients born with skin lesions have rarely been reported. Additionally, there have been few significant non‑cutaneous complications reported with DSH. The present study reported two sporadic cases of patients born with DSH, confirmed by the identification of ADAR1 mutations. Additionally, comorbidity of DSH, congenital heart disease (CHD) and hemangioma disease were first reported. In the patient with isolated DSH from birth, a nonsense mutation (p.Y1192X) was identified, whereas in the second patient with DSH, CHD and hemangioma from birth, a frameshift mutation (p.Glu673ValfsX652) in ADAR1 was identified. To the best of the authors' knowledge, >120 mutations in ADAR1 have been reported to cause DSH; however, no previous studies have reported mutations in ADAR1 in DSH at birth, with CHD and hemangioma. The novel variants described in the current study add to the current knowledge of ADAR1 mutations in DSH. [ABSTRACT FROM AUTHOR]

Background: The growth rate often varies among individual broilers of the same breed under a common management condition. To investigate whether a variation in the growth rate is associated with a difference in hormone levels and myogenic gene expression profile in broilers, a feeding trial was conducted with 10,000 newly hatched Ross 308 chicks in a commercial production facility under standard management. At 38 d of age, 30 fast-, 30 medium- and 30 slow-growing broilers were selected among 600 healthy male individuals. The levels of insulin-like growth factor-1 (IGF-1), triiodothyronine (T3), thyroxine (T4) and growth hormone in the serum or breast muscle were assayed by ELISA or RIA kits and the expression levels of several representative pro and anti-myogenic genes in the breast muscle were also measured by real-time PCR. Results: Results showed that both absolute and relative weights of the breast muscle were in linear positive correlations with the body weight of broilers (P < 0.001). Fast-growing broilers had higher concentrations of IGF-1 than slow-growing broilers (P < 0.05) in both the serum and breast muscle. The serum concentration of T3 was significantly higher in fast-growing birds than in slow-growing birds (P<0.05). However, no difference was observed in growth hormone or T4 concentration among three groups of birds. Additionally, a decreased expression of an anti-myogenic gene (myostatin) and increased expressions of pro-myogenic genes such as myogenic differentiation factor 1, myogenin, muscle regulatory factor 4, myogenic factor 5, IGF-1 and myocyte enhancer factor 2B, C and D were observed in fast-growing broilers (P < 0.05), relative to slow-growing broilers. Conclusions: Collectively, these findings suggested that the growth rate is linked to the hormone and myogenic gene expression levels in broiler chickens. Some of these parameters such as serum concentrations of IGF-1 and T3 could be employed to breed for enhanced growth. [ABSTRACT FROM AUTHOR]

We conducted a comprehensive field campaign on exploring the optical characteristics of mineral dust in Dunhuang farmland nearby the Gobi deserts of northwest China during spring of 2012. The day-to-day and diurnal variations of dust aerosol showed prominent features throughout the experiment, primarily attributable to frequent dust events and local anthropogenic emissions. The overall average mass concentration of the particulate matter with an aerodynamic diameter less than 10 μm (PM10), light scattering coefficient (Σsp,670), absorption coefficient (Σap,670), and single-scattering albedo (SSA670) were 113±169 μgm-3, 53.3 ± 74.8 Mm-1, 3.2± 2.4 Mm-1, and 0.913 ± 0.05, which were comparable to the background levels in southern United States, but smaller than that in the eastern and other northwestern China. The anthropogenic dust produced by agricultural cultivations (e.g., land planning, plowing, and disking) exerted a significant superimposed effect on high dust concentrations in Dunhuang farmland prior to the growing season (i.e., from 1 April to 10 May). Strong south valley wind and vertical mixing in daytime scavenged the pollution and weak northeast mountain wind and stable inversion layer at night favorably accumulated the air pollutants near the surface. In the afternoon (13:00-18:00 LT), mean SSA670 was 0.945 ± 0.04 that was predominant by dust particles, whereas finer particles and lower SSA670 values (~ 0.90-0.92) were measured at night, suggesting the potential influence by the mixed dust-pollutants. During a typical biomass burning event on 4 April 2012, Σap,670 changed from ~ 2.0 Mm-1 to 4.75 Mm-1 and SSA670 changed from ~ 0.90 to ~ 0.83, implying remarkable modification of aerosol absorptive properties induced by human activities. The findings of this study would help to advance an in-depth understanding of the interaction among dust aerosol, atmospheric chemistry, and climate change in desert source region. [ABSTRACT FROM AUTHOR]

The Weather Research and Forecasting Model with chemistry (WRF-Chem model) was used to investigate a typical dust storm event that occurred from 18 to 23 March 2010 and swept across almost all of China, Japan, and Korea. The spatial and temporal variations in dust aerosols and the meteorological conditions over East Asia were well reproduced by the WRF-Chem model. The simulation results were used to further investigate the details of processes related to dust emission, long-range transport, and radiative effects of dust aerosols over the Taklimakan Desert (TD) and Gobi Desert (GD). The results indicated that weather conditions, topography, and surface types in dust source regions may influence dust emission, uplift height, and transport at the regional scale. The GD was located in the warm zone in advance of the cold front in this case. Rapidly warming surface temperatures and cold air advection at high levels caused strong instability in the atmosphere, which strengthened the downward momentum transported from the middle and low troposphere and caused strong surface winds. Moreover, the GD is located in a relatively flat, high-altitude region influenced by the confluence of the northern and southern westerly jets. Therefore, the GD dust particles were easily lofted to 4 km and were the primary contributor to the dust concentration over East Asia. In the dust budget analysis, the dust emission flux over the TD was 27.2 ± 4.1 μg m-2 s-1, which was similar to that over the GD (29 ± 3.6 μg m-2 s-1). However, the transport contribution of the TD dust (up to 0.8 ton d-1) to the dust sink was much smaller than that of the GD dust (up to 3.7 ton d-1) because of the complex terrain and the prevailing wind in the TD. Notably, a small amount of the TD dust (PM2.5 dust concentration of approximately 8.7 μg m-3) was lofted to above 5 km and transported over greater distances under the influence of the westerly jets. Moreover, the direct radiative forcing induced by dust was estimated to be -3 and -7 W m-2 at the top of the atmosphere, -8 and -10 W m-2 at the surface, and +5 and +3 W m-2 in the atmosphere over the TD and GD, respectively. This study provides confidence for further understanding the climate effects of the GD dust. [ABSTRACT FROM AUTHOR]

Asian dust particulate is one of the primary aerosol constituents in the Earth-atmosphere system that exerts profound influences on environmental quality, human health, the marine biogeochemical cycle, and Earth's climate. To date, the absorptive capacity of dust aerosol generated from the Asian desert region is still an open question. In this article, we compile columnar key absorption and optical properties of mineral dust over East and Central Asian areas by utilizing the multiyear quality-assured datasets observed at 13 sites of the Aerosol Robotic Network (AERONET). We identify two types of Asian dust according to threshold criteria from previously published literature. (1) The particles with high aerosol optical depth at 440 nm (AOD440 ≥ 0.4) and a low Ångström wavelength exponent at 440-870 nm (α < 0.2) are defined as Pure Dust (PDU), which decreases disturbance of other non-dust aerosols and keeps high accuracy of pure Asian dust. (2) The particles with AOD440 ≥ 0.4 and 0.2 < α < 0.6 are designated as Transported Anthropogenic Dust (TDU), which is mainly dominated by dust aerosol and might mix with other anthropogenic aerosol types. Our results reveal that the primary components of high AOD days are predominantly dust over East and Central Asian regions, even if their variations rely on different sources, distance from the source, emission mechanisms, and meteorological characteristics. The overall mean and standard deviation of single-scattering albedo, asymmetry factor, real part and imaginary part of complex refractive index at 550 nm for Asian PDU are 0.935±0.014, 0.742±0.008, 1.526±0.029, and 0.00226±0.00056, respectively, while corresponding values are 0.921±0.021, 0.723±0.009, 1.521±0.025, and 0.00364±0.0014 for Asian TDU. Aerosol shortwave direct radiative effects at the top of the atmosphere (TOA), at the surface (SFC), and in the atmospheric layer (ATM) for Asian PDU (α < 0.2) and TDU (0.2 < α < 0.6) computed in this study, are a factor of 2 smaller than the results of Optical Properties of Aerosols and Clouds (OPAC) mineral-accumulated (mineral-acc.) and mineral-transported (mineral-tran.) modes. Therefore, we are convinced that our results hold promise for updating and improving accuracies of Asian dust characteristics in present-day remote sensing applications and regional or global climate models. [ABSTRACT FROM AUTHOR]

Nagashima-type palmoplantar keratosis (NPPK) is an autosomal recessive form of palmoplantar keratoderma (PPK), which is caused by mutations in the SERPINB7 gene. NPPK has only been reported in Japanese and Chinese populations. The present study was conducted on 12 unrelated Chinese patients who were clinically predicted to suffer from NPPK. Mutation screening was performed by direct sequencing of the entire coding regions of SERPINB7, SLURP1, AQP5, CSTA, KRT1 and KRT9 genes. Direct sequencing of SERPINB7 revealed five homozygous founder mutations (c.796C>T) and four compound heterozygous mutations in nine patients, including one novel mutation (c.122_127delTGGTCC). Nine out of the 12 patients were diagnosed with NPPK due to SERPINB7 pathogenic mutations, and the results expanded the known mutation spectrum of NPPK. Taking the other seven reported Chinese patients, who had been definitively diagnosed with NPPK by genetic testing, into account, the present study further demonstrated that NPPK is a common entity in Mainland China, and c.796C>T is the most prevalent mutation and exerts a founder effect. Furthermore, the NPPK cases described in the current study presented a consistently mild phenotype, as compared with the degrees of phenotypic variability associated with other types of relatively severe PPK, including Mal de Meleda and Olmsted syndrome. [ABSTRACT FROM AUTHOR]

Pro-inflammatory cytokines play a critical role in the pathophysiology of muscle atrophy. We hypothesized that glycine exerted an anti-inflammatory effect and alleviated lipopolysaccharide (LPS)-induced muscle atrophy in piglets. Pigs were assigned to four treatments including the following: 1) nonchallenged control, 2) LPS-challenged control, 3) LPS+1.0% glycine, and 4) LPS+2.0% glycine. After receiving the control, 1.0 or 2.0% glycine-supplemented diets, piglets were treated with either saline or LPS. At 4 h after treatment with saline or LPS, blood and muscle samples were harvested. We found that 1.0 or 2.0% glycine increased protein/DNA ratio, protein content, and RNA/DNA ratio in gastrocnemius or longissimus dorsi (LD) muscles. Glycine also resulted in decreased mRNA expression of muscle atrophy F-box (MAFbx) and muscle RING finger 1 (MuRF1) in gastrocnemius muscle. In addition, glycine restored the phosphorylation of Akt, mammalian target of rapamycin (mTOR), eukaryotic initiation factor 4E binding protein 1 (4E-BP1), and Forkhead Box O 1 (FOXO1) in gastrocnemius or LD muscles. Furthermore, glycine resulted in decreased plasma tumor necrosis factor-α (TNF-α) concentration and muscle TNF-α mRNA abundance. Moreover, glycine resulted in decreased mRNA expresson of Toll-like receptor 4 (TLR4), nucleotide-binding oligomerization domain protein 2 (NOD2), and their respective downstream molecules in gastrocnemius or LD muscles. These results indicate glycine enhances muscle protein mass under an inflammatory condition. The beneficial roles of glycine on the muscle are closely associated with maintaining Akt-mTOR-FOXO1 signaling and suppressing the activation of TLR4 and/or NOD2 signaling pathways. [ABSTRACT FROM AUTHOR]

Background: Dyschromatosis symmetrica hereditaria (DSH) is a rare autosomal dominant cutaneous disorder caused by the mutations of adenosine deaminase acting on RNA1 (ADAR1) gene. We present a clinical and genetic study of seven unrelated families and two sporadic cases with DSH for mutations in the full coding sequence of ADAR1 gene. Methods: ADAR1 gene was sequenced in seven unrelated families and two sporadic cases with DSH and 120 controls. Functional significance of the observed ADAR1 mutations was analyzed using PolyPhen 2, SIFT and DDIG-in. Results: We describe six novel mutations of the ADAR1 gene in Chinese patients with DSH including a nonstop mutation p.Stop1227R, which was firstly reported in ADAR1 gene. In silico analysis proves that all the mutations reported here are pathogenic. Conclusion: This study is useful for functional studies of the protein and to define a diagnostic strategy for mutation screening of the ADAR1 gene. A three-generation family exhibiting phenotypic variability with a single germline ADAR1 mutation suggests that chilblain might aggravate the clinical phenotypes of DSH. [ABSTRACT FROM AUTHOR]

Host defense peptides (HDPs) are an important first line of defense with antimicrobial and immunomoduatory properties. Because they act on the microbial membranes or host immune cells, HDPs pose a low risk of triggering microbial resistance and therefore, are being actively investigated as a novel class of antimicrobials and vaccine adjuvants. Cathelicidins and β-defensins are two major families of HDPs in avian species. More than a dozen HDPs exist in birds, with the genes in each HDP family clustered in a single chromosomal segment, apparently as a result of gene duplication and diversification. In contrast to their mammalian counterparts that adopt various spatial conformations, mature avian cathelicidins are mostly α-helical. Avian β-defensins, on the other hand, adopt triple-stranded β-sheet structures similar to their mammalian relatives. Besides classical β-defensins, a group of avian-specific β-defensin-related peptides, namely ovodefensins, exist with a different six-cysteine motif. Like their mammalian counterparts, avian cathelicidins and defensins are derived from either myeloid or epithelial origin expressed in a majority of tissues with broad-spectrum antibacterial and immune regulatory activities. Structure-function relationship studies with several avian HDPs have led to identification of the peptide analogs with potential for use as antimicrobials and vaccine adjuvants. Dietary modulation of endogenous HDP synthesis has also emerged as a promising alternative approach to disease control and prevention in chickens. [ABSTRACT FROM AUTHOR]

Routine use of antibiotics at subtherapeutic levels in animal feed drives the emergence of antimicrobial resistance. Development of antibiotic-alternative approaches to disease control and prevention for food animals is imperatively needed. Previously, we showed that butyrate, a major species of short-chain fatty acids (SCFAs) fermented from undigested fiber by intestinal microflora, is a potent inducer of endogenous antimicrobial host defense peptide (HDP) genes in the chicken (PLoS One 2011, 6: e27225). In the present study, we further revealed that, in chicken HD11 macrophages and primary monocytes, induction of HDPs is largely in an inverse correlation with the aliphatic hydrocarbon chain length of free fatty acids, with SCFAs being the most potent, medium-chain fatty acids moderate and long-chain fatty acids marginal. Additionally, three SCFAs, namely acetate, propionate, and butyrate, exerted a strong synergy in augmenting HDP gene expression in chicken cells. Consistently, supplementation of chickens with a combination of three SCFAs in water resulted in a further reduction of Salmonella enteritidis in the cecum as compared to feeding of individual SCFAs. More importantly, free fatty acids enhanced HDP gene expression without triggering proinflammatory interleukin-1b production. Taken together, oral supplementation of SCFAs is capable of boosting host immunity and disease resistance, with potential for infectious disease control and prevention in animal agriculture without relying on antibiotics. [ABSTRACT FROM AUTHOR]

The article presents a study that offers pathogenicity and molecular analysis of an encephalomyocarditis virus (EMCV) isolate from mideastern China. The study isolated EMCV strain (NJ08) from newborn pigs with clinical signs on a pig farm. It reveals that an EMCV isolate from pigs could be fatal to mice and provided new epidemiologic data on EMCV in the nation.

Host defense peptides (HDPs) constitute a large group of natural broad-spectrum antimicrobials and an important first line of immunity in virtually all forms of life. Specific augmentation of synthesis of endogenous HDPs may represent a promising antibiotic-alternative approach to disease control. In this study, we tested the hypothesis that exogenous administration of butyrate, a major type of short-chain fatty acids derived from bacterial fermentation of undigested dietary fiber, is capable of inducing HDPs and enhancing disease resistance in chickens. We have found that butyrate is a potent inducer of several, but not all, chicken HDPs in HD11 macrophages as well as in primary monocytes, bone marrow cells, and jejuna and cecal explants. In addition, butyrate treatment enhanced the antibacterial activity of chicken monocytes against Salmonella enteritidis, with a minimum impact on inflammatory cytokine production, phagocytosis, and oxidative burst capacities of the cells. Furthermore, feed supplementation with 0.1% butyrate led to a significant increase in HDP gene expression in the intestinal tract of chickens. More importantly, such a feeding strategy resulted in a nearly 10-fold reduction in the bacterial titer in the cecum following experimental infections with S. enteritidis. Collectively, the results indicated that butyrate-induced synthesis of endogenous HDPs is a phylogenetically conserved mechanism of innate host defense shared by mammals and aves, and that dietary supplementation of butyrate has potential for further development as a convenient antibiotic-alternative strategy to enhance host innate immunity and disease resistance. [ABSTRACT FROM AUTHOR]

Dyschromatosis symmetrica hereditaria (DSH) is a rare autosomal dominant cutaneous disorder characterized by a mixture of hyperpigmented and hypopigmented macules of various sizes on the extremities and caused by the mutations of adenosine deaminase acting on RNA1 ( ADAR1) gene. We screened 14 unrelated families or sporadic cases for mutation in the full coding sequence of this gene. Eight novel heterozygous mutations of ADAR1 and four known mutations were identified, including four missense mutations (p.R26K, p.Y1192D, p.R916Q, p.R1155W), six frameshift mutations (p.N205fsX217, p.V211fsX217, p.V404fsX417, p.I914fsX927, p.L1053fsX1076, p.L1070fs1092), and two nonsense mutations (p.R474X, p.R1096X). Interestingly, we failed to detect any mutations of ADAR1 in one family. Including our data, there are now 93 different mutations reported in 105 independent patients that we have tabulated. From the review of clinical features in these reports, we found that the same mutation could lead to different phenotypes even in the same family and did not establish a clear correlation between genotypes and phenotypes. Finally this study is useful for functional studies of the protein and to define a diagnostic strategy for mutation screening of the ADAR1 gene. [ABSTRACT FROM AUTHOR]

Background: Extramammary Paget's disease (EMPD) is an uncommon skin neoplasm characterized by Paget's cells with pale-staining cytoplasm in the epidermis, and cases with distinguished acantholysis but lacking characteristic Paget's cells were rarely reported in the literature. Methods: An 80-year-old male with lesion on scrotum was screened histologically and immunohistologically for the diagnosis of his tumor. Results: Histological examination showed acanthosis with cellular atypia and focal acantholysis, consistent with acantholytic squamous cell carcinoma in situ (SCCIS). No characteristic Paget's cells were observed in low magnification. Immunohistochemical staining showed carcinoembryonic antigen (CEA), cytokeratin 7 (CK7) and cytokeratin 8 (CK8) to be strongly expressed in the nests and singly arranged large tumor cells, and the surrounding epidermis was positive for CK5/6 and negative for CEA. Sporadic periodic acid-schiff (PAS)-positive cells could be seen in some areas. Conclusions: These findings strongly indicated the diagnosis of EMPD mimicking acantholytic SCCIS. Du X, Yin X, Zhou N, Zhang G, Shi H, Cao S. Extramammary Paget's disease mimicking acantholytic squamous cell carcinoma in situ: a case report. [ABSTRACT FROM AUTHOR]

β-Defensins are a major group of mammalian antimicrobial peptides. Although more than 30 β-defensins have been identified in humans, only one porcine β-defensin has been reported. In this article we report the identification and initial characterization of 11 novel porcine β-defensins (pBD). Using bioinformatic approaches, we screened 287,821 porcine expressed sequence tags for similarity of their predicted peptides to known human β-defensins and identified full-length or partial sequences for the 11 novel pBDs. Similar to the previously identified pBD1, all of these peptides have a consensus β-defensin motif. A differential expression pattern for these newly identified genes was found. For example, unlike most β-defensins, pBD2 and pBD3 were expressed in bone marrow and in other lymphoid tissues including thymus, spleen, lymph nodes, duodenum, and liver. Including pBD2 and pBD3, six porcine β-defensins were expressed in lung and skin. Several newly identified porcine β-defensins, including pBD123, pBD125, and pBD129, were expressed in male reproductive tissues, including lobuli testis and some segments of the epididymis. Phylogenetic analysis indicates that in most cases the evolutionary relationship between individual porcine β-defensins and their human orthologs is closer than the relationship among β-defensins in the same species. These findings establish the existence of multiple porcine β-defensins and suggest that the pig may be an ideal model for the characterization of β-defensin diversity and function. [ABSTRACT FROM AUTHOR]

Cationic antimicrobial peptides are naturally occurring antibiotics that are actively being explored as a new class of anti-infective agents. We recently identified three cathelicidin antimicrobial peptides from chicken, which have potent and broad-spectrum antibacterial activities in vitro (Xiao Y, Cai Y, Bommineni YR, Fernando SC, Prakash O, Gilliland SE & Zhang G (2006) J Biol Chem 281, 2858–2867). Here we report that fowlicidin-1 mainly adopts an α-helical conformation with a slight kink induced by glycine close to the center, in addition to a short flexible unstructured region near the N terminus. To gain further insight into the structural requirements for function, a series of truncation and substitution mutants of fowlicidin-1 were synthesized and tested separately for their antibacterial, cytolytic and lipopolysaccharide (LPS)-binding activities. The short C-terminal helical segment after the kink, consisting of a stretch of eight amino acids (residues 16–23), was shown to be critically involved in all three functions, suggesting that this region may be required for the peptide to interact with LPS and lipid membranes and to permeabilize both prokaryotic and eukaryotic cells. We also identified a second segment, comprising three amino acids (residues 5–7) in the N-terminal flexible region, that participates in LPS binding and cytotoxicity but is less important in bacterial killing. The fowlicidin-1 analog, with deletion of the second N-terminal segment (residues 5–7), was found to retain substantial antibacterial potency with a significant reduction in cytotoxicity. Such a peptide analog may have considerable potential for development as an anti-infective agent. [ABSTRACT FROM AUTHOR]

Background: Defensins comprise a large family of cationic antimicrobial peptides that are characterized by the presence of a conserved cysteine-rich defensin motif. Based on the spacing pattern of cysteines, these defensins are broadly divided into five groups, namely plant, invertebrate, α-, β-, and θ-defensins, with the last three groups being mostly found in mammalian species. However, the evolutionary relationships among these five groups of defensins remain controversial. Results: Following a comprehensive screen, here we report that the chicken genome encodes a total of 13 different β-defensins but with no other groups of defensins being discovered. These chicken β-defensin genes, designated as Gallinacin 1-13, are clustered densely within a 86-Kb distance on the chromosome 3q3.5-q3.7. The deduced peptides vary from 63 to 104 amino acid residues in length sharing the characteristic defensin motif. Based on the tissue expression pattern, 13 β-defensin genes can be divided into two subgroups with Gallinacin 1-7 being predominantly expressed in bone marrow and the respiratory tract and the remaining genes being restricted to liver and the urogenital tract. Comparative analysis of the defensin clusters among chicken, mouse, and human suggested that vertebrate defensins have evolved from a single β-defensin-like gene, which has undergone rapid duplication, diversification, and translocation in various vertebrate lineages during evolution. Conclusions: We conclude that the chicken genome encodes only β-defensin sequences and that all mammalian defensins are evolved from a common β-defensin-like ancestor. The α-defensins arose from θ-defensins by gene duplication, which may have occurred after the divergence of mammals from other vertebrates, and θ-defensins have arisen from α-defensins specific to the primate lineage. Further analysis of these defensins in different vertebrate lineages will shed light on the mechanisms of host defense and evolution of innate immunity. [ABSTRACT FROM AUTHOR]

Septic shock, caused by exaggerated host responses to various microbial products typified by lipopolysaccharide (LPS), remains the leading cause of death in trauma patients. Gaining insight into the nature of host interactions with LPS will certainly facilitate attempts to develop effective anti-sepsis drugs. Tremendous progress has been made during the past few years in understanding the mechanisms of pathogen-induced host responses. Toll-like receptor (TLR) 4 and 2 have been implicated as major receptors for signaling initiated by LPS and many other microbial products following their binding to CD14. In addition, many signaling intermediates involved in LPSinduced cell activation, particularly activation of the transcription factor NF-κB, have been identified and characterized. Further investigations with these molecules will certainly reward us with more effective therapeutic drugs to treat septic shock as well as many other inflammatory and infectious disorders. [ABSTRACT FROM PUBLISHER]