Adenosine A2A receptor activation regulates the M1 macrophages activation to initiate innate and adaptive immunity in psoriasis.

Psoriasis is a common inflammatory systemic disease characterized by pro-inflammatory macrophages activation (M1 macrophage) infiltrated in the dermal layer. How M1 macrophage contributes to psoriasis remains unknown. In this study, we found that adenosine A2A receptor (A2AR) agonist CGS 21680 HCl alleviated the imiquimod (IMQ) and mouse IL-23 Protein (rmIL-23)-induced psoriasis inflammation through reducing infiltration of M1. Conversely, Adora2a deletion in mice exacerbated psoriasis-like phenotype. Mechanistically, A2AR activation inhibited M1 macrophage activation via the NF-κB-KRT16 pathway to reduce the secretion of CXCL10/11 and inhibit Th1/17 differentiation. Notably, the KRT16 expression was first found in M1 macrophage in our study, not only in keratinocytes (KCs). CXCL10/11 are first identified as primarily derived from macrophages and dendritic cells (DCs) rather than KCs in psoriasis using single cell RNA sequencing (scRNA-Seq). In total, the study emphasizes the importance of M1 as an innate immune cell in pathogenesis of psoriasis.

Ultra-Compact Low-Pass Spoof Surface Plasmon Polariton Filter Based on Interdigital Structure.

An ultra-compact low-pass spoof surface plasmon polariton (SSPP) filter based on an interdigital structure (IS) is designed. Simulated dispersion curves show that adding the interdigital structure in an SSPP unit effectively reduces its asymptotic frequency compared with traditional and T-shaped SSPP geometries, and the unit dimensions can be conversely reduced. Based on that, three IS-based SSPP units are, respectively, designed with different maximum intrinsic frequencies and similar asymptotic frequencies to constitute the matching and waveguide sections of the proposed filter, and the unit number in the waveguide section is adjusted to improve the out-of-band suppression. Simulation results illustrate the efficient transmission in the 0~5.66 GHz passband, excellent out-of-band suppression (over 24 dB) in the 5.95~12 GHz stopband and ultra-shape roll-off at 5.74 GHz of the proposed filter. Measurement results on a fabricated prototype validate the design, with a measured cut-off frequency of 5.53 GHz and an ultra-compact geometry of 0.5 × 0.16 λ02.

Establishment of reference intervals of complete blood count for twin pregnancy.

BACKGROUND: Twin pregnancy poses a high risk, and its incidence has increased in recent years. Establishment of reference intervals of complete blood count (CBC) for women with twin pregnancies during pregnancy may aid in the prognosis of adverse outcomes. METHODS: The incidence of complications and the intensity associated with adverse outcomes were analyzed in 1153 cases of twin pregnancy. A total of 253 cases in the twin pregnancy reference cohort were screened from all candidates after complications and adverse pregnancy outcomes were excluded. Complete blood count data were collected during the mid- and late-term of pregnancy and analyzed using SPSS to establish the reference intervals for peripheral blood in twin pregnancy. RESULTS: Premature rupture of the membrane and pelvic inflammatory disease were highly positively correlated with adverse outcomes, with OR values of 3.31 and 3.81, respectively. Within the interval population with normal outcomes, red blood cell (RBC), hemoglobin (HGB), hematocrit (HCT), and platelet (PLT) values were lower in twin-pregnant women during gestation than in healthy nulligravida women, but the levels of white blood cells (WBC), neutrophils (NEU), and the NEU% increased, especially in the mid-term. The reference intervals of late-term pregnancy were validated using 20 twin pregnancies samples, and then utilized to determine the distinctive CBC characteristics in preterm birth (PTB) pregnancy. Absolute WBC and NEU values increased in PTB pregnancy based on our established reference intervals, which suggests that these may might be prognostic indicators of this adverse outcome. CONCLUSION: Establishing the reference interval of blood cell-related indicators of normal twin pregnancy is helpful for the monitoring and prognosis of gestation.

Molecular epidemiologic study of citrin deficiency by screening for four reported pathogenic SLC25A13 variants in the Shaanxi and Guangdong provinces, China.

BACKGROUND: Citrin deficiency (CD) is an autosomal recessive disease resulting from biallelic mutations of the SLC25A13 gene. This study aimed to investigate the molecular epidemiological features of CD in the Guangdong and Shaanxi provinces of China. METHODS: A total of 3,409 peripheral blood samples from Guangdong and 2,746 such samples from Shaanxi province were collected. Four prevalent SLC25A13 mutations NG_012247.2 (NM_014251.3): c.852_855del, c.1638_1660dup, c.615+5G>A, and c.1751-5_1751-4ins(2684) were screened by using the conventional polymerase chain reaction (PCR)/PCR-restriction fragment length polymorphism and newly-developed multiplex PCR methods, respectively. The mutated SLC25A13 allele frequencies, carrier frequencies, and CD morbidity rates were calculated and then compared with the Chi-square and Fisher's exact tests. RESULTS: The mutations were detected in 68 out of 6,818 SLC25A13 alleles in Guangdong and 29 out of 5,492 alleles in the Shaanxi population. The carrier frequencies were subsequently calculated to be 1/51 and 1/95, while the CD morbidity rates were 1/10,053 and 1/35,865, in the 2 populations, respectively. When compared with the Shaanxi population, Guangdong exhibited a higher frequency of mutated SLC25A13 allele (68/6,818 vs. 29/5,492, χ2=8.570, P=0.003) in general, with higher c.852_855del (54/6,818 vs. 13/5,492, χ2=17.328, P=0.000) but lower c.1751-5_1751 -4ins(2684) (2/6,818 vs. 9/5,492, P=0.015) allele frequencies. The distribution of c.615+5G>A and c.1638_1660dup between the 2 provinces, as well as all 4 prevalent mutations among different geographic regions within the 2 provinces, did not differed significantly. CONCLUSIONS: Our findings depicted the CD molecular epidemiological features in Guangdong and Shaanxi populations, providing preliminary but significant laboratory evidences for the subsequent CD diagnosis and management in the 2 provinces of mainland China.

[Identification of a novel mutation of AGL gene in two siblings affected with glycogen storage disease type IIIa].

OBJECTIVE: To detect potential mutation of the AGL gene in two siblings affected with glycogen storage disease type IIIa. METHODS: Clinical data of the two siblings was collected and analyzed. Genomic DNA was extracted from peripheral venous blood samples from the patients and their parents. All exons and their flanking sequences of the AGL gene were subjected to PCR amplification and Sanger sequencing. Suspected mutation was verified in 75 healthy controls. RESULTS: The main clinical features of the two siblings included hypoglycemia and hepatomegaly, along with markedly elevated liver and myocardial enzymes. Genetic analysis revealed that both siblings harbored compound heterozygous mutations c.1735+1G>T and c.959-1G>C of the AGL gene. Among these, the splicing mutation c.959-1G>C was a novel one with an allele frequency of <1%. CONCLUSION: Based on their clinical features and genetic analysis, the siblings were diagnosed with glycogen storage disease type IIIa. The c.959-1G>C has enriched the spectrum of AGL gene mutations.

[Clinical characteristics of urticaria in children versus adults].

OBJECTIVE: To study the clinical characteristics of urticaria in children versus adults, and to provide reference for the etiological analysis, disease evaluation, and treatment of urticaria in children. METHODS: The clinical data of 2 411 patients with urticaria who visited the Department of Dermatology at Xiangya Hospital of Central South University from January 2013 to May 2017 were collected to study their socio-demographic characteristics. The clinical characteristics of urticaria were compared between the 68 children and 672 adults of the 740 patients with complete follow-up data. RESULTS: Among the 411 pediatric patients, 314 (76.4%) had acute urticaria; among the 2 000 adult patients, 896 (44.8%) had chronic spontaneous urticaria. The causes of acute urticaria in children included infection (41%, 16/39). The accompanying symptoms of acute urticaria in children mainly included abdominal pain and diarrhea (44%, 17/39), while those in adults mainly included chest distress and shortness of breath (32%, 11/34). Compared with the adult patients, the pediatric patients had significantly lower chronic urticaria activity scores before and after treatment (P<0.05), a significantly higher rate of response to second-generation antihistamines (82.1% vs 62.2%; P<0.05), and a significantly higher proportion of individuals with a personal and family history of urticaria (P<0.05). CONCLUSIONS: Acute urticaria is more commonly seen than chronic urticaria in children with urticaria, and the main accompanying symptoms are abdominal pain and diarrhea, which are different from adults with urticaria. Chronic urticaria has a better treatment outcome in children than in adults. The most frequently seen cause of acute urticaria is infection in children. Atopic children may be susceptible to urticaria.

[Phenotypic and genetic analysis of a family affected with microvillus inclusion disease].

OBJECTIVE: To explore the clinical features and mutations of MYO5B gene in a family affected with microvillus inclusion disease. METHODS: Clinical data of an infant affected with microvillus inclusion disease was collected. Genomic DNA was extracted from peripheral blood samples from the patient and her parents. PCR amplification and Sanger sequencing were performed to analyze all the exons and their flanking sequences of the MYO5B gene. RESULTS: The patient presented with complicated manifestations including respiratory distress syndrome, dehydration, acidosis, bowel dilatation, liver and kidney dysfunction, and severe and intractable diarrhea. A compound mutation of the MYO5B gene, i.e., IVS37-1G>C/c.2729_2731delC (p.R911Afs916X), was discovered in the patient. The former was a splice-site mutation inherited from the mother, while the latter was a frameshift mutation inherited from the father. Both were not reported previously. CONCLUSION: Based on the clinical and molecular evidence, the patient was diagnosed with microvillus inclusion disease. Above finding has expanded the mutation spectrum of the MYO5B gene, which can provide valuable information for genetic counseling for the family.

Clinical and molecular study of a pediatric patient with sodium taurocholate cotransporting polypeptide deficiency.

The human solute carrier family 10 member 1 (SLC10A1) gene encodes sodium taurocholate cotransporting polypeptide (NTCP), the principal transporter of conjugated bile salts from the plasma into hepatocytes. Although the function of NTCP has been studied extensively and a number of SLC10A1 variations have been identified in humans, information regarding NTCP deficiency is limited. To date, only one patient with NTCP deficiency has been described; however, in the present study a pediatric patient who experienced intractable and striking hypercholanemia is presented. Analysis of the SLC10A1 gene in the patient revealed a homozygous p.Ser267Phe (c.800C>T) variation, which proved to be a single-nucleotide polymorphism (SNP) in the allele frequency of 4.7% of healthy controls. This variation involved a conserved amino acid residue on the orthologous alignment that was predicted to be 'disease-causing' by functional analysis using a number of bioinformatic tools. Next generation sequencing was performed; however, no other genetic causes were identified that would affect the bile acid homeostasis in the patient. Moreover, an adult, with the same genotype as the pediatric patient, was identified for the first time as experiencing mild hypercholanemia. The molecular and clinical findings in the present study suggest, for the first time, that there is an association between p.Ser267Phe SNP and hypercholanemia, and this information may be used to clinically identify NTCP deficiency worldwide.

Molecular diagnosis of pediatric patients with citrin deficiency in China: SLC25A13 mutation spectrum and the geographic distribution.

Citrin deficiency (CD) is a Mendelian disease due to biallelic mutations of SLC25A13 gene. Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is the major pediatric CD phenotype, and its definite diagnosis relies on SLC25A13 genetic analysis. China is a vast country with a huge population, but the SLC25A13 genotypic features of CD patients in our country remains far from being well clarified. Via sophisticated molecular analysis, this study diagnosed 154 new CD patients in mainland China and identified 9 novel deleterious SLC25A13 mutations, i.e. c.103A > G, [c.329 - 154_c.468 + 2352del2646; c.468 + 2392_c.468 + 2393ins23], c.493C > T, c.755 - 1G > C, c.845_c.848 + 1delG, c.933_c.933 + 1insGCAG, c.1381G > T, c.1452 + 1G > A and c.1706_1707delTA. Among the 274 CD patients diagnosed by our group thus far, 41 SLC25A13 mutations/variations were detected. The 7 mutations c.775C > T, c.851_854del4, c.1078C > T, IVS11 + 1G > A, c.1364G > T, c.1399C > T and IVS16ins3kb demonstrated significantly different geographic distribution. Among the total 53 identified genotypes, only c.851_854del4/c.851_854del4 and c.851_854del4/c.1399C > T presented different geographic distribution. The northern population had a higher level of SLC25A13 allelic heterogeneity than those in the south. These findings enriched the SLC25A13 mutation spectrum and brought new insights into the geographic distribution of the variations and genotypes, providing reliable evidences for NICCD definite diagnosis and for the determination of relevant molecular targets in different Chinese areas.

Six new sesquiterpenes from Cacalia ainsliaeflora.

Five new eremophilane sesquiterpenes, 3beta,6beta-diangeloyloxy-8beta,10beta-dihydroxyeremophilenolide (1); 6beta-acetoxy-3beta-angeloyloxy-8beta,10beta-dihydroxyeremophilenolide (2); 3beta-angeloyloxy-6beta-methoxyeremophil-7(11),9(10)-dien-8alpha,12-olide (3), 3beta-angeloyloxy-8-oxo-eremophil-6(7)-en-12-oic acid (4); 3beta-angeloyloxy-10beta-hydroxy-8-oxo-eremophil-6(7)-en-12-oic acid (5), and a novel nor-eremophilane derivative, 3beta-angeloyloxy-10beta-hydroxy-8-oxo-eremophil-6(7)-en (6), were isolated from the roots of Cacalia ainsliaeflora. Their structures were elucidated by spectroscopic methods, including 2DNMR. Compounds 1 and 2 were assayed against P388 and A549 Carcinoma cell lines. No positive activities were observed.