Food-specific IgG4-guided diet elimination improves allergy symptoms in children.

Allergic diseases in children are major public health concerns due to their widespread and rising prevalence. Food-specific immunoglobulin G4(FS-IgG4) has been detected in patients with allergic diseases, but its clinical significance is still debated. In the present study, 407 children with allergic diseases were recruited and categorized into three groups according to the different systems involved: the respiratory system group, the skin system group, and a multiple system group, with the collection of clinical symptoms and serum antibodies, including total immunoglobulin E (IgE), house dust mite (HDM) IgE, food-specific IgE (FS-IgE), and FS-IgG4. Part of these patients were followed up with the intervention of FS-IgG4-guided diet elimination with or without add-on probiotics supplement. The analysis at baseline revealed distinct serum levels of different antibodies. The positive rate of FS-IgG4 in all groups was more than 80%, and the proportion of total IgE and FS-IgG4 both positive in the multi-system group was the highest (p=0.039). Egg and milk were the foods with the highest positive rate of FS-IgG4 in all groups. After diet elimination for more than 3 months, serum FS-IgG4 in children significantly decreased (P<0.05) along with the improvement of clinical symptoms, regardless of the add-on of probiotics. However, the intervention did not impact the serum levels of total IgE, FS-IgE, and HDM IgE. There was no further decrease of serum FS-IgG4 level in children followed up for more than 1 year, which may be related to noncompliance with diet elimination. Multivariate regression analysis revealed that the decline of serum FS-IgG4 was an independent predictable factor for the improvement of clinical symptoms (adjusted OR:1.412,95%CI 1.017-1.96, p=0.039). The add-on of probiotics showed less efficiency in reducing the FS-IgG4 level in more patients with relief of clinical symptoms. Our results confirmed the correlation between FS-IgG4 and allergic diseases, and the decreased FS-IgG4 could be a useful predictor for the improvement of allergic symptoms. FS-IgG4-guided diet elimination is an efficient treatment for allergic diseases. Our study adds solid data to the clinical significance of FS-IgG4 in allergic diseases.

Phalaenopsiszhanhouana (Orchidaceae, Vandeae), a new species from Yunnan, China.

A new species of Orchidaceae, Phalaenopsiszhanhouana, from Xichou County, Yunnan, China, is described and illustrated. The novelty is close to P.taenialis, P.wilsonii, and P.stobartiana, but differs from them by having a distinct, fleshy anterior callus with a deeply lobed apex at the base of the labellum and lateral lobes of labellum reflexed and facing outward.

Plastome phylogenomics and morphological traits analyses provide new insights into the phylogenetic position, species delimitation and speciation of Triplostegia (Caprifoliaceae).

BACKGROUND: The genus Triplostegia contains two recognized species, T. glandulifera and T. grandiflora, but its phylogenetic position and species delimitation remain controversial. In this study, we assembled plastid genomes and nuclear ribosomal DNA (nrDNA) cistrons sampled from 22 wild Triplostegia individuals, each from a separate population, and examined these with 11 recently published Triplostegia plastomes. Morphological traits were measured from herbarium specimens and wild material, and ecological niche models were constructed. RESULTS: Triplostegia is a monophyletic genus within the subfamily Dipsacoideae comprising three monophyletic species, T. glandulifera, T. grandiflora, and an unrecognized species Triplostegia sp. A, which occupies much higher altitude than the other two. The new species had previously been misidentified as T. glandulifera, but differs in taproot, leaf, and other characters. Triplotegia is an old genus, with stem age 39.96 Ma, and within it T. glandulifera diverged 7.94 Ma. Triplostegia grandiflora and sp. A diverged 1.05 Ma, perhaps in response to Quaternary climate fluctuations. Niche overlap between Triplostegia species was positively correlated with their phylogenetic relatedness. CONCLUSIONS: Our results provide new insights into the species delimitation of Triplostegia, and indicate that a taxonomic revision of Triplostegia is needed. We also identified that either rpoB-trnC or ycf1 could serve as a DNA barcode for Triplostegia.

Case series: Primary aldosteronism diagnosed despite normal screening investigations: A report of three cases.

RATIONALE: Since the introduction of the aldosterone-to-renin ratio (ARR) as a screening tool for primary aldosteronism (PA), there has been a marked increase in the reported prevalence of this condition among hypertensive, even normotensive, subjects. PATIENT CONCERNS: But ARR as a spot blood draw for estimating a patient's aldosterone secretory status is influenced by many factors. DIAGNOSES: Here, we describe a series of patients with biochemically confirmed PA, whose diagnosis was delayed by the initial ARR assessment with non-suppressed renin. INTERVENTIONS: Patient 1 had a history of resistant hypertension for many years and had a negative initial screening for secondary hypertension (including ARR). At the reevaluation, ARR was close to cutoff still with normal renin after strict and extended drug washout, and the further workup for PA demonstrated a unilateral aldosterone producing adenoma that was surgically removed, with subsequent complete biochemical remission and partial clinical success. Patient 2 was diagnosed with idiopathic hyperaldosteronism combined with obstructive sleep apnea syndrome, which could increase renin resulting in a negative ARR, and finally got a better treatment effect with PA-specific spironolactone, as well as continuous positive airway pressure. Patient 3 with hypokalemia as the main presentation was finally diagnosed with PA after excluding other diseases, and proceeded to laparoscopic adrenalectomy and histologically confirmed an aldosterone producing adenoma. Postoperatively, patient 3 achieved complete biochemical success without any medicine. OUTCOMES: The clinical status of all three patients was effectively managed, resulting in either complete resolution or notable improvement of their respective conditions. LESSONS: After rigorous standardized diagnostic evaluation, there are still many reasons for ARR negative in PA, but they all basically occur in the background of normal or normal-high renin without suppression. A negative screening test result should be repeated and analyzed carefully if this is not consistent with the clinical picture. If, despite a repeatedly negative ARR, clinical suspicion remains high, we recommend consideration of further evaluation, including confirmatory tests and adrenal venous blood sampling (AVS) or even 68Ga-pentixafor PET/CT to better confirm the diagnosis and improve patient outcomes.

Contrasting range changes of terrestrial orchids under future climate change in China.

Climate change has impacted the distribution and abundance of numerous plant and animal species during the last century. Orchidaceae is one of the largest yet most threatened families of flowering plants. However, how the geographical distribution of orchids will respond to climate change is largely unknown. Habenaria and Calanthe are among the largest terrestrial orchid genera in China and around the world. In this paper, we modeled the potential distribution of eight Habenaria species and ten Calanthe species in China under the near-current period (1970-2000) and the future period (2081-2100) to test the following two hypotheses: 1) narrow-ranged species are more vulnerable to climate change than wide-ranged species; 2) niche overlap between species is positively correlated with their phylogenetic relatedness. Our results showed that most Habenaria species will expand their ranges, although the climatic space at the southern edge will be lost for most Habenaria species. In contrast, most Calanthe species will shrink their ranges dramatically. Contrasting range changes between Habenaria and Calanthe species may be explained by their differences in climate-adaptive traits such as underground storage organs and evergreen/deciduous habits. Habenaria species are predicted to generally shift northwards and to higher elevations in the future, while Calanthe species are predicted to shift westwards and to higher elevations. The mean niche overlap among Calanthe species was higher than that of Habenaria species. No significant relationship between niche overlap and phylogenetic distance was detected for both Habenaria and Calanthe species. Species range changes in the future was also not correlated with their near current range sizes for both Habenaria and Calanthe. The results of this study suggest that the current conservation status of both Habenaria and Calanthe species should be adjusted. Our study highlights the importance of considering climate-adaptive traits in understanding the responses of orchid taxa to future climate change.

Protective Effect of Anoectochilus formosanus Polysaccharide against Cyclophosphamide-Induced Immunosuppression in BALB/c Mice.

In this study, Anoectochilus formosanus polysaccharide (AFP) was acquired a via water extraction and alcohol precipitation method. The immunoregulatory activity of AFP was first evaluated on cyclophosphamide (Cy)-treated mice. Galacturonic acid, glucose and galactose were confirmed to be the main components of AFP. AFP demonstrated the ability to stimulate the production of TNF-α and IL-6 in RAW 264.7 macrophages. Not surprisingly, the activation of the NF-κB signaling pathway by AFP was validated via Western blot analysis. Furthermore, AFP could alleviate Cy-induced immunosuppression, and significantly enhance the immunity of mice via increasing the thymus index and body weight, stimulating the production of cytokines (IgA, IgG, SIgA, IL-2, IL-6 and IFN-γ). The improvement in the intestinal morphology of immunosuppressed mice showed that AFP could alleviate Cy-induced immune toxicity. These results have raised the possibility that AFP may act as a natural immunomodulator. Overall, the study of AFP was innovative and of great significance for AFP's further application and utilization.

The extremely reduced, diverged and reconfigured plastomes of the largest mycoheterotrophic orchid lineage.

BACKGROUND: Plastomes of heterotrophic plants have been greatly altered in structure and gene content, owing to the relaxation of selection on photosynthesis-related genes. The orchid tribe Gastrodieae is the largest and probably the oldest mycoheterotrophic clade of the extant family Orchidaceae. To characterize plastome evolution across members of this key important mycoheterotrophic lineage, we sequenced and analyzed the plastomes of eleven Gastrodieae members, including representative species of two genera, as well as members of the sister group Nervilieae. RESULTS: The plastomes of Gastrodieae members contain 20 protein-coding, four rRNA and five tRNA genes. Evolutionary analysis indicated that all rrn genes were transferred laterally and together, forming an rrn block in the plastomes of Gastrodieae. The plastome GC content of Gastrodia species ranged from 23.10% (G. flexistyla) to 25.79% (G. javanica). The plastome of Didymoplexis pallens contains two copies each of ycf1 and ycf2. The synonymous and nonsynonymous substitution rates were very high in the plastomes of Gastrodieae among mycoheterotrophic species in Orchidaceae and varied between genes. CONCLUSIONS: The plastomes of Gastrodieae are greatly reduced and characterized by low GC content, rrn block formation, lineage-specific reconfiguration and gene content, which might be positively selected. Overall, the plastomes of Gastrodieae not only serve as an excellent model for illustrating the evolution of plastomes but also provide new insights into plastome evolution in parasitic plants.

Putative variants, genetic diversity and population structure among Soybean cultivars bred at different ages in Huang-Huai-Hai region.

Soybean cultivars bred in the Huang-Huai-Hai region (HR) are rich in pedigree information. To date, few reports have exposed the genetic variants, population structure and genetic diversity of cultivars in this region by making use of genome-wide resequencing data. To depict genetic variation, population structure and composition characteristics of genetic diversity, a sample of soybean population composed all by cultivars was constructed. We re-sequenced 181 soybean cultivar genomes with an average depth of 10.38×. In total, 11,185,589 single nucleotide polymorphisms (SNPs) and 2,520,208 insertion-deletions (InDels) were identified on all 20 chromosomes. A considerable number of putative variants existed in important genome regions that may have an incalculable influence on genes, which participated in momentous biological processes. All 181 varieties were divided into five subpopulations according to their breeding years, SA (1963-1980), SB (1983-1988), SC (1991-2000), SD (2001-2011), SE (2012-2017). PCA and population structure figured out that there was no obvious grouping trend. The LD semi-decay distances of sub-population D and E were 182 kb, and 227 kb, respectively. Sub-population A (SA) had the highest value of nucleotide polymorphism (π). With the passage of time, the nucleotide polymorphism of SB and SC decreased gradually, however that of SD and SE, opposite to SB and SC, gave a rapid up-climbing trend, which meant a sharp increase in genetic diversity during the latest 20 years, hinting that breeders may have different breeding goals in different breeding periods in HR. Analysis of the PIC statistics exhibited very similar results with π. The current study is to analyze the genetic variants and characterize the structure and genetic diversity of soybean cultivars bred in different decades in HR, and to provide a theoretical reference for other identical studies.

Successful treatment of dupilumab in Kimura disease independent of IgE: A case report with literature review.

Kimura disease (KD) is a rare and benign chronic inflammatory disease of unknown cause. It is characterized by subcutaneous granuloma of soft tissues in the head and neck region, increased eosinophil count, and elevated serum IgE. Currently, no definitive treatments are recommended. A 57-year-old Chinese man was diagnosed with KD after 7 years of slow subcutaneous masses growth. The patient underwent treatment of oral glucocorticoids for 1 year, but the masses recurred as the dosage was tapered down. Subsequent anti-IgE therapy of omalizumab administered subcutaneously at 450 mg/day at a 4-week interval did not show improvement. The size of masses and serum IgE and circulating eosinophils did not decrease significantly after 19 cycles of continuous treatment. Ultimately, switched strategy of dupilumab was applied at an initial dose of 600 mg, followed by 300 mg every 2 weeks for 4 months. This treatment demonstrated dramatical effects with reduced masses in each area and fast dropdown of eosinophil counts, while the high level of serum IgE remained without changes. Recently, different biologics including anti-IgE, anti-IL-5, and anti-IL-4/IL-13 have been applied to treat KD with satisfied results and help to explore the pathogenesis of this rare disease. To our knowledge, this is the first report that demonstrates the effects of two different biologics in the same patient and reveals the impressive clinical efficacy of dupilumab to treat KD independent of IgE. Therefore, further investigation of the underlying mechanism and the development of diagnosis and treatment of KD is valuable.

Batesian mimicry in the nonrewarding saprophytic orchid Danxiaorchis yangii.

Batesian mimicry, a type of deceptive pollination, is a complicated strategy used by nonrewarding plants to attract pollinators, but some hypotheses concerning this have not been systematically verified. In order to show in detail a case of Batesian mimicry on saprophytic orchid Danxiaorchis yangii, the ecological relationship between Danxiaorchis yangii, Lysimachia alfredi and Dufourea spp. was explored. Lysimachia alfredi could provide a reward to Dufourea sp., whereas Danxiaorchis yangii not. The floral morphology and geographical distribution of these two plants were highly overlapping, and the fruit set rate of Danxiaorchis yangii was significantly positively correlated with the number of nearby L. alfredi individuals. In a glass cylinder experiment, Danxiaorchis yangii and L. alfredi attracted Dufourea spp. through visual signals, but the insect could not distinguish between flowers of the two plants before landing on flowers. The ultraviolet reflection spectra of flowers between the two plant species were highly similar. In the hexagonal color models constructed according to the visual characteristics of bees, the flower color signals of these two plant species highly overlap, indicating that the visual signals of the flowers of the two plants to the pollinator were greatly similar. All of these results provided evidence that Danxiaorchis yangii simulated the visual signals of L. alfredi through Batesian mimicry, thereby deceptively attracting Dufourea spp.

The pollination of Habenaria rhodocheila (Orchidaceae) in South China: When butterflies take sides.

Habenaria is one of the largest terrestrial genera in the family Orchidaceae. Most field studies on Habenaria species with greenish-white and nocturnal scented flowers are pollinated by nocturnal hawkmoths and settling moths. However, H. rhodocheila presents reddish flowers lacking a detectable scent and fails to fit the moth pollination syndrome. We investigated the pollinators, breeding system, and functional traits of H. rhodocheila in South China and found that two diurnal swallowtail butterflies Papilio helenus and Papilio nephelus (Papilionidae) were the effective pollinators. When butterflies foraged for nectar in the spur, the pollinia became attached between the palpi. A triangular projected median rostellar lobe was found at the entrance (sinus) of the spur of H. rhodocheila. This lobe divided the spur opening into two entrances forcing butterflies to enter their proboscides through the left or right side. When the projection of median rostellar lobe was removed, the site of pollinium attachment changed to the eyes of the butterflies, leading to a higher rate of pollinium removal but lower rate of pollinium deposition. Our quartz glass cylinder choice experiment suggested that visual rather than olfactory cues provided the major stimuli for butterflies to locate these flowers. Hand pollination experiments suggested this species was self-compatible but pollinator-dependent. However, the proportion of seeds with large embryos produced in self-pollinated fruits was significantly lower than in cross-pollinated fruits, indicating a significant inbreeding depression. Unlike many other orchid species, fruit set was higher than rates of pollinium removal, indicating a high level of pollination efficiency in a species with friable pollinia. Shifts from moth to butterfly pollination in the genus Habenaria parallel other orchid lineages providing insights into the potential for pollinator-mediated floral trait selection.

Purification, structure and conformation characterization of a novel glucogalactan from Anoectochilus roxburghii.

Anoectochilus roxburghii (AR) has been used in food, medicine and ornamental industries for a long time. Anion exchange resin was proposed to purify the sub-fraction of water-extracted AR polysaccharide (ARPP-70), and a homogeneous polysaccharide ARPP-70a was obtained. The structural features of ARPP-70a were characterized using gas chromatography-mass spectrometry (GC-MS), nuclear magnetic resonance (NMR) spectroscopy, and high performance size exclusion chromatograph coupled with multi-angle laser light scattering (HPSEC-MALLS). The relative weight average molecular weight for ARPP-70a was determined to be 14.8 kDa, and the molar ratio of glucose to galactose was 1.0:3.2. The structure of ARPP-70a was elucidated to be glucogalactan, with backbone comprising ß-1,4-linked Galp and some α-1,4-linked Glcp. The conformation characteristics of ARPP-70a were supposed to exist as a random coil chain in 0.1 M NaNO3 solution. Moreover, in vitro antioxidant activity assays revealed ARPP-70a exhibited appreciable antioxidant potential. To the best of our knowledge, this is the first study to obtain this type of glucogalactan, and provide systematic information on its structural and conformational properties. This study improved the understanding of the physicochemical characteristics of AR polysaccharide, which is beneficial for its further application in food and medicinal industry.

Diversification in Qinghai-Tibet Plateau: Orchidinae (Orchidaceae) clades exhibiting pre-adaptations play critical role.

We explore the origins of the extraordinary plant diversity in the Qinghai-Tibetan Plateau (QTP) using Orchidinae (Orchidaceae) as a model. Our results indicate that six major clades in Orchidinae exhibited substantial variation in the temporal and spatial sequence of diversification. Our time-calibrated phylogenetic model suggests that the species-richness of Orchidinae arose through a combination of in situ diversification, colonisation, and local recruitment. There are multiple origins of species-richness of Orchidinae in the QTP, and pre-adaptations in clades from North Temperate and alpine regions were crucial for in situ diversification. The geographic analysis identified 29 dispersals from Asia, Africa and Europe into the QTP and 15 dispersals out. Most endemic species of Orchidinae evolved within the past six million years.

Calanthe sieboldopsis (Orchidaceae, Epidendroideae, Collabieae), a new species from Luoxiao Mountains, eastern China.

Calanthe sieboldopsis, a new species, is here described and illustrated from Luoxiao Mountains, Jiangxi Province, eastern China. It is morphologically similar to C. sieboldii Decne. ex Regel, but differs from the latter in having smaller flowers, longer spurs, rectangular mid-lobes with emarginate apex (vs. elliptic mid-lobes with mucronate apex), disc with 3 ridges and the proximal ends of the lateral 2 ridges enlarged with light reddish spots and minute white hairs (vs. disc with 5 ridges and 2 rows of white short hairs at base) and pollinia equal in size (vs. unequal in size). A preliminary risk-of-extinction assessment, according to the IUCN Red List Categories and Criteria, is given for the new species.

A novel mutation in gene of PRPS1 in a young Chinese woman with X-linked gout: a case report and review of the literature.

Pyrophosphate synthetase-1(PRS-1) is a crucial enzyme that catalyzes the synthesis of phosphoribosylpyrophosphate (PRPP) with substrate: adenosine triphosphate (ATP) and ribose-5-phophate(R5P) in the de novo pathways of purine and pyrimidine nucleotide synthesis. Mutation in PRPS1 can result in a series of diseases of purine metabolism, which includes PRS-1 superactivity. The common clinical phenotypes are hyperuricemia and hyperuricosuria. We identified a novel missense mutation in X-chromosomal gene PRPS1 in a young Chinese woman while her mother has heterogeneous genotype and phenotype. A 24-year-old Chinese female patient suffered hyperuricemia, gout, and recurrent hyperpyrexia for more than 6 years, and then was diagnosed with hyperandrogenism, insulin resistance (IR), and polycystic ovary syndrome (PCOS). A novel missense mutation, c.521(exon)G>T, p.(Gly174Val) was detected by next-generation sequencing (NGS) and confirmed by Sanger sequencing in the patient and her parents. Interestingly, her mother has the same heterozygous missense mutation but without uric acid overproduction which can be explained by the phenomenon of the skewed X-chromosome inactivation. The substituted amino acid Val for Gly174 is positioned in the pyrophosphate (PPi) binding loop, and this mutation impacts the binding rate of Mg2+-ATP complex to PRS-1, thus the assembling of homodimer is affected by changed Val174 leading to the instability of the allosteric site. Our report highlights the X-linked inheritance of gout in females caused by mutation in PRPS1 accompanied with severe metabolic disorders and recurrent hyperpyrexia.

[Impacts of climate change on the distribution of Cymbidium kanran and the simulation of distribution pattern]. / æ°”å€™å˜åŒ–å¯¹å¯’å °åˆ†å¸ƒçš„å½±å“åŠå ¶åˆ†å¸ƒæ ¼å±€æ¨¡æ‹Ÿ.

In this study, data of 19 climatic factors were downloaded from the World Climate website. A total of 233 Cymbidium kanran distribution data were obtained through online review and field visits. Using MaxEnt model and combined with ArcGIS spatial analysis technology, the potential distribution area and distribution pattern of C. kanran in different periods were simulated, as well as its distribution during the last glacial period and 2070. The results showed that the curve indexes (AUC) value of the model training set was 0.957, and the AUC value of the verification set was 0.953, indicating that the prediction accuracy of the model was very high. The current distribution of C. kanran was mostly affected by the driest quarter precipitation, mean annual precipitation, wettest quarter precipitation, and mean annual temperature range. The contribution rates were 50.3%, 15.9%, 8.4% and 4.4%, respectively, with the total contribution rate being 79.0%. In the last glacial period, C. kanran mainly distributed in Wuyi Mountain, Luojing Mountain, Nanling, Taiwan's five major mountains and some hills in the northern part of Guangxi. From now to 2070, the distribution of C. kanran area will decrease by 22.4%. The southwestern part of Guangxi, the central part of Yunnan, and the junctions of Jiangxi, Fujian and Guangdong provinces will expand, while that in eastern Jiangxi, western Fujian, and the border between these two provinces will shrink.

Development of polymorphic microsatellite markers by using de novo transcriptome assembly of Calanthe masuca and C. sinica (Orchidaceae).

BACKGROUND: Calanthe masuca and C. sinica are two genetically closely related species in Orchidaceae. C. masuca is widely distributed in Asia, whereas C. sinica is restricted to Yunnan and Guangxi Provinces in southwest China. Both play important roles in horticulture and are under the pressure of population decline. Understanding their genetic background can greatly help us develop effective conservation strategies for these species. Simple sequence repeats (SSRs) are useful for genetic diversity analysis, presumably providing key information for the study and preservation of the wild populations of the two species we are interested in. RESULTS: In this study, we performed RNA-seq analysis on the leaves of C. masuca and C. sinica, obtaining 40,916 and 71,618 unigenes for each species, respectively. In total, 2,019/3,865 primer pairs were successfully designed from 3,764/7,189 putative SSRs, among which 197 polymorphic SSRs were screened out according to orthologous gene pairs. After mononucleotide exclusion, a subset of 129 SSR primers were analysed, and 13 of them were found to have high polymorphism levels. Further analysis demonstrated that they were feasible and effective against C. masuca and C. sinica as well as transferable to another species in Calanthe. Molecular evolutionary analysis revealed functional pathways commonly enriched in unigenes with similar evolutionary rates in the two species, as well as pathways specific to each species, implicating species-specific adaptation. The divergence time between the two closely related species was tentatively determined to be 3.42 ± 1.86 Mya. CONCLUSIONS: We completed and analysed the transcriptomes of C. masuca and C. sinica, assembling large numbers of unigenes and generating effective polymorphic SSR markers. This is the first report of the development of expressed sequence tag (EST)-SSR markers for Calanthe. In addition, our study could enable further genetic diversity analysis and functional and comparative genomic studies on Calanthe.

Effect of Hydrogen-Bonding Interaction on the Arrangement and Dynamics of Water Confined in a Polyamide Membrane: A Molecular Dynamics Simulation.

An increasing demand for freshwater inspires further understanding of the mechanism of water diffusion in reverse-osmosis membranes for the development of high-performance membranes for desalination. Water diffusion has a close relationship with the structural and dynamical characteristics of hydrogen bonds, which is not well-understood for the confining environment inside the polyamide membrane at the molecular level. In this work, an atomistic model of a highly cross-linked polyamide membrane was built with an equilibrated mixture of m-phenylenediamine and trimesoyl chloride monomers. The structure and dynamics of water in the regions from the bulk phase to the membrane interior were investigated by molecular dynamics simulations. Explicit hydrogen bond criteria were determined for hydrogen-bonding analysis. The local distribution and orientation of water reveal that the hydrogen-bonding affinity of the hydrophilic functional groups of polymers inhibits water diffusion inside the membrane. The affinity helps to produce percolated water channels across the membrane. The hydrogen-bonding structures of water in different regions indicate dehydration is required for the entry of water into the polyamide membrane, which dominates water flux across the membrane. This paper not only deepens the understanding of the structure and dynamics of water confined in the polyamide membrane but also stimulates the future work on high-performance reverse-osmosis membranes.

High glucose and free fatty acids induce endothelial progenitor cell senescence via PGC-1α/SIRT1 signaling pathway.

The objective of the research was to investigate the function of endothelial progenitor cells (EPCs) in the conditions of high glucose and lipids, which has been widely used to mimic the metabolic disorder that occurs in type 2 diabetic mellitus, and further to verify the role of PGC-1α and SIRT1, cellular energy metabolism regulators, in the process of senescence of EPCs with these combined stimuli. Circulating EPCs were incubated in absence or presence of high glucose (25 mM), FFA (200 µM) or both. EPCs senescence was assessed by ß-galactosidase staining, EPCs telomerase activity was measured by telomeric repeat ampli-fication protocol assay, in vitro angiogenesis assay and MTT assays were performed to assess angiogenesis and proliferation ability of EPCs. The results showed that combined stimuli inhibited EPCs reendothelialization ability in vitro, accelerated EPCs senescence and decreased the telomerase activity. Meanwhile, with combined stimuli, the expression of PGC-1α increased whereas SIRT1 expression decreased in EPCs accompanied by activation of P53/P21 signaling pathway. Conversely, transfection of EPCs with PGC-1α-siRNA rescued EPCs premature senescence and up-regulated SIRT1 and decreased P53/P21 expression, correlating closely with the down-regulation of PGC-1α itself. In addition, the combined stimuli induced up-regulation of PGC-1α expression was partly mediated by ROS and P38 signaling pathway. Overall, the data presented here identify PGC-1α as a potent negative regulator of EPCs' senescence under combined stimuli, which is partly mediated by SIRT1/P53/P21 signaling pathway.

Computational analysis of functional single nucleotide polymorphisms associated with the CYP11B2 gene.

Single nucleotide polymorphisms (SNPs) are the most common type of genetic variations in humans and play a major role in the genetics of human phenotype variation and the genetic basis of human complex diseases. Recently, there is considerable interest in understanding the possible role of the CYP11B2 gene with corticosterone methyl oxidase deficiency, primary aldosteronism, and cardio-cerebro-vascular diseases. Hence, the elucidation of the function and molecular dynamic behavior of CYP11B2 mutations is crucial in current genomics. In this study, we investigated the pathogenic effect of 51 nsSNPs and 26 UTR SNPs in the CYP11B2 gene through computational platforms. Using a combination of SIFT, PolyPhen, I-Mutant Suite, and ConSurf server, four nsSNPs (F487V, V129M, T498A, and V403E) were identified to potentially affect the structure, function, and activity of the CYP11B2 protein. Furthermore, molecular dynamics simulation and structure analyses also confirmed the impact of these nsSNPs on the stability and secondary properties of the CYP11B2 protein. Additionally, utilizing the UTRscan, MirSNP, PolymiRTS and miRNASNP, three SNPs in the 3'UTR region were predicted to exhibit a pattern change in the upstream open reading frames (uORF), and eight microRNA binding sites were found to be highly affected due to 3'UTR SNPs. This cataloguing of deleterious SNPs is essential for narrowing down the number of CYP11B2 mutations to be screened in genetic association studies and for a better understanding of the functional and structural aspects of the CYP11B2 protein.