P(V)-Promoted Rh-Catalyzed Highly Regioselective Hydroformylation of Styrenes under Mild Conditions.

Hydroformylation of olefins is widely used in the chemical industry due to its versatility and the ability to produce valuable aldehydes with 100% atom economy. Herein, a hybrid phosphate promoter was found to efficiently promote rhodium-catalyzed hydroformylation of styrenes under remarkably mild conditions with high regioselectivities. Preliminary mechanistic studies revealed that the weak coordination between the Rhodium and the P=O double bond of this pentavalent phosphate likely induced exceptional reactivity and high ratios of branched aldehydes to linear products.

Genomes, repeatomes and interphase chromosome organization in the meadowfoam family (Limnanthaceae, Brassicales).

The meadowfoam family (Limnanthaceae) is one of the smallest and genomically underexplored families of the Brassicales. The Limnanthaceae harbor about seven species in the genus Limnanthes (meadowfoam) and Floerkea proserpinacoides (false mermaidweed), all native to North America. Because all Limnanthes and Floerkea species have only five chromosome pairs, i.e., a chromosome number rare in Brassicales and shared with Arabidopsis thaliana (Arabidopsis), we examined the Limnanthaceae genomes as a potential model system. Using low-coverage whole-genome sequencing data, we reexamined phylogenetic relationships and characterized the repeatomes of Limnanthaceae genomes. Phylogenies based on complete chloroplast and 35S rDNA sequences corroborated the sister relationship between Floerkea and Limnanthes and two major clades in the latter genus. The genome size of Limnanthaceae species ranges from 1.5 to 2.1 Gb, apparently due to the large increase in DNA repeats, which constitute 60-70% of their genomes. Repeatomes are dominated by long terminal repeat retrotransposons, while tandem repeats represent only less than 0.5% of the genomes. The average chromosome size in Limnanthaceae species (340-420 Mb) is more than 10 times larger than in Arabidopsis (32 Mb). A three-dimensional fluorescence in situ hybridization analysis demonstrated that the five chromosome pairs in interphase nuclei of Limnanthes species adopt the Rabl-like configuration.

Recurrent Plant-Specific Duplications of KNL2 and Its Conserved Function as a Kinetochore Assembly Factor.

KINETOCHORE NULL2 (KNL2) plays key role in the recognition of centromeres and new CENH3 deposition. To gain insight into the origin and diversification of the KNL2 gene, we reconstructed its evolutionary history in the plant kingdom. Our results indicate that the KNL2 gene in plants underwent three independent ancient duplications in ferns, grasses and eudicots. Additionally, we demonstrated that previously unclassified KNL2 genes could be divided into two clades αKNL2 and ßKNL2 in eudicots and γKNL2 and δKNL2 in grasses, respectively. KNL2s of all clades encode the conserved SANTA domain, but only the αKNL2 and γKNL2 groups additionally encode the CENPC-k motif. In the more numerous eudicot sequences, signatures of positive selection were found in both αKNL2 and ßKNL2 clades, suggesting recent or ongoing adaptation. The confirmed centromeric localization of ßKNL2 and mutant analysis suggests that it participates in loading of new CENH3, similarly to αKNL2. A high rate of seed abortion was found in heterozygous ßKNL2 plants and the germinated homozygous mutants did not develop beyond the seedling stage. Taken together, our study provides a new understanding of the evolutionary diversification of the plant kinetochore assembly gene KNL2, and suggests that the plant-specific duplicated KNL2 genes are involved in centromere and/or kinetochore assembly for preserving genome stability.

In vitro gastrointestinal digestion and fermentation models and their applications in food carbohydrates.

Food nutrients plays a crucial role in human health, especially in gastrointestinal (GI) health. The effect of food nutrients on human health mainly depends on the digestion and fermentation process in the GI tract. In vitro GI digestion and fermentation models had the advantages of reproducibility, simplicity, universality, and could integrally simulate the in vivo conditions to mimic oral, gastric, small intestinal and large intestinal digestive processes. They could not only predict the relationship among material composition, structure and digestive characteristics, but also evaluate the bioavailability of material components and the impact of digestive metabolites on GI health. This review systematicly summarized the current state of the in vitro simulation models, and made detailed descriptions for their applications, advantages and disadvantages, and specially their applications in food carbohydrates. In addition, it also provided the suggestions for the improvement of in vitro models and firstly proposed to establish a set of standardized methods of in vitro dynamic digestion and fermentation conditions for food carbohydrates, which were in order to further evaluate more effects of the nutrients on human health in future.

[Identification of mouse lines with HA-tagged prostaglandin receptors].

Prostaglandins are a class of poly-unsaturated fatty acids-derived bioactive lipids with important physiological function by binding to specific receptors. Prostaglandin receptors lack specific antibodies, which greatly impedes the research on our understanding of the signaling of prostaglandins. The aim of this study was to identify nine mouse lines with amino terminal (-NH2, -N) HA-tagged prostaglandin receptors by using the combination of artificial sperm and CRISPR-Cas9 technology. The guide RNA expression plasmid and labeled targeting vector plasmids were transferred into "artificial sperm cells". The "artificial sperm cells" containing labeled proteins were selected and injected into mouse oocytes, and implanted into pseudopregnant mice to obtain labeled mice. The genomic DNA of the prostaglandin receptor tagged mice was extracted, and the genotypes of mice were detected by PCR method. We also isolated mouse peritoneal macrophages to verify the protein expression of HA-labeled prostaglandin receptor by Western blot. Specific DNA bands were amplified in prostaglandin receptor labeled mice, and specific HA protein bands were detected in macrophage proteins, which was not detected in wild type mice. In summary, we successfully constructed 9 mouse lines with HA-tagged prostaglandin receptors, providing a powerful tool for further study of the pathophysiological functions of prostaglandin signaling both in vivo and in vitro.

Centromeric DNA characterization in the model grass Brachypodium distachyon provides insights on the evolution of the genus.

Brachypodium distachyon is a well-established model monocot plant, and its small and compact genome has been used as an accurate reference for the much larger and often polyploid genomes of cereals such as Avena sativa (oats), Hordeum vulgare (barley) and Triticum aestivum (wheat). Centromeres are indispensable functional units of chromosomes and they play a core role in genome polyploidization events during evolution. As the Brachypodium genus contains about 20 species that differ significantly in terms of their basic chromosome numbers, genome size, ploidy levels and life strategies, studying their centromeres may provide important insight into the structure and evolution of the genome in this interesting and important genus. In this study, we isolated the centromeric DNA of the B. distachyon reference line Bd21 and characterized its composition via the chromatin immunoprecipitation of the nucleosomes that contain the centromere-specific histone CENH3. We revealed that the centromeres of Bd21 have the features of typical multicellular eukaryotic centromeres. Strikingly, these centromeres contain relatively few centromeric satellite DNAs; in particular, the centromere of chromosome 5 (Bd5) consists of only ~40 kb. Moreover, the centromeric retrotransposons in B. distachyon (CRBds) are evolutionarily young. These transposable elements are located both within and adjacent to the CENH3 binding domains, and have similar compositions. Moreover, based on the presence of CRBds in the centromeres, the species in this study can be grouped into two distinct lineages. This may provide new evidence regarding the phylogenetic relationships within the Brachypodium genus.

Cardiac autonomic function in patients with acute exacerbation of chronic obstructive pulmonary disease with and without ventricular tachycardia.

BACKGROUND: Autonomic dysfunction in patients with chronic obstructive pulmonary disease (COPD) may increase the risks of arrhythmia and sudden death. We studied cardiac autonomic function in patients with acute exacerbation of COPD (AECOPD). METHODS: Patients with AECOPD were classified into ventricular tachycardia (VT) and non-VT groups according to the presence or absence of VT. The following parameters derived from 24-h Holter monitoring were compared between groups: average heart rate, heart rate deceleration capacity (DC), heart rate acceleration capacity (AC), standard deviation of normal RR intervals (SDNN), standard deviation of average RR interval in 5-min segments (SDANN), root mean square of standard deviations of differences between adjacent normal RR intervals (rMSSD), low-frequency power (LF), high-frequency power (HF) and LF/HF ratio. RESULTS: Seventy patients were included, 22 in the VT group and 48 in the non-VT group. The groups had similar clinical characteristics (except for more common amiodarone use in the VT group, P < 0.05) and general ECG characteristics. DC, SDNN, SDANN and rMSSD were lower and AC higher in the VT group (P < 0.05). In the VT group, DC was correlated positively with SDNN (r = 0.716), SDANN (r = 0.595), rMSSD (r = 0.571) and HF (r = 0.486), and negatively with LF (r = -0.518) and LF/HF (r = -0.458) (P < 0.05). AC was correlated negatively with SDNN (r = -0.682), SDANN (r = -0.567) and rMSSD (r = -0.548) (P < 0.05). CONCLUSIONS: DC decreased and AC increased in patients with AECOPD and VT, reflecting an imbalance in autonomic regulation of the heart that might increase the risk of sudden death.

Identification of miR-20b-5p as an inhibitory regulator in cardiac differentiation via TET2 and DNA hydroxymethylation.

BACKGROUND: Congenital heart disease (CHD) is a prevalent congenital cardiac malformation, which lacks effective early biological diagnosis and intervention. MicroRNAs, as epigenetic regulators of cardiac development, provide potential biomarkers for the diagnosis and treatment of CHD. However, the mechanisms underlying miRNAs-mediated regulation of cardiac development and CHD malformation remain to be further elucidated. This study aimed to explore the function of microRNA-20b-5p (miR-20b-5p) in cardiac development and CHD pathogenesis. METHODS AND RESULTS: miRNA expression profiling identified that miR-20b-5p was significantly downregulated during a 12-day cardiac differentiation of human embryonic stem cells (hESCs), whereas it was markedly upregulated in plasma samples of atrial septal defect (ASD) patients. Our results further revealed that miR-20b-5p suppressed hESCs-derived cardiac differentiation by targeting tet methylcytosine dioxygenase 2 (TET2) and 5-hydroxymethylcytosine, leading to a reduction in key cardiac transcription factors including GATA4, NKX2.5, TBX5, MYH6 and cTnT. Additionally, knockdown of TET2 significantly inhibited cardiac differentiation, which could be partially restored by miR-20b-5p inhibition. CONCLUSIONS: Collectively, this study provides compelling evidence that miR-20b-5p functions as an inhibitory regulator in hESCs-derived cardiac differentiation by targeting TET2, highlighting its potential as a biomarker for ASD.

Construction of Vicinal All-Carbon Stereogenic Centers via Copper-Catalyzed Asymmetric Decarboxylative Propargylation: Enantio- and Diastereoselective Synthesis of Substituted Spirolactones.

The formation of vicinal all-carbon quaternary stereocenters remains a formidable challenge. We report herein the synthesis of such highly congested structural dyads by copper-catalyzed decarboxylative propargylation between propargyl carbonates and indanone-based nucleophiles. The implementation of diphenylethylenediamine (DPEN)-based ligands is the key to success. A wide range of functional groups was tolerated, delivering the indanone-based spirolactones in good yields with high diastereo- and enantioselectivity. The mechanistic observations suggest the capability of the new copper complex to enable stereocontrolled addition to copper-allenylidene species.

Targeted modification of gut microbiota and related metabolites via dietary fiber.

Intake of dietary fiber has been proven to have several beneficial effects in maintaining host homeostasis and health. Here, we investigated the effects of different fibers on gut microbiota and related metabolites in rats. Healthy rats were supplemented with guar gum, carrageenan, glucomannan, ß-glucan, arabinoxylan, apple pectin, xylan, arabinogalactan, and xanthan gum, and these dietary fibers exhibited commonality and specificity on gut microbiota and related metabolites. The abundance of Phascolarctobacterium, Prevotella, Treponema, Butyricimonas, Bacteroides, and Lactobacillus was selectively increased by different dietary fibers, whereas the abundance of Clostridium perfringens and Bacteroides fragilis were decreased by all of these fibers. Indole-3-lactic acid was significantly increased by ß-glucan treatment, indicating the relationship between indole-3-lactic acid and Lactobacillus. Furthermore, Some species from Bacteroides were validated to produce indole-3-lactic acid, indole-3-acetic acid, and kynurenine (such as B. fragilis, B. ovatus, B. thetaiotaomicron, and B. xylanisolvens). These results provide important information on dietary guidelines based on the modification of gut microecology.

High temperature increases centromere-mediated genome elimination frequency and enhances haploid induction in Arabidopsis.

Double haploid production is the most effective way to create true-breeding lines in a single generation. In Arabidopsis, haploid induction via mutation of the centromere-specific histone H3 (cenH3) has been shown when the mutant is outcrossed to the wild-type, and the wild-type genome remains in the haploid progeny. However, factors that affect haploid induction are still poorly understood. Here, we report that a mutant of the cenH3 assembly factor Kinetochore Null2 (KNL2) can be used as a haploid inducer when pollinated by the wild-type. We discovered that short-term temperature stress of the knl2 mutant increased the efficiency of haploid induction 10-fold. We also demonstrated that a point mutation in the CENPC-k motif of KNL2 is sufficient to generate haploid-inducing lines, suggesting that haploid-inducing lines in crops can be identified in a naturally occurring or chemically induced mutant population, avoiding the generic modification (GM) approach at any stage. Furthermore, a cenh3-4 mutant functioned as a haploid inducer in response to short-term heat stress, even though it did not induce haploids under standard conditions. Thus, we identified KNL2 as a new target gene for the generation of haploid-inducer lines and showed that exposure of centromeric protein mutants to high temperature strongly increases their haploid induction efficiency.

Parabacteroides distasonis ameliorates insulin resistance via activation of intestinal GPR109a.

Gut microbiota plays a key role in insulin resistance (IR). Here we perform a case-control study of Chinese adults (ChiCTR2200065715) and identify that Parabacteroides distasonis is inversely correlated with IR. Treatment with P. distasonis improves IR, strengthens intestinal integrity, and reduces systemic inflammation in mice. We further demonstrate that P. distasonis-derived nicotinic acid (NA) is a vital bioactive molecule that fortifies intestinal barrier function via activating intestinal G-protein-coupled receptor 109a (GPR109a), leading to ameliorating IR. We also conduct a bioactive dietary fiber screening to induce P. distasonis growth. Dendrobium officinale polysaccharide (DOP) shows favorable growth-promoting effects on P. distasonis and protects against IR in mice simultaneously. Finally, the reduced P. distasonis and NA levels were also validated in another human type 2 diabetes mellitus cohort. These findings reveal the unique mechanisms of P. distasonis on IR and provide viable strategies for the treatment and prevention of IR by bioactive dietary fiber.

Genome Sequencing of Rahnella victoriana JZ-GX1 Provides New Insights Into Molecular and Genetic Mechanisms of Plant Growth Promotion.

Genomic information for bacteria within the genus Rahnella remains limited. Rahnella sp. JZ-GX1 was previously isolated from the Pinus massoniana rhizosphere in China and shows potential as a plant growth-promoting (PGP) bacterium. In the present work, we combined the GridION Nanopore ONT and Illumina sequencing platforms to obtain the complete genome sequence of strain JZ-GX1, and the application effects of the strain in natural field environment was assessed. The whole genome of Rahnella sp. JZ-GX1 comprised a single circular chromosome (5,472,828 bp, G + C content of 53.53%) with 4,483 protein-coding sequences, 22 rRNAs, and 77 tRNAs. Based on whole genome phylogenetic and average nucleotide identity (ANI) analysis, the JZ-GX1 strain was reidentified as R. victoriana. Genes related to indole-3-acetic acid (IAA), phosphorus solubilization, nitrogen fixation, siderophores, acetoin, 1-aminocyclopropane-1-carboxylate (ACC) deaminase, gamma-aminobutyric acid (GABA) production, spermidine and volatile organic compounds (VOCs) biosynthesis were present in the genome of strain JZ-GX1. In addition, these functions were also confirmed by in vitro experiments. Importantly, compared to uninoculated control plants, Pyrus serotina, Malus spectabilis, Populus euramericana (Dode) Guinier cv. "San Martino" (I-72 poplar) and Pinus elliottii plants inoculated with strain JZ-GX1 showed increased heights and ground diameters. These findings improve our understanding of R. victoriana JZ-GX1 as a potential biofertilizer in agriculture.

[Urodynamic changes in patients with obstructive sleep apnea-hypopnea syndrome and nocturnal polyuria].

OBJECTIVE: To investigate the urodynamic changes in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) and nocturnal polyuria. METHODS: From Sept. 2002 to Jun. 2008, 23 patients with nocturnal polyuria were diagnosed as having OSAHS by polysomnography (PSG). The number and output of nocturia, the osmotic pressure and the excretion of Na(+) were recorded during both the PSG night and CPAP titrating night. Plasma levels of brain natriuretic peptide (BNP) and atrial natriuretic peptides (ANP) were also measured at 11PM in the 2 nights and 7AM in the next mornings. Urodynamic studies including urine flow, bladder pressure during filling, pressure-flow study during voiding and urethral pressure were carried out in these patients. Urodynamic studies were performed again after treatment with CPAP for 3 months. RESULTS: PSG showed that the patients with nocturnal polyuria had moderate to severe OSAHS, in which the apnea-hypopnea index (AHI) being 48 ± 15 events per hour. The number of nocturnal voiding during the PSG night was more than that during the CPAP titrating night. During the PSG night, the output of nocturia, the nocturia excretion of Na(+), ANP levels (at 7am in the next morning after PSG night) increased and the osmotic pressure of nocturia decreased. CPAP therapy could reverse these abnormalities. The main characteristics of urodynamics in these patients included weak detrusor contraction, hypoesthesia in filling cystometry, and decreased bladder compliance, and detrusor external sphincter dyssynergia. After 3 months of CPAP treatment, both the motility of the detrusor of bladder and the bladder compliance improved. CONCLUSIONS: CPAP therapy can effectively reverse the nocturnal polyuria in OSAHS patients. In OSAHS patients, the features of nocturia, including the changes of output, osmotic pressure and the excretion of Na(+), may be related to the secretion of high-level of ANP. During the course of chronic progressively OSAHS pathophysiology, detrusor function of bladder may be damaged. CPAP therapy could decrease the nocturnal excretion of ANP, and improve the motility of the detrusor of bladder.

Bioactive Dietary Fibers Selectively Promote Gut Microbiota to Exert Antidiabetic Effects.

High intake of dietary fibers was found to be inversely associated with type-2 diabetes (T2D), whereas the difference among different dietary fibers on T2D remains unclear. Therefore, we have investigated the effects of different dietary fibers on T2D. Nine types of dietary fibers were used to investigate and evaluate their effects on type-2 diabetic rats via physiology, genomics, and metabolomics. We found that supplementation with ß-glucan, arabinogalactan, guar gum, apple pectin, glucomannan, and arabinoxylan significantly reduced the fasting blood glucose, whereas carrageenan, xylan, and xanthan gum did not affect glycemic control in diabetic rats. Also, bioactive dietary fibers (ß-glucan, arabinogalactan, guar gum, and apple pectin) associated with the increased butyric acid level and abundance of beneficial bacteria (Lachnobacterium, Parabacteroides, Faecalibacterium, Akkermansia, and some butyric acid-producing bacteria), as well as improved host metabolism by decreasing 12α-hydroxylated bile acids, acylcarnitines, and amino acids (leucine, phenylalanine, citrulline, etc.), thereby exert beneficial effects on T2D. It was also found that ß-glucan might attenuate insulin resistance via downregulation of Prevotella copri-mediated biosynthesis of branched-chain amino acids in T2D. Together, our study uncovered the effects of different dietary fibers on T2D, along with their potential mechanism.

Preventive effects of pectin with various degrees of esterification on ulcerative colitis in mice.

This work investigated the physiochemical characteristics and preventive effects of purified pectin (H121, L13 and L102) with different esterification degrees on dextran sulfate sodium (DSS)-induced colitis in mice. Three doses of each type of pectin were administered to C57BL/6J mice for 7 days before the DSS treatment, with dextran and mesalazine as positive controls. Results showed that pathological factors including the body weight, the disease activity index (DAI), the colonic weight/length ratio and the organ index of the spleen were improved with pre-intervention of a high dose of L13 or L102. Further studies showed that administration of a low dose of L13, low dose and medium dose of L102 or dextran improved intestinal permeability and tight junction function in colitis mice. Treatments of L13 of all doses and L102 of a high dose downregulated the oxidative stress-associated factors, while L102 of a low dose and H121 ameliorated the inflammatory cytokine production in serum and the colon. The above results suggested that pectin could attenuate DSS-induced intestinal epithelial injury, inflammation and oxidative stress. Specifically, compared to high esterified pectin, low esterified pectin displayed better protective effects in acute colitis mice.

Comparative study on antidiabetic function of six legume crude polysaccharides.

The antidiabetic function of polysaccharides prepared from six legumes: soybean, white kidney bean, red kidney bean, small black soybean, field bean, lentil were studied. Six legume polysaccharides' antidiabetic function in high-fat diet and streptozotocin-induced type II diabetic mice were compared. Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested. Results showed that red kidney bean polysaccharides (RK) could alleviate the symptoms of emaciation, decreased the levels of FBG, GSP, TC, LDL-c and obviously reduced the concentration of TG and HOMA-IR (p < 0.05). RK exhibited greater antidiabetic potential in type II diabetic mice, compared with other legume polysaccharides. The chemical composition of six legume polysaccharides were determined. Composition analysis indicated that the six legume polysaccharides were obviously different in moisture, ash, neutral sugar, uronic acid, total phenolic content, total flavonoid content, amino acid composition and monosaccharide composition. Results indicated that the antidiabetic activities of RK might due to its higher content and specific structure of polysaccharide.

CXCL16 Induces the Progression of Pulmonary Fibrosis through Promoting the Phosphorylation of STAT3.

Aim: The transmembrane chemokine (C-X-C motif) ligand 16 (CXCL16) plays a vital role in the pathogenesis of organ fibrosis, including the liver and kidney. However, the detailed biological function of CXCL16 is still not fully understood in the progression of pulmonary fibrosis (PF). The aim of present study is to examine the function of CXCL16 in PF. Materials and Methods: In this study, we constructed the PF model on mouse by using bleomycin and analyzed the effect of the mouse recombinant protein CXCL16 on mouse lung fibroblast L929 (LF) as well. To further examine the connection between CXCL16 and STAT3 in mouse LF cells, the STAT3 inhibitor AG490 was utilized to inhibit the expression of STAT3. Meanwhile, lipopolysaccharide was used to enhance the phosphorylation of STAT3 (p-STAT3) in mouse LF cells. Results: Our results indicated that the level of CXCL16/CXCR6 was significantly upregulated in the mouse PF model. Moreover, the level of p-STAT3 was also promoted. In addition, the mouse recombinant protein CXCL16 not only contributed to the proliferation of mouse LF cells but also induced the expression of p-STAT3 in LF cells. However, the effect of CXCL16 was deeply abolished by the STAT3 inhibitor AG490 in LF cells. Meanwhile, the antibody of CXCL16 deeply reduced the phosphorylation of STAT3 in lipopolysaccharide (LPS) cultured cells. Conclusions: All these results demonstrated that CXCL16 promoted the phosphorylation of STAT3 and further demonstrated that STAT3 was a critical component in CXCL16/CXCR6 signaling pathway. This research not only enhanced the comprehension of CXCL16 but also indicated its potential value as a target in the treatment for human PF.

A biomimetic cascade nanoreactor for tumor targeted starvation therapy-amplified chemotherapy.

Targeted drug delivery with precisely controlled drug release and activation is highly demanding and challenging for tumor precision therapy. Herein, a biomimetic cascade nanoreactor (designated as Mem@GOx@ZIF-8@BDOX) is constructed for tumor targeted starvation therapy-amplified chemotherapy by assembling tumor cell membrane cloak and glucose oxidase (GOx) onto zeolitic imidazolate framework (ZIF-8) with the loading prodrug of hydrogen peroxide (H2O2)-sensitive BDOX. Biomimetic membrane camouflage affords superior immune evasion and homotypic binding capacities, which significantly enhance the tumor preferential accumulation and uptake for targeted drug delivery. Moreover, GOx-induced glycolysis would cut off glucose supply and metabolism pathways for tumor starvation therapy with the transformation of tumor microenvironments. Importantly, this artificial adjustment could trigger the site-specific BDOX release and activation for cascade amplified tumor chemotherapy regardless of the complexity and variability of tumor physiological environments. Both in vitro and in vivo investigations indicate that the biomimetic cascade nanoreactor could remarkably improve the therapeutic efficacy with minimized side effects through the synergistic starvation therapy and chemotherapy. This biomimetic cascade strategy would contribute to developing intelligent drug delivery systems for tumor precision therapy.

[The association between polymorphism of the serotonin 2A, 2C receptor genes and obstructive sleep apnea-hypopnea syndrome in Han population].

OBJECTIVE: To investigate the association between polymorphisms of the serotonin 2A, 2C receptor genes and obstructive sleep apnea-hypopnea syndrome (OSAHS), and therefore to explore the genotypes related to OSAHS. METHODS: The T102C and A1438G polymorphisms of the serotonin 2A receptor genes and the G796C polymorphisms of the serotonin 2C receptor genes were identified by polymerase chain reaction-restricted fragment length polymorphism assay in 119 unrelated subjects (including 65 OSAHS patients and 54 normal controls) of "Han" population of China. The genotype distribution and the allele frequencies of the polymorphisms were compared between the OSAHS group and the control group. The effects of polymorphisms in the OSAHS group on parameters of polysomnography and indexes correlated with obesity were analyzed. RESULTS: There was no significant difference in genotype distribution and allele frequencies of the T102C polymorphisms of the serotonin 2A receptor genes between the two groups; the frequencies of TT/TC/CC genotype and T/C allele were 27.7% (18/65), 46.2% (30/65), 26.1% (17/65), 50.8% (66/130) and 49.2% (64/130), respectively in the OSAHS group; but were 27.8% (15/54), 51.8% (28/54), 20.4% (11/54), 53.7% (58/108) and 46.3% (50/108), respectively in the control group (chi(2) = 0.616 and 0.203, respectively, P > 0.05). The G796C polymorphisms of the serotonin 2C receptor genes were as follows: the frequencies of male's G/C allele, female's GG/GC genotype and G/C allele were 88.9% (48/54), 11.1% (6/54), 63.6% (7/11), 36.4% (4/11), 81.8% (18/22) and 18.2% (4/22), respectively in the OSAHS group; but were 90.5% (38/42), 9.5% (4/42), 66.7% (8/12), 33.3% (4/12), 83.3% (20/24) and 16.7% (4/24), respectively in the control group (chi(2) = 0.007, 0.002 and 0.064, respectively, P > 0.05). The frequencies of AA genotype and A allele in the A1438G polymorphisms of the serotonin 2A receptor genes in the OSAHS group [63.1% (41/65) and 74.6% (97/130), respectively] were significantly higher than those of the control one [27.8% (15/54) and 40.7% (44/108), respectively; chi(2) = 18.779 and 28.035, respectively, P < 0.01]. The OSAHS patients with AA genotype had higher obstructive apnea-hypopnea index (OAHI) and longest apnea time (LAT) than those with AG/GG genotype [OAHI were (40 +/- 9)/h, (25 +/- 9)/h and (20 +/- 11)/h, respectively, t = 6.674 and 7.753, respectively, P < 0.05; LAT were (94 +/- 10) s, (88 +/- 9) s and (75 +/- 12) s, respectively, t = 3.278 and 5.682, respectively, P < 0.05]. The lowest saturation of blood oxygen in patients with AA genotype was significantly lower than that in patients with AG/GG genotype [(69 +/- 12)%, (78 +/- 10)% and (80 +/- 9)%, respectively, t = 4.025 and 4.153, respectively, P < 0.05]. There was no significant difference in body mass index [(26.9 +/- 2.8) kg/m(2), (25.2 +/- 2.7) kg/m(2) and (26.0 +/- 3.7) kg/m(2), respectively], neck circumference [(43.3 +/- 2.7) cm, (42.6 +/- 1.8) cm and (42.8 +/- 2.1) cm, respectively] and waist/hip rate (0.89 +/- 0.12), (0.92 +/- 0.11) and (0.90 +/- 0.09), respectively, F = 0.859, 1.296 and 1.078, respectively, P > 0.05). CONCLUSION: The T102C polymorphisms of the serotonin 2A receptor gene and the G796C polymorphisms of the serotonin 2C receptor gene may be not associated with OSAHS in subjects of "Han" population of China. The 1438 AA genotype of the serotonin 2A receptor gene may be involved in OSAHS, and the A allele may be an important candidate gene for OSAHS.