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The succulent xerophyte Zygophyllum xanthoxylum (Bunge) Engl. can absorb Na+ from the soil as an osmoticum in order to resist osmotic stress. The tonoplast Na+/H+ antiporter ZxNHX1 is essential for maintaining the salt-accumulation characteristics of Z. xanthoxylum by compartmentalizing Na+ into vacuoles. Previous results revealed that the silencing of ZxNHX1 greatly decreased Na+ accumulation in Z. xanthoxylum under 50 mM NaCl due to the weakened compartmentalisation; in addition, K+ concentration also significantly reduced in ZxNHX1 -RNAi lines. Yet, whether the reduction of K+ concentration was directly triggered by the silencing of ZxNHX1 remains unclear. In this study, the growth parameters and expression levels of ZxSOS1 , ZxHKT1 ; 1 , ZxAKT1 and ZxSKOR were measured in wild-type and ZxNHX1 -RNAi lines under control or –0.5 MPa osmotic stress. The results showed that the silencing of ZxNHX1 inhibited the plant growth, decreased Na+ concentration in leaves, reduced the transcript abundance of ZxSOS1 and dramatically increased that of ZxHKT1 ; 1 in roots of Z. xanthoxylum under osmotic stress; whereas tissue K+ concentrations and the expression level of ZxSKOR displayed no significant variations, and the expression of ZxAKT1 were significantly reduced in ZxNHX1 -RNAi lines under osmotic stress, compared with the wild type. These results suggest that in Z. xanthoxylum , ZxNHX1 can maintain the normal growth by compartmentalizing Na+ into vacuoles, and regulate the spatial distribution of Na+ indirectly by affecting the expressions of ZxSOS1 and ZxHKT1 ; 1. Moreover, the silencing of ZxNHX1 is not the main reason that led to the reduction of K+ concentration in ZxNHX1 -RNAi lines under 50 mM NaCl, and ZxNHX1 might be indirectly involved in regulating K+ homeostasis. In Zygophyllum xanthoxylum , a xerophytic shrub, the silencing of ZxNHX1 (tonoplast Na +/ H + antiporter) triggered the reduction of Na+ and K+ concentration under 50 mM NaCl treatment. In this work, the K+ concentration displayed no significant variation in ZxNHX1 -RNAi lines compared with the wild type under osmotic stress, indicating that ZxNHX1 might not directly participate in controlling K+ homeostasis. The results provide a basis for further researches on the transport of Na+ and K+ in Z. xanthoxylum. [ABSTRACT FROM AUTHOR]

The inward-rectifying K+ channel AKT1 constitutes an important pathway for K+ acquisition in plant roots. In glycophytes, excessive accumulation of Na+ is accompanied by K+ deficiency under salt stress. However, in the succulent xerophyte Zygophyllum xanthoxylum, which exhibits excellent adaptability to adverse environments, K+ concentration remains at a relatively constant level despite increased levels of Na+ under salinity and drought conditions. In this study, the contribution of Zx AKT1 to maintaining K+ and Na+ homeostasis in Z. xanthoxylum was investigated. Expression of Zx AKT1 rescued the K+-uptake-defective phenotype of yeast strain CY162, suppressed the salt-sensitive phenotype of yeast strain G19, and complemented the low-K+-sensitive phenotype of Arabidopsis akt1 mutant, indicating that Zx AKT1 functions as an inward-rectifying K+ channel. Zx AKT1 was predominantly expressed in roots, and was induced under high concentrations of either KCl or NaCl. By using RNA interference technique, we found that Zx AKT1-silenced plants exhibited stunted growth compared to wild-type Z. xanthoxylum. Further experiments showed that Zx AKT1-silenced plants exhibited a significant decline in net uptake of K+ and Na+, resulting in decreased concentrations of K+ and Na+, as compared to wild-type Z. xanthoxylum grown under 50 m m NaCl. Compared with wild-type, the expression levels of genes encoding several transporters/channels related to K+/Na+ homeostasis, including Zx SKOR, Zx NHX, Zx SOS1 and Zx HKT1; 1, were reduced in various tissues of a Zx AKT1-silenced line. These findings suggest that Zx AKT1 not only plays a crucial role in K+ uptake but also functions in modulating Na+ uptake and transport systems in Z. xanthoxylum, thereby affecting its normal growth. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this review was to evaluate the current literature on phosphoribosylpyrophosphate synthetase 1 ( PRPS1)-related diseases and their consequences on hearing function. Design: A literature search of peer-reviewed, published journal articles was conducted in online bibliographic databases. Study sample: Three databases for medical research were included in this review. Results: Mutations in PRPS1 are associated with a spectrum of non-syndromic to syndromic hearing loss. Hearing loss in male patients with PRPS1 mutations is bilateral, moderate to profound, and can be prelingual or postlingual, progressive or non-progressive. Audiogram shapes associated with PRPS1 deafness are usually residual and flat. Female carriers can have unilateral or bilateral hearing impairment. Gain of function mutations in PRPS1 cause a superactivity of the PRS-I protein whereas the loss-of-function mutations result in X-linked nonsyndromic sensorineural deafness type 2 (DFN2), or in syndromic deafness including Arts syndrome and X-linked Charcot-Marie-Tooth disease-5 (CMTX5). Conclusions: Lower residual activity in PRS-I leads to a more severe clinical manifestation. Clinical and molecular findings suggest that the four PRPS1 disorders discovered to date belong to the same disease spectrum. Dietary supplementation with S-adenosylmethionine (SAM) appeared to alleviate the symptoms of Arts syndrome patients, suggesting that SAM could compensate for PRS-I deficiency. [ABSTRACT FROM AUTHOR]

With the release of large-scale genomic resources from ancient and modern populations, advancements in computational biology tools, and the enhancement of data mining capabilities, the field of genomics is undergoing a revolutionary transformation. These advancements and changes have not only significantly deepened our understanding of the complex evolutionary processes of human origins, migration, and admixture but have also unveiled the impact of these processes on human health and disease. They have accelerated research into the genetic basis of human health and disease and provided new avenues for uncovering the evolutionary trajectories recorded in the human genome related to population history and disease genetics. The ancestral recombination graph (ARG) reconstructs the evolutionary relationships between genomic segments by analyzing recombination events and coalescence patterns across different regions of the genome. An ARG provides a record of all coalescence and recombination events since the divergence of the sequences under study and specifies a complete genealogy at each genomic position, which is the ideal data structure for genomic analysis. Here, we review the theoretical foundations and research advancements of the ARG, and explore its translational applications and future prospects across various disciplines, including forensic genomics, population genetics, evolutionary medicine, and medical genomics. Our goal is to promote the application of this technique in genomic research, thereby deepening our understanding of the human genome.

Elucidating the quality markers(Q-markers) of traditional Chinese medicines is essential for understanding the mechanisms of action and promoting the rational use of traditional Chinese medicines as well as for developing traditional Chinese medicine-derived drugs. Studies have shown that surface plasmon resonance(SPR) is promising in this field. This study proposed a method based on pull-down with SPR chips to predict the Q-markers of Angong Niuhuang pills(AGNHP). Firstly, 71 main chemical components of AGNHP were analyzed by UPLC-Q-TOF-MS, and then network pharmacology was employed to predict the potential targets of AGNHP against stroke. Secondly, the STAT3 protein chip was constructed, and the extract of AGNHP was recovered by pull-down of the SPR system for STAT3 ligand. The potential active ingredients were collected, enriched, and identified as coptisine, palmatine, epiberberine, berberine, worenine, demethyleneberberine, jatrorrhizine, tetrahydrocoptisine, baicalein, and baicalin methyl ester. Next, the affinity constants of the 10 active ingredients were determined as 44.7, 44, 58.1, 51.3, 39.7, 32.1, 49.2, 69.1, 19.7, and 24.9 μmol·L~(-1), respectively. The molecular docking results showed that the 10 compounds could compete for binding with STAT3. This is the first report that SPR combined with UPLC-Q-TOF-MS is reliable and feasible for determining the active ingredients of AGNHP at the molecular level from complex systems. STAT3 could be used as a potential target for the biological quality evaluation of AGNHP.

The succulent xerophyte Zygophyllum xanthoxylum (Bunge) Engl. can absorb Na+ from the soil as an osmoticum in order to resist osmotic stress. The tonoplast Na+/H+ antiporter ZxNHX1 is essential for maintaining the salt-accumulation characteristics of Z. xanthoxylum by compartmentalizing Na+ into vacuoles. Previous results revealed that the silencing of ZxNHX1 greatly decreased Na+ accumulation in Z. xanthoxylum under 50 mM NaCl due to the weakened compartmentalisation; in addition, K+ concentration also significantly reduced in ZxNHX1-RNAi lines. Yet, whether the reduction of K+ concentration was directly triggered by the silencing of ZxNHX1 remains unclear. In this study, the growth parameters and expression levels of ZxSOS1, ZxHKT1;1, ZxAKT1 and ZxSKOR were measured in wild-type and ZxNHX1-RNAi lines under control or -0.5 MPa osmotic stress. The results showed that the silencing of ZxNHX1 inhibited the plant growth, decreased Na+ concentration in leaves, reduced the transcript abundance of ZxSOS1 and dramatically increased that of ZxHKT1;1 in roots of Z. xanthoxylum under osmotic stress; whereas tissue K+ concentrations and the expression level of ZxSKOR displayed no significant variations, and the expression of ZxAKT1 were significantly reduced in ZxNHX1-RNAi lines under osmotic stress, compared with the wild type. These results suggest that in Z. xanthoxylum, ZxNHX1 can maintain the normal growth by compartmentalizing Na+ into vacuoles, and regulate the spatial distribution of Na+ indirectly by affecting the expressions of ZxSOS1 and ZxHKT1;1. Moreover, the silencing of ZxNHX1 is not the main reason that led to the reduction of K+ concentration in ZxNHX1-RNAi lines under 50 mM NaCl, and ZxNHX1 might be indirectly involved in regulating K+ homeostasis.

To estabish ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for simultaneous determination of quercetin(QCT), isorhamnetin(ISR), kaempferol(KMF), ginkgolide A(GA), ginkgolide B(GB), ginkgolide C(GC) and bilobalide(BB) in rat plasma and investigate the pharmacokinetic process of seven compounds after oral administration of Yindan Xinnaotong Ruanjiaonang, The results indicated that all calibrations curves showed good linearity (r≥0.997 1). RSD of intra-day and inter-day precisions were all within 11%. The matrix effects and extraction recovery were in the range of 93.28%-103.6% and 72.43%-95.77% respectively. The peak concentration (Cmax) of QCT, ISR, KMF, GA, GB, GC and BB were (45.02±11.28), (49.90±13.82), (27.85±8.38), (76.31±18.19), (76.54±15.43), (35.35±10.28), (48.70±12.34) μg•L⁻¹, respectively. The peak time (tmax) of seven constituents were (0.33±0.11), (0.50±0.23), (0.33±0.14), (0.75±0.29), (1.0±0.35), (1.5±0.23), (0.75±0.50) h, respectively. UPLC-MS/MS method established in this research was proved to be so rapid and sensitive that it can be applied to the pharmacokinetic study of seven bioactive constituents in Yindan Xinnaotong Ruanjiaonang., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

The inward-rectifying K + channel AKT1 constitutes an important pathway for K + acquisition in plant roots. In glycophytes, excessive accumulation of Na + is accompanied by K + deficiency under salt stress. However, in the succulent xerophyte Zygophyllum xanthoxylum, which exhibits excellent adaptability to adverse environments, K + concentration remains at a relatively constant level despite increased levels of Na + under salinity and drought conditions. In this study, the contribution of ZxAKT1 to maintaining K + and Na + homeostasis in Z. xanthoxylum was investigated. Expression of ZxAKT1 rescued the K + -uptake-defective phenotype of yeast strain CY162, suppressed the salt-sensitive phenotype of yeast strain G19, and complemented the low-K + -sensitive phenotype of Arabidopsis akt1 mutant, indicating that ZxAKT1 functions as an inward-rectifying K + channel. ZxAKT1 was predominantly expressed in roots, and was induced under high concentrations of either KCl or NaCl. By using RNA interference technique, we found that ZxAKT1-silenced plants exhibited stunted growth compared to wild-type Z. xanthoxylum. Further experiments showed that ZxAKT1-silenced plants exhibited a significant decline in net uptake of K + and Na + , resulting in decreased concentrations of K + and Na + , as compared to wild-type Z. xanthoxylum grown under 50 mm NaCl. Compared with wild-type, the expression levels of genes encoding several transporters/channels related to K + /Na + homeostasis, including ZxSKOR, ZxNHX, ZxSOS1 and ZxHKT1;1, were reduced in various tissues of a ZxAKT1-silenced line. These findings suggest that ZxAKT1 not only plays a crucial role in K + uptake but also functions in modulating Na + uptake and transport systems in Z. xanthoxylum, thereby affecting its normal growth., (© 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.)

Hearing loss (HL) is the most common birth defect. Elucidating the genetic basis of hereditary deafness can not only assist diagnosis, provide the basis for genetic counseling and the prevention of deafness, but also bring a deeper understanding of the disease pathogenesis. In the genomic era, high-throughput sequencing technologies, represented by whole genome sequencing (WGS), whole exome sequencing (WES) or target region sequencing, have been widely used in the studies of hereditary HL. Here, we summarize the application and progress of WES and target region sequencing in the research of causative genes and clinical molecular diagnosis of hereditary HL, hoping to be helpful for the development and improvement of clinical genetic diagnosis of deafness in China.

Objective: To analyze the clinical features and pathogenic gene of the patients with hereditary hemorrhagic telangiectasia (HHT)., Methods: The clinical features of 3 HHT families were collected. And the patients were diagnosed according to clinical diagnostic analyzed criteria of HHT, the ACVRL1 gene screened and the conservation of mutation protein., Results: Three probands and 1 patient were diagnostic for HHT and 2 patients were suspected. In family I, there was a missense mutation of ACVRL1 gene in c.287A > G on 2 patients, leading to the transferal of amino acids from Asn to Ser at 96(th) place. In family II, there was a missense mutation of c.1271C > T on ACVRL1 in 2 patients, leading to the transfer of amino acids from Pro to Leu at 424(th) place. In family III, there was a deletion mutation of c.147delC on ACVRL1 so as to produce only the former 53 amino acids of ALK1 protein. Through an analysis of multi-species conservation, the mutations were conserved between multiple species. By querying the National Center for Biotechnology Information (NCBI) database, we confirmed that the mutation was not of a single nucleotide polymorphism (SNP)., Conclusion: The genetic screening of HHT patients may identify their virulence gene. And genetic screening of their offspring is helpful for the early diagnosis and prevention before disease onset.

Objective: To establish the genetic test technique of trisomy 21 concurrently conducts with prenatal diagnosis for hereditary hearing loss., Methods: Fifty-four pregnant women who underwent prenatal diagnosis for hearing loss of their fetuses in Chinese People's Liberation Army General Hospital from March 2009 to May 2010 were enrolled in this study. All probands from the deaf families have confirmed the causative mutation for hearing loss in Genetic Testing Center in Chinese People's Liberation Army General Hospital. The mean age of 54 pregnant women is 31 years at pregnancy of 18 - 26 weeks, 5 cases > pregnancy of 23 weeks, 9 cases ≥ 35 years. All subjects did not conduct the serologic tests for trisomy 21 before. Fifteen to twenty ml amniotic fluid was drawn from 49 cases at pregnancy of 18 - 23 weeks and 5 cases > pregnancy of 23 weeks. One to two ml umbilical blood was drawn from 5 cases > pregnancy of 23 weeks. For 9 cases ≥ 35 years, amniotic fluid cell culture and karyotyping analysis were conducted concurrently. A multiple quantitative fluorescent (QF) PCR and six microsatellite markers were applied to diagnosis trisomy 21. The samples with peaks of 1:1:1 or 2:1 at two microsatellite markers can be diagnosed as trisomy 21., Results: (1) Fifty-four fetuses were successfully conducted prenatal genetic diagnosis for hearing loss (included GJB2 and SLC26A4). Ten fetuses copied the exactly same genotypes as the probands. The other 44 cases fetuses did not copy the same genotypes as the probands and won't develop hearing loss. The hearing test showed normal hearing for the neonates. (2) All the 54 fetuses were excluded of trisomy 21 by QF-PCR and were verified after birth. Five fetuses with advanced maternal age were performed karyotyping analysis and showed normal. The diagnostic results of QF-PCR can be obtained in 1-3 days without misdiagnosed., Conclusions: QF-PCR is an efficient, rapid and accurate technique for detection of trisomy 21 without increasing sample amount. It can be used for fetuses who were undertaken hearing loss gene test or other prenatal gene test.

Objective: To analyze the relationship between the gene polymorphism of IL-2R (rs2104286) and IL-7R (rs6897932) and the susceptibility to idiopathic demyelinating optic neuritis (IDON)., Methods: A case-control study was performed in 72 IDON patients and 81 healthy individuals as the control group. DNA was extracted from peripheral blood leukocytes. PCR was used to amplify the aim genes; the SNP of IL-2R were analyzed by restriction fragment length polymorphism (RFLP) assay and the SNP of IL-7R were analyzed by gene sequencing. The χ2 test was used to compare genotype and allele frequencies between the IDON and control populations. Odds ratio (OR) was calculated using the approximation of Woolf for the 95% confidence interval (CI)., Results: No significant difference of genotype (χ2=0.410, P=0.815) and allele frequency(χ2=0.413, P=0.520) of IL-2R gene existed in IDON group(AA:54/AG:15/GG:3;A:123/G:21) as compared with the control group (AA:57/AG:20/GG:4;A:134/G:28). No significant difference of genotype frequency (χ2=3.787, P=0.150) of IL-7R existed in IDON group (CC:56/CT:13/TT:3) as compared with the control group (CC:52/CT:21/TT:8). However, there was a significant difference in IL-7R allele (C/T) between IDON group (C:125/T:19) and the controls (C:125/T:37) (χ2=4.743, P=0.029), OR=1.95 (95%CI: 1.07-3.55)., Conclusions: There is no significant difference in IL-2R rs2104286 polymorphism between IDON group and the controls; the frequencies of IL-7R rs6897932 C allele in IDON group was significantly greater than that of the controls. Polymorphism of IL-7R gene (rs6897932) may contribute to the risk of IDON.

In this study we have established a technique of multiple quantitative fluorescent polymerase chain reaction (QF-PCR) for prenatal diagnosis of common chromosomal abnormality using multiple short tandem repeat markers (STR-marker) on chromosomes 21 and 18 with the DNA samples from 20 cases of Down's syndrome, 3 cases of trisomy 18 and 40 cases normal controls. The technique established was applied in prenatal diagnosis in 165 clinical cases and 4 cases of newborn infants with digestive tract obstruction. The result this technique was compared with the results of karyotyping. Four cases of trisomy 21 and 1 case of trisomy 18 were identified among 169 samples, which was completely concordant with the results of karyotyping. All clinical samples were diagnosed in 1-3 days without misdiagnosis and missed diagnosis. Five cases were diagnosed by QF-PCR only due to the failure of karyotyping. Twenty-two cases of fetuses with structure malformation indicated by B-ultrasonography were subjected to karyotyping. One case of 45, X and 1 case of 47, XXY were identified. In conclusion, QF-PCR technique is rapid and accurate for the detection of trisomy 21 and trisomy 18. It is suitable for prenatal diagnosis of common chromosomal abnormality for pregnant women with advanced ages who were identified as having a high risk by serum screening. QF-PCR technique combined with karyotyping can provide better service for clinical demanding of prenatal diagnosis.

Objective: To study the chemical constituents from Clematis brevicaudata., Methods: The compounds were isolated by column chromatography and their structures were elucidated through spectroscopic analysis (NMR)., Results: Eight compounds were isolated and identified as: palmitic acid (1), 1-docosanol (2), pentacosanoic acid-2', 3'-dihydroxypropyl ester (3), beta-sitosterol (4), daucosterol (5), a mixture of the trans-p-coumarate of the n-alkanols (6), 3,4-dihydroxy-trans coumatate ethyl ester (7), syringaresinol-O-D-glucopyranoside (8)., Conclusion: All these compounds are obtained from Clematis brevicaudata for the first time.

Objective: To investigate the molecular etiology of non-syndromic hearing impairment in two patients in a maternal inherited deafness Chinese family., Methods: Peripheral blood specimens were collected and DNA templates extracted. The complete mitochondrial genomes and GJB2 gene were sequenced in an ABI 3100 Avant sequencer., Results: The proband (III-5) and her elder sister (III-1) were found to carry the mtDNA 12SrRNA C1494T mutation. The GJB2 gene showed no mutations. The proband had the history of using aminoglycosides before hearing loss, and exhibited severe sensorineural hearing impairment; the proband's sister had no history of using aminoglycosides, and showed moderate sensorineural hearing impairment., Conclusion: The molecular etiology of each individual patient in a family yaries with individual genetic background.