One case of congenital myopathy caused by new mutation of RYR1 gene and literature review.

OBJECTIVE: To report a case of congenital myopathy caused by RYR1 gene complex heterozygous mutation and analyze the pathogenicity of the mutation. Method The clinical manifestation, laboratory examination, imaging findings, muscle pathology and gene test results of a child with congenital myopathy were analyzed retrospectively. Combined with literature review, it is analyzed and discussed. Result The child, female, was admitted to hospital because of "dyspnea for 22 min after asphyxia resuscitation". The main manifestations are low muscle tension, the original reflex cannot be drawn out, the trunk and proximal muscles are weak, and the tendon reflex is not drawn out. The pathological signs were negative. The electrolyte of blood liver and kidney function, blood thyroid and blood ammonia were not abnormal, and creatine kinase increased temporarily. Electromyography suggests myogenic damage. Whole exome sequencing showed that there was a new compound heterozygous variation in RYR1 gene c.14427_ 14429del/c.14138C＞T.Western blot showed that the expression of RYR1 protein in patients was significantly lower than that in normal controls. Conclusion The compound heterozygous variation of RYR1 gene c.14427 was reported for the first time in China_ 14429del/c.14138c > t is the pathogenic gene of the child. The new discovery of RYR1 gene spectrum was revealed, which expanded the RYR1 gene spectrum.

Facilitators and barriers in the development and implementation of depression prevention and treatment policies in China: a qualitative study.

BACKGROUND: Depression is one of the leading causes of avoidable suffering and premature death worldwide, leading to the disease burden among mental disorders. Depression-related deaths can be prevented by developing and implementing good depression prevention and treatment policies. The goal of this study is to provide theoretical direction and useful references for examining the outstanding service work of depression prevention and treatment. It also aims to describe how depression prevention and treatment policies were developed and put into practice in China, along with the associated facilitators and barriers. METHODS: We integrated two data sources using a case study approach: a document review of relevant policy documents, published articles and reports between 2004 and 2022 (N = 12 papers) and in-depth interviews (N = 41). Participants were drawn from pertinent sectors to managing depression: research and academia, relevant government departments, health care providers, people with depression and their families, and community organisations. Thematic analysis was used to analyse all data. RESULTS: A comprehensive programme of work exploring specific services for depression prevention and treatment was developed in China in 2020. Facilitators of policy development and implementation include (1) political commitment and strong leadership, (2) coordination mechanisms, (3) stakeholder enthusiasm and commitment, (4) resources, and (5) the use of digital technologies. The main barriers leading to delays in policy development and implementation include (1) insufficient awareness and lack of depression literacy, (2) lack of resources and (3) stigma and social discrimination (4) lack of united action. CONCLUSION: Although the process of implementing a distinctive service programme for depression prevention and treatment in China has been long, the current policy is in line with current global efforts. Strategies to reduce Stigma and increase knowledge about depression are part of a national and international approach to reducing the burden of depression. Political commitment and the involvement of all stakeholders remain necessary. An adequate response to depression will require the involvement of society as a whole, with joint action to reduce the risk of exposure to adversity and enhance protective factors.

Individual characteristics of adolescent psychiatric patients accessing psychotherapy in China.

Most mental health problems develop during childhood and adolescence, so identifying the mental health needs and care pathways of adolescents is crucial to improving prevention. This study aimed to understand the characteristics of adolescent patients with mental disorders receiving psychotherapy in China. Data were collected retrospectively from the psychotherapy records of 116 patients at the Weifang Mental Health Centre. Information collected included demographics, stressors, duration of psychotherapy, and clinical diagnosis. Chi-square tests and negative binomial regression models were used to explore the relationship between demographic and clinical variables. The results showed that depression was the most common diagnosis, followed by anxiety and stress-related disorders and bipolar and related disorders. Rural patients were more likely to report family stress, while urban patients were more likely to report school stress. Female patients were more likely to report family stress and to be diagnosed with depression. Family stress, social stress, school stress, patient origin and economic conditions were all significant predictors of the duration of psychological treatment. This study helps to understand the characteristics and psychotherapeutic needs of adolescents with mental disorders who receive psychotherapy in China so that the positive role of psychotherapy in the prevention, treatment and rehabilitation of mental disorders can be better utilised.

Root growth and architecture of Tamarix chinensis in response to the groundwater level in the Yellow River Delta.

AIMS: Investigate the growth adaptation law of the Tamarix chinensis root system in response to the groundwater level in a muddy coastal zone. METHODS: The high groundwater level (0.7-0.9 m), medium groundwater level (1.1-1.3 m) and low groundwater level (1.5-1.7 m) T. chinensis forests on the beaches of the Yellow River Delta were used as the research objects. Full excavation methods were used to excavate root systems with different groundwater levels; then, the aboveground biomass, root biomass, root spatial distribution, root topological structure and fractal characteristics of T. chinensis response characteristics to groundwater level were measured and analysed. RESULTS: The results showed that with the decrease in the groundwater level, the soil water content and soil salt content showed upward trends. At high groundwater levels, T. chinensis reduced root biomass allocation to reduce the damage to roots caused by salinity. At low groundwater levels, T. chinensis strengthened the development of root systems, which greatly enhanced the ability of T. chinensis to balance its water intake. The root biomass at the high groundwater level was 43.06% lower than that at the low groundwater level. The relationship between root and shoot growth of T. chinensis at high groundwater levels and medium groundwater levels indicated allometric growth, and at low groundwater levels, roots and shoots grew uniformly. The root distribution of T. chinensis tended to be shallow at the different groundwater levels, showing the characteristics of a horizontal root type. At high groundwater levels, the root topological structure tended to be dichotomous, and the fractal dimension and fractal abundance values were both large, at 1.31 and 2.77, respectively. The branch complexity increased to achieve spatial expansion and increase plant stability. However, the topological structure of the medium and low groundwater level T. chinensis tended to be herringbone-like, the fractal dimension and fractal abundance values were small, the second branch was limited, and the structure was simple. The topological structure and fractal characteristics of the T. chinensis root system responded to different groundwater levels in a coordinated manner. CONCLUSIONS: Based on the differences in the growth and architecture of the T. chinensis root system, the T. chinensis root system has strong phenotypic plasticity to the heterogeneous water-salt habitat of the groundwater-soil system, and the T. chinensis root system shows strong root adaptability to water and salt stress.

Structural basis of a novel repressor, SghR, controlling Agrobacterium infection by cross-talking to plants.

Agrobacterium tumefaciens infects various plants and causes crown gall diseases involving temporal expression of virulence factors. SghA is a newly identified virulence factor enzymatically releasing salicylic acid from its glucoside conjugate and controlling plant tumor development. Here, we report the structural basis of SghR, a LacI-type transcription factor highly conserved in Rhizobiaceae family, regulating the expression of SghA and involved in tumorigenesis. We identified and characterized the binding site of SghR on the promoter region of sghA and then determined the crystal structures of apo-SghR, SghR complexed with its operator DNA, and ligand sucrose, respectively. These results provide detailed insights into how SghR recognizes its cognate DNA and shed a mechanistic light on how sucrose attenuates the affinity of SghR with DNA to modulate the expression of SghA. Given the important role of SghR in mediating the signaling cross-talk during Agrobacterium infection, our results pave the way for structure-based inducer analog design, which has potential applications for agricultural industry.

Agrobacteria reprogram virulence gene expression by controlled release of host-conjugated signals.

It is highly intriguing how bacterial pathogens can quickly shut down energy-costly infection machinery once successful infection is established. This study depicts that mutation of repressor SghR increases the expression of hydrolase SghA in Agrobacterium tumefaciens, which releases plant defense signal salicylic acid (SA) from its storage form SA ß-glucoside (SAG). Addition of SA substantially reduces gene expression of bacterial virulence. Bacterial vir genes and sghA are differentially transcribed at early and later infection stages, respectively. Plant metabolite sucrose is a signal ligand that inactivates SghR and consequently induces sghA expression. Disruption of sghA leads to increased vir expression in planta and enhances tumor formation whereas mutation of sghR decreases vir expression and tumor formation. These results depict a remarkable mechanism by which A. tumefaciens taps on the reserved pool of plant signal SA to reprogram its virulence upon establishment of infection.

Survey of transient process during melting of silver below the equilibrium melting point.

Understanding the melting behavior of metals at the microlevel and atomic level has been experimentally challenging due to the involvement of multiple phases at ultrafast time scale. By using the confocal scanning laser high-temperature microscope, differential scanning calorimetry, and environmental transmission electron microscope, we observed the transient process during melting of silver (Ag) nanoparticles below the equilibrium melting point. The melting point of Ag nanoparticles with the diameter of 60-120 nm is found to decrease by 100-400 °C, and the melting process is accompanied by a geometrical transformation at 840 °C, from an irregular polyhedron to a nearly spherical crystallinelike liquid with smooth facets. These results indicate that the melting of metal nanoparticles is not a direct sharp transformation from crystal to liquid but a gradual process via a certain intermediate state.

Cloning, expression, purification and crystallization of a pair of novel virulence factors, SghA and SghR, from Agrobacterium tumefaciens.

Two proteins, SghA and SghR, which were recently identified and characterized as novel bacterial virulence factors regulating the infection of plant hosts by Agrobacterium, were cloned, overexpressed and purified with high yield. Both SghA and SghR form dimers in solution. The purified SghA and SghR were crystallized and the crystals diffracted to 1.9 and 2.1 Šresolution, respectively. Data were collected and processed, and the crystallographic parameters were within acceptable ranges. These results will help in the determination of their structures in order to uncover the molecular mechanism of how these two proteins together control the release of plant defence signals against agrobacteria during pathogen-host interaction.

Determination of nifedipine in dog plasma by high-performance liquid chromatography with tandem mass spectrometric detection.

Nifedipine is a dihydropyridine calcium channel blocker used widely in the management of hypertension and other cardiovascular disorders. In this work, a simple, rapid and sensitive liquid chromatography/tandem mass spectrometry method was developed and validated to determine nifedipine in dog plasma using nimodipine as the internal standard. Chromatographic separation was carried out on a C8 column. The mobile phase consisted of a mixture of acetonitrile, water and formic acid (60:40:0.2, v/v/v) at a flow rate of 0.5 mL/min. Detection was performed on a triple quadrupole tandem mass spectrometer in selected reaction monitoring mode via an atmospheric pressure chemical ionization source. The method has a lower limit of quantification of 0.20 ng/mL with consumption of plasma as low as 0.05 mL. The linear calibration curves were obtained in the concentration range of 0.20-50.0 ng/mL (r = 0.9948). The recoveries of the liquid extraction method were 74.5-84.1%. Intra-day and inter-day precisions were 4.1-8.8 and 6.7-7.4%, respectively. The quantification was not interfered with by other plasma components and the method was applied to determine nifedipine in plasma after a single oral administration of two controlled-release nifedipine tablets to beagle dogs.

Structural insights into RISC assembly facilitated by dsRNA-binding domains of human RNA helicase A (DHX9).

Intensive research interest has focused on small RNA-processing machinery and the RNA-induced silencing complex (RISC), key cellular machines in RNAi pathways. However, the structural mechanism regarding RISC assembly, the primary step linking small RNA processing and RNA-mediated gene silencing, is largely unknown. Human RNA helicase A (DHX9) was reported to function as an RISC-loading factor, and such function is mediated mainly by its dsRNA-binding domains (dsRBDs). Here, we report the crystal structures of human RNA helicase A (RHA) dsRBD1 and dsRBD2 domains in complex with dsRNAs, respectively. Structural analysis not only reveals higher siRNA duplex-binding affinity displayed by dsRBD1, but also identifies a crystallographic dsRBD1 pair of physiological significance in cooperatively recognizing dsRNAs. Structural observations are further validated by isothermal titration calorimetric (ITC) assay. Moreover, co-immunoprecipitation (co-IP) assay coupled with mutagenesis demonstrated that both dsRBDs are required for RISC association, and such association is mediated by dsRNA. Hence, our structural and functional efforts have revealed a potential working model for siRNA recognition by RHA tandem dsRBDs, and together they provide direct structural insights into RISC assembly facilitated by RHA.

Separation and identification of flavonoids from fistular onion stalk (Allium fisturosum L. var. Caespitosum Makio).

The chemical constituents of fistular onion stalk obtained by supercritical CO(2) extraction were separated and purified by silica gel and sephadex LH-20 gel column chromatography and the preparative TLC method and four flavonoids were obtained. On the basis of the spectral data, they were structurally identified as (+)-catechin, (-)-epicatechin, astragalin, and 3-O-beta-D(2-O-beta-D-glucopyranosyl)-glucopyranosides of kaempferol.