Reproducibility of Diffusion MRI-Based Tractography in the Fetal Brain.

BACKGROUND: Tractography based on diffusion MRI (dMRI) is a useful tool to study white matter of the developing brain. However, its application in fetal brains is limited due to motion artifacts and low resolution of in utero dMRI, leading to reduced reliability, which was scarcely investigated in previous studies. PURPOSE: To identify reliably traceable fibers in fetal brains and assess whether reproducibility varies with gestational age (GA) and varies between brain regions. STUDY TYPE: Prospective cohort study. SUBJECTS: A total of 44 healthy fetuses with GAs between 25 and 37 (31 ± 6). FIELD STRENGTH/SEQUENCE: 3-T, diffusion-weighted echo-planar imaging sequence (2-5 repeated dMRI scans within the same session per subject). ASSESSMENT: We fitted dMRI with constrained spherical deconvolution model and conducted tractography on eight fibers. We extracted volume, fractional anisotropy, and fiber count for each fiber and assessed the reproducibility of these metrics between repeated scans within each subject. Data were divided into two age-based subgroups (≤30 weeks, N = 28, and >30 weeks, N = 16) for further tests. STATISTICAL TESTS: The reproducibility were compared between fibers by analysis of variance and two-sample t tests. Multiple comparisons were corrected by the false discovery rate (5% was accepted). RESULTS: The reproducibility of the anterior thalamic radiation, inferior longitudinal fasciculus (ILF), genu of the corpus callosum (GCC), and body of the corpus callosum (BCC) significantly decreased with advancing GA (correlation coefficient = 0.525-0.823), as confirmed by group comparisons between fetuses in early GA (≤30 weeks) and late GA (>30 weeks) groups. Corticospinal tract, inferior fronto-occipital fasciculus, and GCC showed high reproducibility for fiber count (weighted dice average = 0.846 vs. 0.814), while BCC and ILF exhibited the lowest reproducibility in both age groups. DATA CONCLUSION: The study indicates that the reliability of fetal brain tractography depends on GA and varies among different fibers. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Development of human white matter pathways in utero over the second and third trimester.

During the second and third trimesters of human gestation, rapid neurodevelopment is underpinned by fundamental processes including neuronal migration, cellular organization, cortical layering, and myelination. In this time, white matter growth and maturation lay the foundation for an efficient network of structural connections. Detailed knowledge about this developmental trajectory in the healthy human fetal brain is limited, in part, due to the inherent challenges of acquiring high-quality MRI data from this population. Here, we use state-of-the-art high-resolution multishell motion-corrected diffusion-weighted MRI (dMRI), collected as part of the developing Human Connectome Project (dHCP), to characterize the in utero maturation of white matter microstructure in 113 fetuses aged 22 to 37 wk gestation. We define five major white matter bundles and characterize their microstructural features using both traditional diffusion tensor and multishell multitissue models. We found unique maturational trends in thalamocortical fibers compared with association tracts and identified different maturational trends within specific sections of the corpus callosum. While linear maturational increases in fractional anisotropy were seen in the splenium of the corpus callosum, complex nonlinear trends were seen in the majority of other white matter tracts, with an initial decrease in fractional anisotropy in early gestation followed by a later increase. The latter is of particular interest as it differs markedly from the trends previously described in ex utero preterm infants, suggesting that this normative fetal data can provide significant insights into the abnormalities in connectivity which underlie the neurodevelopmental impairments associated with preterm birth.

Genome-Wide Identification, Expression, and Interaction Analysis of the Auxin Response Factor and AUX/IAA Gene Families in Vaccinium bracteatum.

BACKGROUND: Auxin, a plant hormone, plays diverse roles in the modulation of plant growth and development. The transport and signal transduction of auxin are regulated by various factors involved in shaping plant morphology and responding to external environmental conditions. The auxin signal transduction is primarily governed by the following two gene families: the auxin response factor (ARF) and auxin/indole-3-acetic acid (AUX/IAA). However, a comprehensive genomic analysis involving the expression profiles, structures, and functional features of the ARF and AUX/IAA gene families in Vaccinium bracteatum has not been carried out to date. RESULTS: Through the acquisition of genomic and expression data, coupled with an analysis using online tools, two gene family members were identified. This groundwork provides a distinguishing characterization of the chosen gene families in terms of expression, interaction, and response in the growth and development of plant fruits. In our genome-wide search of the VaARF and VaIAA genes in Vaccinium bracteatum, we identified 26 VaARF and 17 VaIAA genes. We analyzed the sequence and structural characteristics of these VaARF and VaIAA genes. We found that 26 VaARF and 17 VaIAA genes were divided into six subfamilies. Based on protein interaction predictions, VaIAA1 and VaIAA20 were designated core members of VaIAA gene families. Moreover, an analysis of expression patterns showed that 14 ARF genes and 12 IAA genes exhibited significantly varied expressions during fruit development. CONCLUSION: Two key genes, namely, VaIAA1 and VaIAA20, belonging to a gene family, play a potentially crucial role in fruit development through 26 VaARF-IAAs. This study provides a valuable reference for investigating the molecular mechanism of fruit development and lays the foundation for further research on Vaccinium bracteatum.

TRIM21 of Micropterus salmoides exerts antiviral roles against largemouth bass ulcer syndrome virus.

Tripartite motif 21 (TRIM21), a member of the TRIM family, plays an important role in apoptosis, autophagy and ubiquitination in human, and has been proven to play antiviral roles in different organisms. In this study, the TRIM21 gene of Micropterus salmoides (MsTRIM21) was cloned, and it encoded 376 amino acids, which showed 89.3% similarity with Micropterus dolomieu and 38.3% with homo sapiens. Bioinformatics analysis revealed MsTRIM21 contained four domains: C4HC3-type RING-variant (RINGv), coiled coil, PRY and SPRY. The high expression level of MsTRIM21 could be detected in liver, stomach and muscle of healthy Micropterus salmoides, and it was significantly upregulated in head kidney, muscle, gill and brain and significantly down-regulated in the stomach of Micropterus salmoides infected with largemouth bass ulcer syndrome virus (LBUSV). The overexpression of MsTRIM21 could significantly inhibit the viral replication in vitro, evidenced by the reduction of CPE severity and the downregulation of the viral gene transcription. In addition, the overexpression of MsTRIM21 could significantly increase the expression level of interferon regulatory factor (IRF) 3, IRF7, myxovirus resistance 1 (Mx1), interferon stimulated gene 15 (ISG15), double-stranded RNA-activated protein kinase (PKR) and tumor necrosis factor α (TNF-α) in vitro, indicating the enhancement of innate immune response and inflammatory response, which may directly affect the replication of LBUSV. Thus, these results provide new lights on the roles of fish TRIM21 in innate immune response against iridovirus.

Multi-channel optical sensing system with a BP-ANN for heavy metal detection.

A multi-channel optical sensing system for heavy metal concentration detection is presented in this paper. The system utilizes a multi-channel optical path combined with a unique circuit design and BP neural network (BP-ANN) to perform the online analysis of multi-wavelength signals, achieving accurate concentration detection of a heavy metal solution. An array photodiode is used to detect the transmission light intensities at multiple wavelengths through the optical path of the system, which enables the collection of useful spectral information of the solution. The system uses a unique signal acquisition method to effectively improve the efficiency of both signal acquisition and operation. BP-ANN is applied to the online analysis of multi-channel information, which overcomes the influential issue of nonlinear effect on data detection, optimizes the anti-interference ability, and lowers the detection limit of the system. This system eliminates the necessary employment of the expensive and large spectrometers and therefore greatly reduces the instrument cost and occupying space. Additionally, the detection limit of the system is extended lower than that of the conventional spectrophotometer. Compared with the detection limits of heavy metal solution obtained by using a single characteristic light wavelength, the detection limits of Cd2+, Cu2+ and Cr6+ achieved through using multi-channel detection system can be reduced by 42.64%, 38.12%, and 20.62%, respectively, and these detection limits are found as 0.0041mg/L, 0.0091mg/L, and 0.0112mg/L, respectively.

Construction and validation of a database of head models for functional imaging of the neonatal brain.

The neonatal brain undergoes dramatic structural and functional changes over the last trimester of gestation. The accuracy of source localisation of brain activity recorded from the scalp therefore relies on accurate age-specific head models. Although an age-appropriate population-level atlas could be used, detail is lost in the construction of such atlases, in particular with regard to the smoothing of the cortical surface, and so such a model is not representative of anatomy at an individual level. In this work, we describe the construction of a database of individual structural priors of the neonatal head using 215 individual-level datasets at ages 29-44 weeks postmenstrual age from the Developing Human Connectome Project. We have validated a method to segment the extra-cerebral tissue against manual segmentation. We have also conducted a leave-one-out analysis to quantify the expected spatial error incurred with regard to localising functional activation when using a best-matching individual from the database in place of a subject-specific model; the median error was calculated to be 8.3 mm (median absolute deviation 3.8 mm). The database can be applied for any functional neuroimaging modality which requires structural data whereby the physical parameters associated with that modality vary with tissue type and is freely available at www.ucl.ac.uk/dot-hub.

Genome-Wide Identification and Expression Analysis of Tomato ADK Gene Family during Development and Stress.

Adenylate kinase (ADK) is widely distributed in organisms and plays an important role in cellular energy homeostasis. In plants, ADK has important functions in plant growth and development regulation as well as in adaptation to the environment. However, little information is available about the ADK genes in tomato (Solanum lycopersicum), an important economic crop. To investigate the characteristics and functions of ADK genes in tomato, a total of 11 ADK genes were identified and named according to their chromosomal locations. The ADK family in Arabidopsis, tomato, potato, and rice was divided into six groups, and motif analysis revealed that each SlADK protein contained five to eight conserved motifs. A total of 4 to 19 exons were identified in tomato ADK gene family members, and interestingly, most members possessed 4 exons. Several stress response elements were identified in the promoter regions of SlADKs. The 11 SlADKs were randomly distributed on 9 of the 12 tomato chromosomes. Three duplication events were observed between tomato chromosomes, and a high degree of conservation of synteny was demonstrated between tomato and potato. The online TomExpress platform prediction revealed that SlADKs were expressed in various tissues and organs, basically consistent with the data obtained from real-time quantitative PCR (qPCR). The qPCR verification was also performed to determine the expression level of SlADKs and demonstrated that the genes responded to multiple abiotic stresses, such as drought, salt, and cold. Besides, the qPCR results showed that SlADK transcription was responsive to most of the applied hormone treatment. For correlation network analysis under 44 global conditions, the results showed that the number of 17, 3, 4, and 6 coexpressed genes matched with SlADK5, 8, 9, and 11, respectively. For specific gene function analysis, expression of SlADK10 was inhibited using virus-induced gene silencing (VIGS). Compared to wild-type plants, plants with silenced SlADK10 gene had poor drought resistance, indicating SlADK10 regulated drought tolerance of tomato positively. In summary, the information provided in the present study will be helpful to understand the evolutionary relationship and their roles of tomato ADK gene family in further research.

[Inspirations of Rome â £ on clinical evaluation of traditional Chinese medicine for functional gastrointestinal disease].

The Rome Foundation released the Rome Ⅳ for functional gastrointestinal diseases (FGIDs) in 2016, which fully presented the latest advances and views on the disease origin, definition, diagnosis, classification, pathology, mechanism, clinical features, influential factors, interventions, clinical evaluation, clinical research design and so on, showing high positive effects on global researches. Traditional Chinese medicines (TCM) have cognitive advantages and well-recognized and-demonstrated efficacy in the prevention and treatment for FGIDs. However, the monotonous presentation ways and weak interpretation on clinical evaluation have also hindered the inherent advantages explanation, characteristics quantization, evidence and communication accumulation. This study first analyzed the background and key points on clinical evaluation of Rome Ⅳ and corresponding inspirations, believed that its concept and viewpoints were assimilated with systematic medicine, and emphasized the important influence of subjective factors such as mental psychology and social culture on the disease and its importance in clinical evaluation. Its views on several aspects such as the theoretical model, internal and external causes, and transfer process were highly consistent with TCM. Therefore, TCM researchers should devote more dedication and courage on the innovation and collaboration with global researches to advance related studies. Then, based on 59 TCM clinical researches for FGIDs funded by national projects upon searching in CNKI with strict search strategy, the clinical evaluation methods and indexes and their correlations were summarized and analyzed, and it was found that more attention was paid to the disease symptoms and impact, symptom/syndrome score, patient report outcome, et al. However, many limitations were also founded, such as disordered relationships among different indexes, ambiguous explanation of research results, and extremely few domestic evaluation instruments in Chinese culture. Therefore, it is suggested that future research should regress and highlight the subjective features of patients and diseases, standardize the elemental structure and management mode of clinical evaluation, enhance the values and status of reported outcomes. It is highly recommended that the domestic disease-specific instruments developed in Chinese culture should be adopted as primary outcome for clinical evaluation, assisted with symptoms/signs assessment tools and doctors reporting outcome scale, et al. The common used TCM syndrome scores in current researches are not recommended as the primary outcome. However, there are some limitations in the above suggestions. We hope that more relevant researches will explore and establish a unified outcome assessment system for FGIDs and improve the quality of TCM clinical research.

Molecularly Imprinted Heterostructure-Based Electrochemosensor for Ultratrace and Precise Detection of 2-Methylisoborneol in Water.

Ultratrace 2-methylisoborneol (2-MIB, ∼ng/L) in source water is the main odorant in the algae-derived odor episodes, whose accurate on-site detection will have a promising application potential. Due to the chemical inertness of 2-MIB, sensitive and selective detection of 2-MIB remains much challenging. Herein, molecularly imprinted polymer cavities were polymerized on the heterostructure Ti3C2Tx@CuFc-metal-organic framework to selectively capture 2-MIB, where the heterostructure could catalyze the probe redox reaction of [Fe(CN)63-/4-] and amplify the corresponding current signals. The prepared electrochemical sensor showed higher sensitivity on 2-MIB detection than the reported ones. Excellent stability, reusability, and selectivity for 2-MIB detection were also verified. The linear range and limit of detection of our sensor for 2-MIB were optimized to 0.0001-100 µg/L and 30 pg/L, respectively, performing much better than the reported sensors. Comparable performance to gas chromatography-mass spectrometry was achieved when the sensor was applied to real water samples with or without 2-MIB standards. Overall, our research has made great progress in the application of an on-site sensor in 2-MIB detection and well advances the development of molecularly imprinted polymer-based electrochemical sensors.

Leaf litter from Cynanchum auriculatum Royle ex Wight leads to root rot outbreaks by Fusarium solani, hindering continuous cropping.

Cynanchum auriculatum Royle ex Wight (CA) is experiencing challenges with continuous cropping obstacle (CCO) due to soil-borne fungal pathogens. The leaf litter from CA is regularly incorporated into the soil after root harvesting, but the impact of this practice on pathogen outbreaks remains uncertain. In this study, a fungal strain D1, identified as Fusarium solani, was isolated and confirmed as a potential factor in CCO. Both leave extract (LE) and root extract (RE) were found to inhibit seed germination and the activities of plant defense-related enzymes. The combinations of extracts and D1 exacerbated these negative effects. Beyond promoting the proliferation of D1 in soil, the extracts also enhanced the hypha weight, spore number, and spore germination rate of D1. Compared to RE, LE exhibited a greater degree of promotion in the activities of pathogenesis-related enzymes in D1. Additionally, caffeic acid and ferulic acid were identified as potential active compounds. LE, particularly in combination with D1, induced a shift in the composition of fungal communities rather than bacterial communities. These findings indicate that the water extract of leaf litter stimulated the growth and proliferation of fungal strain D1, thereby augmenting its pathogenicity toward CA and ultimately contributing to the CCO process.

A Better Fruit Quality of Grafted Blueberry Than Own-Rooted Blueberry Is Linked to Its Anatomy.

To further clarify the impact of different rootstocks in grafted blueberry, fruit quality, mineral contents, and leaf gas exchange were investigated in 'O'Neal' blueberry (Vaccinium corymbosum) grafted onto 'Anna' (V. corymbosum) (AO), 'Sharpblue' (V. corymbosum) (SO), 'Baldwin' (V. virgatum) (BO), 'Plolific' (V. virgatum) (PO), and 'Tifblue' (V. virgatum) (TO) rootstocks and own-rooted 'O'Neal' (NO), and differences in anatomic structures and drought resistance were determined in AO, TO, and NO. The findings revealed that fruit quality in TO and PO was excellent, that of BO and SO was good, and that of AO and NO was medium. 'Tifblue' and 'Plolific' rootstocks significantly increased the levels of leaf phosphorus and net photosynthetic rate of 'O'Neal', accompanied by a synchronous increase in their transpiration rates, stomatal conductance, and intercellular CO2. Additionally, the comprehensive evaluation scores from a principal component analysis based on anatomic structure traits from high to low were in the order TO > AO > NO. The P50 (xylem water potential at 50% loss of hydraulic conductivity) values of these grafted plants descended in the order NO > AO > TO, and the branch hydraulic conductivity of TO and sapwood hydraulic conductivity of TO and AO were significantly lower than those of NO. Thus, TO plants exhibited the strongest drought resistance, followed by AO, and NO, and this trait was related to the effects of different rootstocks on the fruit quality of 'O'Neal' blueberry. These results provided a basis for a deeper understanding of the interaction between rootstocks and scions, as well mechanisms to improve blueberry fruit quality.

Effect of sacubitril/valsartan on sinus rhythm maintenance after catheter ablation in patients with persistent atrial fibrillation without reduced ejection fraction heart failure: a study protocol for a multi-center, open-label, randomized, controlled, superiority clinical trial.

Introduction: A high recurrence rate of atrial fibrillation was monitored after catheter ablation for persistent atrial fibrillation. Sacubitril/valsartan can improve outcomes for patients with heart failure and ventricular tachycardia, but few studies examined whether it can reduce recurrence or improve cardiovascular outcomes in patients with persistent atrial fibrillation after catheter ablation. In this study, we will assess the effect of sacubitril/valsartan on sinus rhythm maintenance and incidence of major adverse cardiovascular events (MACE) in patients with persistent atrial fibrillation after catheter ablation through a randomized controlled trial (RCT). Methods: This is a multi-center, randomized, controlled, open-label, superiority clinical trial involving 462 patients without reduced ejection fraction heart failure after catheter ablation of persistent atrial fibrillation. Patients will be randomized to (1) receive the standard treatment strategy plus sacubitril/valsartan titration, or (2) receive the standard treatment strategy without taking sacubitril/valsartan. The primary outcome will be sinus rhythm maintenance rate over 12 months, monitored by random electrocardiogram and 24-h Holter electrocardiogram. Discussion: This study is designed to evaluate the effect of sacubitril/valsartan on sinus rhythm maintenance and incidence of major adverse cardiovascular events (MACE) in patients with persistent atrial fibrillation after catheter ablation. The results will evaluate sacubitril/valsartan as a novel treatment for improving prognosis and a complement to conventional drug therapy. Trial Registration: Registered with Chinese Clinical Trials Registry on 27 August 2022, identifier: ChiCTR2200062995.

Identification and Characterization of Nigrospora Species and a Novel Species, Nigrospora anhuiensis, Causing Black Leaf Spot on Rice and Wild Rice in the Anhui Province of China.

Rice production in the Anhui province is threatened by fungal diseases. We obtained twenty-five fungal isolates from rice and wild rice leaves showing leaf spot disease collected along the Yangtze River. A phylogenetic analysis based on internal transcribed spacer (ITS), translation elongation factor 1 alpha (TEF1-α), and beta tubulin (TUB2) sequences revealed one isolate (SS-2-JB-1B) grouped with Nigrospora sphaerica, one (QY) with Nigrospora chinensis, twenty-two with Nigrospora oryzae, and one isolate (QY-2) grouped in its own clade, which are related to but clearly different from N. oryzae. Nineteen tested isolates, including sixteen strains from the N. oryzae clade and the three isolates of the other three clades, caused disease on detached rice leaves. The three isolates that did not belong to N. oryzae were also able to cause disease in rice seedlings, suggesting that they were rice pathogens. Isolate QY-2 differed from the other isolates in terms of colony morphology, cell size, and susceptibility to fungicides, indicating that this isolate represents a new species that we named Nigrospora anhuiensis. Our analysis showed that N. sphaerica, N. chinensis, and the new species, N. anhuiensis, can cause rice leaf spot disease in the field. This research provides new knowledge for understanding rice leaf spot disease.

Facile synthesis of Ag/ZIF-8@ZIF-67 as an electrochemical sensing platform for sensitive detection of halonitrophenols in drinking water.

Halonitrophenols (HNPs) are an emerging type of aromatic disinfection byproduct, with detected concentrations of ∼nmol L-1 in source water and drinking water. Currently, there are no standard methods for identifying HNPs, and most of the reported methods are time-consuming and equipment-dependent. A core-shell metal-organic framework (MOF) based electrochemical sensor (Ag/ZIF-8@ZIF-67) capable of detecting 2,6-dichloro-4-nitrophenol (2,6-DCNP) is reported in this study. The electrochemical sensor obtains the concentration of 2,6-DCNP by detecting the peak current passing through the sensor. In this sensor, Ag nanoparticles (AgNPs) play a key role in electrochemical sensing by reducing nitro groups via electron transfer, and porous structure with a large surface area is offered by ZIF-8@ZIF-67. The cyclic voltammetry (CV) response of Ag/ZIF-8@ZIF-67 was found to be approximately 1.75 times and 2.23 times greater than that of Ag/ZIF-8 and Ag/ZIF-67, respectively, suggesting an ideal synergistic effect of the core-shell structures. The Ag/ZIF-8@ZIF-67 sensor exhibited exceptional sensitivity to 2,6-DCNP, exhibiting a broad linear response range (R2 = 0.992) from 240 nmol L-1 to 288 µmol L-1 and a low detection limit of 20 nmol L-1. Furthermore, the sensor exhibited good anti-interference for isomers and common distractors in water, excellent stability and reproducibility, and high recovery in actual water samples. Our reported sensor gives a novel strategy for sensitive, selective, and in situ detection of 2,6-DCNP in practical analysis.

Transcriptome and physiological analysis of increase in drought stress tolerance by melatonin in tomato.

Drought stress seriously affects tomato growth, yield and quality. Previous reports have pointed out that melatonin (MT) can alleviate drought stress damage to tomato. To better understand the possible physiological and molecular mechanisms, chlorophyll fluorescence parameters and leaf transcriptome profiles were analyzed in the "Micro Tom" tomato cultivar with or without melatonin irrigation under normal and drought conditions. Polyethylene glycol 6000 (PEG6000) simulated continuous drought treatment reduced plant height, but melatonin treatment improved plant growth rate. Physiological parameter measurements revealed that the drought-induced decreases in maximum efficiency of photosystem II (PSII) photochemistry, the effective quantum yield of PSII, electron transfer rate, and photochemical quenching value caused by PEG6000 treatment were alleviated by melatonin treatment, which suggests a protective effect of melatonin on PSII. Comparative transcriptome analysis identified 447, 3982, 4526 and 3258 differentially expressed genes (DEGs) in the comparative groups plus-melatonin vs. minus-melatonin (no drought), drought vs. no drought (minus-melatonin), drought vs. no drought (melatonin) and plus-melatonin vs. minus-melatonin (drought), respectively. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis revealed that DEGs in the four comparative groups were involved in multiple metabolic processes and closely related to hormone signal transduction and transcription factors. Transcriptome data revealed that melatonin changed the expression pattern of most hormone signal transduction related DEGs induced by drought, and improved plant drought resistance by down-regulating the expression of linoleic acid catabolic enzyme genes. These results provide new insights into a probable mechanism of the melatonin-induced protection of photosynthesis and enhancement of drought tolerance in tomato plants.

Association of uterine fibroids with increased blood pressure: a cross-sectional study and meta-analysis.

Uterine fibroids (UFs) are the most common benign gynecological tumor and greatly affect reproductive health in women of reproductive age. Some studies have indicated an association between UFs and several cardiovascular disease (CVD) risk factors. To determine whether UFs are associated with increased blood pressure, we performed a cross-sectional study and meta-analysis. In the cross-sectional study, 8401 participants who underwent a physical examination at the First Affiliated Hospital of Shantou University Medical College from June 2011 to June 2013 were divided into a uterine fibroid group (1617 cases) and a control group (6784 cases) to assess the relationship between UFs and blood pressure. Then, we conducted a systematic review to confirm the results. The cross-sectional study showed that UFs were associated with an increased rate of elevated blood pressure [OR = 1.35, 95% confidence interval (CI): 1.016-1.792]. The meta-analysis revealed a significant association between UFs and the prevalence of hypertension [pooled OR = 1.44, 95% CI: 1.17-1.75, P = 0.0004; I2 = 68%]. Thus, UFs may be associated with the prevalence of hypertension. Women with uterine fibroids should be closely monitored for hypertension.

Placebo response varies between different types of sham acupuncture: A randomized double-blind trial in neck pain patients.

BACKGROUND: In prospective experimental studies of neck pain patients, it is difficult to determine whether responses to sham acupuncture differ from responses to real acupuncture due to the heterogeneous methodologies in control/sham interventions. Here we aim to compare the specific and nonspecific effects of electroacupuncture with four types of sham acupuncture. METHODS: In this double-blind, sham-controlled study, we randomly assigned 175 patients with neck pain to receive 10 sessions of electroacupuncture, shallow puncture, nonacupoint deep puncture, nonacupoint shallow puncture, or nonpenetration acupuncture. We used the Northwick Park Neck Pain Questionnaire (NPQ) as our primary outcome, and Short-form McGill Pain Questionnaire, visual analog scale (VAS), and Pain Threshold as secondary outcomes to measure the changes from baseline to a 3-month follow up. RESULTS: All groups, except nonacupoint shallow puncture, had significant improvement in all outcome measurements. Electroacupuncture only showed superior improvements than the shallow puncture, nonacupoint shallow puncture, and nonpenetration groups when compared using the NPQ and VAS scale (*p < 0.001). Interestingly, the nonacupoint shallow puncture produced even less placebo response than nonpenetration acupuncture. CONCLUSION: Our study demonstrates the high variability of placebo response among different types of sham controls depending on the depth of needle insertion and the puncture location. An important implication of our results is nonacupoint deep puncture produced similar analgesic effects as electroacupuncture. Our study may shed a new light on the predominant underlying mechanisms among different types of sham acupuncture controls, which can help with interpreting the effect of acupuncture in other studies. TRIAL REGISTRATION: Chinese clinical trial registry (ChiCTR-IOR-15006886). SIGNIFICANCE: This study compared the observed specific and nonspecific analgesia effect in four different types of sham acupuncture stimulation with neck pain patients, assessed by four outcomes. Although all of the sham controls produced significant reduction in neck pain, electroacupuncture had superior significant improvement. Importantly, placebo responses differed significantly between the sham controls and responses were inconsistent according to different outcome assessments. This study emphasizes the importance of taking into consideration which sham control and method of outcome measurement were used in a pain research study when evaluating its results.

The Transcription Factor VpxlnR Is Required for the Growth, Development, and Virulence of the Fungal Pathogen Valsa pyri.

Pears (Pyrus sp.) are widely cultivated in China, and their yield accounts for more than 60% of global pear production. The fungal pathogen Valsa pyri is a major causal agent of pear canker disease, which results in enormous losses of pear production in northern China. In this study, we characterized a Zn2Cys6 transcription factor that contains one GAL4 domain and a fungal-trans domain, which are present in VpxlnR. The vpxlnR gene expression was upregulated in the invasion stage of V. pyri. To investigate its functions, we constructed gene deletion mutants and complementary strains. We observed that the growth of the vpxlnR mutants was reduced on potato dextrose agar (PDA), Czapek plus glucose or sucrose compared with that of the wild-type strain. Additionally, vpxlnR mutants exhibited loss of function in fruiting body formation. Moreover, vpxlnR mutants were more susceptible to hydrogen peroxide (H2O2) and salicylic acid (SA) and were reduced in their virulence at the early infection stage. According to a previous study, VpxlnR-interacting motifs containing NRHKGNCCGM were searched in the V. pyri genome, and we obtained 354 target genes, of which 148 genes had Clusters of Orthologous Groups (COG) terms. PHI-BLAST was used to identify virulence-related genes, and we found 28 hits. Furthermore, eight genes from the 28 PHI-BLAST hits were further assessed by yeast one-hybrid (Y1H) assays, and five target genes, salicylate hydroxylase (VP1G_09520), serine/threonine-protein kinase (VP1G_03128), alpha-xylosidase (VP1G_06369), G-protein beta subunit (VP1G_02856), and acid phosphatase (VP1G_03782), could interact with VpxlnR in vivo. Their transcript levels were reduced in one or two vpxlnR mutants. Taken together, these findings imply that VpxlnR is a key regulator of growth, development, stress, and virulence through controlling genes involved in signaling pathways and extracellular enzyme activities in V. pyri. The motifs interacting with VpxlnR also provide new insights into the molecular mechanism of xlnR proteins.

Validation of reference genes for gene expression analysis in fruit development of Vaccinium bracteatum Thunb. using quantitative real-time PCR.

Vaccinium bracteatum Thunb. (VBT) is widely distributed in the mountainous areas in eastern and southern China. VBT leaves have great medical value and can be used to stain rice to produce "Wumifan". Its fruits also contain rich nutrients. However, there has been limited attention to exploring the molecular content of VBT. Previously, we performed RNA-seq on three typical VBT fruits that were at various stages of ripening, although a reliable reference gene was lost in validation.In this study, we selected ten candidate reference genes based on previous studies and transcriptomics analyses. Subsequently, these genes were evaluated using a combination of methods, including geNorm, NormFinder, and Bestkeeper, with a comprehensive ranking assessment. As a result, we found that the actin2, NADH, and ADK genes have high reliability for analysing the expression levels of genes involved in fruit development. Furthermore, the transcript levels of 15 DEGs from transcriptomic analysis were assessed using NADH as a reference gene, and RT-qPCR data were highly consistent with the transcriptomic data. These results provide reliable reference genes for further studying gene expression, which will be beneficial for comprehensively exploring VBT.

Association of Impaired Fasting Blood Glucose With Triple Coronary Artery Stenosis and Myocardial Infarction Among Patients With Coronary Artery Stenosis.

Background: The association between impaired fasting glucose level (IFG) and coronary heart disease (CAD) remain controversial. In the present study, we sought to ascertain a relationship of IFG with the number of diseased coronary artery and occurrence of myocardial infarction, among CAD cases. Methods: We studied 1,451 consecutive no-diabetic patients who underwent coronary angiography at the First Affiliated Hospital of Shantou University Medical College in Southern China. Demographic, biochemical, clinical and angiographic data were collected. Results: The prevalence of IFG was higher in patients with angiographically confirmed CAD than in subjects without angiographic evidence of CAD (33.4 versus 28.2%, p = 0.034). Compared with CAD cases without IFG, CAD cases with IFG had a higher odds ratio (OR) of having triple-vessel disease as opposed to having single- or double-vessel disease [OR = 1.53, 95% confidence interval (CI) = 1.13-2.07]. Furthermore, the occurrence of MI was higher in CAD cases with IFG than in CAD cases without IFG (OR = 1.73, 95% CI = 1.27-2.36). Conclusions: There is an association between IFG and a predisposition to severe CAD indicated by triple vessel disease or myocardial infarction.