A spatiotemporal barrier formed by Follistatin is required for left-right patterning.

How left-right (LR) asymmetry emerges in a patterning field along the anterior-posterior axis remains an unresolved problem in developmental biology. Left-biased Nodal emanating from the LR organizer propagates from posterior to anterior (PA) and establishes the LR pattern of the whole embryo. However, little is known about the regulatory mechanism of the PA spread of Nodal and its asymmetric activation in the forebrain. Here, we identify bilaterally expressed Follistatin (Fst) as a regulator blocking the propagation of the zebrafish Nodal ortholog Southpaw (Spaw) in the right lateral plate mesoderm (LPM), and restricting Spaw transmission in the left LPM to facilitate the establishment of a robust LR asymmetric Nodal patterning. In addition, Fst inhibits the Activin-Nodal signaling pathway in the forebrain thus preventing Nodal activation prior to the arrival, at a later time, of Spaw emanating from the left LPM. This contributes to the orderly propagation of asymmetric Nodal activation along the PA axis. The LR regulation function of Fst is further confirmed in chick and frog embryos. Overall, our results suggest that a robust LR patterning emerges by counteracting a Fst barrier formed along the PA axis.

Identification of neutrophil-related genes and development of a prognostic model for cholangiocarcinoma.

BACKGROUND: Cholangiocarcinoma is a prevalent gastrointestinal tumor with limited effective early diagnostic methods. The role of neutrophils in the context of cholangiocarcinoma remains largely unexplored. METHODS: A comprehensive analysis was performed on a cohort of cholangiocarcinoma samples (TCGA-CHOL) from the TCGA database to investigate the relationship between cholangiocarcinoma and neutrophils. Methodologies included single-sample gene set enrichment analysis (ssGSEA), differential expression analysis, weighted gene co-expression network analysis (WGCNA) and gene set enrichment analysis (GSEA). RESULTS: The study identified a significant decrease of neutrophils in cholangiocarcinoma via ssGSEA. WGCNA and differential expression analysis led to the identification of a neutrophil-related gene module comprised of 1059 genes. Cluster 1, showing a higher proportion of neutrophils, was linked to better survival outcomes. GSEA disclosed downregulation of complement, inflammatory response and interferon response pathways in Cluster 2, hinting at possible cholangiocarcinoma development triggers. A notable upregulation of PD1, PD-L1 and CTLA4 was observed in Cluster 1, suggesting potential benefits from immunotherapy. A prognostic model was developed based on clinical data and expression levels of three prognostic genes (SOWAHD, TNFAIP8 and EBF3) showing satisfactory discrimination, calibration and clinical benefits. An overexpression of TNFAIP8 in cholangiocarcinoma cells was found, with its knockdown significantly inhibiting cell proliferation and migration. CONCLUSIONS: This study elucidates a neutrophil-related gene module and prognostic genes, offering insights into the role of neutrophils in cholangiocarcinoma development and progression. It also introduces a clinical prediction model for enhanced prognosis assessment. These findings may lay the groundwork for the development of innovative therapeutic strategies in cholangiocarcinoma treatment.

Large viewing angle integral imaging 3D display system based on a symmetrical compound lens array.

We propose a large viewing angle integral imaging 3D display system based on a symmetrical compound lens array (SCLA). The display system comprises a high-resolution 2D display panel, an SCLA, and a light shaping diffuser. The high-resolution 2D display panel presents an elemental image array, the SCLA modulates the light rays emitted from the 2D display panel to form 3D images in space, and the light shaping diffuser eliminates the gaps between 3D pixels of the 3D images. We find that the lateral aberration is a crucial factor that affects the resolution of the reconstructed 3D image. The symmetrical structure of the SCLA enables a reduced focal length and the elimination of lateral aberration, improving the viewing angle and the 3D image resolution simultaneously. The experimental results confirm that the proposed display system increases the viewing angle to 68.6°, achieving a comparable resolution of the full field of view while maintaining a simple structure.

A novel mutation in hERG gene associated with azithromycin-induced acquired long QT syndrome.

BACKGROUND: Mutations in human ether-à-go-go-related gene (hERG) potassium channels are closely associated with long QT syndrome (LQTS). Previous studies have demonstrated that macrolide antibiotics increase the risk of cardiovascular diseases. To date, the mechanisms underlying acquired LQTS remain elusive. METHODS: A novel hERG mutation I1025N was identified in an azithromycin-treated patient with acquired long QT syndrome via Sanger sequencing. The mutant I1025N plasmid was transfected into HEK-293 cells, which were subsequently incubated with azithromycin. The effect of azithromycin and mutant I1025N on the hERG channel was evaluated via western blot, immunofluorescence, and electrophysiology techniques. RESULTS: The protein expression of the mature hERG protein was down-regulated, whereas that of the immature hERG protein was up-regulated in mutant I1025N HEK-293 cells. Azithromycin administration resulted in a negative effect on the maturation of the hERG protein. Additionally, the I1025N mutation exerted an inhibitory effect on hERG channel current. Moreover, azithromycin inhibited hERG channel current in a concentration-dependent manner. The I1025N mutation and azithromycin synergistically decreased hERG channel expression and hERG current. However, the I1025N mutation and azithromycin did not alter channel gating dynamics. CONCLUSIONS: These findings suggest that hERG gene mutations might be involved in the genetic susceptibility mechanism underlying acquired LQTS induced by azithromycin.

Expression and regulation of HIF-1a in hypoxic pulmonary hypertension: Focus on pathological mechanism and Pharmacological Treatment.

Hypoxia inducible factor-1(HIF-1), a heterodimeric transcription factor, is composed of two subunits (HIF-1α and HIF-1ß). It is considered as an important transcription factor for regulating oxygen changes in hypoxic environment, which can regulate the expression of various hypoxia-related target genes and play a role in acute and chronic hypoxia pulmonary vascular reactions. In this paper, the function and mechanism of HIF-1a expression and regulation in hypoxic pulmonary hypertension (HPH) were reviewed, and current candidate schemes for treating pulmonary hypertension by using HIF-1a as the target were introduced, so as to provide reference for studying the pathogenesis of HPH and screening effective treatment methods.

First report of Lasiodipilodia theobromae Causing leaf spot of Agave sisalana in GuangXi, China.

Agave sisalana, as an excellent fiber producing plant, is mainly planted in Guangxi Province, China. In November 2023, a foliar disease occured on A. sisalana at Liangjiang Town (108.3593 W, 23.4723 N), Wuming District, Nanning in GuangXi, China. Approximately 50 to 60% of the plants (n=200) had obvious leaf spots on more than 70% of the leaves. On the leaves of sisal, circular or irregularly shaped yellow brown spots can be seen, sunken, with no halo on the edges. As time goes on, the lesion gradually expands to the entire blade of the sword (Figure 1A, 1B). To identify the disease etiology, ten agave leaves were collected from GuangXi. Symptomatic midribs were cut into 3×3 mm pieces, surface sterilized with 75 % ethanol for 20 s, rinsed with sterilized distilled water three times, air dried on sterile filter paper, plated on photo dextrose agar (PDA) medium, and incubated at 28 ℃ in the dark. Five isolates (JM01, JM02, JM03, JM05, JM06) with similar morphology were obtained. Colonies on PDA medium were white to grayish-white with atrial mycelia growing initially upward and then forming clusters (Figure 1E). After five days, mycelia turned grayish black. Immature conidia were initially hyaline, aseptate, and ellipsoid. Mature conidia were dark brown, one septate, longitudinal striate, and 22.1 to 26.3×10.2 to 14.9 µm (Figure 1F). Morphologically , the isolates were identified as Lasiodiplodia theobromae (Alves et al. 2008). For molecular identification, genome DNA of five representative isolate was extracted using the Fungi Genomic DNA Purification kit. The internal transcribed spacer (ITS) region of rDNA and translation elongation factor 1-alpha (TEF-1α) and ß-tublin (TUB) gene were amplified with primer pairs ITS1/ITS4 (White et al. 1990), EF1-728F/EF1-986R (Carbone and Kohn 1999), and Bt2a/Bt2b (Glass and Donaldson 1995), respectively, and sequenced. The ITS (PP209594), TEF-1α (PP234629), and TUB (PP234628) sequences of representative isolate JM01 were deposited in GeneBank. BLAST searches showed >99% nucleotide identity to sequences of L. theobromae (ITS, 99.26% to NR111174; TEF-1α, 99.69% to MM840490; TUB, 98.92% to MN172230). Phylogenetic analysis using maximum likelihood based on the combined ITS, TEF-1α, and TUB sequences of the isolates and reference sequences of Lasiodiplodias spp. from GenBank indicated the isolates obtained in this study formed a clade strongly supported based on bootstrap values to the ex-type isolate CBS164.96 sequences of L.theobromae (Figure 2). To test pathogenicity, JM01 was tested by inoculation leaves of one year old agave plants, the epidermis at the inoculation site, 10, 15 and 20 cm below to the crown, was wiped with a 75% alcohol cotton ball, washed three times with sterile water, and punctured (5 mm diameter) with a sterile inoculation needle. A 5 mm block of each isolate cultured on PDA for 3 days was attached to the inoculation site. Controls were inoculated with sterile PDA. The inoculation area was covered with plastic wrap. All plants were kept in a controlled greenhouse at 27℃, 80% relative humidity, and natural daylight, and watered weekly. Each treatment was repeated three times. Remove the block one day later. Three days after inoculation, all inoculated had typical symptoms,but control were healthy (Figure 1C, 1D). Fungal isolates were only recovered from symptomatic stems and were morphologically identical to L. theobromae, completing Koch's postulates. L. Theobromae has been reported as the cause of leaf rot on A. angustifolia in Mexico (Reyes-García et al. 2023). To our knowledge, this is the first report of L. theobromae causing leaf spot on A. sisalana in GuangXi, China. L. theobromae is primarily a plant pathogen that causes rotting and dieback in fruits and plants in tropical and subtropical regions (Puttanna 1967). This study is useful to focus on management strategies for leaf rot disease by L. theobromae of A. sisalana.

[Mechanism of Puerariae Thomsonii Radix in treatment of mild dyslipidemia: based on clinical metabolomics and proteomics].

This study aims to explore the potential metabolic pathways and targets of Puerariae Thomsonii Radix in the clinical treatment of mild dyslipidemia. UPLC-Q-TOF-MS and EASY-nLC-timsTOF-Pro2 were employed to perform metabolomic and proteomic analyses of the plasma samples collected from the patients with mild dyslipidemia at baseline and after 12 weeks of treatment with Puerariae Thomsonii Radix. The multivariate statistical analysis was carried out for comparison between groups, and the correlation analysis was performed for the metabolites and proteins closely related to mild dyslipidemia with the blood lipid indexes. The possible pathways and targets for mitigating mild dyslipidemia were screened out by the Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis. The results showed that 56 differential metabolites and 78 differential proteins in the plasma of patients were associated with Puerariae Thomsonii Radix treatment. In addition, changes were detected for the proteins or metabolites(ApoB-100, 9,10-DHOME, GAPDH, PGK1, PGAM1, ENO1, etc.) involved in lipoprotein, lipid, and glucose metabolism and the proteins or metabolites(oxidized phospholipid, PLA2G7, LTA4H, etc.) related to inflammation and oxidative stress. Puerariae Thomsonii Radix may down-regulate the overexpression of ApoB-100, activate the peroxisome proliferator-activated receptor α/γ(PPARα/γ), promote the catabolism of fat and glycerol, and alleviate the oxidative stress mediated by oxidized phospholipids and leukotriene B4(LTB4) in the treatment of mild dyslipidemia.

[Risk factors for cow's milk protein allergy in infants: a multicenter prospective nested case-control study]. / å©´å„¿ç‰›å¥¶è›‹ç™½è¿‡æ•çš„å±é™©å› ç´ ï¼šä¸€é¡¹å¤šä¸­å¿ƒå‰çž»æ€§å·¢å¼ç— ä¾‹å¯¹ç §ç ”ç©¶.

OBJECTIVES: To explore the risk factors associated with cow's milk protein allergy (CMPA) in infants. METHODS: This study was a multicenter prospective nested case-control study conducted in seven medical centers in Beijing, China. Infants aged 0-12 months were included, with 200 cases of CMPA infants and 799 control infants without CMPA. Univariate and multivariate logistic regression analyses were used to investigate the risk factors for the occurrence of CMPA. RESULTS: Univariate logistic regression analysis showed that preterm birth, low birth weight, birth from the first pregnancy, firstborn, spring birth, summer birth, mixed/artificial feeding, and parental history of allergic diseases were associated with an increased risk of CMPA in infants (P<0.05). Multivariate logistic regression analysis revealed that firstborn (OR=1.89, 95%CI: 1.14-3.13), spring birth (OR=3.42, 95%CI: 1.70-6.58), summer birth (OR=2.29, 95%CI: 1.22-4.27), mixed/artificial feeding (OR=1.57, 95%CI: 1.10-2.26), parental history of allergies (OR=2.13, 95%CI: 1.51-3.02), and both parents having allergies (OR=3.15, 95%CI: 1.78-5.56) were risk factors for CMPA in infants (P<0.05). CONCLUSIONS: Firstborn, spring birth, summer birth, mixed/artificial feeding, and a family history of allergies are associated with an increased risk of CMPA in infants.

Investigations of sequencing data and sample type on HLA class Ia typing with different computational tools.

Human leukocyte antigen (HLA) can encode the human major histocompatibility complex (MHC) proteins and play a key role in adaptive and innate immunity. Emerging clinical evidences suggest that the presentation of tumor neoantigens and neoantigen-specific T cell response associated with MHC class I molecules are of key importance to activate the adaptive immune systemin cancer immunotherapy. Therefore, accurate HLA typing is very essential for the clinical application of immunotherapy. In this study, we conducted performance evaluations of 4 widely used HLA typing tools (OptiType, Phlat, Polysolver and seq2hla) for predicting HLA class Ia genes from WES and RNA-seq data of 28 cancer patients. HLA genotyping data using PCR-SBT method was firstly obtained as the golden standard and was subsequently compared with HLA typing data by using NGS techniques. For both WES data and RNA-seq data, OptiType showed the highest accuracy for HLA-Ia typing than the other 3 programs at 2-digit and 4-digit resolution. Additionally, HLA typing accuracy from WES data was higher than from RNA-seq data (99.11% for WES data versus 96.42% for RNA-seq data). The accuracy of HLA-Ia typing by OptiType can reach 100% with the average depth of HLA gene regions >20x. Besides, the accuracy of 2-digit and 4-digit HLA-Ia typing based on control samples was higher than tumor tissues. In conclusion, OptiType by using WES data from control samples with the high average depth (>20x) of HLA gene regions can present a probably superior performance for HLA-Ia typing, enabling its application in cancer immunotherapy.

Yi Jin Bang exercise versus usual exercise therapy to treat subacromial pain syndrome: a pilot randomised controlled trial.

To evaluate the effect of Yi Jin Bang (YJB) exercise on pain, disability, flexibility, and muscular endurance in individuals with subacromial pain syndrome (SAPS). Fifty-four adults with SAPS were randomly allocated into either a YJB (n = 18), a usual exercise therapy (UET; n = 18), or a control group (n = 18). YJB and UET interventions involved 10 weeks of home-based exercise training, with four sessions per week. The control group received no treatment. Outcome measures included Shoulder Pain and Disability Index (SPADI), pain at rest and during activity, flexion and abduction range of motion (ROM), back scratch test, and shoulder abduction endurance test. These measures were assessed at baseline, immediately after a single face-to-face session (acute effects), and after 10 weeks of intervention (chronic effects). For acute effects, significant group-by-time interactions were observed for flexion ROM, abduction ROM, and the back scratch test (all p < 0.05). For chronic effects, significant group-by-time interactions were found for pain during activity, the SPADI score, and the back scratch test (all p < 0.05). Home-based YJB exercise is comparable to home-based UET in reducing pain and disability and improving flexibility.

[A new cinnamic acid ester derivative from Liquidambaris Resina].

Twelve compounds were isolated from Liquidambaris Resina by silica gel column chromatography and thin layer chromatography. Their structures were identified on the basis of spectral data, electron capture detector data, and physicochemical properties as(2'R, 3'R)-2',3'-dihydroxy-hydrocinnamyl-(E)-cinnamate(1),(E)-cinnamyl-(E)-cinnamate(2), cinnamic acid(3), 28-norlup-20(29)-en-3-one-17ß-hydroperoxide(4), erythrodiol(5), 13ß,28-epoxy-30-hydroxyolean-1-en-3-one(6),(3ß)-olean-12-ene-3,23-diol(7), 2α,3α-dihydroxy-olean-12-en-28-oic acid(8), 28-hydroxyolean-12-en-3-one(9), 3-epi-oleanolic acid(10), 3-oxo-oleanolic acid(11), and hederagenin(12). Compound 1 was a new cinnamic acid ester derivative and compounds 2-4,6-8, and 12 were isolated from Liquidambaris Resina for the first time. Compounds 4, 5, 10, and 12 exerted inhibitory effects on the proliferation of human umbilical vein endothelial cells(HUVEC) with the IC_(50) values of(17.43±2.17),(35.32±0.61),(27.50±0.80), and(46.30±0.30) µmol·L~(-1), respectively.

Injectable Hybrid-Crosslinked Hydrogels as Fatigue-Resistant and Shape-Stable Skin Depots.

Injectable hydrogels have gained considerable attention, but they are typically mechanically weak and subject to repeated physiological stresses in the body. Herein, we prepared polyurethane diacrylate (EPC-DA) hydrogels, which are injectable and can be photocrosslinked into fatigue-resistant implants. The mechanical properties can be tuned by changing photocrosslinking conditions, and the hybrid-crosslinked EPC-DA hydrogels exhibited high stability and sustained release properties. In contrast to common injectable hydrogels, EPC-DA hydrogels exhibited excellent antifatigue properties with >90% recovery during cyclic compression tests and showed shape stability after application of force and immersion in an aqueous buffer for 35 days. The EPC-DA hydrogel formed a shape-stable hydrogel depot in an ex vivo porcine skin model, with establishment of a temporary soft gel before in situ fixing by UV crosslinking. Hybrid crosslinking using injectable polymeric micelles or nanoparticles may be a general strategy for producing hydrogel implants resistant to physiological stresses.

First report of Fusarium proliferatum causing leaf spot on tea plants in Jiangxi Province, China.

Tea (Camellia sinensis (L.) O. Kuntze), a perennial evergreen shrub, is one of the most important cash crops in China. In September 2021, leaf spot symptoms were observed on approximately 30% of tea plants in a 2 ha commercial field of Lushan (29°33'0" N, 115°58'48" E), Jiangxi Province, China. The symptoms initially appeared as small, gray lesions, and later became larger (10-15 mm in diameter) circular to irregular spots with light brown centers and gray borders. To isolate the pathogen, small pieces (3×3 mm) cut from the margins of lesions were sterilized with 75% ethanol for 10 s, 0.1% HgCl2 for 20 s, and then rinsed three times with sterile water. The pieces were placed onto acidified potato dextrose agar (APDA) plates, and incubated in darkness at 28℃. Pure cultures were prepared by subculturing hyphal tips. A total of 16 fungal isolates were obtained, and the colonies of 15 isolates (isolation rate 93.8%) looked identical, resembling those of the genus Fusarium. The colonies were white to pink with purple woolly mycelium. After 10 to 15 days incubation, slightly curved macroconidia with three to four septa measuring 14.0 to 34.5 × 2.0 to 3.5 µm (n = 50), and oval, unicellar microconidia measuring 4.0 to 9.0 × 1.5 to 3.5 µm (n = 50) were observed. These morphological characteristics were similar to that described for Fusarium proliferatum (Leslie and Summerell 2006). Genomic DNA of representative isolates (LSZWY, LSZWY2, LSZWY3) was extracted with the Ezup Column Fungi Genomic DNA Purification Kit (Sangon Biotech Co., Ltd, Shanghai). The translation elongation factor 1 alpha gene (EF-1ɑ) was amplified using primers EF-1H / EF-2T (O'Donnell, et al. 2015). PCR product was sequenced and the sequence was 709 bp (Accession No. OL614004, ON357634, ON595710). BLAST search results showed that it had 99.9% identity with the EF-1ɑ gene sequence of F. proliferatum (MH341215, MT371378). To test pathogenicity, nine leaves from 5-year-old healthy tea plants (Ca. Luyun 3) were wounded using a sterilized needle and inoculated with a 20µl conidial suspension (2 × 107 conidia·mL-1) on one side of the plants and the other side with sterilized distilled water as a control. All leaves were incubated in a growth chamber at 28℃ and 80% relative humidity with a 12 h light/dark photoperiod. Seven days later, all inoculated treatments showed symptoms identical to those observed in the field, while the control remained asymptomatic. The experiment was repeated three times with similar results. Koch's postulates were fulfilled by successful re-isolation and morphological and molecular identification of F. proliferatum from the inoculated leaves. This pathogen can cause diseases of many crops, e.g. tobacco, Polygonatum cyrtonema and others (Li, et al 2017; Zhou, et al. 2021). However, this is the first report of F. proliferatum causing leaf spot on tea plants in China. This new disease poses a threat to the yield and quality of tea and methods need to be developed for its control and to prevent further spread.

From cis-Lobeline to trans-Lobeline: Study on the Pharmacodynamics and Isomerization Factors.

Lobeline is an alkaloid derived from the leaves of an Indian tobacco plant (Lobelia inflata), which has been prepared by chemical synthesis. It is classified as a partial nicotinic agonist and has a long history of therapeutic usage ranging from emetic and respiratory stimulant to tobacco smoking cessation agent. The presence of both cis and trans isomers in lobeline is well known, and many studies on the relationship between the structure and pharmacological activity of lobeline and its analogs have been reported. However, it is a remarkable fact that no studies have reported the differences in pharmacological activities between the two isomers. In this article, we found that different degrees of isomerization of lobeline injection have significant differences in respiratory excitatory effects in pentobarbital sodium anesthetized rats. Compared with cis-lobeline injections, the respiratory excitatory effect was significantly reduced by 50.2% after administration of injections which contained 36.9% trans-lobeline. The study on the influencing factors of isomerization between two isomers shown that this isomerization was a one-way isomerism and only converted from cis to trans, where temperature was the catalytic factor and pH was the key factor. This study reports a new discovery. Despite the widespread use of ventilators, first-aid medicines such as nikethamide and lobeline has retired to second line, but as a nonselective antagonist with high affinity for a4b2 and a3b2 nicotinic acetylcholine receptors (nAChRs). In recent years, lobeline has shown great promise as a therapeutic drug for mental addiction and nervous system disorders, such as depression, Alzheimer disease and Parkinson disease. Therefore, we suggest that the differences between two isomers should be concerned in subsequent research papers and applications.

The molecular mechanism underlying mitophagy-mediated hippocampal neuron apoptosis in diabetes-related depression.

Diabetes-related depression (DD) is a major complication of diabetes mellitus. Our previous studies indicated that glutamate (Glu) and hippocampal neuron apoptosis are key signal and direct factor leading to diabetes-related depression, respectively. However, the accurate pathogenesis remains to be unclear. We hypothesized that diabetes-related depression might be associated with the mitophagy-mediated hippocampal neuron apoptosis, triggered by aberrant Glu-glutamate receptor2 (GluR2)-Parkin pathway. To testify this hypothesis, here the rat model of DD in vivo and in vitro were both established so as to uncover the potential mechanism of DD based on mitophagy and apoptosis. We found that DD rats exhibit an elevated glutamate levels followed by monoamine neurotransmitter deficiency and depressive-like behaviour, and DD modelling promoted autophagosome formation and caused mitochondrial impairment, eventually leading to hippocampal neuron apoptosis via aberrant Glu-GluR2-Parkin pathway. Further, in vitro study demonstrated that the simulated DD conditions resulted in an abnormal glutamate and monoamine neurotransmitter levels followed by autophagic flux increment, mitochondrial membrane potential reduction and mitochondrial reactive oxygen species and lactic dehydrogenase elevation. Interestingly, both GluR2 and mammalian target of rapamycin (mTOR) receptor blocker aggravated mitophagy-induced hippocampal neuron apoptosis and abnormal expression of apoptotic protein. In contrast, both GluR2 and mTOR receptor agonist ameliorated those apoptosis in simulated DD conditions. Our findings revealed that mitophagy-mediated hippocampal neuron apoptosis, triggered by aberrant Glu-GluR2-Parkin pathway, is responsible for depressive-like behaviour and monoamine neurotransmitter deficiency in DD rats. This work provides promising molecular targets and strategy for the treatment of DD.

Genotype-by-environment interactions for reproduction, body composition, and growth traits in maternal-line pigs based on single-step genomic reaction norms.

BACKGROUND: There is an increasing need to account for genotype-by-environment (G × E) interactions in livestock breeding programs to improve productivity and animal welfare across environmental and management conditions. This is even more relevant for pigs because selection occurs in high-health nucleus farms, while commercial pigs are raised in more challenging environments. In this study, we used single-step homoscedastic and heteroscedastic genomic reaction norm models (RNM) to evaluate G × E interactions in Large White pigs, including 8686 genotyped animals, for reproduction (total number of piglets born, TNB; total number of piglets born alive, NBA; total number of piglets weaned, NW), growth (weaning weight, WW; off-test weight, OW), and body composition (ultrasound muscle depth, MD; ultrasound backfat thickness, BF) traits. Genetic parameter estimation and single-step genome-wide association studies (ssGWAS) were performed for each trait. RESULTS: The average performance of contemporary groups (CG) was estimated and used as environmental gradient in the reaction norm analyses. We found that the need to consider heterogeneous residual variance in RNM models was trait dependent. Based on estimates of variance components of the RNM slope and of genetic correlations across environmental gradients, G × E interactions clearly existed for TNB and NBA, existed for WW but were of smaller magnitude, and were not detected for NW, OW, MD, and BF. Based on estimates of the genetic variance explained by the markers in sliding genomic windows in ssGWAS, several genomic regions were associated with the RNM slope for TNB, NBA, and WW, indicating specific biological mechanisms underlying environmental sensitivity, and dozens of novel candidate genes were identified. Our results also provided strong evidence that the X chromosome contributed to the intercept and slope of RNM for litter size traits in pigs. CONCLUSIONS: We provide a comprehensive description of G × E interactions in Large White pigs for economically-relevant traits and identified important genomic regions and candidate genes associated with GxE interactions on several autosomes and the X chromosome. Implementation of these findings will contribute to more accurate genomic estimates of breeding values by considering G × E interactions, in order to genetically improve the environmental robustness of maternal-line pigs.

A CT-based technique to predict optimal projection for self-expanding TAVI in patients with different aortic valve anatomies.

BACKGROUND: Optimal projection is essential for valve deployment during transcatheter aortic valve implantation (TAVI). The purpose of this study was to propose an approach to predict optimal projection in TAVI candidates with different aortic valve anatomies. METHODS: 331 patients undergoing self-expanding TAVI were included and the so-called non-coronary cusp (NCC)-parallel technique was utilized, which generated the predicted projection by connecting NCC commissures on the transverse plane on the pre-procedural computed tomography images. RESULTS: 37.8% of the study cohort were bicuspid aortic valve (BAV) patients. Around 80% of both NCC-parallel views and final views were in the right anterior oblique (RAO) and caudal (CAU) quadrant. There was less than 5° change required from the NCC-parallel view to the final implanted view in 79% of tricuspid aortic valve (TAV) patients but only in 27% (13/48) of type 0 BAV patients with coronary arteries originated from the different cusps. After excluding the above mentioned BAV patients, 62.3% (48/77) of BAV patients needed less than 5° change to achieve optimal projection and only in 8 patients, the angular change was larger than 10° in either left/right anterior oblique or cranial/caudal direction. CONCLUSIONS: The NCC-parallel technique provides reliable prediction for optimal projection in self-expanding TAVI in all TAV and most BAV patients, with a vast majority of views in the RAO and CAU quadrant.

Provision of physical activity advice for patients with chronic diseases in Shenzhen, China.

BACKGROUND: Physical activity (PA) may best be promoted to patients during clinical consultations. Few studies investigated the practice of PA advice given by physicians, especially in China. This study aimed to investigate the prevalence and contents of PA advice given by physicians in China and its association with patients' characteristics. METHODS: Face-to-face questionnaire asking the prevalence and contents of PA advice given by physicians was administered to adult patients in three major hospitals in Shenzhen, China. Attitude of compliance, stature, PA level, and socio-demographic information were also collected. Data was analyzed via descriptive statistics and binary logistic regression. RESULTS: Of the 454 eligible patients (Age: 47.0 ± 14.4 years), only 19.2% (n = 87) reported receiving PA advice, whereas 21.8%, 23.0%, 32.2%, and 55.2% of patients received advices on PA frequency, duration, intensity, and type, respectively. Male patients were more likely to receive PA advice from physicians [odds ratio (OR): 1.81; 95% confidence interval (CI): 1.08-3.05], whereas patients who were unemployed (OR: 0.16; 95% CI: 0.04-0.67), and who already achieved adequate amount of PA (OR: 0.29; 95% CI: 0.12-0.71) were less likely to receive PA advice. CONCLUSIONS: Prevalence of physicians providing physical activity advice to patients is low, there is a pressing need to take intervention measures to educate healthcare providers.

Treating patients with excessively large annuli with self-expanding transcatheter aortic valves: insights into supra-annular structures that anchor the prosthesis.

BACKGROUND: Some patients referred for transcatheter aortic valve replacement (TAVR) have excessively large annuli (ELA) without device options according to current sizing charts. This retrospective study aims to summarize the presentation and outcomes of ELA patients receiving first-generation self-expanding valves. METHODS: The TAVR database was reviewed in search for cases of self-expanding valves. Patients who had annuli exceeding the perimeter limit on the device sizing chart were referred to as the ELA group. Patients who had annuli within the range covered by the two largest sizes and received the corresponding valve size served as the control group (CG). Baseline, procedures, outcomes, and imaging characteristics on multislice computed tomography (MSCT), such as native anatomy and postimplant stent geometry, were compared. RESULTS: A total of 28 patients were included in the ELA group and 82 in the CG. The patients in the ELA group were younger than those in the CG (72.5 ± 6.2 vs. 75.4 ± 5.8 years, P = 0.03). The median intended perimeter oversizing in relation to the annulus in the ELA group was much smaller than in the CG (-0.4 [-4.6, 4.1] % vs. 16.1 [11.7, 20.8] %, P < 0.01). The calcium burden in the aortic root was around 1.3-fold greater in the ELA group than the CG (756.0 [534.5, 1670.9] vs. 582.1 [310.3, 870.9] mm3, P = 0.01). The need for second valve implantation was higher in ELA (21.4% vs. 12.2%, P = 0.23) but no valve embolization was encountered. The 1­year follow-up was comparable, including >mild paravalvular leak. CONCLUSION: Under cautious patient selection using MSCT, TAVR with self-expanding valves in patients with ELA appears feasible. Supra-annular structures likely provide the extra anchoring.

[Klinefelter syndrome: Advances in research].

Klinefelter syndrome (KS) is a most common chromosome abnormality and frequently leads to male infertility. In recent years, deeper insights have been gained into the treatment of KS in children, clinical manifestations of KS, as well as reproductive problems and pre- and postnatal screening of the disease. This article presents an overview of the epidemiology, clinical manifestations, pathophysiological mechanism, laboratory examination, drug therapy and application of assisted reproductive technology, and KS screening, aiming to provide some reference for KS-related clinical practice.