Associations of hearing loss and structural changes in specific cortical regions: a Mendelian randomization study.

INTRODUCTION: Previous studies have suggested a correlation between hearing loss (HL) and cortical alterations, but the specific brain regions that may be affected are unknown. METHODS: Genome-wide association study (GWAS) data for 3 subtypes of HL phenotypes, sensorineural hearing loss (SNHL), conductive hearing loss, and mixed hearing loss, were selected as exposures, and GWAS data for brain structure-related traits were selected as outcomes. The inverse variance weighted method was used as the main estimation method. RESULTS: Negative associations were identified between genetically predicted SNHL and brain morphometric indicators (cortical surface area, cortical thickness, or volume of subcortical structures) in specific brain regions, including the bankssts (ß = -0.006 mm, P = 0.016), entorhinal cortex (ß = -4.856 mm2, P = 0.029), and hippocampus (ß = -24.819 cm3, P = 0.045), as well as in brain regions functionally associated with visual perception, including the pericalcarine (ß = -10.009 cm3, P = 0.013). CONCLUSION: Adaptive changes and functional remodeling of brain structures occur in patients with genetically predicted HL. Brain regions functionally associated with auditory perception, visual perception, and memory function are the main brain regions vulnerable in HL.

RF-controlled mode-locking and optoelectronic pulse compressing with distributed selectable wavelengths.

Mode-locking in laser cavities has attracted great interest due to its wide range of applications in generating optical frequency combs and ultra-short pulse trains. Here, a mode-locked fiber laser with a distributed selectable wavelength feedback is proposed based on radio frequency maneuverability. The laser is capable of generating transform-limited pulses with a selectable wavelength and repetition rates by interrogating different reflectors through active modulation. Intriguing laser pulses were realized, which can have >930 times width compression ratio compared with the modulation signal and can be selectively locked to reflectors separated in centimeter scale.

Metabotropic glutamate receptor 5-mediated inhibition of inward-rectifying K+ channel 4.1 contributes to orofacial ectopic mechanical allodynia following inferior alveolar nerve transection in male mice.

Inward-rectifying K+ channel 4.1 (Kir4.1), which regulates the electrophysiological properties of neurons and glia by affecting K+ homeostasis, plays a critical role in neuropathic pain. Metabotropic glutamate receptor 5 (mGluR5) regulates the expression of Kir4.1 in retinal Müller cells. However, the role of Kir4.1 and its expressional regulatory mechanisms underlying orofacial ectopic allodynia remain unclear. This study aimed to investigate the biological roles of Kir4.1 and mGluR5 in the trigeminal ganglion (TG) in orofacial ectopic mechanical allodynia and the role of mGluR5 in Kir4.1 regulation. An animal model of nerve injury was established via inferior alveolar nerve transection (IANX) in male C57BL/6J mice. Behavioral tests indicated that mechanical allodynia in the ipsilateral whisker pad lasted at least 14 days after IANX surgery and was alleviated by the overexpression of Kir4.1 in the TG, as well as intraganglionic injection of an mGluR5 antagonist (MPEP hydrochloride) or a protein kinase C (PKC) inhibitor (chelerythrine chloride); Conditional knockdown of the Kir4.1 gene downregulated mechanical thresholds in the whisker pad. Double immunostaining revealed that Kir4.1 and mGluR5 were co-expressed in satellite glial cells in the TG. IANX downregulated Kir4.1 and upregulated mGluR5 and phosphorylated PKC (p-PKC) in the TG; Inhibition of mGluR5 reversed the changes in Kir4.1 and p-PKC that were induced by IANX; Inhibition of PKC activation reversed the downregulation of Kir4.1 expression caused by IANX (p < .05). In conclusion, activation of mGluR5 in the TG after IANX contributed to orofacial ectopic mechanical allodynia by suppressing Kir4.1 via the PKC signaling pathway.

Characterization of pathogenic synovial IL-17A-producing CD8+ T cell subsets in collagen-induced arthritis.

Using a murine collagen-induced arthritis model, we characterized the heterogeneity of synovial CD8+ T cells based on the expression of chemokine receptors, cytokines, and nuclear transcription factors. Four subsets, i.e. CXCR3-CCR4- cells, CXCR3+CCR4- cells, CXCR3+CCR4+ cells, and CXCR3-CCR4+ cells, were present in synovial CD8+CD62L-CCR6+IL-23R+CCR10- T cells. CXCR3-CCR4- cells belonged to exhausted CD8+ T cells. CXCR3+CCR4- cells were Tc17.1 cells expressing both IL-17A and IFN-γ. CXCR3+CCR4+ cells were transitional Tc17.1 cells expressing IL-17A but lower IFN-γ, and CXCR3-CCR4+ cells were Tc17 cells expressing IL-17A but no IFN-γ. Transitional Tc17.1 cells can differentiate into Tc17.1 cells in vitro under the instruction of IL-12. Tc17.1 cells and transitional Tc17.1 cells strongly induced the expression of pro-inflammatory mediators in synovial fibroblasts, whereas Tc17 cells were less potent in doing so. IFN-γ was involved in the higher pathogenicity of Tc17.1 cells and transitional Tc17.1 cells on synovial fibroblasts. This study expands the understanding of Tc17 biology by unveiling the phenotypic and functional heterogeneity of synovial IL-17A-expressing CD8+ T cells. These heterogeneous IL-17A-expressing CD8+ T cells could be novel therapeutic targets in future arthritis treatment.

Artificial Intelligence-Based Rapid Design of Grease with Chemically Functionalized Graphene and Carbon Nanotubes as Lubrication Additives.

Rapid chemical functionalization of additives and efficient determination of their optimum concentrations are important for designing high-performance lubricants, especially under multi-additive conditions. Herein, chemically functionalized graphene (FGR) and carbon nanotubes (FCNTs) were rapidly prepared by microwave-assisted ball milling and subsequently introduced into grease as additives. The tribological properties of the additives in grease at different concentrations and ratios were measured using a four-ball test. A reliable artificial neural network (ANN) model was established according to a few test results. Subsequently, the optimal concentration of multiple additives in the grease was predicted using a genetic algorithm and experimentally validated. The results indicated that the introduction of FGR (0.14 wt %) and FCNT (0.16 wt %) improved the antifriction and anti-wear performance of the base grease by 25.66 and 29.34%, respectively. The results of the ANN model analysis and friction interface characterization indicate that such performance is principally attributed to the synergistic lubrication of the FGR and FCNT.

Forensic characteristics and genetic substructure analysis of the Handan Han population, Northern China.

We analysed the forensic characteristics and substructure of the Handan Han population based on 36 Y-STR (short tandem repeat) and Y-SNP (single nucleotide polymorphism) markers. The two most dominant haplogroups in Handan Han, O2a2b1a1a1-F8 (17.95%) and O2a2b1a2a1a (21.51%), and their abundant downstream branches, reflected the strong expansion of the precursor of the Hans in Handan. The present results enrich the forensic database and explore the genetic relationships between Handan Han and other neighbouring and/or linguistically close populations, which suggests that the current concise overview of the Han intricate substructure remains oversimplified.

Anti-inflammatory, cardioprotective effect of gypenoside against isoproterenol-induced cardiac remodeling in rats via alteration of inflammation and gut microbiota.

BACKGROUND: Myocardial infarction (MI), commonly referred to as a heart attack, occurs when the blood flow to a portion of the heart is blocked, causing damage to the heart muscle. In this study, we scrutinized the cardioprotective effect of gypenoside against the isoproterenol (ISO)-induced myocardial injury (MI) in the rats. METHODS: Wistar rats were divided into four groups as follow: normal, gypenoside (10 mg/kg), ISO control, and ISO control treated with the gypenoside (2.5, 5, and 10 mg/kg). Various parameters were estimated such as infract size, hemodynamic, inflammatory, antioxidant, cardiac, cytokines, and apoptotic markers. We also estimated the gut microbiota in the faces of the experimental rats. Finally, heart tissue histopathology performed. RESULT: Dose-dependent treatment of gypenoside significantly (P < 0.001) reduced the infracted size along with suppression of the heart weight and heart ratio along with enhance the body weight. Gypenoside treatment considerably altered the level of cardiac parameters, cardiac membrane stabilizing enzyme, hemodynamic parameters, antioxidant, lipid parameters, hepatic parameters, renal parameters, inflammatory cytokines, and mediators. Gypenoside significantly (P < 0.001) suppressed the level of apoptotic markers such as caspase-3, caspase-6, and caspase-9. Gypenoside significantly (P < 0.001) altered the relative abundance of unclassified bacteria, Tenericutes, Candidatus_Saccharibacteria, Verrucomicrobia, Actinobacteria, Bacteroidetes, Firmicutes and suppressed the ratio of F/B. CONCLUSION: Gypenoside acts as a protective phytoconstituents against the ISO-induced myocardial infraction in the rats via alteration of gut microbiota, inflammatory, and oxidative stress.

The Anti-Apoptotic Role of COX-2 during In Vitro Infection of Human Intestinal Cell Line by Giardia duodenalis and the Potential Regulators.

The protozoan parasite Giardia duodenalis inhabits the upper small intestine of mammals, including humans, and causes a disease known as giardiasis, which can lead to diarrhea, abdominal cramps, and bloating. G. duodenalis was known as a causative factor of intestinal epithelial cell (IEC) apoptosis. Cyclooxygenase-2 (COX-2) has been identified as an influencing factor of pathogen infection by participating in immune response, while its role in host defense against Giardia infection is not clear. Here, we initially observed the involvement of COX-2 in the regulation of Giardia-induced IEC apoptosis. Inhibition of COX-2 activity could promote Giardia-induced reduction of IEC viability, increase of reactive oxygen species (ROS) production, and decrease of nitric oxide (NO) release, which would exacerbate IEC apoptosis. In addition, during Giardia-IEC interactions, COX-2 inhibition was able to accelerate caspase-3 activation and poly(ADP-ribose) polymerase (PARP) cleavage and inhibit the expressions of some anti-apoptotic proteins like cIAP-2 and survivin. In contrast, COX-2 overexpression could reduce Giardia-induced IEC apoptosis. We further investigated the regulatory mechanisms affecting COX-2 expression in terms of anti-apoptosis. The results showed that p38/ERK/AKT/NF-κB signaling could regulate COX-2-mediated ROS/NO production and anti-IEC apoptosis during Giardia infection. We also found that COX-2-mediated anti-IEC apoptosis induced by Giardia was related to Toll-like receptor 4 (TLR4)-dependent activation of p38-NF-κB signaling. Collectively, this study identified COX-2 as a promoter for apoptotic resistance during Giardia-IEC interactions and determined the potential regulators, furthering our knowledge of anti-Giardia host defense mechanisms.

Transcriptome-based gene regulatory network analyses of differential cold tolerance of two tobacco cultivars.

BACKGROUND: Cold is one of the main abiotic stresses that severely affect plant growth and development, and crop productivity as well. Transcriptional changes during cold stress have already been intensively studied in various plant species. However, the gene networks involved in the regulation of differential cold tolerance between tobacco varieties with contrasting cold resistance are quite limited. RESULTS: Here, we conducted multiple time-point transcriptomic analyses using Tai tobacco (TT, cold susceptibility) and Yan tobacco (YT, cold resistance) with contrasting cold responses. We identified similar DEGs in both cultivars after comparing with the corresponding control (without cold treatment), which were mainly involved in response to abiotic stimuli, metabolic processes, kinase activities. Through comparison of the two cultivars at each time point, in contrast to TT, YT had higher expression levels of the genes responsible for environmental stresses. By applying Weighted Gene Co-Expression Network Analysis (WGCNA), we identified two main modules: the pink module was similar while the brown module was distinct between the two cultivars. Moreover, we obtained 100 hub genes, including 11 important transcription factors (TFs) potentially involved in cold stress, 3 key TFs in the brown module and 8 key TFs in the pink module. More importantly, according to the genetic regulatory networks (GRNs) between TFs and other genes or TFs by using GENIE3, we identified 3 TFs (ABI3/VP1, ARR-B and WRKY) mainly functioning in differential cold responses between two cultivars, and 3 key TFs (GRAS, AP2-EREBP and C2H2) primarily involved in cold responses. CONCLUSION: Collectively, our study provides valuable resources for transcriptome- based gene network studies of cold responses in tobacco. It helps to reveal how key cold responsive TFs or other genes are regulated through network. It also helps to identify the potential key cold responsive genes for the genetic manipulation of tobacco cultivars with enhanced cold tolerance in the future.

Oral Probiotic Vaccine Expressing Koi Herpesvirus (KHV) ORF81 Protein Delivered by Chitosan-Alginate Capsules Is a Promising Strategy for Mass Oral Vaccination of Carps against KHV Infection.

Koi herpesvirus (KHV) is highly contagious and lethal to cyprinid fish, causing significant economic losses to the carp aquaculture industry, particularly to koi carp breeders. Vaccines delivered through intramuscular needle injection or gene gun are not suitable for mass vaccination of carp. So, the development of cost-effective oral vaccines that are easily applicable at a farm level is highly desirable. In this study, we utilized chitosan-alginate capsules as an oral delivery system for a live probiotic (Lactobacillus rhamnosus) vaccine, pYG-KHV-ORF81/LR CIQ249, expressing KHV ORF81 protein. The tolerance of the encapsulated recombinant Lactobacillus to various digestive environments and the ability of the probiotic strain to colonize the intestine of carp was tested. The immunogenicity and the protective efficacy of the encapsulated probiotic vaccine was evaluated by determining IgM levels, lymphocyte proliferation, expression of immune-related genes, and viral challenge to vaccinated fish. It was clear that the chitosan-alginate capsules protected the probiotic vaccine effectively against extreme digestive environments, and a significant level (P < 0.01) of antigen-specific IgM with KHV-neutralizing activity was detected, which provided a protection rate of ca. 85% for koi carp against KHV challenge. The strategy of using chitosan-alginate capsules to deliver probiotic vaccines is easily applicable for mass oral vaccination of fish.IMPORTANCE An oral probiotic vaccine, pYG-KHV-ORF81/LR CIQ249, encapsulated by chitosan-alginate capsules as an oral delivery system was developed for koi carp against koi herpesvirus (KHV) infection. This encapsulated probiotic vaccine can be protected from various digestive environments and maintain effectively high viability, showing a good tolerance to digestive environments. This encapsulated probiotic vaccine has a good immunogenicity in koi carp via oral vaccination, and a significant level of antigen-specific IgM was effectively induced after oral vaccination, displaying effective KHV-neutralizing activity. This encapsulated probiotic vaccine can provide effective protection for koi carp against KHV challenge, which is handling-stress free for the fish, cost effective, and suitable for the mass oral vaccination of koi carp at a farm level, suggesting a promising vaccine strategy for fish.

Effect of lipoprotein(a) levels on long-term outcome in octogenarians with coronary artery disease after drug-eluting stent implantation.

BACKGROUND: High levels of lipoprotein(a) [Lp(a)] are linked to adverse cardiovascular events. The significance of Lp(a) for the survival of octogenarians with coronary artery disease (CAD) after drug-eluting stent (DES) insertion is, however, not known. The purpose of the study is to investigated the connection between Lp(a) and outcome in octogenarians with CAD after DES implantation. METHODS: We retrospectively enrolled a total of 506 consecutive octogenarians with CAD and DES implantation in our institution between January 2015 to August 2018. Two patient groups were established: a low group with plasma Lp(a) lower than 50 mg/dL (n = 408) and a high group with values above 50 mg/dL (n = 98). RESULTS: After following up for a median of 31.53 ± 8.22 months, Kaplan-Meier curves indicated that poorer outcome censored for major cardiovascular events (MACE), myocardial infarction (MI), and target vessel revascularization (TVR) in the high group relative to the low group (log-rank test p = 0.001, p = 0.008, and p < 0.001, respectively). High Lp(a) independently predicted MACE (hazard ratio (HR) 1.90; 95% confidence interval (CI) 1.28-2.84; p = 0.002), MI (HR 2.74; 95% CI 1.23-6.11; p = 0.014), and TVR (HR 3.65; 95% CI 1.99-6.69; p < 0.001) after covariate adjustment. CONCLUSIONS: High Lp(a) was also significantly related to poor long-term outcome in octogenarians with CAD after DES implantation.

Combined analysis of imaging tumor capsule with imaging tumor size guides the width of resection margin for solitary hepatocellular carcinoma.

BACKGROUND: The optimal width of resection margin (RM) for hepatocellular carcinoma (HCC) remains controversial. This study aimed to investigate the value of imaging tumor capsule (ITC) and imaging tumor size (ITS) in guiding RM width for patients with HCC. METHODS: Patients who underwent hepatectomy for HCC in our center were retrospectively reviewed. ITC (complete/incomplete) and ITS (≤ 3 cm/> 3 cm) were assessed by preoperative magnetic resonance imaging (MRI). Using subgroup analyses based on ITC and ITS, the impact of RM width [narrow RM (< 5 mm)/wide RM (≥ 5 mm)] on recurrence-free survival (RFS), overall survival (OS), and RM recurrence was analyzed. RESULTS: A total of 247 patients with solitary HCC were included. ITC and ITS were independent predictors for RFS and OS in the entire cohort. In patients with ITS ≤ 3 cm, neither ITC nor RM width showed a significant impact on prognosis, and the incidence of RM recurrence was comparable between the narrow RM and wide RM groups (15.6% vs. 4.3%, P = 0.337). In patients with ITS > 3 cm and complete ITC, the narrow RM group exhibited comparable RFS, OS, and incidence of RM recurrence with the wide RM group (P = 0.606, 0.916, and 0.649, respectively). However, in patients with ITS > 3 cm and incomplete ITC, the wide RM group showed better RFS and OS and a lower incidence of RM recurrence compared with the narrow RM group (P = 0.037, 0.018, and 0.046, respectively). CONCLUSIONS: As MRI-based preoperative markers, conjoint analysis of ITC with ITS aids in determining RM width for solitary HCC patients. Narrow RM is applicable in patients with ITS ≤ 3 cm regardless of ITC status and in those with ITS > 3 cm and complete ITC. Wide RM is preferred in those with ITS > 3 cm and incomplete ITC.

ChrNet: A re-trainable chromosome-based 1D convolutional neural network for predicting immune cell types.

Cells from our immune system detect and kill pathogens to protect our body against various diseases. However, current methods for determining cell types have some major limitations, such as being time-consuming and with low throughput, etc. Immune cells that are associated with cancer tissues play a critical role in revealing tumor development. Identifying the immune composition within tumor microenvironment in a timely manner will be helpful in improving clinical prognosis and therapeutic management for cancer. Although unsupervised clustering approaches have been prevailing to process scRNA-seq datasets, their results vary among studies with different input parameters and sizes, and the identification of the cell types of the clusters is still very challenging. Genes in human genome can be aligned to chromosomes with specific orders. Hence, we hypothesize incorporating this information into our learning model will potentially improve the cell type classification performance. In order to utilize gene positional information, we introduced ChrNet, a novel chromosome-specific re-trainable supervised learning method based on one-dimensional convolutional neural network (1D-CNN). By benchmarking with several models, our model shows superior performance in immune cell type profiling with larger than 90% accuracy. It is expected that this approach can become a reference architecture for other cell type classification methods. Our ChrNet tool is available online at: https://github.com/Krisloveless/ChrNet.

Quantifiable Effect of Interparticle Plasmonic Coupling on Sensitivity and Tuning Range for Wavelength-Mode LSPR Fiber Sensor Fabricated by Simple Immobilization Method.

Herein a gold nanosphere (AuNS)-coated wavelength-mode localized surface plasmon resonance (LSPR) fiber sensor was fabricated by a simple and time-saving electrostatic self-assembly method using poly(allylamine hydrochloride). Based on the localized enhanced coupling effect between AuNSs, the LSPR spectrums of the AuNS monolayer with good dispersity and high density exhibited a favourable capability for refractive index (RI) measurement. Based on the results obtained from the optimization for AuNS distribution, sensing length, and RI range, the best RI sensitivity of the fiber modified by 100 nm AuNS reached up to about 2975 nm/RIU, with the surrounding RI range from 1.3322 to 1.3664. Using an 80 nm AuNS-modified fiber sensor, the RI sensitivity of 3953 nm/RIU was achieved, with the RI range increased from 1.3744 to 1.3911. The effect of sensing length to RI sensitivity was proven to be negligible. Furthermore, the linear relationship between the RI sensitivity and plasma resonance frequency of the bulk metal, which was dependent on the interparticle plasmon coupling effect, was quantified. Additionally, the resonance peak was tuned from 539.18 nm to 820.48 nm by different sizes of AuNSs-coated fiber sensors at a RI of 1.3322, which means the spectrum was extended from VIS to NIR. It has enormous potential in hypersensitive biochemistry detection at VIS and NIR ranges.

De novo transcriptome sequencing and anthocyanin metabolite analysis reveals leaf color of Acer pseudosieboldianum in autumn.

BACKGROUND: Leaf color is an important ornamental trait of colored-leaf plants. The change of leaf color is closely related to the synthesis and accumulation of anthocyanins in leaves. Acer pseudosieboldianum is a colored-leaf tree native to Northeastern China, however, there was less knowledge in Acer about anthocyanins biosynthesis and many steps of the pathway remain unknown to date. RESULTS: Anthocyanins metabolite and transcript profiling were conducted using HPLC and ESI-MS/MS system and high-throughput RNA sequencing respectively. The results demonstrated that five anthocyanins were detected in this experiment. It is worth mentioning that Peonidin O-hexoside and Cyanidin 3, 5-O-diglucoside were abundant, especially Cyanidin 3, 5-O-diglucoside displayed significant differences in content change at two periods, meaning it may be play an important role for the final color. Transcriptome identification showed that a total of 67.47 Gb of clean data were obtained from our sequencing results. Functional annotation of unigenes, including comparison with COG and GO databases, yielded 35,316 unigene annotations. 16,521 differentially expressed genes were identified from a statistical analysis of differentially gene expression. The genes related to leaf color formation including PAL, ANS, DFR, F3H were selected. Also, we screened out the regulatory genes such as MYB, bHLH and WD40. Combined with the detection of metabolites, the gene pathways related to anthocyanin synthesis were analyzed. CONCLUSIONS: Cyanidin 3, 5-O-diglucoside played an important role for the final color. The genes related to leaf color formation including PAL, ANS, DFR, F3H and regulatory genes such as MYB, bHLH and WD40 were selected. This study enriched the available transcriptome information for A. pseudosieboldianum and identified a series of differentially expressed genes related to leaf color, which provides valuable information for further study on the genetic mechanism of leaf color expression in A. pseudosieboldianum.

A survey of jaagsiekte sheep retrovirus (JSRV) infection in sheep in the three northeastern provinces of China.

Ovine pulmonary adenomatosis (OPA) is caused by jaagsiekte sheep retrovirus (JSRV) and is a chronic, progressive, and infectious neoplastic lung disease in sheep, which causes significant economic losses to the sheep industry. Neither a vaccine nor serological diagnostic methods to detect OPA are available. We performed a JSRV infection survey in sheep using blood samples (n = 1,372) collected in the three northeastern provinces of China (i.e., Inner Mongolia, Heilongjiang, and Jilin) to determine JSRV infection status in sheep herds using a real-time PCR assay targeting the gag gene of JSRV. The ovine endogenous retrovirus sequence was successfully amplified in all sheep samples tested (296 from the Inner Mongolia Autonomous Region, 255 from Jilin province, and 821 from Heilongjiang province). Subsequently, we attempted to distinguish exogenous JSRV (exJSRV) and endogenous JSRV (enJSRV) infections in these JSRV-positive samples using a combination assay that identifies a ScaI restriction site in an amplified 229-bp fragment of the gag gene of JSRV and a "LHMKYXXM" motif in the cytoplasmic tail region of the JSRV envelope protein. The ScaI restriction site is present in all known oncogenic JSRVs but absent in ovine endogenous retroviruses, while the "LHMKYXXM" motif is in all known exJSRVs but not in enJSRVs. Interestingly, one JSRV strain (HH13) from Heilongjiang province contained the "LHMKYXXM" motif but not the ScaI enzyme site. Phylogenetic analysis showed that strain HH13 was closely related to strain enJSRV-21 reported in the USA, indicating that HH13 could be an exogenous virus. Our results provide valuable information for further research on the genetic evolution and pathogenesis of JSRV.

Associations between hyperhomocysteinemia and the presence and severity of acute coronary syndrome in young adults ≤ 35 years of age.

BACKGROUND: The prevalence of acute coronary syndrome (ACS) continues to increase among young Chinese adults. Homocysteine (HCY) has been suggested as a promoter of atherosclerosis leading to coronary artery disease (CAD). Yet, it remains uncertain whether HCY is associated with the ACS and the severity of coronary artery stenosis in young adults. METHODS: Young patients (18-35 years of age) diagnosed with ACS who underwent coronary angiography (CAG) at Anzhen Hospital between January 2013 and June 2019 were assigned to the ACS group. As confirmed by CAG during the same period, an equivalent age-matched population without CAD was assigned to the non-CAD group. A serum HCY level > 15 µmol/L was defined as hyperhomocysteinemia (HHCY). The Gensini score assessed the severity of coronary artery stenosis. RESULTS: A total of 1103 participants, including 828 ACS patients and 275 non-CAD subjects, were enrolled in this study. Young ACS patients had higher level of serum HCY and greater prevalence of HHCY compared with non-CAD subjects [for HCY, 16.55 (11.93-29.68) vs 12.50 (9.71-17.42), P < 0.001; for HHCY prevalence, 62.08% vs 26.18%, P < 0.001]. Multivariate logistic regression analysis with the stepwise method indicated that HHCY was an independent predictor associated with the presence of ACS, after adjusting for traditional confounders (OR, 4.561; 95% CI, 3.288-6.327; P < 0.001). Moreover, young ACS patients with HHCY had increased prevalence of ST-segment elevation myocardial infarction (STEMI) (P = 0.041), multi-vessel disease (P = 0.036), and decreased value of left ventricular ejection fraction (LVEF) (P = 0.01). Also, the HCY level was significantly correlated with Gensini Score in ACS patients (r = 0.142, P < 0.001). CONCLUSION: HHCY is significantly associated with the presence of ACS and the severity of coronary artery stenosis in young adults ≤ 35 years of age.

Combined effect of hyperhomocysteinemia and smoking on the severity of coronary artery disease in young adults ≤ 35 years of age: a hospital-based observational study.

BACKGROUND: The prevalence of coronary artery disease (CAD) continues to increase among young Chinese adults. Current smoking has been recognized as a major risk factor for premature CAD, and hyperhomocysteinaemia (HHcy) has also been suggested to be associated with CAD progression. However, the combined effect of current smoking and HHcy on the severity of coronary artery stenosis in young adults is still uncertain. METHODS: We consecutively collected young patients (18-35 years of age), diagnosed with CAD and underwent coronary angiography (CAG) at Anzhen Hospital between January 2013 and May 2020. HHcy was defined as serum homocysteine (Hcy) level > 15 µmol/L. The severity of coronary artery stenosis was evaluated by Gensini Score. The co-effect of current smoking and HHcy on CAD severity as well as the relationship between plasma Hcy, pack-years of smoking and CAD severity were assessed by multivariate linear regression analysis. RESULTS: A total of 989 participants (mean age, 33 years; 96.2% male) fulfilling the criteria were enrolled in this study. Patients with both HHcy and current smoking accounted for 39.1% of all the subjects. Multivariate liner analysis indicated both serum Hcy levels (ß 0.302; 95% CI 0.141-0.462; P < 0.001) and pack-years of smoking (ß 0.523; 95% CI 0.265-0.781; P < 0.001) were independently associated with the severity of coronary artery stenosis after adjusting for other traditional confounders. In addition, serum Hcy levels were correlated with pack-years of smoking in young CAD patients (r = 0.116, P = 0.001). Moreover, combination of HHcy and current smoking was suggested to have higher risk for CAD severity (ß 17.892; 95% CI 11.314-24.469; P < 0.001), compared with HHcy (ß 7.471; 95% CI 0.009-14.934; P = 0.048) or current smoking (ß 7.421; 95% CI 0.608-14.233; P = 0.033) alone. CONCLUSION: Combination of HHcy and smoking is independently associated with the severity of CAD in young patients ≤ 35 years of age.

Exploration of interventions to enhance return-to-work for cancer patients: A scoping review.

OBJECTIVE: With the increasing incidence and earlier onset of cancer, more and more cancer patients are facing the problems of return-to-work. This review is to explore the types, contents, and results of return-to-work interventions for cancer patients. METHODS: This scoping review followed Arksey and O'Malley's framework and PRISMA-ScR List. Three Chinese databases and five English databases were searched from the establishment of databases to 31 March, 2021. Article selection and data extraction were conducted by two researchers. RESULTS: Thirty-two studies and 1916 cancer patients with mainly breast and gastrointestinal cancer were included. According to the contents, interventions could be divided into four types: (1) physical interventions (n = 6), including high-intensity exercise, low-to-moderate intensity exercise, yoga, and upper limb functional training, (2) psychological interventions (n = 2), including early active individualized psychosocial support and mindfulness-based recovery, (3) vocational interventions (n = 14), including making work plans, educational leaflets, vocational consultations, electronic health intervention, and interventions targeting at employers, (4) multidisciplinary interventions (n = 10), including any combination of above interventions. Physical exercises, making working plans, vocational consultations, educational leaflets, two combinations of vocational and physical interventions were validated to have positive results in enhancing cancer patients' return-to-work. CONCLUSIONS: Return-to-work interventions for cancer patients are diversified and can be divided into physical, psychological, vocational, and multidisciplinary interventions. Medical staffs can utilize physical exercises, making working plans, vocational consultation, educational leaflets, combinations of vocational and physical interventions to enhance cancer patients' return-to-work. Other interventions still need to be developed and validated.

A novel bHLH transcription factor, NtbHLH1, modulates iron homeostasis in tobacco (Nicotiana tabacum L.).

Iron (Fe) is a major micronutrient which influences plant growth, development, quality and yield. Although basic helix-loop-helix (bHLH) transcription factors (TFs) which respond to iron deficiency have been identified, the molecular mechanisms have not been fully elucidated. In this study, a novel bHLH TF, NtbHLH1, was found to be induced by iron deficiency. Further analysis indicated that NtbHLH1 is localized to the nucleus and functions as a transcriptional activator. Moreover, overexpression of NtbHLH1 resulted in longer roots, altered rhizosphere pH and increased ferric-chelate reductase activity in iron deficient conditions. Overall these changes resulted in increased iron uptake relative to wild type plants. NtbHLH1 mutants, on the other hand, had an opposite phenotype. In addition, transcript levels of seven genes associated with iron deficiency response were higher in the NtbHLH1 overexpression transgenic plants and lower in ntbhlh1 relative to the WT under iron deficiency treatment. Taken together, these results demonstrated that NtbHLH1 plays a key role in iron deficiency response and they provide new insights into the molecular basis of iron homeostasis in tobacco.