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By polymerization of gadolinium methacrylate (Gd (MAA)3), lead methacrylate (Pb(MAA)2) and methyl methacrylate (MMA), Gd and Pb were chemically bonded into polymers. The X-ray shielding performance was evaluated by Monte Carlo simulation method, and the results showed that the more metal functional organic monomer, the better the shielding performance of terpolymers. When the X-ray energy is 65 keV, Gd (MAA)3-containing polymers have better shielding performance than Pb(MAA)2-containing polymers. Gd could compensate for the weak absorption region of Pb. Therefore, polymers containing both Gd and Pb enhanced shielding efficiency against X-ray in various low-energy ranges. For obtaining terpolymers with uniform monomer compositions, the relationship between the monomer composition of the terpolymers and the conversion level was optimized by calculating the reactivity ratios. The value of reactivity ratios of r (Gd (MAA)3/Pb(MAA)2), r (Pb(MAA)2/Gd (MAA)3), r (Gd (MAA)3/MMA), r (MMA/Gd (MAA)3), r (Pb(MAA)2/MMA) and r (MMA/Pb(MAA)2) was 0.483, 0.004, 0.338, 2.508, 0.255, 0.029. The terpolymers with uniform monomer composition could be obtained by controlling the monomer compositions or conversion levels. The results can provide new radiation protection materials and contribute to the improvement in nuclear safety.

Background: The widely divergent responsiveness of Parkinson’s disease (PD) patients to levodopa is an important clinical issue because of its relationship with quality of life and disease prognosis. Preliminary animal experiments have suggested that degeneration of the locus coeruleus (LC) attenuates the efficacy of levodopa treatment. Objective: To explore the relationship between LC degeneration and levodopa responsiveness in PD patients in vivo. Methods: Neuromelanin-sensitive magnetic resonance imaging (NM-MRI), a good indicator of LC and substantia nigra (SN) degeneration, and levodopa challenge tests were conducted in 57 PD patients. Responsiveness to levodopa was evaluated by the rates of change of the Unified Parkinson’s Disease Rating Scale Part III score and somatomotor network synchronization calculated from resting-state functional MRI before and after levodopa administration. Next, we assessed the relationship between the contrast-to-noise ratio of LC (CNRLC) and levodopa responsiveness. Multiple linear regression analysis was conducted to rule out the potential influence of SN degeneration on levodopa responsiveness. Results: A significant positive correlation was found between CNRLC and the motor improvement after levodopa administration (R = 0.421, p = 0.004). CNRLC also correlated with improvement in somatomotor network synchronization (R = –0.323, p = 0.029). Furthermore, the relationship between CNRLC and levodopa responsiveness was independent of SN degeneration. Conclusion: LC degeneration might be an essential factor for levodopa resistance. LC evaluation using NM-MRI might be an alternative tool for predicting levodopa responsiveness and for helping to stratify patients into clinical trials aimed at improving the efficacy of levodopa.

Aims An improved left ventricular ejection fraction (HFiEF) was observed across heart failure (HF) patients with a reduced or mid‐range ejection fraction (HFrEF or HFmrEF, respectively). We postulated that HFiEF patients are clinically distinct from non‐HFiEF patients. Methods and results A total of 447 patients hospitalized due to a clinical diagnosis of HF (LVEF

Glioblastoma (GBM) is a prevalent and highly lethal form of glioma, with rapid tumor progression and frequent recurrence. Excessive outgrowth of pericytes in GBM governs the ecology of the perivascular niche, but their function in mediating chemoresistance has not been fully explored. Herein, we uncovered that pericytes potentiate DNA damage repair (DDR) in GBM cells residing in the perivascular niche, which induces temozolomide (TMZ) chemoresistance. We found that increased pericyte proportion correlates with accelerated tumor recurrence and worse prognosis. Genetic depletion of pericytes in GBM xenografts enhances TMZ-induced cytotoxicity and prolongs survival of tumor-bearing mice. Mechanistically, C-C motif chemokine ligand 5 (CCL5) secreted by pericytes activates C-C motif chemokine receptor 5 (CCR5) on GBM cells to enable DNA-dependent protein kinase catalytic subunit (DNA-PKcs)-mediated DDR upon TMZ treatment. Disrupting CCL5-CCR5 paracrine signaling through the brain-penetrable CCR5 antagonist maraviroc (MVC) potently inhibits pericyte-promoted DDR and effectively improves the chemotherapeutic efficacy of TMZ. GBM patient-derived xenografts with high CCL5 expression benefit from combined treatment with TMZ and MVC. Our study reveals the role of pericytes as an extrinsic stimulator potentiating DDR signaling in GBM cells and suggests that targeting CCL5-CCR5 signaling could be an effective therapeutic strategy to improve chemotherapeutic efficacy against GBM.

To explore the microstructural alterations in subcortical nuclei in Parkinson's disease (PD) at different stages with diffusion kurtosis imaging (DKI) and tensor imaging and to test the performance of diffusion metrics in identifying PD.108 PD patients (64 patients in early-stage PD group (EPD) and 44 patients in moderate-late-stage PD group (MLPD)) and 64 healthy controls (HC) were included. Tensor and kurtosis metrics in the subcortical nuclei were compared. Partial correlation was used to correlate the diffusion metrics and Unified Parkinson's Disease Rating Scale part-III (UPDRS-III) score. Logistic regression and receiver operating characteristic analysis were applied to test the diagnostic performance of the diffusion metrics.Compared with HC, both EPD and MLPD patients showed higher fractional anisotropy and axial diffusivity, lower mean kurtosis (MK) and axial kurtosis in substantia nigra, lower MK and radial kurtosis (RK) in globus pallidus (GP) and thalamus (all p 0.05). Compared with EPD, MLPD patients showed lower MK and RK in GP and thalamus (all p 0.05). MK and RK in GP and thalamus were negatively correlated with UPDRS-III score (all p 0.01). The logistic regression model combining kurtosis and tensor metrics showed the best performance in diagnosing PD, EPD, and MLPD (areas under curve were 0.817, 0.769, and 0.914, respectively).PD has progressive microstructural alterations in the subcortical nuclei. DKI is sensitive to detect microstructural alterations in GP and thalamus during PD progression. Combining kurtosis and tensor metrics can achieve a good performance in diagnosing PD.

Related to ABI3/VP1 (RAV) transcription factors play important roles in regulating plant growth and stress tolerance, which have been studied in many plant species, but have remained largely unidentified in legumes. To functionally characterize RAV in legumes, MtRAV3 from legume model plant Medicago truncatula was isolated and its function was investigated by overexpressing MtRAV3 in M. truncatula. Expression analysis demonstrated that MtRAV3 was markedly induced by NaCl and polyethylene glycol (PEG). MtRAV3 overexpression enhanced tolerance of transgenic M. truncatula to mannitol, drought and salt stresses, and induced the expression of adversity-related genes, including MtWRKY76, MtMYB61, cold-acclimation specific protein 31 (MtCAS31), alternative oxidase 1 (MtAOX1) and ethylene response factor 1 (MtERF1). There were lower relative electrolyte leakage and higher chlorophyll content of leaves in the MtRAV3 overexpression plants than in wild type plants under both salt and drought stress. MtRAV3 overexpression M. truncatula were featured by some phenotypes of dwarfing, late flowering, more branches, smaller flower and leaf organs. Further investigations showed that the expression levels of DWARF14 (MtD14), CAROTENOID CLEAVAGE DIOXYGENASES 7 (MtCCD7) and GA3-oxidase1 (MtGA3ox1), which related to dwarf and branch phenotype, were obviously reduced, as well as MtGA3ox1' (MTR_1g011580), GA20-oxidase1 (MtGA20ox1), MtGA20ox1' (MTR_1g102070) and GA20-oxidase2 (MtGA20ox2) involved in gibberellins (GAs) pathway. Overall, our results revealed that MtRAV3 exerted an important role in adversity response and plant growth, was a multifunctional gene in M. truncatula, which provided reference for genetic improvement of alfalfa (Medicago sativa).

Introduction and hypothesis Pelvic organ prolapse (POP) is a common condition in older women that affects quality of life. Mechanical injury of the pelvic floor support system contributes to POP development. In our study, we aimed to examine the mechanical damage to human uterosacral ligament fibroblasts (hUSLFs) to preliminarily explore the mechanism of mechanical transduction in POP. Methods hUSLFs were derived from POP and non-POP patients. Mechanical stress was induced by the FX-5000 T-cell stress loading system. Student’s t-test was used for comparisons between different groups. Results We found that hUSLFs from POP patients were larger and longer than those from non-POP patients and exhibited cytoskeleton F-actin rearrangement. Collagen I and III expression levels were lower and matrix metalloproteinase 1 (MMP1) levels were higher in POP patients than in non-POP patients. Additionally, the apoptosis rate was significantly increased in POP patients compared to non-POP patients. After mechanical stretching, hUSLFs underwent a POP-like transformation. Cells became longer, and the cytoskeleton became thicker and rearranged. The extracellular matrix (ECM) was remodelled because of the upregulation of collagen I and III expression and downregulation of MMP1 expression. Mechanical stress also induced hUSLF apoptosis. Notably, we found that the p38 MAPK pathway was activated by mechanical stretching. Conclusions Mechanical stress induced morphological changes in ligament fibroblasts, leading to cytoskeleton and ECM remodelling and cell apoptosis. p38 MAPK might be involved in this process, providing novel insights into the mechanical biology of and possible therapies for this disease.

BACKGROUND Excessive iron accumulation is one of the main pathogeneses of Parkinson's disease (PD). Ceruloplasmin plays an important role in keeping the iron homoeostasis. PURPOSE To explore the association between serum ceruloplasmin depletion and subcortical iron distribution in PD. STUDY TYPE Prospective. POPULATION One hundred and twenty-one normal controls, 34 PD patients with low serum ceruloplasmin (PD-LC), and 28 patients with normal serum ceruloplasmin (PD-NC). SEQUENCE Enhanced susceptibility-weighted angiography (ESWAN) on a 3 T scanner. ASSESSMENT Quantitative susceptibility mapping was employed to quantify the regional iron content by using a semi-automatic method. Serum ceruloplasmin concentration was measured from peripheral blood sample. Clinical assessments were conducted by a neurologist. STATISTICAL TESTS General linear model was used to compare the intergroup difference of region iron distribution among groups, and the statistics was adjusted by Bonferroni method (P

Upon infection of hepatocyte, Hepatitis B virus (HBV) genomic DNA in nucleocapsid is transported into the nucleus and converted into a covalently closed circular (ccc) DNA to serve as the template for transcription of viral RNAs. Viral DNA in the cytoplasmic progeny nucleocapsid is another resource to fuel cccDNA amplification. Apparently, nucleocapsid disassembly, or viral genomic DNA uncoating, is an essential step for cccDNA synthesis from both de novo infection and intracellular amplification pathways, and has a potential to activate DNA sensors and induce an innate immune response in infected hepatocytes. However, where and how the nucleocapsid disassembly occurs is not well understood. The work reported herein showed that the enhanced disassembly of progeny mature nucleocapsids in the cytoplasm supported cccDNA intracellular amplification, but failed to activate the cGAS-STING-mediated innate immune response in hepatocytes. Interestingly, while expression of a cytoplasmic exonuclease TREX1 in human hepatoma cells supporting HBV replication significantly reduced the amounts of cccDNA as well as its precursor, deproteinized relaxed circular (rc) DNA, expression of TREX1 in sodium taurocholate cotransporting polypeptide-expressing human hepatoma cells did not inhibit cccDNA synthesis from de novo HBV infection. The results from this cytoplasmic nuclease protection assay imply that the disassembly of progeny mature nucleocapsids and removal of viral DNA polymerase covalently linked to the 5′ end of minus strand of rcDNA take place in the cytoplasm. On the contrary, the disassembly of virion-derived nucleocapsids during de novo infection may occur at a different subcellular compartment and possibly via distinct mechanisms.

Long-term use of a unilateral cochlear implant (CI) may lead to abnormal development of contralateral auditory pathway.To investigate the usefulness of measuring the electrically evoked auditory brainstem response (eABR) with the electrical stimulation at the round window membrane and the effect of unilateral CI use on the contralateral auditory pathway functions.According to duration of unilateral CI use, 45 children with severe or profound sensorineural hearing loss were divided into sCI (≤12 months), lCI (≥24 months) and nCI (no CI use) groups. Intra-operative eABRs evoked by electrical stimulation at the round window membrane were recorded.The latencies of eIII and eV were significantly longer in lCI group than in sCI group and in nCI group, respectively, but not significantly different between sCI group and nCI group. The eABR thresholds and eIII-eV latency intervals were not significantly different among three groups.The eABR evoked by the electrical stimulation at the round window membrane is a reliable and effective way of evaluating functions of the auditory pathway in deaf children. Long-term use of a unilateral CI may promote the degenerative process of the contralateral auditory pathway to the level of the brainstem.

Early seedling vigor (ESV) is a major breeding target in rice, especially under direct seeding. To identify quantitative trait locus (QTL) affecting ESV, a recombinant inbred line population derived from a cross between 02428 and YZX, two cultivars differing in vigor during early seedling growth, was used for QTL analysis. Nine traits associated with ESV were examined using a high-density map. Of 16 additive loci identified, three were detected in two generations and thus considered stable. Four epistatic interactions were detected, one of which was repeated in two generations. Further analysis of the pyramiding effect of the three stable QTL showed that the phenotypic value could be effectively improved with an increasing number of QTL. These results were combined with results from our previous QTL analysis of the germination index. The lines G58 and G182 combined all the favourable alleles of all three stable QTL for ESV and three QTL for germination speed. These two lines showed rapid germination and strong ESV. A total of 37 candidate differentially expressed genes were obtained from the regions of the three stable QTL by analysis of the dynamic transcriptomic expression profile during the seedling growth period of the two parents. The QTL are targets for ESV breeding and the candidate genes await functional validation. This study provides a theoretical basis and a genetic resource for the breeding of direct-seeded rice.

The differential diagnosis of immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) and cholangiocarcinoma (CC) remains a clinical challenge. Imaging modalities play critical roles in the diagnosis of IgG4-SC. The present study aimed to evaluate the differential diagnosis of IgG4-SC and CC based on images of endoscopic ultrasound (EUS). The biliary inflammation scoring (BIS) method for EUS was developed based on the comparison between images of IgG4-SC and that of cholangiocarcinoma (CC) and other acute or chronic cholangitis. In the BIS diagnostic phase, the EUS images from 66 IgG4-SC patients and 44 CC patients were blindly evaluated using the BIS methods. The sensitivity, specificity, and accuracy of the newly established BIS in distinguishing IgG4-SC from CC were 86% [95% confidence interval (CI) 75–93%], 95% (95% CI 83–99%), and 90% (95% CI 83–94%), respectively. EUS should be considered to be added to the workup algorithm in patients with suspected IgG4-SC as a useful diagnostic procedure. BIS is a promising diagnostic method to discriminate IgG4-SC during the ongoing endoscopy.

Objective To investigate the outcomes of humeral head replacement in the treatment of patients with comminuted proximal humeral fracture. Methods Between February 2013 and September 2016, 56 patients underwent humeral head replacement in our hospital. Of them, 18 cases were diagnosed as comminuted proximal humeral fracture before the operation. The mean age of the patients was 69.5 years old (ranging from 61 to 79 years old). Of them, there were six males and 12 females. All the patients in this group had fresh fractures. They were all treated by artificial humeral head replacements. After the prosthesis was fixed by bone cement reliably, the greater or lesser trochanter and prosthesis handle were sutured and fixed firmly. The interval time from injury to operation ranged from 1 to 5 days. The Constant Functional Score, operation time, blood loss, nerve injury, joint dislocation rate, and infection rate were recorded at the final follow-up. The clinical data of these patients were retrospectively studied. All of the data were recorded in average form. Results In this study, the mean duration of follow-up was 4 years, ranging from 3 to 6 years. The operation time ranged from 75 to 120 min, with the average of 82 min. The blood loss ranged from 100 to 400 mL, with the average of 210 mL. The mean score of Constant Functional Score was 83.5 ± 3.1. Of them, 14 cases achieved excellent and good (scores of more than 80), and four cases achieved moderate and poor (scores of less than 80). No patient suffered from joint dislocation, unstable joint, or infection after the operation. There were two patients with axillary nerve injury before the operation. However, the function could be recovered within 3-6 weeks after the surgery. Conclusion The artificial humeral head replacement could be applied for the treatment of patients with comminuted proximal humeral fracture. During the surgery process, the stable structure of shoulder joint could be completely restructured, and the rehabilitation plan should be adjusted reasonably and timely after the operation.

As an anthracycline antibiotic, doxorubicin (DOX) is one of the most potent and widely used chemotherapeutic agents for treating various types of tumors. Unfortunately, the clinical application of this drug results in severe side effects, particularly dose-dependent cardiotoxicity. There are multiple mechanisms involved with the cardiotoxicity caused by DOX, among which intracellular iron homeostasis plays an essential role based on a recent discovery. In this mini-review, we summarize the clinical features and symptoms of DOX-dependent cardiotoxicity, discuss the correlation between iron and cardiotoxicity, and highlight the involvement of iron-dependent ferroptotic cell death therein. Recent advances in this topic will aid the development of novel DOX delivery systems with reduced adverse effects, and expand the clinical application of anthracycline.

Objective. To estimate the relationship between obesity (defined by both BMI and SAD) and various levels of depressive symptoms in women in the United States. Methods. This is a cross-sectional design. All data were collected from NHANES 2011-2012 and 2013-2014. The Patient Health Questionnaire (PHQ-9) was the primary variable used to index depressive symptoms. SAD was assessed using an abdominal caliper. We stratified participates into three groups according to SAD (trisection): T1: low (11.8-18.4 cm), T2: middle (18.5-22.8 cm), and T3: high (22.9-40.1 cm). Other data were collected following the NHANES protocols. We aimed to investigate the effects of obesity on the depression in the NHANES populations. Results. A total of 4477 women were enrolled in the final study population. Participants with a high SAD had the highest risk of clinical depression symptoms ( OR = 1.2 , 95% CI: 1.1-1.4), which was, in particular, the case for moderate-severe depression ( OR = 1.4 , 95% CI: 1.1-1.7) and severe depression ( OR = 1.4 , 95% CI: 1.0-1.9). We also found a significant relationship between SAD and BMI ( r = 0.836 ). We did, however, not find a significant relationship between BMI and severe depression. Conclusions. SAD had a better correlation with clinical depression symptoms than BMI, especially regarding severe depression symptoms.

We describe 4 cases of Chlamydia psittaci pneumonia among medical staff in a coronavirus disease 2019 (COVID-19) screening ward, as well as the experience of dealing with this nosocomial infection event. Atypical pneumonia, in addition to COVID-19, should be considered when clustering cases occur, even during a COVID-19 pneumonia pandemic.

BACKGROUND: Epigenome-wide association studies identified the cg00574958 DNA methylation site at the carnitine palmitoyltransferase-1A (CPT1A) gene to be associated with reduced risk of metabolic diseases (hypertriglyceridemia, obesity, type 2 diabetes, hypertension, metabolic syndrome), but the mechanism underlying these associations is unknown. OBJECTIVES: We aimed to elucidate whether carbohydrate and fat intakes modulate cg00574958 methylation and the risk of metabolic diseases. METHODS: We examined associations between carbohydrate (CHO) and fat (FAT) intake, as percentages of total diet energy, and the CHO/FAT ratio with CPT1A-cg00574958, and the risk of metabolic diseases in 3 populations (Genetics of Lipid Lowering Drugs and Diet Network, n = 978; Framingham Heart Study, n = 2331; and REgistre GIroní del COR study, n = 645) while adjusting for confounding factors. To understand possible causal effects of dietary intake on the risk of metabolic diseases, we performed meta-analysis, CPT1A transcription analysis, and mediation analysis with CHO and FAT intakes as exposures and cg00574958 methylation as the mediator. RESULTS: We confirmed strong associations of cg00574958 methylation with metabolic phenotypes (BMI, triglyceride, glucose) and diseases in all 3 populations. Our results showed that CHO intake and CHO/FAT ratio were positively associated with cg00574958 methylation, whereas FAT intake was negatively correlated with cg00574958 methylation. Meta-analysis further confirmed this strong correlation, with β = 58.4 ± 7.27, P = 8.98 x 10(-16) for CHO intake; β = −36.4 ± 5.95, P = 9.96 x 10(-10) for FAT intake; and β = 3.30 ± 0.49, P = 1.48 x 10(-11) for the CHO/FAT ratio. Furthermore, CPT1A mRNA expression was negatively associated with CHO intake, and positively associated with FAT intake, and metabolic phenotypes. Mediation analysis supports the hypothesis that CHO intake induces CPT1A methylation, hence reducing the risk of metabolic diseases, whereas FAT intake inhibits CPT1A methylation, thereby increasing the risk of metabolic diseases. CONCLUSIONS: Our results suggest that the proportion of total energy supplied by CHO and FAT can have a causal effect on the risk of metabolic diseases via the epigenetic status of CPT1A. Study registration at https://www.clinicaltrials.gov/: the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN)—NCT01023750; and the Framingham Heart Study (FHS)—NCT00005121.

The ligament of Marshall (LOM) is a remnant of the embryonic sinus venosus and left cardinal vein and contains fat and fibrous tissues, blood vessels, muscle bundles, nerve fibers and ganglia. The complexity of LOM's structure makes it as a source of triggers and drivers as well as substrates of reentry for atrial arrhythmias, especially for atrial fibrillation (AF). LOM also serves as a portion of left atrial macro-reentrant circuit, especially peri-mitral isthmus reentrant circuit. Experimental studies demonstrate that the LOM acts as a sympathetic conduit between the left stellate ganglion and the ventricles and participates in the initiation and maintenance of ventricular arrhythmias. Endocardial or epicardial catheter ablation or ethanol infusion into the vein of Marshall may serve as an important adjunct therapy to pulmonary vein isolation in patients with advanced stage of AF and may help alleviate ventricular arrhythmias as well. This article is protected by copyright. All rights reserved.

The significance of the polypeptide N-acetyl-galactosaminyl transferase-3 (GalNAc-T3) and mucin 1 (MUC1) in solitary pulmonary adenocarcinoma (SPA) initially diagnosed as malignant solitary pulmonary nodule (≤ 3 cm), especially as a combined predictor of prognosis and recurrence, was explored in this study. A retrospective analysis of 83 patients with SPA (≤ 3 cm), which revealed postoperative pathological diagnosis was lung adenocarcinoma after complete resection. Immunohistochemical staining was used to detect the expression of GalNAc-T3 and MUC1 in primary tumor specimens. The relationship between expression and various clinicopathological factors was analyzed, as well as the effects of patients' overall survival (OS) and disease-free survival (DFS). In all patients, GalNAc-T3 was highly expressed in 53 (63.9%) cases; MUC1 was highly expressed in 31 (37.3%) cases. The GalNAc-T3 expression was correlated with differentiation, pathological risk group, N stage, and TNM stage. The group with high GalNAc-T3 expression and low MUC1 expression (GalNAc-T3Hig/MUC1Low) is correlated to pathological differentiation and has a trend related to the TNM stage. The patients with better differentiation, lower pathological risk group, lower N stage, and GalNAc-T3 high expression had better overall survival, especially the GalNAc-T3Hig/MUC1Low group. Moreover, the moderate differentiation, N3 stage, and GalNAc-T3Hig/MUC1Low group were independent predictive factors for OS. Besides, patients with lower N stage, lower TNM stage, higher GalNAc-T3 expression got better disease-free survival (DFS), especially the GalNAc-T3Hig/MUC1Low group. The GalNAc-T3Hig/MUC1Low group was an independent predictive factor for DFS. In conclusion, GalNAc-T3 and MUC1 were combined predictors of prognosis and recurrence in SPA (≤ 3 cm).

Background Seed germination and young seedling growth are important agricultural traits for developing populations of both irrigated and directly seeded rice. Previous studies have focused on the identification of QTLs. However, there are few studies on the metabolome or transcriptome of germination and young seedling growth in rice. Results Here, an indica rice and a japonica rice were used as materials, and the transcripts and metabolites were detected during the germination and young seedling growth periods on a large scale by using RNA sequencing and a widely targeted metabolomics method, respectively. Fourteen shared transcripts and 15 shared metabolites that were continuously differentially expressed in the two materials were identified and may be essential for seed germination and young seedling growth. Enrichment analysis of differentially expressed genes in transcriptome expression profiles at different stages indicated that cell wall metabolism, lipid metabolism, nucleotide degradation, amino acid, etc., were enriched at 0–2 days, and most of the results are consistent with those of previous reports. Specifically, phenylpropanoid biosynthesis and glutathione metabolism were continuously enriched during the seed germination and young seedling growth stages. Next, KO enrichment analysis was conducted by using the differentially expressed genes of the two materials at 2, 3 and 4 days. Fourteen pathways were enriched. Additionally, 44 differentially expressed metabolites at 2, 3 and 4 days were identified. These metabolites may be responsible for the differences in germination and young seedling growth between the two materials. Further attention was focused on the ascorbate–glutathione pathway, and it was found that differences in ROS-scavenging abilities mediated by some APX, GPX and GST genes may be directly involved in mediating differences in the germination and young seedling growth speed of the two materials. Conclusions In summary, these results may enhance the understanding of the overall mechanism of seed germination and young seedling growth, and the outcome of this study is expected to facilitate rice breeding for direct seeding.

This study aimed to compare the expression levels of extracellular matrix (ECM) and apoptosis proteins in the uterosacral ligament (USL) of patients with and without pelvic organ prolapse (POP). The USL were obtained from patients with POP-Q ≥ III (n = 35) and without POP (n = 20). Immunohistochemistry (IHC) staining and RT-qPCR were conducted to assess the protein and mRNA levels, respectively. The levels of type I collagen (COLI), type III collagen (COLIII), matrix metalloproteinase (MMP)1, MMP2, MMP9, tissue inhibitor of metalloproteinase (TIMP)1, TIMP2, estrogen receptor (ER)α, ERβ and apoptosis-related gene B cell lymphoma 2 (Bcl-2)-associated agonist of cell death (Bad) and Bcl-2-associated X (Bax) in the USL were analyzed. The protein expression and mRNA levels of MMP2 and MMP9, mRNA levels of BAD and BAX, and protein expression of active cleaved-Caspase3 were significantly higher in the POP group. There were no evident differences in COLIII, MMP1 or ERβ expression at either the mRNA or protein level or in TIMP1, TIMP2 or Caspase3 by IHC between the two groups. However, obvious decreases in COLI and ERα were evident at both the mRNA and protein levels in the POP group, and the mRNA levels of TIMP1 and TIMP2 were also decreased compared to those of the control group. ECM in the USL tissues of POP patients is remodeled compared with non-POP patients and is characterized by decreased synthesis and increased degradation of collagen; moreover, the levels of the main proteins involved in apoptosis are increased in POP tissue.

Background: Histological heterogeneity of lung adenocarcinoma may result in different prognosis among patients with the same TNM pathological stage. However, no objective evaluation system of lung adenocarcinoma based on pathological features has been widely accepted for assessing the prognosis. Methods: We retrospectively analyzed 179 patients with stage I lung adenocarcinoma after complete surgical resection. The pathological classification was according to the IASLC/ATS/ERS adenocarcinoma classifications, and the detailed abundance ratio using HE staining of primary tumor specimens was recorded. A new additional scoring formula on the pathological features (ASP) was established. The association of the ASP score with the patients' survival was examined. Results: The ASP scoring was significantly associated with smoking history (p=0.004), lymphatic vessel invasion (p

Parkinson's disease (PD) is characterized by complex clinical symptoms, including classic motor and nonmotor disturbances. Patients with PD vary in clinical manifestations and prognosis, which point to the existence of subtypes. This study aimed to find the fiber connectivity correlations with several crucial clinical symptoms and identify PD subtypes using unsupervised clustering analysis. One hundred and thirty‐four PD patients and 77 normal controls were enrolled. Canonical correlation analysis (CCA) was performed to define the clinically relevant connectivity features, which were then used in the hierarchical clustering analysis to identify the distinct subtypes of PD patients. Multimodal neuroimaging analyses were further used to explore the neurophysiological basis of these subtypes. The methodology was validated in an independent data set. CCA revealed two significant clinically relevant patterns (motor‐related pattern and depression‐related pattern; r = .94, p, Parkinson's disease (PD) is a heterogeneous syndrome, which points to the subtypes in PD patients. This study used a data‐driven approach based on fiber connectivity to automatically identify subtypes in PD patients with distinct clinical features. Neuroimaging analyses revealed significant brain alterations behind each subtype.

BACKGROUND This study aimed to identify factors associated with antibiotic-associated diarrhea (AAD) in patients in the department of intensive care medicine who received antibiotic monotherapy in order to reduce the incidence of AAD and improve rational use of antibiotics in these patients. AIM To report the incidence of AAD and the factors associated with AAD in patients receiving antibiotic monotherapy. METHODS The study used a single-center retrospective design. A total of 209 patients were enrolled. Patients were divided into two groups: No-AAD group (without AAD) and AAD group (with AAD). There were 45 cases in the AAD group and 164 cases in the no-AAD group. Clinical data of all patients were collected. Data were analyzed using SPSS (version 18.0), and statistical significance was set at P < 0.05. RESULTS The overall incidence of AAD was 21.53%. Age [odds ratio (OR) 1.022, 95% confidence interval (CI): 1.001-1.044, P = 0.040], proton pump inhibitor usage time (OR 1.129, 95%CI: 1.020-1.249, P = 0.019), antibiotic usage time (OR 1.163, 95%CI: 1.024-1.320, P = 0.020), and intensive care unit (ICU) stay time (OR 1.133, 95%CI: 1.041-1.234, P = 0.004) were associated with AAD in ICU patients receiving antibiotic monotherapy. mean ± SD ICU stay time was lower in the no-AAD group (8.49 ± 6.31 vs 15.89 ± 10.69, P < 0.001). However, there was no significant difference in ICU-related mortality rates between the two groups (P = 0.729). CONCLUSION Older age, longer ICU stay time, duration of use of proton pump inhibitors, and duration of antibiotic increase the incidence of AAD in ICU patients receiving antibiotic monotherapy.

Tumor‐immune crosstalk within the tumor microenvironment (TME) occurs at all stages of tumorigenesis. Tumor‐associated M2 macrophages play a central role in tumor development, but the molecular underpinnings have not been fully elucidated. We demonstrated that M2 macrophages produce interleukin 1β (IL‐1β), which activates phosphorylation of the glycolytic enzyme glycerol‐3‐phosphate dehydrogenase (GPD2) at threonine 10 (GPD2 pT10) through phosphatidylinositol‐3‐kinase‐mediated activation of protein kinase‐delta (PKCδ) in glioma cells. GPD2 pT10 enhanced its substrate affinity and increased the catalytic rate of glycolysis in glioma cells. Inhibiting PKCδ or GPD2 pT10 in glioma cells or blocking IL‐1β generated by macrophages attenuated the glycolytic rate and proliferation of glioma cells. Furthermore, human glioblastoma tumor GPD2 pT10 levels were positively correlated with tumor p‐PKCδ and IL‐1β levels as well as intratumoral macrophage recruitment, tumor grade and human glioblastoma patient survival. These results reveal a novel tumorigenic role for M2 macrophages in the TME. In addition, these findings suggest possible treatment strategies for glioma patients through blockade of cytokine crosstalk between M2 macrophages and glioma cells., Tumor‐associated macrophages regulate glioma cell glycolysis through GPD2. GPD2 pT10 correlates with grades and prognosis in glioblastoma patients.

Reverse transcriptase (RT) enzymes are indispensable tools for interrogating diverse aspects of RNA metabolism and transcriptome composition. Due to the growing interest in sequence and structural complexity of long RNA molecules, processive RT enzymes are now required for preserving linkage and information content in mixed populations of transcripts, and the low-processivity RT enzymes that are commercially available cannot meet this need. MarathonRT is encoded within a eubacterial group II intron, and it has been shown to efficiently copy highly structured long RNA molecules in a single pass. In this work, we systematically characterize MarathonRT as a tool enzyme and optimize its performance in a variety of applications that include single-cycle reverse transcription of long RNAs, dimethyl sulfate mutational profiling (DMS-MaP), selective 2′-hydroxyl acylation analyzed by primer extension and mutational profiling (SHAPE-MaP), using ultra-long amplicons and the detection of natural RNA base modifications. By diversifying MarathonRT reaction protocols, we provide an upgraded suite of tools for cutting-edge RNA research and clinical application.

It is essential to develop new carriers for laryngeal drug delivery in light of the lack of therapy in laryngeal related diseases. When the inhalable micron-sized crystals of γ-cyclodextrin metal-organic framework (CD-MOF) was utilized as dry powder inhalers (DPIs) carrier with high fine particle fraction (FPF), it was found in this research that the encapsulation of a glycoside compound, namely, scutellarin (SCU) in CD-MOF could significantly enhance its laryngeal deposition. Firstly, SCU loading into CD-MOF was optimized by incubation. Then, a series of characterizations were carried out to elucidate the mechanisms of drug loading. Finally, the laryngeal deposition rate of CD-MOF was 57.72 ± 2.19% improved by SCU, about two times higher than that of CD-MOF, when it was determined by Next Generation Impactor (NGI) at 65 L/min. As a proof of concept, pharyngolaryngitis therapeutic agent dexamethasone (DEX) had improved laryngeal deposition after being co-encapsulated with SCU in CD-MOF. The molecular simulation demonstrated the configuration of SCU in CD-MOF and its contribution to the free energy of the SCU@CD-MOF, which defined the enhanced laryngeal anchoring. In conclusion, the glycosides-like SCU could effectively enhance the anchoring of CD-MOF particles to the larynx to facilitate the treatment of laryngeal diseases., Graphical abstract Glycoside scutellarin enhanced inhalable γ-cyclodextrin metal-organic framework particles anchoring in larynx. As a proof-of-concept, dexamethasone co-delivered with scutellarin (SCU) had enhanced laryngeal deposition. Laryngeal deposition of dried powders was evaluated using the Next Generation Pharmaceutical Impactor. Molecular simulation revealed the scutellarin incorporation in CD-MOF and its effect to the surface properties.Image 1

N-Glycosylation, one of the most prominent and abundant protein post-translational modifications in eukaryotic cells, is involved in diverse biological processes. To date, large-scale profiling of the N-glycoproteome has been only reported in rice germinating embryos, but that in rice leaves has not been profiled. Here, we report the first rice N-glycoproteome in leaves, determined by combining Concanavalin A (ConA) lectin affinity chromatography enrichment and high-resolution LC–MS/MS. In total, 282 N-glycopeptides, corresponding to 556 proteins and 643 sites, were identified from the leaves of H4 (indica) and LTH (japonica). Two conserved canonical N-glycosylation motifs N-X-T and N-X-S and two more non-canonical motifs N-X-S-X-N and A-X-X-N-X-S were revealed in rice. More than 50% of the identified proteins are localized to the chloroplast, extracellular part, and plasma membrane. Bioinformatics analysis revealed that N-glycosylation occurs on proteins involved in a wide variety of biological processes, especially photosynthesis and carbon metabolism. Protein–protein interaction networks of these proteins provided further evidence that N-glycosylation contributes to a wide range of regulatory functions. In summary, these findings revealed the complexity of the rice N-glycoproteome and provided useful information to further explore the regulatory roles of N-glycosylation in the growth, development, and stress responses of rice.

Seasonal estrus is a key factor limiting animal fertility, and understanding the molecular mechanisms that regulate animal estrus is important for improving animal fertility. The pituitary gland, which is the most important endocrine gland in mammals, plays an important role in regulating the physiological processes such as growth, development, and reproduction of animals. Here, we used RNA-seq technology to study the expression profile of lncRNAs in the anterior pituitary of sheep during estrus and anestrus. In this study, we identified a total of 995 lncRNAs, of which 335 lncRNAs were differentially expressed in two states (including 38 up-regulated and 297 down-regulated lncRNAs). RT-qPCR verified the expression levels of several lncRNAs. Target predictive analysis revealed that these lncRNAs can act in cis or trans and regulate the expression of genes involved in the regulation of sheep estrus. Target gene enrichment analysis of differentially expressed lncRNAs indicates that these lncRNAs can regulate sheep estrus by regulating hormone metabolism and energy metabolism. Through our research, we provide the expression profile of lncRNAs in the pituitary of sheep, which provides a valuable resource for further understanding of the genetic regulation of seasonal estrus in sheep from the perspective of lncRNAs.

Background/Aims: Congenital heart disease (CHD) is one of the most common and severe congenital defects. The incidence of fetal cardiac malformation is increased in the context of maternal gestational diabetes mellitus (GDM). Therefore, we wanted to determine whether abnormalities in the insulin signaling pathway are associated with the occurrence of nonsyndromic CHD (ns-CHD). Methods: We used digital gene expression profiling (DGE) of right atrial myocardial tissue samples from eight ns-CHD patients and four controls. The genes potentially associated with CHD were validated by real-time fluorescence quantitative PCR analysis of right atrial myocardial tissues from 37 patients and 10 controls and the H9C2 cell line. Results: The results showed that the insulin signaling pathway, which is mediated by the SHC gene family, was inhibited in the ns-CHD patients. The expression levels of five genes (PTPRF, SHC4, MAP2K2, MKNK2, and ELK1) in the pathway were significantly down-regulated in the patients’ atrial tissues (P

High‐fat diet (HFD) leads to obesity, type II diabetes mellitus (T2DM) and increases the coincidence of cardiovascular diseases and cancer. Insulin resistance (IR) is considered as the ‘common soil’ of those diseases. Furthermore, people on HFD showed restrained glycolysis and enhanced fatty acid oxidation, which is the so‐called metabolic reprogramming. However, the relationship between metabolic reprogramming and IR induced by HFD is still unclear. Here, we demonstrate that PANK1 and miR‐107 were up‐regulated in the liver tissue of mice on HFD for 16 weeks and involved in metabolic reprogramming induced by palmitate acid (PA) incubation. Importantly, miR‐107 within an intron of PANK1 gene facilitated IR by targeting caveolin‐1 in AML12 cells upon PA incubation. Moreover, we identify that HFD enhanced P53 expression, and activation of P53 with nutlin‐3a induced PANK1 and miR‐107 expression simultaneously in transcriptional level, leading to metabolic reprogramming and IR, respectively. Consistently, inhibition of P53 with pifithrin‐α hydrobromide ameliorated PA‐induced metabolic reprogramming and IR. Thus, our results revealing a new mechanism by which P53 regulate metabolism. In addition, the results distinguished the different roles of PANK1 and its intron miR‐107 in metabolic regulation, which will provide more accurate intervention targets for the treatment of metabolic diseases.

Context Lilium davidii var. unicolour Cotton (Lilium genus, Liliaceae) is an edible plant and a herb used in China to alleviate insomnia. Objective To investigate the alleviating insomnia mechanism of L. davidii (LD). Materials and methods Wistar rats were intraperitoneally injected with p-chlorophenylalanine (PCPA) to establish an insomnia model. Rats were divided into six groups (n = 8): Control, PCPA, Estazolam (0.5 mg/kg), LD extract in low, medium and high doses (185.22, 370.44, 740.88 mg/kg). Serum hormone levels of the HPA axis, levels of 5-HT, NE and MT, and the expression of GABAA and 5-HT1A receptors in hypothalamus were determined. Moreover, behavioural and pathological changes in the hypothalamus were evaluated. Results After LD administration, body weight and brain coefficient increased by 2.74% and 8.22%, respectively, and the adrenal coefficient decreased by 25%, compared with PCPA group. Elevation of the serum hypothalamic-pituitary-adrenal (HPA) axis hormone CRH (11.24 ± 3.16 ng/mL), ACTH (565.87 ± 103.44 pg/mL) and CORT (44.28 ± 8.73 ng/mL) in the PCPA group was reversed after LD treatment. Furthermore, abnormal excitatory behaviour [5 min movement distance (2096.34 ± 259.51 cm), central exercise time (5.28 ± 1.08 s)] of insomnia rats in the PCPA group was also relieved. LD extract increased 5-HT and MT levels, reduced NE level in the hypothalamus, and upregulated the expression of GABAA R and 5-HT1A. Moreover, LD extract may improve the pathology of neurons in the hypothalamus. Conclusions LD can be considered to develop health-care food or novel drugs to cope with the increasing number of insomniacs.

Background Thermal ablation (TA), as an alternative to surgery, has shown some benefits in the treatment of papillary thyroid microcarcinoma (PTMC) patients, especially for those who are at high risk for surgery or refuse surgery. We performed a systematic review and meta-analysis to evaluate the efficiency, safety, and economy of TA, compared with those of routine surgery (RS), for the treatment of PTMC. Methods PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, and VIP databases were retrieved from inception to 10 January 2020 to identify relevant original studies on comparison of TA and RS for treatment of PTMC. The recurrence rate, recurrence-free survival (RFS), complication rate, operation time, postoperative length of stay, and cost during the perioperative period were extracted as main indices. The pooled standardized mean difference (SMD) or odds ratio (OR) with 95% confidence intervals (CI) were calculated and analyzed. Chi-square test and I2 statistic were applied to determine the heterogeneity among studies. The sensitivity analysis was applied to explore the origin of heterogeneity, and the publication bias was evaluated by Egger’s test. Results Seven retrospective studies with a total of 867 patients met the eligibility criteria and were included in the final meta-analysis. Our study demonstrated that TA showed significant reduction in complication with a pooled OR 0.24 (95% CI 0.13 to 0.43), postoperative length of stay with a pooled SMD −3.14 (95% CI −4.77 to −1.51) and cost during the perioperative period with a pooled SMD of −1.69 (95% CI −3.18 to −0.20). It also demonstrated that both TA and RS had similar pooled proportion of recurrence of OR 0.93 (95% CI 0.38 to 2.30) and recurrence-free survive (RFS). The sensitivity analysis showed that each included study had no significant effect on the results and the results were stable and reliable. The Egger’s test demonstrated publication bias was acceptable. Conclusions TA may not be oncologically inferior to RS, and it is a relatively safe and economical alternative for the treatment of PTMC.

Macrophage activation participates in the pathogenesis of pulmonary inflammation. As a coenzyme, vitamin B6 (VitB6) is mainly involved in the metabolism of amino acids, nucleic acids, glycogen and lipids. We have previously reported that activation of AMP‐activated protein kinase (AMPK) produces anti‐inflammatory effects both in vitro and in vivo. Whether VitB6 via AMPK activation prevents pulmonary inflammation remains unknown. The model of acute pneumonia was induced by injecting mice with lipopolysaccharide (LPS). The inflammation was determined by measuring the levels of interleukin‐1 beta (IL‐1β), IL‐6 and tumour necrosis factor alpha (TNF‐α) using real time PCR, ELISA and immunohistochemistry. Exposure of cultured primary macrophages to VitB6 increased AMP‐activated protein kinase (AMPK) Thr172 phosphorylation in a time/dose‐dependent manner, which was inhibited by compound C. VitB6 downregulated the inflammatory gene expressions including IL‐1β, IL‐6 and TNF‐α in macrophages challenged with LPS. These effects of VitB6 were mirrored by AMPK activator 5‐aminoimidazole‐4‐carboxamide ribonucleoside (AICAR). However, VitB6 was unable to inhibit LPS‐induced macrophage activation if AMPK was in deficient through siRNA‐mediated approaches. Further, the anti‐inflammatory effects produced by VitB6 or AICAR in LPS‐treated macrophages were abolished in DOK3 gene knockout (DOK3 −/−) macrophages, but were enhanced in macrophages if DOK3 was overexpressed. In vivo studies indicated that administration of VitB6 remarkably inhibited LPS‐induced both systemic inflammation and acute pneumonia in wild‐type mice, but not in DOK3 −/− mice. VitB6 prevents LPS‐induced acute pulmonary inflammation in mice via the inhibition of macrophage activation.

Helicobacter pylori (H. pylori) recurrence remains a significant public health concern. The study aimed to assess H. pylori reinfection rate and identify its risk factors in China. This prospective open cohort, observational study was performed at 18 hospitals across 15 provinces in China. Consecutive patients who received the successful initial eradication during 1 January 2012 and 31 December 2018 were eligible for enrolment. H. pylori recurrence was defined as reinfection that occurred at more than the 12-month interval after successful initial eradication. Surveyed risk factors that might be associated with reinfection were preliminarily estimated by log-rank test and further determined by Cox regression model to calculate the hazard ratio (HR) and 95% confidence interval (CI). A total of 5193 subjects enrolled in the study. The follow-up intervals varied from 6 to 84 months with a general follow-up rate of 67.9%. Annual reinfection rate was 1.5% (95% CI: 1.2–1.8) per person-year. H. pylori reinfection was independently associated with the following five risk factors: minority groups (HR = 4.7, 95% CI: 1.6–13.9), the education at lower levels (HR = 1.7, 95% CI: 1.1–2.6), a family history of gastric cancer (HR = 9.9, 95% CI: 6.6–14.7), and the residence located in Western China (HR = 5.5, 95% CI: 2.6–11.5) following by in Central China (HR = 4.9, 95% CI: 3–8.1) (all P

Low-temperature tolerance during the germination and bud stages is an important characteristic of direct-seeded rice (DSR). Recombinant inbred lines (RILs) derived from indica rice H335, which is highly tolerant to low temperature, and indica rice CHA-1, which is sensitive to low temperature, were used to identify quantitative trait loci (QTLs) associated with low-temperature tolerance during the germination and bud stages. a total of 11 QTLs were detected based on a high-density genetic map; among these, six QTLs explained 5.13-9.42% of the total phenotypic variation explained (PVE) during the germination stage, and five QTLs explained 4.17-6.42% of the total PVE during the bud stage. All QTLs were distributed on chromosome 9, and all favourable alleles originated from H335. The physical position of each QTL was determined, and 11 QTLs were combined into five genetic loci; three of these loci are involved during the germination stage (loci 1, 2, and 3), and three are involved during the bud stage (loci 3, 4, and 5). Loci 2, 4 and 5 were repeatedly detected in the wet season (WS) and dry season (DS). Notably, loci 3 was detected during both the germination and bud stages. These loci are good candidates for future studies of gene function and could serve as highly valuable genetic factors for improving cold tolerance during the germination and bud stages of rice.

MDS is a heterogeneous disease with diverse clinical manifestations, and an effective prognostic evaluation tool for MDS patients is needed. To achieve more accurate prognosis assessment for Chinese MDS patients, here we examined several scoring systems and explored the implications of gene mutations. The prognostic conditions were stratified against three different score systems (International Prognostic Scoring System (IPSS), WHO Prognostic Scoring System (WPSS), and Revised International Prognostic Scoring System (IPSS-R)) were retrospectively applied to 110 de novo MDS patients in study cohort in our hospital and the prognostic conditions were stratified respectively. IPSS-R out-performed the others, since it had less overlaps in survival curve, especially in the relatively low-risk group. Furthermore, genetic mutations were identified in 84 out of 110 patients and their association with overall survival (OS) were determined. Among them, sixty-three percent patients had at least one-point mutation, including thirty-five patients with normal karyotypes. The presence of TP53 mutations, but not TET2, DNMT3A or ASXL1 mutations was significantly correlated with shorter OS. A new model incorporating IPSS-R and TP53 mutations into survival analysis was proposed, and the prognostic value of this model was validated to be predominant in a 190-primary MDS patient independent cohort. Our data suggested that IPSS-R was more suitable for Chinese population. Attentions should be paid to the unfavourable mutations that might exert impact on the survival, especially in patients with relatively low risk.

The placement of left ventricular (LV) pacing lead at the latest activation sites with viable myocardium confers better cardiac resynchronization therapy (CRT) response ([1–3][1]). However, placing LV lead at the appropriate site remains a challenge for achieving an adequate CRT response. This

Cardiac fibrosis is a key factor to determine the prognosis in patient with myocardial infarction (MI). The aim of this study is to investigate whether the transcriptional factor paired‐related homeobox 2 (Prrx2) regulates Wnt5a gene expression and the role in myocardial fibrosis following MI. The MI surgery was performed by ligation of left anterior descending coronary artery. Cardiac remodelling was assessed by measuring interstitial fibrosis performed with Masson staining. Cell differentiation was examined by analysis the expression of alpha‐smooth muscle actin (α‐SMA). Both Prrx2 and Wnt5a gene expressions were up‐regulated in mice following MI, accompanied with increased mRNA and protein levels of α‐SMA, collagen I and collagen III, compared to mice with sham surgery. Adenovirus‐mediated gene knock down of Prrx2 increased survival rate, alleviated cardiac fibrosis, decreased infarction sizes and improved cardiac functions in mice with MI. Importantly, inhibition of Prrx2 suppressed ischaemia‐induced Wnt5a gene expression and Wnt5a signalling. In cultured cardiac fibroblasts, TGF‐β increased gene expressions of Prrx2 and Wnt5a, and induced cell differentiations, which were abolished by gene silence of either Prrx2 or Wnt5a. Further, overexpression of Prrx2 or Wnt5a mirrored the effects of TGF‐β on cell differentiations of cardiac fibroblasts. Gene silence of Wnt5a also ablated cell differentiations induced by Prrx2 overexpression in cardiac fibroblasts. Mechanically, Prrx2 was able to bind with Wnt5a gene promoter to up‐regulate Wnt5a gene expression. In conclusions, targeting Prrx2‐Wnt5a signalling should be considered to improve cardiac remodelling in patients with ischaemic heart diseases.

Direct seeding is becoming a popular method of rice production in many rice-growing areas. Therefore, rice early seedling vigour (ESV) has also become an important agricultural research topic. To explore more genetic loci related to ESV, we used a germplasm resource containing 200 indica varieties genotyped by sequencing (GBS), and 161,657 high-quality SNPs were obtained. Nine phenotypes associated with ESV were evaluated. A genome-wide association study (GWAS) based on a mixed linear model (MLM) revealed 224 genetic loci for all traits, among which 70 genetic loci were repeatedly detected across two seasons and were reliable. In total, 1609 genes were predicted in the 200-kb genomic region harbouring these 70 loci. Furthermore, 16,184 differentially expressed genes (DEGs) were identified using RNA sequencing (RNA-seq). With the combination of RNA sequencing and GWAS, 666 candidate DEGs were obtained. Based on gene annotation and quantitative real-time PCR (qRT-PCR), we predicted the 5 most promising candidate genes (Os09g0278000, Os09g0279100, Os09g0279400, Os09g0279500 and Os09g0280300) at locus 167, which had a strong association signal. These findings provide valuable information for understanding the genetic control of ESV and for molecular marker-assisted breeding of indica rice.

Background:A comprehensive and thorough understanding of functional acetabular component orientation is essential for optimizing the clinical outcome after total hip arthroplasty (THA). This study aimed to quantify the functional acetabular anteversion and inclination of unilateral THA patients during walking and static standing and to determine whether the functional acetabular orientation falls within the Lewinnek safe zone.Methods:Seventeen patients with unilateral THA received a CT scan and dual fluoroscopic imaging during level walking and static standing to evaluatein vivohip kinematics. The pelvic functional coordinate system of the 3D CT-based computer model was defined by the line of gravity and anterior pelvic plane (APP) to measure functional acetabular anteversion and inclination in different postures. The Lewinnek safe zone was used to determine the acetabular malposition during functional activities.Results:The THA side demonstrated an average of 10.1° (± 9.6°, range –7.5° to 29.9°) larger functional anteversion and 16.0° (± 9.2°, range –7.2° to 29.9°) smaller inclination than native hips during level walking. Functional acetabular anteversion in the THA side during level walking and static standing was significantly larger than anatomical measurements (p< 0.05). Acetabular orientation of most well-placed THA components anatomically in the Lewinnek safe zone fell outside the safe zone during more than half of the gait cycle and static standing.Conclusion:The current study revealed that an anatomically well-placed acetabular cup does not guarantee a well-functional orientation during daily activities. Thein vivomechanical performance and loading conditions of the THA component during other weight-bearing activities should be investigated in further studies.

Bovine Viral Diarrhea Virus (BVDV) is the main pathogen of bovine viral diarrhea disease (BVD), which leads to enormous economic losses in the cattle industry. A sensitive and specific detection for BVDV is advantageous to the control of BVDV. Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems have been used for detecting virus RNA. In this study, the expression and purification of LwCas13a protein was optimized and the RNase activity of LwCas13a in vitro was verified. CRISPR-LwCas13a system could detect BVDV virus and BVDV RNA with high specificity and simplicity. The detection limit of the LwCas13a system was 103 pM, and there were no cross-reactions with HEK293T and MDBK. In summary, a sensitive, specific, and simple nucleic acid detection method based on CRISPR-Cas13a was developed for BVDV. This method provides a new detection strategy for early diagnosis of BVDV.

Objection: Cumulative studies have identified the effectiveness of cardiac shock wave therapy (CSWT) in treating heart failure after acute myocardial infarction (AMI), but little have been discussed with regard to the beneficial effects of CSWT on anti-fibrosis along with the underlying mechanism. In this study, we investigated whether CSWT could reduce post-AMI fibrosis and further explored the molecular mechanism.Methods: Rat heart failure (HF) models induced by ligating the left anterior descending coronary artery were established and validated by echocardiography. Eligible animals were randomly categorized into five groups: the sham group, the HF group, the HF + CSWT group, the HF + LY294002 group, and the HF + CSWT + LY294002 group. The cardiac weight, serum level of BNP, NT-pro BNP and echocardiography parameters were measured to assess cardiac function in different groups. Masson's trichrome staining was used to assess the proportions of the fibrotic area. The expression level of CD34, αSMA was measured by RT-PCR, Immunohistochemistry and Immunofluorescent analyses and the level of PI3K/Akt was quantified by Immunohistochemistry and Western blotting.Results: The application of CSWT significantly improved cardiac function and reduced myocardial fibrosis and level of CD34 and αSMA, compared to the HF group. CSWT led to significant elevations of p-PI3K and p-Akt expression levels compared to that of the HF group and the inhibition of the PI3K/Akt pathway abolished the observed beneficial effects of CSWT.Conclusion: CSWT can facilitate the alleviation of cardiac fibrosis induced by AMI through the activation of PI3K/Akt signaling pathway.

Teratomas are germline tumors commonly composed of multiple cell types derived from embryonic germ cell layers. Teratomas in head and neck region are exceptionally rare and present during the neonatal and infantile period. We describe a male adult with a mature teratoma originating from sphenoid body. A 24-year-old male patient presented with left-sided intermitted headache and facial numbness. Radiographic imaging showed a 3 cm × 2.3 cm mass with heterogeneous density in the sphenoid region. The endoscopic sphenoid sinus opening surgery was performed through endonasal transpterygoid approach. The final pathologic diagnosis was confirmed as mature teratoma. The patient has been followed-up for 18 months without recurrence. We suggest endonasal transpterygoid approach could be an effective and safe treatment for patients with mature teratoma in the sphenoid bone.

Knowledge of protein–DNA binding specificity has important implications in understanding DNA metabolism, transcriptional regulation and developing therapeutic drugs. Previous studies demonstrated hydrogen bonds between amino acid side chains and DNA bases play major roles in specific protein–DNA interactions. In this paper, we investigated the roles of individual DNA strands and protein secondary structure types in specific protein–DNA recognition based on side chain-base hydrogen bonds. By comparing the contribution of each DNA strand to the overall binding specificity between DNA-binding proteins with different degrees of binding specificity, we found that highly specific DNA-binding proteins show balanced hydrogen bonding with each of the two DNA strands while multi-specific DNA binding proteins are generally biased towards one strand. Protein-base pair hydrogen bonds, in which both bases of a base pair are involved in forming hydrogen bonds with amino acid side chains, are more prevalent in the highly specific protein–DNA complexes than those in the multi-specific group. Amino acids involved in side chain-base hydrogen bonds favor strand and coil secondary structure types in highly specific DNA-binding proteins while multi-specific DNA-binding proteins prefer helices.

Peripheral T‑cell lymphomas (PTCLs) are heterogeneous malignancies that are types of non‑Hodgkin lymphomas; patients with this disease have poor prognoses. The IL‑2‑inducible T‑cell kinase‑spleen tyrosine kinase (ITK‑SYK) fusion gene, the first recurrent chromosome translocation in PTCL‑not otherwise specified (NOS), can drive cellular transformation and the development of T‑cell lymphoma in mouse models. The aim of the current study was to investigate the signal transduction pathways downstream of ITK‑SYK. The authors constructed a lentiviral vector to overexpress the ITK‑SYK fusion gene in Jurkat cells. By using Signal‑Net and cluster analyses of microarray data, the authors identified the tyrosine‑protein kinase JAK (JAK)3/STAT5 signalling pathway as a downstream pathway of ITK‑SYK, activation of which mediates the effects of ITK‑SYK on tumourigenesis. JAK3‑selective inhibitor tofacitinib abrogated the phosphorylation of downstream signalling molecule STAT5, supressed cell growth, induced cell apoptosis and arrested the cell cycle at the G1/S phase in ITK‑SYK+ Jurkat cells. In a xenograft mouse model, tumour growth was significantly delayed by tofacitinib. Since JAK3 associates with interleukin‑2 receptor subunit γ (IL2RG) only, siRNA‑specific knockdown of IL2RG showed the same effect as tofacitinib treatment in vitro. These results first demonstrated that the activation of the IL2RG/JAK3/STAT5 signalling pathway contributed greatly to the oncogenic progress regulated by ITK‑SYK, supporting further investigation of JAK3 inhibitors for the treatment of PTCLs carrying the ITK‑SYK fusion gene.

Chimeric antigen receptor-modified T-cell (CAR-T) therapy is effective and safe for patients with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL), but its value has been limited in terms of long-term leukemia-free survival. New strategies that can help CAR-T therapy achieve lasting effect are urgently warranted. This non-randomized interventional pragmatic clinical trial had a particular aim. It explored whether consolidative allogeneic hematopoietic stem cell transplantation (allo-HSCT) could improve the long-term prognosis of the minimal residual disease-negative complete remission (MRD- CR) patients after CAR-T therapy. In the first stage, 58 r/r B-ALL patients received split doses of CAR-T cells after lymphodepleting chemotherapy, and 51 (87.9%) achieved CR. In the second stage, 21/47 MRD- CR patients without previous allo-HSCT and contraindications or other restrictions, on their own accord, received consolidative allo-HSCT within three months after CAR-T therapy. There was no difference in overall survival (OS) between the MRD- CR patients who received allo-HSCT and those who did not. However, event-free survival (EFS) and relapse-free survival (RFS) were significantly prolonged by allo-HSCT in the subgroups. This was with either high (≥5%) pre-infusion bone marrow MRD assessed by flow cytometry (BM-FCM-MRD) or poor prognostic markers (P .05). To conclude, CAR-T therapy bridging to allo-HSCT is a safe and effective therapeutic strategy for r/r B-ALL patients, and may prolong their EFS and RFS, especially when they have high pre-infusion BM-FCM-MRD or poor prognostic markers.

As sessile organisms, plants have evolved numerous strategies to acclimate to changes in environmental temperature. However, the molecular basis of this acclimation remains largely unclear. In this study we identified a tRNAHis guanylyltransferase, AET1, which contributes to the modification of pre-tRNAHis and is required for normal growth under high-temperature conditions in rice. Interestingly, AET1 possibly interacts with both RACK1A and eIF3h in the endoplasmic reticulum. Notably, AET1 can directly bind to OsARF mRNAs including the uORFs of OsARF19 and OsARF23, indicating that AET1 is associated with translation regulation. Furthermore, polysome profiling assays suggest that the translational status remains unaffected in the aet1 mutant, but that the translational efficiency of OsARF19 and OsARF23 is reduced; moreover, OsARF23 protein levels are obviously decreased in the aet1 mutant under high temperature, implying that AET1 regulates auxin signaling in response to high temperature. Our findings provide new insights into the molecular mechanisms whereby AET1 regulates the environmental temperature response in rice by playing a dual role in tRNA modification and translational control.

Objective: To evaluate different targeted anticancer agents for patients with advanced or unresectable hepatocellular carcinoma (HCC) based on network meta-analysis. Methods: Literature retrieval was conducted in globally recognized databases, namely, MEDLINE, PMC, EMBASE and Cochrane Central to find relevant randomized controlled trials (RCTs). Relative parametric data, including overall survival (OS), progression-free survival (PFS) and adverse event (AE), were quantitatively pooled and estimated based on the Bayesian theorem. The values of the surface under the cumulative ranking (SUCRA) probabilities regarding each parameter were calculated and ranked. Node-splitting analysis was performed to test the inconsistency of the main results, and publication bias was assessed by examining funnel-plot symmetry. Results: After a detailed review, 31 RCTs containing 20 different agents or combinations were finally included for network meta-analysis. For patients without previously systematic treatments, lenvatinib had the best clinical effects on OS (SUCRA, 0.22), and apatinib was superior regarding PFS (SUCRA, 0.41) and AE (SUCRA, 0.15). For patients who received previously targeted agents therapies, regorafenib exhibited the superior clinical effects on OS (SUCRA, 0.42) and PFS (SUCRA, 0.30), while codrituzumab showed the greatest safety benefit on AE (SUCRA, 0.75). Moreover, node-splitting analysis and funnel-plot symmetries illustrated no inconsistency or obvious publication bias in the current study. Conclusions: According to current evidence, lenvatinib and apatinib had superior clinical effects for patients without previously systematic treatments, and regorafenib seemed to be more suitable for patients with previously targeted agent therapies. However, our conclusions still need more statistical validations, and more high-quality trials are expected.

Aims Cognitive impairment is a common symptom in the trajectory of Parkinson's disease (PD). However, the pathological underpinning is not fully known. We aimed to explore the critical structural alterations in the process of cognitive decline and its relationships with the dopaminergic deficit and the level of related cerebrospinal fluid (CSF) proteins. Methods Ninety‐four patients with PD and 32 controls were included in this study. Neuropsychological tests were performed at baseline and after 28 months to identify which patients had normal cognition and which ones developed PD‐MCI after follow‐up (“converters”). Gray matter atrophy was assessed in cross‐sectional and longitudinal analyses, respectively. The associations between altered GMV with dopamine transporter (DAT) results and the level of CSF proteins were assessed. Results Among the 94 patients with normal cognition at baseline, 24 (mean age, 63.1 years) developed PD‐MCI after 28 months of follow‐up, and 70 (mean age, 62.3 years) remained nonconverters. The converters showed significant right temporal atrophy at baseline and extensive atrophy in temporal lobe at follow‐up. Progressive bilateral frontal lobe atrophy was found in the converters. Baseline right temporal atrophy was correlated with the striatal dopaminergic degeneration in the converters. No correlation was found between the right temporal atrophy and the alterations of CSF proteins. Conclusion Early atrophy in temporal lobes and progressive atrophy in frontal lobes might be a biomarker for developing multidomain impairment of cognition and converting to PD‐MCI. Furthermore, cognition‐related temporal atrophy might be associated with dopaminergic deficit reflected by DAT scan but independent of CSF proteins in patients with PD who convert to PD‐MCI.