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Ca2+ sparks constitute the fundamental units of Ca2+ release in cardiomyocytes. Here we investigate how ryanodine receptors (RyRs) collectively generate these events by employing a transgenic mouse with a photoactivated label on RyR2. This allowed correlative imaging of RyR localization, by super-resolution photoactivated localization microscopy, and Ca2+ sparks, by high-speed imaging. Two populations of Ca2+ sparks were observed: stationary events and ‘traveling’ events that spread between neighboring RyR clusters. Traveling sparks exhibited up to eight distinct releases, sourced from local or distal junctional sarcoplasmic reticulum. Quantitative analyses showed that sparks may be triggered by any number of RyRs within a cluster, and that acute β-adrenergic stimulation augments intracluster RyR recruitment to generate larger events. In contrast, RyR ‘dispersion’ during heart failure facilitates the generation of traveling sparks. Thus, RyRs cooperatively generate Ca2+ sparks in a complex, malleable fashion, and channel organization regulates the propensity for local propagation of Ca2+ release.

The objective of this study is to analyze and summarize the characteristics of the clinical data of patients with systemic lupus erythematosus (SLE) complicated with liver failure, and to improve the cognition of the disease. The clinical data of patients with SLE complicated with liver failure hospitalized in Beijing Youan Hospital from January 2015 to December 2021 were collected retrospectively, including general information and laboratory examination data, and the clinical characteristics of the patients were summarized and analyzed. Twenty-one SLE patients with liver failure were analyzed. The diagnosis of liver involvement was earlier in 3 cases than that of SLE, and later in 2 cases. Eight patients were diagnosed with SLE and autoimmune hepatitis at the same time. The medical history is between 1 month and 30 years. This was the first case report of SLE complicated with liver failure. We found that: (1) among the 21 patients, organ cysts (liver and kidney cysts) were more common and the proportion of cholecystolithiasis and cholecystitis was higher than that in previous studies, but the proportion of renal function damage and joint involvement was lower. (2) The inflammatory reaction was more obvious in SLE patients with acute liver failure. The degree of liver function injury in SLE patients with autoimmune hepatitis was less than that in patients with other liver diseases. (3) The use of glucocorticoid in SLE patients with liver failure was worthy of further discussion. Key Points• Patients with SLE complicated with liver failure have a lower proportion of renal impairment and joint involvement.• The study firstly reported SLE patients with liver failure.• Glucocorticoids in the treatment of SLE patients with liver failure are worthy of further discussion.

Flowering plants have evolved numerous intraspecific and interspecific prezygotic reproductive barriers to prevent production of unfavourable offspring1. Within a species, self-incompatibility (SI) is a widely utilized mechanism that rejects self-pollen2,3 to avoid inbreeding depression. Interspecific barriers restrain breeding between species and often follow the SI × self-compatible (SC) rule, that is, interspecific pollen is unilaterally incompatible (UI) on SI pistils but unilaterally compatible (UC) on SC pistils1,4–6. The molecular mechanisms underlying SI, UI, SC and UC and their interconnections in the Brassicaceae remain unclear. Here we demonstrate that the SI pollen determinant S-locus cysteine-rich protein/S-locus protein 11 (SCR/SP11)2,3 or a signal from UI pollen binds to the SI female determinant S-locus receptor kinase (SRK)2,3, recruits FERONIA (FER)7–9 and activates FER-mediated reactive oxygen species production in SI stigmas10,11 to reject incompatible pollen. For compatible responses, diverged pollen coat protein B-class12–14 from SC and UC pollen differentially trigger nitric oxide, nitrosate FER to suppress reactive oxygen species in SC stigmas to facilitate pollen growth in an intraspecies-preferential manner, maintaining species integrity. Our results show that SRK and FER integrate mechanisms underlying intraspecific and interspecific barriers and offer paths to achieve distant breeding in Brassicaceae crops.

Sensitive and specific blood-based assays for the detection of pulmonary and extrapulmonary tuberculosis would reduce mortality associated with missed diagnoses, particularly in children. Here we report a nanoparticle-enhanced immunoassay read by dark-field microscopy that detects twoMycobacterium tuberculosisvirulence factors (the glycolipid lipoarabinomannan and its carrier protein) on the surface of circulating extracellular vesicles. In a cohort study of 147 hospitalized and severely immunosuppressed children living with HIV, the assay detected 58 of the 78 (74%) cases of paediatric tuberculosis, 48 of the 66 (73%) cases that were missed by microbiological assays, and 8 out of 10 (80%) cases undiagnosed during the study. It also distinguished tuberculosis from latent-tuberculosis infections in non-human primates. We adapted the assay to make it portable and operable by a smartphone. With further development, the assay may facilitate the detection of tuberculosis at the point of care, particularly in resource-limited settings.

A new positive-sense single-stranded RNA (+ssRNA) mycovirus, Verticillium dahliae magoulivirus 1 (VdMoV1), was isolated from two strains (2-19 and XLZ70) of Verticillium dahliae. The complete genome of VdMoV1 is 2303 nucleotides (nt) in length and has a large open reading frame (nt positions from 61 to 1938) encoding an RNA-dependent RNA polymerase (RdRp). A multiple sequence alignment indicated that the central region of the RdRp encoded by VdMoV1 contains eight typical viral RdRp motifs. BLASTp analysis demonstrated that VdMoV1 has the highest sequence identity (86.88%) to Bremia lactucae associated ourmia-like virus 2 (BlaOLV2). Phylogenetic analysis revealed that VdMoV1 is a new member of the genus Magoulivirus. As far as we know, VdMoV1 is the first reported member of the family Botourmiaviridae infecting V. dahliae.

The aim is to clarify the evolution mechanism of Network Public Opinion (NPO) in public emergencies. This work makes up for the insufficient semantic understanding in NPO-oriented emotion analysis and tries to maintain social harmony and stability. The combination of the Edge Computing (EC) and Deep Learning (DL) model is applied to the NPO-oriented Emotion Recognition Model (ERM). Firstly, the NPO on public emergencies is introduced. Secondly, three types of NPO emergencies are selected as research cases. An emotional rule system is established based on the One-Class Classification (OCC) model as emotional standards. The word embedding representation method represents the preprocessed Weibo text data. Convolutional Neural Network (CNN) is used as the classifier. The NPO-oriented ERM is implemented on CNN and verified through comparative experiments after the CNN's hyperparameters are adjusted. The research results show that the text annotation of the NPO based on OCC emotion rules can obtain better recognition performance. Additionally, the recognition effect of the improved CNN is significantly higher than the Support Vector Machine (SVM) in traditional Machine Learning (ML). This work realizes the technological innovation of automatic emotion recognition of NPO groups and provides a basis for the relevant government agencies to handle the NPO in public emergencies scientifically.

Network pharmacology, a holistic approach based on the theory of biological network technology, integrates information from biological systems, drugs, and diseases. Here, this theory was used to predict the targets of Wu-Wei-Wen-Tong Chubi capsule (WWWT) to explore the mechanism in the treatment of rheumatoid arthritis (RA). The ingredients of each herbal medicine in WWWT were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the active ingredients were screened through bioavailability (OB) ≥30% and drug-likeness (DL) ≥ 0.18. SwissTargetPrection and TCMSP were utilized to calculate and predict the targets of active ingredients. RA-related targets were obtained by searching the Genecards and OMIM databases. The common targets of RA and WWWT were used for gene ontology (GO), KEGG pathway enrichment, protein-protein interaction (PPI) analysis, and molecular docking. And then, four key genes were screened for subsequent verification experiments. In total, 90 active compounds and 330 potential targets of WWWT, 1310 targets of RA, and 135 intersection targets were found. Additionally, GO and pathway analysis identified 4610 significant GO terms and 147 significant KEGG pathways. Based on the PPI network, 11 key genes including IL-6, MMP-9, and TNF-α were screened out for molecular docking. Molecular docking showed that these key genes have good binding activities to active compounds of WWWT such as oroxylin a, kaempferol, and luteolin. Simultaneously, Western blot experimental validation demonstrated that the protein expressions of IL-6, MMP-9, TNF-α, and VEGFA significantly decreased after WWWT treatment. The mechanism of WWWT in treating RA involves multiple active compounds acting on multiple targets, and multiple pathways, which provides an important reference for further elucidation the mechanism and clinical applications of WWWT in the treatment of RA.

ZF2001, a protein subunit vaccine against coronavirus disease 2019 (COVID-19), contains recombinant tandem repeat of dimeric receptor-binding domain (RBD) protein of the SARS-CoV-2 spike protein with an aluminium-based adjuvant. During the development of this vaccine, two nonclinical studies were conducted to evaluate female fertility, embryo-fetal development, and postnatal developmental toxicity in Sprague‒Dawley rats according to the ICH S5 (R3) guideline. In Study 1 (embryo-fetal developmental toxicity, EFD), 144 virgin female rats were randomly assigned into four groups and received three doses of vaccine (25 μg or 50 μg RBD protein/dose, containing the aluminium-based adjuvant), the aluminium-based adjuvant or a sodium chloride injection administered intramuscularly on days 21 and 7 prior to mating and on gestation day (GD) 6. In Study 2 (pre- and postnatal developmental toxicity, PPND), ZF2001 at a dose of 25 μg RBD protein/dose or sodium chloride injection was administered intramuscularly to female rats (n = 28 per group) 7 days prior to mating and on GD 6, GD 20 and postnatal day (PND) 10. There were no obvious adverse effects in dams, except for local injection site reactions related to the aluminium-based adjuvant (yellow nodular deposits in the interstitial muscle fibres). There were also no effects of ZF2001 on the mating performance, fertility or reproductive performance of parental females, embryo-fetal development, postnatal survival, growth, physical development, reflex ontogeny, behavioural and neurofunctional development, or reproductive performance of the offspring. The strong immune responses associated with binding and neutralising antibodies were both confirmed in dams and fetuses or offspring in these two studies. These results would support clinical trials or the use of ZF2001 in maternal immunisation campaigns, including those involving women with childbearing potential, regardless of pregnancy status.

Background Plant architecture associated with increased grain yield and adaptation to the local environments is selected during wheat (Triticum aestivum) breeding. The internode length of individual stems and tiller length of individual plants are important for the determination of plant architecture. However, few studies have explored the genetic basis of these traits. Results Here, we conduct a genome-wide association study (GWAS) to dissect the genetic basis of geographical differentiation of these traits in 306 worldwide wheat accessions including both landraces and traditional varieties. We determine the changes of haplotypes for the associated genomic regions in frequency in 831 wheat accessions that are either introduced from other countries or developed in China from last two decades. We identify 83 loci that are associated with one trait, while the remaining 247 loci are pleiotropic. We also find 163 associated loci are under strong selective sweep. GWAS results demonstrate independent regulation of internode length of individual stems and consistent regulation of tiller length of individual plants. This makes it possible to obtain ideal haplotype combinations of the length of four internodes. We also find that the geographical distribution of the haplotypes explains the observed differences in internode length among the worldwide wheat accessions. Conclusion This study provides insights into the genetic basis of plant architecture. It will facilitate gene functional analysis and molecular design of plant architecture for breeding.

A comprehensive understanding of endothelial cell lineage specification will advance cardiovascular regenerative medicine. Recent studies found that unique epigenetic signatures preferentially regulate cell identity genes. We thus systematically investigate the epigenetic landscape of endothelial cell lineage and identify MECOM to be the leading candidate as an endothelial cell lineage regulator. Single-cell RNA-Seq analysis verifies that MECOM-positive cells are exclusively enriched in the cell cluster of bona fide endothelial cells derived from induced pluripotent stem cells. Our experiments demonstrate that MECOM depletion impairs human endothelial cell differentiation, functions, and Zebrafish angiogenesis. Through integrative analysis of Hi-C, DNase-Seq, ChIP-Seq, and RNA-Seq data, we find MECOM binds enhancers that form chromatin loops to regulate endothelial cell identity genes. Further, we identify and verify the VEGF signaling pathway to be a key target of MECOM. Our work provides important insights into epigenetic regulation of cell identity and uncovered MECOM as an endothelial cell lineage regulator.

Fusarium verticillioides is a filamentous fungus that causes plant diseases and harms human health through cancer-inducing mycotoxin and life-threatening Fusariosis. Given its threat to agriculture and public health, genome assembly of this fungus is critical to our understanding of its pathobiology and developing antifungal drugs. Here, we report a gap-free genome assembly of F. verticillioides using PacBio HiFi data and high-throughput chromosome capture (Hi-C) sequencing data. The assembled 42.0 Mb sequence contains eleven gapless chromosomes capturing all centromeres and 19 of all 22 telomeres. This assembly represents a significant improvement over previous version on contiguity (contig N50: 4.3 Mb), completeness (BUSCO score: 99.0%) and correctness (QV: 88.8). A total of 15,230 protein-coding genes were predicted, 6.2% of which are newly annotated genes. In addition, we identified three-dimension chromatin structures such as TADs-like structures and chromatin loops based on Hi-C data of ultra-high coverage. This gap-free genome of F. verticillioides is an excellent resource for further panoramic understanding mechanisms of fungal genome evolution, mycotoxin production and pathogenesis on plant and human host.

Background Methotrexate is an anticancer drug from the antimetabolite class. It is also used in gynecology and obstetrics for the medical treatment of ectopic pregnancies. Low-dose methotrexate-induced adverse toxic effects are rare. We report a case of toxic effect associated with severe renal insufficiency induced by LD-MTX (Low-Dose Methotrexate) for ectopic pregnancy. Case presentation A 46-year-old Chinese woman was in an operation for an ectopic pregnancy of tubal interstitial pregnancy. The embryo villus was so little that we were not sure if it was evacuated, then it was followed with 50 mg methotrexate injection of intramuscular adjacent the uterine horn in the operation. 48 hour later after injection the patient presented with renal failure. The personalized genetic testing showed that MTHFR (677C > T) and ABCB1 (3435T > C) were detected. Gradually, the symptoms improved after calcium leucovorin (CF) rescue, continuous renal replacement therapy (CRRT), promoting blood system regeneration, and multiple supportive treatments. Conclusions When toxic effects are suspected, detecting the polymorphisms of an MTHFR gene and monitoring MTX concentration in blood could assist us to formulate individualized and active treatments. The management should be multidisciplinary and as much as possible within an intensive care unit.

The development of low-cost, high-activity, and durable integrated bifunctional flexible air electrodes for use in Zn-air batteries is both challenging and important. We report a simple and scalable electropolymerization method used to prepare an electrode material comprising heavily N-doped carbon covering single-walled carbon nanotube (N/C-SWCNT) networks. The resulting core/shell structure of the hybrid electrode enabled the flexibility, mechanics, and three-dimensional interconnected porous structure of SWCNT films while containing abundant pyridinic N, which provided excellent catalytic activity for both the oxygen reduction and evolution reactions (overpotential gap = 0.76 V). A binder-free Zn-air battery using the N/C-SWCNT film as an oxygen electrode was assembled and showed a high peak power density of 181 mW/cm2, a high specific capacity of 810 mAh/g and stable discharge‒charge cycling performance. We also constructed a flexible solid-state Zn-air battery featuring not only a high power density of 22 mW/cm2 but also good flexibility and stability.

Background Exercise tolerance plays a vital role in the process of cardiac rehabilitation in patients undergoing percutaneous coronary intervention (PCI). The study sought to determine the characteristics, risks and correlates of post-PCI exercise tolerance in patients with coronary artery disease (CAD). Methods We analyzed clinical data of 299 CAD patients undergoing elective PCI and completing cardiopulmonary exercise testing (CPET). According to the Weber classification, post-PCI exercise tolerance was evaluated by peak oxygen uptake (VO2 peak). We assessed the impact of 34 predefined clinical features, cardiac functional parameters, and blood biochemistry data on exercise tolerance by univariate analysis and logistics regression analysis. Results Of 299 patients, 74.92% were men and average age was 60.90 ± 10.68 years. VO2 peak in the entire population was 17.54 ± 3.38 ml/kg/min, and 24.41% (n = 73) were less than 16 ml/kg/min, who were considered to have exercise intolerance. Multivariate logistics regression results showed that sex, diabetes mellitus, number of stents, left atrial diameter (LAD), end-diastolic volume (EDV), and hemoglobin influenced the peak oxygen uptake of CAD patients undergoing elective PCI. (All p Conclusions Nearly one quarter of CAD patients have exercise intolerance in the early post-PCI period. Female, diabetes mellitus, number of stents, LAD, EDV might negatively impacted post-PCI exercise tolerance, which need further warrant by large scale cohort study.

Background Extracellular vesicles (EVs) derived from bone marrow mesenchymal stem cells (MSCs) pretreated with atorvastatin (ATV) (MSCATV-EV) have a superior cardiac repair effect on acute myocardial infarction (AMI). The mechanisms, however, have not been fully elucidated. This study aims to explore whether inflammation alleviation of infarct region via macrophage polarization plays a key role in the efficacy of MSCATV-EV. Methods MSCATV-EV or MSC-EV were intramyocardially injected 30 min after coronary ligation in AMI rats. Macrophage infiltration and polarization (day 3), cardiac function (days 0, 3, 7, 28), and infarct size (day 28) were measured. EV small RNA sequencing and bioinformatics analysis were conducted for differentially expressed miRNAs between MSCATV-EV and MSC-EV. Macrophages were isolated from rat bone marrow for molecular mechanism analysis. miRNA mimics or inhibitors were transfected into EVs or macrophages to analyze its effects on macrophage polarization and cardiac repair in vitro and in vivo. Results MSCATV-EV significantly reduced the amount of CD68+ total macrophages and increased CD206+ M2 macrophages of infarct zone on day 3 after AMI compared with MSC-EV group (P ATV-EV much more significantly improved the cardiac function than MSC-EV with the infarct size markedly reduced (P ATV-EV also significantly reduced the protein and mRNA expressions of M1 markers but increased those of M2 markers in lipopolysaccharide-treated macrophages (P ATV-EV significantly attenuated while overexpression of it in MSC-EV enhanced the effect on promoting M2 polarization by suppressing downstream signal transducer and activator of transcription 1 (Stat1). Furthermore, MSCATV-EV loaded with miR-139-3p inhibitors decreased while MSC-EV loaded with miR-139-3p mimics increased the expressions of M2 markers and cardioprotective efficacy. Conclusions We uncovered a novel mechanism that MSCATV-EV remarkably facilitate cardiac repair in AMI by promoting macrophage polarization via miR-139-3p/Stat1 pathway, which has the great potential for clinical translation.

Background Intrauterine growth restriction (IUGR) can cause lipid disorders in infants and have long-term adverse effects on their growth and development. Clostridium butyricum (C. butyricum), a kind of emerging probiotics, has been reported to effectively attenuate lipid metabolism dysfunctions. Therefore, the objective of this study was to investigate the effects of C. butyricum supplementation on hepatic lipid disorders in IUGR suckling piglets. Methods Sixteen IUGR and eight normal birth weight (NBW) neonatal male piglets were used in this study. From d 3 to d 24, in addition to drinking milk, the eight NBW piglets (NBW-CON group, n = 8) and eight IUGR piglets (IUGR-CON group, n = 8) were given 10 mL sterile saline once a day, while the remaining IUGR piglets (IUGR-CB group, n = 8) were orally administered C. butyricum at a dose of 2 × 108 colony-forming units (CFU)/kg body weight (suspended in 10 mL sterile saline) at the same frequency. Results The IUGR-CON piglets exhibited restricted growth, impaired hepatic morphology, disordered lipid metabolism, increased abundance of opportunistic pathogens and altered ileum and liver bile acid (BA) profiles. However, C. butyricum supplementation reshaped the gut microbiota of the IUGR-CB piglets, characterized by a decreased abundance of opportunistic pathogens in the ileum, including Streptococcus and Enterococcus. The decrease in these bile salt hydrolase (BSH)-producing microbes increased the content of conjugated BAs, which could be transported to the liver and function as signaling molecules to activate liver X receptor α (LXRα) and farnesoid X receptor (FXR). This activation effectively accelerated the synthesis and oxidation of fatty acids and down-regulated the total cholesterol level by decreasing the synthesis and promoting the efflux of cholesterol. As a result, the growth performance and morphological structure of the liver improved in the IUGR piglets. Conclusion These results indicate that C. butyricum supplementation in IUGR suckling piglets could decrease the abundance of BSH-producing microbes (Streptococcus and Enterococcus). This decrease altered the ileum and liver BA profiles and consequently activated the expression of hepatic LXRα and FXR. The activation of these two signaling molecules could effectively normalize the lipid metabolism and improve the growth performance of IUGR suckling piglets.

Background Two cases of orbitofrontal cholesterol granuloma masquerading as frontal sinus mucoceles were reported to understand image findings, clinical and histopathologic features of orbitofrontal cholesterol granuloma to improve its diagnosis and treatment. Case presentation Two East Asian patients aged 41 and 27 without personal or familial medical or trauma history presented with the common complaint of proptosis and inferomedial displacement of the eyeballs. The computed tomography (CT) of both cases showed an irregularly shaped, well-defined lesion in the left frontal bone associated with bony erosion. The lesions resulted in the bone absorption of frontal bone and orbital roof, which extended into the superior orbital space. Anterior orbitotomy through subbrow incision by drainage and curettage resulted in a curative outcome. The histopathological examination revealed inflammatory granulation tissues, fibrous capsule wall, cholesterol clefts with altered blood pigments, and calcifications, consistent with the diagnosis of cholesterol granuloma. No recurrence was observed for one year after surgery in one case and three years in the other. Conclusions When the following features are observed: orbital CT exhibits cystic lesion with irregular bone destruction in the superolateral orbit, magnetic resonance imaging (MRI) depicts lesions are hyperintense signals on T1 weighted images (T1WI), and T2 weighted images (T2WI), and the contrast-enhanced imaging reveals that the most of tumor is showed a non-significant enhancement, orbitofrontal cholesterol granuloma should be considered.

Although esophageal smooth muscle fibrosis of achalasia (AC) patients has been described, the role and mechanism remain unclear. The aim of this study was to evaluate the fibrosis in the distal esophageal muscle in patients with AC and explore its relationship with prognosis of per-oral endoscopic myotomy (POEM).Lower esophageal sphincter (LES) muscle from forty patients undergoing POEM for AC were obtained at the time of surgery. Control specimens consisted of similar muscle taken from distal esophagectomy for gastric tumors. The muscle fibrosis were assessed by Masson staining and confirmed by immunohistochemistry for collagen I and III. The total number of eosinophil within the myenteric propria were counted. In addition, clinical data were obtained through electronic medical records. Statistical comparison between groups were made.A significantly higher proportion of fibrosis in AC as compared with controls (P = 0.000). Eosinophil count, TGF-β1, collagen I, and III were higher than those of control (P = 0.000, P = 0.001, P = 0.011, and P = 0.002, respectively). TGF-β1, collagen I, and III were positively correlated with eosinophil count (all P lt; 0.05). Furthermore, the proportion of severe LES fibrosis in patients who failed to respond to POEM two years after operation was higher than that in responders (P = 0.028). And, Eckardt score two years after POEM was also positively correlated with degree of fibrosis-related cytokines (all P lt; 0.05).Smooth muscle fibrosis was prominent in lower part of esophagus of AC and positively correlated with severity of symptoms two years after POEM. The fibrosis might be relevant to eosinophil infiltration and TGF-β1. Further studies are required to more clearly delineate the mechanism of muscle fibrosis and its correlation with prognosis of therapy for this idiopathic disease.

To evaluate the potential of intravoxel incoherent motion (IVIM) and apparent diffusion coefficient (ADC) in the prediction of tumor grade, lymph node metastasis and pleural invasion of non-small cell lung cancer (NSCLC) before surgery.65 patients diagnosed with NSCLC by surgery were enrolled. IVIM-DWI (10 b-values, 0-1000 s/mmThe ADCIVIM is useful for predicting the tumor differentiation, lymph node metastasis and pleural invasion in NSCLC patients before surgery.

A superior allele of wheat gene TaGL3.3-5B was identified and could be used in marker-assisted breeding in wheat. Identifying the main genes which mainly regulate the yield-associated traits can significantly increase the wheat production. In this study, gene TaGL3.3 was cloned from common wheat according to the sequence of OsPPKL3. A SNP in the 8th exon of TaGL3.3-5B, T/C in coding sequence (CDS), which resulted in an amino acid change (Val/Ala), was identified between the low 1000-kernel weight (TKW) wheat Chinese Spring and the high TKW wheat Xinong 817 (817). Subsequently, association analysis in the mini-core collection (MCC) and the recombinant inbred lines (RIL) revealed that the allele TaGL3.3-5B-C (from 817) was significantly correlated with higher TKW. The high frequency of TaGL3.3-5B-C in the Chinese modern wheat cultivars indicated that it was selected positively in wheat breeding programs. The overexpression of TaGL3.3-5B-C in Arabidopsis resulted in shorter pods and longer grains than those of wild-type counterparts. Additionally, TaGL3.3 expressed a tissue-specific pattern in wheat as revealed by qRT-PCR. We also found that 817 showed higher expression of TaGL3.3 than that in Chinese Spring (CS) during the seed development. These results demonstrate that TaGL3.3 plays an important role in the formation of seed size and weight. Allele TaGL3.3-5B-C is associated with larger and heavier grains that are beneficial to wheat yield improvement.

Circadian rhythm disorders can accelerate atherosclerosis. This study aimed to determine the role of circadian disordered macrophages in atherosclerotic development. Mice were divided into NC group (normal circadian rhythm), L24 group (constant light), D12L12 group (weekly shift light/dark cycle), and D24 group (constant dark). Atherosclerotic progression was significantly accelerated in L24, D12L12, and D24 groups. Peritoneal macrophages from circadian disruption groups exhibited enhanced cytokine secretion and foam cell formation. Migration and proliferation of vascular smooth muscle cells (VSMCs) were increased under the conditioned medium of circadian disordered macrophages. The blockade of CD36 markedly inhibited foam cell formation. Compared with blocking CD36 or TLR4 alone, the co-inhibition of CD36 and TLR4 in macrophages further reduced cytokine secretion and more effectively inhibited VSMC migration and proliferation. In conclusion, the activation of CD36 and TLR4 in circadian disordered macrophages promotes foam cell formation and cytokine secretion and enhances VSMC migration and proliferation. Circadian rhythm disorders promote lipid uptake and cytokine secretion of macrophages by regulating CD36 and TLR4, and enhance VSMC migration and proliferation through the paracrine effect of macrophages.

Global control of the tuberculosis epidemic is threatened by increasing prevalence of drug resistant M. tuberculosis isolates. Many genome-wide studies focus on SNP-associated drug resistance mechanisms, but drug resistance in 5–30% of M. tuberculosis isolates (varying with antibiotic) appears unrelated to reported SNPs, and alternative drug resistance mechanisms involving variation in gene/protein expression are not well-studied. Here, using an omics approach, we identify 388 genes with lineage-related differential expression and 68 candidate drug resistance-associated gene pairs/clusters in 11 M. tuberculosis isolates (variable lineage/drug resistance profiles). Structural, mutagenesis, biochemical and bioinformatic studies on Rv3094c from the Rv3093c-Rv3095 gene cluster, a gene cluster selected for further investigation as it contains a putative monooxygenase/repressor pair and is associated with ethionamide resistance, provide insights on its involvement in ethionamide sulfoxidation, the initial step in its activation. Analysis of the structure of Rv3094c and its complex with ethionamide and flavin mononucleotide, to the best of our knowledge the first structures of an enzyme involved in ethionamide activation, identify key residues in the flavin mononucleotide and ethionamide binding pockets of Rv3094c, and F221, a gate between flavin mononucleotide and ethionamide allowing their interaction to complete the sulfoxidation reaction. Our work broadens understanding of both lineage- and drug resistance-associated gene/protein expression perturbations and identifies another player in mycobacterial ethionamide metabolism.

Background Anti-IgLON5 disease is a rare chronic autoimmune-mediated tauopathy, featured by the sleep disturbance. Several studies have described its clinical characteristics, however, the simultaneous occurrence of anti-IgLON5 disease and rectal cancer has not been reported. We described an unusual entity of anti-IgLON5 disease complicated with rectal cancer. Case presentation A 76-year-old man initially presented with slurred speech and limb tremors, followed by epileptic-like seizures, lethargy, and sleep apnea. IgG anti-IgLON5 antibodies were positive in both serum and cerebrospinal fluid. The patient responded well to the treatment of plasma exchange and a pulse and gradual reduction of steroids therapy. When the oral steroids started, mycophenolate mofetil was added. Two months later, the patient had bloody stools and pathological-confirmed moderately differentiated adenocarcinoma of the rectum. Conclusions Whereas sleep disturbance is the most common feature in patients with anti-IgLON5 disease, our case presented with slurred speech and limb tremors. Anti-IgLON5 disease complicated with rectal cancer is very rare. Tumor screening should be considered in patients with anti-IgLON5 disease to investigate the association between tumor and this disease.