Embryonic stem cell related gene regulates alternative splicing of transcription factor 3 to maintain human embryonic stem cells' self-renewal and pluripotency.

Exploring the mechanism of self-renewal and pluripotency maintenance of human embryonic stem cells (hESCs) is of great significance in basic research and clinical applications, but it has not been fully elucidated. Long non-coding RNAs (lncRNAs) have been shown to play a key role in the self-renewal and pluripotency maintenance of hESCs. We previously reported that the lncRNA ESRG, which is highly expressed in undifferentiated hESCs, can maintain the self-renewal and pluripotency of hPSCs. RNA pull-down mass spectrometry showed that ESRG could bind to other proteins, among which heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) attracted our attention. In this study, we showed that HNRNPA1 can maintain self-renewal and pluripotency of hESCs. ESRG bound to and stabilized HNRNPA1 protein through the ubiquitin-proteasome pathway. In addition, knockdown of ESRG or HNRNPA1 resulted in alternative splicing of TCF3, which originally and primarily encoded E12, to mainly encode E47 and inhibit CDH1 expression. HNRNPA1 could rescue the biological function changes of hESCs caused by ESRG knockdown or overexpression. Our results suggest that ESRG regulates the alternative splicing of TCF3 to affect CDH1 expression and maintain hESCs self-renewal and pluripotency by binding and stabilizing HNRNPA1 protein. This study lays a good foundation for exploring the new molecular regulatory mechanism by which ESRG maintains hESCs self-renewal and pluripotency.

Enhanced Cycling Stability of All-Solid-State Lithium-Sulfur Battery through Nonconductive Polar Hosts.

All-solid-state lithium-sulfur batteries (ASSLSBs) are promising next-generation battery technologies with a high energy density and excellent safety. Because of the insulating nature of sulfur/Li2S, conventional cathode designs focus on developing porous hosts with high electronic conductivities such as porous carbon. However, carbon hosts boost the decomposition of sulfide electrolytes and suffer from sulfur detachment due to their weak bonding with sulfur/Li2S, resulting in capacity decays. Herein, we propose a counterintuitive design concept of host materials in which nonconductive polar mesoporous hosts can enhance the cycling life of ASSLSBs through mitigating the decomposition of adjacent electrolytes and bonding sulfur/Li2S steadily to avoid detachment. By using a mesoporous SiO2 host filled with 70 wt % sulfur as the cathode, we demonstrate steady cycling in ASSLSBs with a capacity reversibility of 95.1% in the initial cycle and a discharge capacity of 1446 mAh/g after 500 cycles at C/5 based on the mass of sulfur.

Transcriptome and small RNA analysis unveils novel insights into the C4 gene regulation in sugarcane.

MAIN CONCLUSION: This study reveals miRNA indirect regulation of C4 genes in sugarcane through transcription factors, highlighting potential key regulators like SsHAM3a. C4 photosynthesis is crucial for the high productivity and biomass of sugarcane, however, the miRNA regulation of C4 genes in sugarcane remains elusive. We have identified 384 miRNAs along the leaf gradients, including 293 known miRNAs and 91 novel miRNAs. Among these, 86 unique miRNAs exhibited differential expression patterns, and we identified 3511 potential expressed targets of these differentially expressed miRNAs (DEmiRNAs). Analyses using Pearson correlation coefficient (PCC) and Gene Ontology (GO) enrichment revealed that targets of miRNAs with positive correlations are integral to chlorophyll-related photosynthetic processes. In contrast, negatively correlated pairs are primarily associated with metabolic functions. It is worth noting that no C4 genes were predicted as targets of DEmiRNAs. Our application of weighted gene co-expression network analysis (WGCNA) led to a gene regulatory network (GRN) suggesting miRNAs might indirectly regulate C4 genes via transcription factors (TFs). The GRAS TF SsHAM3a emerged as a potential regulator of C4 genes, targeted by miR171y and miR171am, and exhibiting a negative correlation with miRNA expression along the leaf gradient. This study sheds light on the complex involvement of miRNAs in regulating C4 genes, offering a foundation for future research into enhancing sugarcane's photosynthetic efficiency.

Intact quantitation of cysteine-conjugated antibody-drug conjugates using native mass spectrometry.

RATIONALE: A common strategy for antibody-drug conjugate (ADC) quantitation from in vivo study samples involves measurement of total antibody, conjugated ADC, and free payload concentrations using multiple reaction monitoring (MRM) mass spectrometry. This not only provides a limited picture of biotransformation but can also involve lengthy method development. Quantitation of ADCs directly at the intact protein level in native conditions using high-resolution mass spectrometers presents the advantage of measuring exposure readout as well as monitoring the change in average drug-to-antibody ratio (DAR) and in vivo stability of new linker payloads with minimal method development. Furthermore, site-specific cysteine-conjugated ADCs often rely on non-covalent association to retain their quaternary structure, which highlights the unique capabilities of native mass spectrometry (nMS) for intact ADC quantitation. METHODS: We developed an intact quantitation workflow involving three stages: automated affinity purification, nMS analysis, and data processing in batch fashion. The sample preparation method was modified to include only volatile ion-pairing reagents in the buffer systems. A capillary size-exclusion chromatography (SEC) column was coupled to a quadrupole time-of-flight high-resolution mass spectrometer for high-throughput nMS analysis. Samples from two mouse pharmacokinetic (PK) studies were analyzed using both intact quantitation workflow and the conventional MRM-based approach. RESULTS: A linear dynamic range of 5-100 µg/mL was achieved using 20 µL of serum sample volume. The results of mouse in vivo PK measurement using the intact quantitation workflow and the MRM-based approach were compared, revealing excellent method agreement. CONCLUSIONS: We demonstrated the feasibility of utilizing nMS for the quantitation of ADCs at the intact protein level in preclinical PK studies. Our results indicate that this intact quantitation workflow can serve as an alternative generic method for high-throughput analysis, enabling an in-depth understanding of ADC stability and safety in vivo.

Low-Dose Valganciclovir Prophylaxis Against Cytomegalovirus in Intermediate-Risk Liver and Dual-Abdominal Transplant Recipients.

BACKGROUND: Low-dose valganciclovir (VGC) for cytomegalovirus (CMV) prophylaxis post-transplant has been employed due to cost and safety. The incidence of CMV disease in CMV intermediate-risk liver recipients at 1-year after standard-dose prophylaxis is approximately 5%. However, there are limited data on outcomes after using a "true" low-dose VGC prophylaxis regimen in liver and dual-abdominal transplant recipients as VGC was not dose-adjusted in all patients with impaired renal function in prior studies. OBJECTIVE: The objective was to assess the incidence of CMV associated with low-dose VGC prophylaxis in CMV intermediate-risk liver, simultaneous pancreas-kidney (SPK), and simultaneous liver-kidney (SLK) recipients with creatinine clearance (CrCl) >60 mL/min. METHODS: This was a retrospective review of CMV intermediate-risk liver, SPK, and SLK recipients with CrCl >60 mL/min transplanted January 2018 to June 2022 who received VGC 450 mg daily for prophylaxis. The primary outcome was incidence of CMV infection 6-months post-transplant. RESULTS: Ninety-nine transplant recipients were included (79 liver, 11 SPK, 9 SLK). The primary outcome occurred in 13% of patients (liver 10%, SPK 36%, SLK 10%), including 1 case of CMV disease and 3 breakthrough infections. In addition, 6 patients experienced CMV infection between 6-months and 1-year. Recurrence occurred in 3 patients. There was no evidence of CMV resistance. Thirty patients experienced neutropenia within 1-year, 32 were prescribed granulocyte-colony stimulating factors, and 5 experienced thrombocytopenia. Two patients died due to graft-vs-host disease. CONCLUSION AND RELEVANCE: Low-dose VGC prophylaxis led to comparable CMV infection rates at 6-months in CMV intermediate-risk liver and SLK recipients. However, as SPK recipients displayed higher rates of CMV infection, low-dose VGC should be avoided in this population.

Long-Term Effects of Reproduction and Lactation on the Rat Supraspinatus Tendon and Proximal Humerus.

During pregnancy and breastfeeding, women undergo hormonal fluctuations required for fetal development, parturition, and infant growth. These changes have secondary consequences on the maternal musculoskeletal system, increasing the risk for joint pain and osteoporosis. Though hormone levels return to prepregnancy levels postpartum, women may experience lasting musculoskeletal pain. Sex disparities exist in the prevalence of musculoskeletal disorders, but it remains unclear how reproductive history may impact sex differences. Specifically, the effects of both reproductive history and sex on the rotator cuff have not been studied. Pregnancy and lactation affect bone microstructure, suggesting possible impairments at the enthesis of rotator cuff tendons, where tears commonly occur. Therefore, our objective was to evaluate how reproductive history affects sex differences of the supraspinatus tendon and proximal humerus using male, virgin female, and female rats with a history of reproduction (referred to as reproductive females). We hypothesized tendon mechanical properties and humeral bone microstructure would be inferior in reproductive females compared to virgin females. Results showed sex differences independent of reproductive history, including greater tendon midsubstance modulus but lower subchondral bone mineral density (BMD) in females. When considering reproductive history, reproductive rats exhibited reduced tendon insertion site modulus and trabecular bone micro-architecture compared to virgin females with no differences from males. Overall, our study identified long-term changes in supraspinatus tendon mechanical and humeral trabecular bone properties that result following pregnancy and lactation, highlighting the importance of considering reproductive history in investigations of sex differences in the physiology and pathology of rotator cuff injuries.

Altered Neuromagnetic Activity in the Default Mode Network in Migraine and Its Subgroups (Episodic Migraine and Chronic Migraine).

BACKGROUND: The differences in the resting state spectral power and functional connectivity of the default mode network between people with migraine without aura (MwoA) and its subgroups differentiated by frequency (episodic migraine (EM) and chronic migraine (CM)) and healthy controls (HC) were investigated using magnetoencephalography. METHODS: In the resting state, the topological spatial structure of the brain in 33 MwoA patients and 22 HC was first studied using magnetoencephalography, followed by probing the neuroelectrical activity of 17 CM and 16 EM patients, to identify damage to their default mode network (DMN). The techniques used to investigate both spectral power and functional connectivity were minimum-paradigm estimation combined with Welch's technique and corrected amplitude envelope correlation. RESULTS: The differences between MwoA and its subgroups (CM and EM) and HC based on spectral power were mainly in the delta, theta, and alpha bands, while the differences in functional connectivity were primarily in the delta, alpha, and beta bands. In the delta and theta bands, the spectral power of MwoA and its subgroups (CM and EM) was higher than in the HC group. The spectral power of MwoA and its subgroups (CM and EM) was lower in the alpha band. In terms of functional connectivity, the corrected amplitude envelope correlation of MwoA and its subgroups (CM and EM) was lower than the HC group in the bands with spectral differences. People with EM and CM differed in the spectral power in the left medial prefrontal cortex and the right lateral temporal cortex in the alpha band, where correlation analysis and logistic regression analysis showed that the intensity of the spectral power of the left medial prefrontal cortex was negatively correlated with headache frequency. CONCLUSIONS: The spectral power of the left medial prefrontal cortex in the alpha band may serve as a biomarker that is associated with the number of monthly headache attacks and may be a potential neuromodulatory target for controlling migraine chronicity.

Rare diseases in developing countries: Insights from China's collaborative network.

Rare diseases (RDs) are complex conditions and a worldwide healthcare challenge. The healthcare policymakers in developing countries lack templates from countries at the same level of development. This article introduced and discussed the combination of top-down strategies and bottom-up interventions in addressing RDs in a developing country, China, as an example. The government leads the formulation of laws, policies, and guidance to coordinate national resources, while local authorities and nongovernment organisations (NGOs) are responsible for policy localisation and complement policy gaps. This article may inspire other developing countries of improving RD healthcare.

Addressing the influencing path of social noise exposure risk perception on noise mitigation behavior.

Noise interference has become a common health risk in population-densified urban areas where social noise occurs frequently. However, the influence of an individual's perception of social noise exposure risk on reactive behavior remains unknown. This study developed an integrative psychosocial perspective-based model that includes constructs from two theoretical frameworks (the Theory of Planned Behavior and the Value-Belief-Norm theory) to analyze noise risk perception and behavioral intention for social noise mitigation. Haidian District, Beijing, was selected as the case study area and 300 questionnaires were distributed. The results showed that personal attributes had significant effects on residents' noise exposure risk perception and noise-mitigation behavioral intentions. Noise perception, as represented by awareness of consequences and ascription of responsibility, was significantly related to noise mitigation behavioral intention. Awareness of consequences directly positively influenced behavioral intention (ß = 0.235, p < 0.001) and indirectly positively influenced behavioral intention through the mediating effect of the ascription of responsibility, which accounted for 24 % of the total effect of awareness of consequences on behavioral intention. This study provides valuable insights into the risks of social noise and encourages adaptive measures to reduce it.

Upadacitinib for the treatment of active non-radiographic axial spondyloarthritis (SELECT-AXIS 2): a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Upadacitinib, a Janus kinase inhibitor, has been shown to be effective in patients with ankylosing spondylitis. We aimed to assess the efficacy and safety of upadacitinib in non-radiographic axial spondyloarthritis. METHODS: The SELECT-AXIS 2 non-radiographic axial spondyloarthritis study was a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial at 113 sites across 23 countries (Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, China, Czech Republic, France, Germany, Hungary, Israel, Japan, Mexico, Poland, Russia, Slovakia, South Korea, Spain, Taiwan, Turkey, Ukraine, and the USA). Eligible adults had active non-radiographic axial spondyloarthritis, with objective signs of inflammation based on MRI or elevated C-reactive protein and an inadequate response to non-steroidal anti-inflammatory drugs. Patients were randomly assigned (1:1) to receive oral upadacitinib 15 mg once daily or placebo using interactive response technology. Random treatment assignment was stratified by MRI inflammation in the sacroiliac joints and screening high-sensitivity C-reactive protein status (MRI-positive and C-reactive protein-positive, MRI-positive and C-reactive protein-negative, and MRI-negative and C-reactive protein-positive) and previous exposure to biologic disease-modifying antirheumatic drugs (yes vs no). Treatment assignment was masked from patients, investigators, study site personnel, and the study sponsor. The primary endpoint was the proportion of patients with an Assessment of SpondyloArthritis international Society 40 (ASAS40) response at week 14. Analyses were performed on the full analysis set of patients, who underwent random allocation and received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT04169373. FINDINGS: Between Nov 26, 2019, and May 20, 2021, 314 patients with active non-radiographic axial spondyloarthritis were enrolled into the study, and 313 received study drug (156 in the upadacitinib group and 157 in the placebo group); 295 (94%) patients (145 in the upadacitinib group and 150 in the placebo group) received treatment for the full 14 weeks. A significantly higher ASAS40 response rate was achieved with upadacitinib compared with placebo at week 14 (70 [45%] of 156 patients vs 35 [23%] of 157 patients; p<0·0001; treatment difference 22%, 95% CI 12-32). The rate of adverse events up to week 14 was similar in the upadacitinib group (75 [48%] of 156 patients) and placebo group (72 [46%] of 157 patients). Serious adverse events and adverse events leading to discontinuation of study drug occurred in four (3%) of 156 patients in the upadacitinib group and two (1%) of 157 patients in the placebo group. Few patients had serious infections or herpes zoster in either treatment group (each event occurred in two [1%] of 156 patients in the upadacitinib group and one [1%] of 157 patients in the placebo group). Five (3%) of 156 patients in the upadacitinib group had neutropenia; no events of neutropenia occurred in the placebo group. No opportunistic infections, malignancies, major adverse cardiovascular events, venous thromboembolic events, or deaths were reported with upadacitinib treatment. INTERPRETATION: Upadacitinib significantly improved the signs and symptoms of non-radiographic axial spondyloarthritis compared with placebo at week 14. These findings support the potential of upadacitinib as a new therapeutic option in patients with active non-radiographic axial spondyloarthritis. FUNDING: AbbVie.

BarleyExpDB: an integrative gene expression database for barley.

BACKGROUND: RNA-sequencing (RNA-seq) has been widely used to study the dynamic expression patterns of transcribed genes, which can lead to new biological insights. However, processing and analyzing these huge amounts of histological data remains a great challenge for wet labs and field researchers who lack bioinformatics experience and computational resources. RESULTS: We present BarleyExpDB, an easy-to-operate, free, and web-accessible database that integrates transcriptional profiles of barley at different growth and developmental stages, tissues, and stress conditions, as well as differential expression of mutants and populations to build a platform for barley expression and visualization. The expression of a gene of interest can be easily queried by searching by known gene ID or sequence similarity. Expression data can be displayed as a heat map, along with functional descriptions as well as Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Proteins Families Database, and Simple Modular Architecture Research Tool annotations. CONCLUSIONS: BarleyExpDB will serve as a valuable resource for the barley research community to leverage the vast publicly available RNA-seq datasets for functional genomics research and crop molecular breeding.

Association of oily fish and nonoily fish intakes with all-cause mortality and cause-specific mortality: a large population-based prospective study.

BACKGROUND: There are inconsistent results of cohort studies analyzing the association between fish intake and mortality. OBJECTIVE: This study was performed to explore the association of oily fish consumption and nonoily fish consumption with all-cause mortality and cause-specific mortality. METHODS: A total of 431,062 participants from the UK Biobank who were without cancer or cardiovascular disease (CVD) at baseline between 2006 and 2010 were included in this study, and they were followed up through 2021. We constructed Cox proportional hazard models to calculate the hazard ratio (HR) and 95% confidence interval (CI) to assess the correlation of oily fish and nonoily fish intakes with mortality. Then, we performed subgroup analyses, and sensitivity analyses were developed and performed to examine the robustness of this study. RESULTS: Among the participants, 383,248 (88.9%) and 410,499 (95.2%) consumed oily fish and nonoily fish, respectively. Compared with the participants who did not consume oily fish, the adjusted HRs for the association of oily fish consumption (1 serving/week) with all-cause mortality and CVD mortality were 0.93 (0.87 to 0.98; p < 0.05) and 0.85 (0.74 to 0.98; p < 0.05), respectively. The multivariable-adjusted HRs of all-cause mortality for those who reported consuming < 1 serving/week of oily fish were 0.92 (0.86 to 0.98; p < 0.05). CONCLUSION: Compared with participants who reported never consuming oily fish, the consumption of oily fish with 1 serving/week was more beneficial for all-cause and CVD mortality.

Upadacitinib in patients with psoriatic arthritis and inadequate response to biologics: 3-year results from the open-label extension of the randomised controlled phase 3 SELECT-PsA 2 study.

OBJECTIVES: To assess the long-term safety and efficacy of upadacitinib in patients with psoriatic arthritis (PsA) and an inadequate response (IR) to biologic disease-modifying anti-rheumatic drugs (bDMARDs) who completed up to 152 weeks of treatment in the SELECT-PsA 2 study (ClinicalTrials.gov: NCT03104374). METHODS: Patients were randomised to receive blinded upadacitinib 15 or 30 mg once daily (QD), or placebo for 24 weeks followed by upadacitinib 15 or 30 mg QD. After 56 weeks, patients were eligible to enter an open-label extension (OLE) in which they continued their assigned dose of upadacitinib. Efficacy and safety were assessed through 152 weeks. A subanalysis of patients with IR to tumour necrosis factor inhibitors (TNFis) was also conducted. RESULTS: In total, 450 patients entered the OLE and 358 completed 152 weeks of treatment. Improvements in efficacy outcomes observed at week 56, including the proportion of patients achieving: 20/50/70% improvement in American College of Rheumatology criteria, minimal disease activity, and 75/90/100% improvement in Psoriasis Area and Severity Index, were maintained through week 152. Efficacy outcomes in the TNFi-IR subgroup were similar to those reported in the overall population. Upadacitinib was well tolerated throughout long-term treatment, with no cumulative adverse effects observed through 152 weeks. CONCLUSIONS: Efficacy of upadacitinib was maintained up to 152 weeks of treatment in this highly treatment-refractory population of patients with PsA. The long-term safety profile of upadacitinib 15 mg was consistent with its known safety profile across indications; no new safety signals were identified.

A Fluorescence Turn On-off-on Method for Sensitive Detection of Sn2+ and Glycine Using Waste Eggshell Membrane Derived Carbon Nanodots as Probe.

Changes in Sn2+ and glycine levels are relevant to many important physiological procedures in human health. However, investigation of their physiological functions is limited because few versatile methods towards Sn2+ and glycine detection have been developed. In this work, a fluorescence turn on-off-on strategy was firstly constructed for rapid and sensitive detection of Sn2+ and glycine through the specific binding between Sn2+ and glycine. Carbon nanodots (CDs) with a quantum yield of 19.5% were synthesized by utilizing inner film of waste eggshell as carbon source and employed as fluorescent probe. In the presence of Sn2+, the fluorescence of CDs was quenched by Sn2+ via the primary inner filter effect (IFE). However, the binding between Sn2+ and glycine prevented the IFE between Sn2+ and CDs, resulting in fluorescence recovery of CDs. Under optimized conditions, the fluorescent response of CDs displayed good linear relationships with the concentrations of Sn2+ in the range of 10-200 µM and 200-5000 µM, and the limit of detection (LOD) was 2.4 µM. For glycine detection, a good linear relationship was obtained in the concentration range of 5-1000 µM with a low LOD down to 0.76 µM. Moreover, the practicability of the assay was also demonstrated by measuring glycine content in human serum samples. This work provides an economical, green and fast method for biological analysis of Sn2+ and glycine.

Differences in generation and maintenance between ictal and interictal generalized spike-and-wave discharges in childhood absence epilepsy: A magnetoencephalography study.

PURPOSE: Childhood absence epilepsy (CAE) is characterized by impaired consciousness and distinct electroencephalogram (EEG) patterns. However, interictal epileptiform discharges (IEDs) do not lead to noticeable symptoms. This study examines the disparity between ictal and interictal generalized spike-and-wave discharges (GSWDs) to determine the mechanisms behind CAE and consciousness. METHODS: We enrolled 24 patients with ictal and interictal GSWDs in the study. The magnetoencephalography (MEG) data were recorded before and during GSWDs at a sampling rate of 6000 Hz and analyzed across six frequency bands. The absolute and relative spectral power were estimated with the Minimum Norm Estimate (MNE) combined with the Welch technique. All the statistical analyses were performed using paired-sample tests. RESULTS: During GSWDs, the right lateral occipital cortex indicated a significant difference in the theta band (5-7 Hz) with stronger power (P = 0.027). The interictal group possessed stronger spectral power in the delta band (P < 0.01) and weaker power in the alpha band (P < 0.01) as early as 10 s before GSWDs in absolute and relative spectral power. Additionally, the ictal group revealed enhanced spectral power inside the occipital cortex in the alpha band and stronger spectral power in the right frontal regions within beta (15-29 Hz), gamma 1 (30-59 Hz), and gamma 2 (60-90 Hz) bands. CONCLUSIONS: GSWDs seem to change gradually, with local neural activity changing even 10 s before discharge. During GSWDs, visual afferent stimulus insensitivity could be related to the impaired response state in CAE. The inhibitory signal in the low-frequency band can shorten GSWD duration, thereby achieving seizure control through inhibitory effect strengthening.

The correlation between prenatal maternal active smoking and neurodevelopmental disorders in children: a systematic review and meta-analysis.

OBJECTIVE: To systematically evaluate the association between maternal active smoking during pregnancy and Tourette syndrome (TS), chronic tic disorder (CTD), and developmental coordination disorder (DCD) in children, and to provide evidence-based medical references to reduce the incidence of neurodevelopmental disorders in children. METHOD: We searched PubMed, Web of Science, Embase, and Cochrane Library to obtain relevant articles published before 4 August 2021. Two reviewers independently assessed the articles for eligibility and extracted data. RESULTS: We included eight studies involving a total of 50,317 participants (3 cohort, 3 case-control, and 2 cross-sectional studies). The pooled effect estimates suggested that prenatal maternal active smoking is related to an increased risk of neurodevelopmental disorders (OR = 1.91, 95% CI: 1.30-2.80), especially DCD (OR = 2.25, 95% CI: 1.35-3.75). Maternal active smoking during pregnancy is not associated with TS (OR = 1.07, 95% CI: 0.66-1.73) in children. CONCLUSION: In this meta-analysis, we found evidence for a correlation between active smoking exposure in pregnant women and neurodevelopmental disorders in children. Owing to the differences in sample size, smoking categories and diagnostic methods, further research is needed to validate our results.

Probing the effects of silicon amendment on combined stressors on rice: Lead pollution and blast fungus (Magnaporthe oryzae) infection.

As agroecology deteriorates, agricultural production is threatened by the combined stressors of exposure to environmental pollutants and pathogenic microbes. Proper agronomic practices for crop growth management and fertilization require understanding plant tolerance strategies. Both rice blast and heavy metals substantially impair rice crops, while silicon (Si) is an effective amendment to alleviate the combined stressors. Herein, this study was conducted to investigate the rice physiology and pathology perspective on the mechanism of Si alleviation against both lead (Pb) toxicity and Magnaporthe oryzae infection, utilizing pot experiments with inoculation of the virulent Magnaporthe oryzae strain. Exogenous Si reduced the phyto-availability and plant absorption of Pb, resulting in a 73.5% reduction in exchangeable Pb concentration in soil and a 40.23% reduction in rice plants. Furthermore, Si addition boosted the plant antioxidant system by increasing the activities of related enzymes, as the activities of catalase, superoxide dismutase, and polyphenol oxidase were significantly improved while the activity of peroxidase in rice panicles decreased. As a result, an improvement in dry matter quantity by 19.19% was observed compared to treatments without Si application, and the panicle blast severity (PBS) was reduced by 0.4-37.52%. Notwithstanding the interaction between the combined stressors, this study revealed that the speciation of Pb formation in the rhizosphere was the primary contributor to the alleviation of abiotic stresses, whereas the regulation of oxidative stress by enzymatic antioxidants played a dominant role in alleviating Magnaporthe oryzae colonization and impairments. The regulation process may reveal the mechanism of siliceous fertilizer functioning in the paddy system. Thereby the role of exogenous Si in anti-fungal, heavy metal toxicology, and plant physiology needs further study to fully elucidate the role of Si amendment, which is proposed to be considered from the perspective of soil chemistry and plant physiology.

Leukocyte surface biomarkers implicate deficits of innate immunity in sporadic Alzheimer's disease.

INTRODUCTION: Blood-based diagnostics and prognostics in sporadic Alzheimer's disease (AD) are important for identifying at-risk individuals for therapeutic interventions. METHODS: In three stages, a total of 34 leukocyte antigens were examined by flow cytometry immunophenotyping. Data were analyzed by logistic regression and receiver operating characteristic (ROC) analyses. RESULTS: We identified leukocyte markers differentially expressed in the patients with AD. Pathway analysis revealed a complex network involving upregulation of complement inhibition and downregulation of cargo receptor activity and Aß clearance. A proposed panel including four leukocyte markers - CD11c, CD59, CD91, and CD163 - predicts patients' PET Aß status with an area under the curve (AUC) of 0.93 (0.88 to 0.97). CD163 was the top performer in preclinical models. These findings have been validated in two independent cohorts. CONCLUSION: Our finding of changes on peripheral leukocyte surface antigens in AD implicates the deficit in innate immunity. Leukocyte-based biomarkers prove to be both sensitive and practical for AD screening and diagnosis.

Transcriptomics Reveals the Effect of Short-Term Freezing on the Signal Transduction and Metabolism of Grapevine.

Low temperature is an important factor limiting plant growth. Most cultivars of Vitis vinifera L. are sensitive to low temperatures and are at risk of freezing injury or even plant death during winter. In this study, we analyzed the transcriptome of branches of dormant cv. Cabernet Sauvignon exposed to several low-temperature conditions to identify differentially expressed genes and determine their function based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG)enrichment analyses. Our results indicated that exposure to subzero low temperatures resulted in damage to plant cell membranes and extravasation of intracellular electrolytes, and that this damage increased with decreasing temperature or increasing duration. The number of differential genes increased as the duration of stress increased, but most of the common differentially expressed genes reached their highest expression at 6 h of stress, indicating that 6 h may be a turning point for vines to tolerate extreme low temperatures. Several pathways play key roles in the response of Cabernet Sauvignon to low-temperature injury, namely: (1) the role of calcium/calmodulin-mediated signaling; (2) carbohydrate metabolism, including the hydrolysis of cell wall pectin and cellulose, decomposition of sucrose, synthesis of raffinose, and inhibition of glycolytic processes; (3) the synthesis of unsaturated fatty acids and metabolism of linolenic acid; and (4) the synthesis of secondary metabolites, especially flavonoids. In addition, pathogenesis-related protein may also play a role in plant cold resistance, but the mechanism is not yet clear. This study reveals possible pathways for the freezing response and leads to new insights into the molecular basis of the tolerance to low temperature in grapevine.

Genome-wide identification, expression analysis and evolutionary relationships of the IQ67-domain gene family in common wheat (Triticum aestivum L.) and its progenitors.

BACKGROUND: The plant-specific IQ67-domain (IQD) gene family plays an important role in plant development and stress responses. However, little is known about the IQD family in common wheat (Triticum aestivum L), an agriculturally important crop that provides more than 20% of the calories and protein consumed in the modern human diet. RESULTS: We identified 125 IQDs in the wheat genome and divided them into four subgroups by phylogenetic analysis. The IQDs belonging to the same subgroup had similar exon-intron structure and conserved motif composition. Polyploidization contributed significantly to the expansion of IQD genes in wheat. Characterization of the expression profile of these genes revealed that a few T. aestivum (Ta)IQDs showed high tissue-specificity. The stress-induced expression pattern also revealed a potential role of TaIQDs in environmental adaptation, as TaIQD-2A-2, TaIQD-3A-9 and TaIQD-1A-7 were significantly induced by cold, drought and heat stresses, and could be candidates for future functional characterization. In addition, IQD genes in the A, B and D subgenomes displayed an asymmetric evolutionary pattern, as evidenced by their different gain or loss of member genes, expression levels and nucleotide diversity. CONCLUSIONS: This study elucidated the potential biological functions and evolutionary relationships of the IQD gene family in wheat and revealed the divergent fates of IQD genes during polyploidization.