This study aimed to investigate the association of high-sensitivity C-reactive protein (hs-CRP) with incident frailty as well as its effects on pre-frailty progression and regression among ...middle-aged and older adults.
Based on the frailty index (FI) calculated with 41 items, 6890 eligible participants without frailty at baseline from China Health and Retirement Longitudinal Study (CHARLS) were categorized into health, pre-frailty, and frailty groups. Logistic regression models were used to estimate the longitudinal association between baseline hs-CRP and incident frailty. Furthermore, a series of genetic approaches were conducted to confirm the causal relationship between CRP and frailty, including Linkage disequilibrium score regression (LDSC), pleiotropic analysis, and Mendelian randomization (MR). Finally, we evaluated the association of hs-CRP with pre-frailty progression and regression.
The risk of developing frailty was 1.18 times (95% CI: 1.03-1.34) higher in participants with high levels of hs-CRP at baseline than low levels of hs-CRP participants during the 3-year follow-up. MR analysis suggested that genetically determined hs-CRP was potentially positively associated with the risk of frailty (OR: 1.06, 95% CI: 1.03-1.08). Among 5241 participants with pre-frailty at baseline, we found pre-frailty participants with high levels of hs-CRP exhibit increased odds of progression to frailty (OR: 1.39, 95% CI: 1.09-1.79) and decreased odds of regression to health (OR: 0.84, 95% CI: 0.72-0.98) when compared with participants with low levels of hs-CRP.
Our results suggest that reducing systemic inflammation is significant for developing strategies for frailty prevention and pre-frailty reversion in the middle-aged and elderly population.
N6-Methyladenosine (m6A) RNA methylation plays important roles during development in different species. However, knowledge of m6A RNA methylation in monocots remains limited. In this study, we ...reported that OsFIP and OsMTA2 are the components of m6A RNA methyltransferase complex in rice and uncovered a previously unknown function of m6A RNA methylation in regulation of plant sporogenesis. Importantly, OsFIP is essential for rice male gametogenesis. Knocking out of OsFIP results in early degeneration of microspores at the vacuolated pollen stage and simultaneously causes abnormal meiosis in prophase I. We further analyzed the profile of rice m6A modification during sporogenesis in both WT and OsFIP loss-of-function plants, and identified a rice panicle specific m6A modification motif "UGWAMH". Interestingly, we found that OsFIP directly mediates the m6A methylation of a set of threonine protease and NTPase mRNAs and is essential for their expression and/or splicing, which in turn regulates the progress of sporogenesis. Our findings revealed for the first time that OsFIP plays an indispensable role in plant early sporogenesis. This study also provides evidence for the different functions of the m6A RNA methyltransferase complex between rice and Arabidopsis.
The cereal endosperm is a major factor determining seed size and shape. However, the molecular mechanisms of endosperm development are not fully understood. Long noncoding RNAs (lncRNAs) function in ...various biological processes. Here we show a lncRNA, MISSEN, that plays an essential role in early endosperm development in rice (Oryza sativa). MISSEN is a parent-of-origin lncRNA expressed in endosperm, and negatively regulates endosperm development, leading to a prominent dent and bulge in the seed. Mechanistically, MISSEN functions through hijacking a helicase family protein (HeFP) to regulate tubulin function during endosperm nucleus division and endosperm cellularization, resulting in abnormal cytoskeletal polymerization. Finally, we revealed that the expression of MISSEN is inhibited by histone H3 lysine 27 trimethylation (H3K27me3) modification after pollination. Therefore, MISSEN is the first lncRNA identified as a regulator in endosperm development, highlighting the potential applications in rice breeding.
Ionic liquids (ILs)‐incorporated solid‐state polymer electrolytes (iono‐SPEs) have high ionic conductivities but show non‐uniform Li+ transport in different phases. This work greatly promotes Li+ ...transport in polymer phases by employing a poly (vinylidene fluoride‐trifluoroethylene‐chlorotrifluoroethylene) P(VDF‐TrFE‐CTFE), PTC as the framework of ILs to prepare iono‐SPEs. Unlike PVDF, PTC with suitable polarity shows weaker adsorption energy on IL cations, reducing their possibility of occupying Li+‐hopping sites. The significantly higher dielectric constant of PTC than PVDF facilitates the dissociation of Li‐anions clusters. These two factors motivate Li+ transport along PTC chains, narrowing the difference in Li+ transport among varied phases. The LiFePO4/PTC iono‐SPE/Li cells cycle steadily with capacity retention of 91.5 % after 1000 cycles at 1 C and 25 °C. This work paves a new way to induce uniform Li+ flux in iono‐SPEs through polarity and dielectric design of polymer matrix.
The P(VDF‐TrFE‐CTFE) shows lower adsorption energy on Pyr13+ from ionic liquids (ILs) than PVDF, which reduces the chance for Pyr13+ to occupy transport sites of Li+ and lower the Li+ migration barrier. In consequence, the Li+ transport in polymer phases is promoted, which narrows the gap of Li+ mobility between polymer phases with ILs and polymer‐ILs interfaces, contributing to uniform Li+ flux to inhibit the lithium dendrites’ growth.
Our previous works have indicated that extracellular ATP is an important prometastasis factor. However, the molecular mechanism involved needs to be further studied. We demonstrated that ...extracellular ATP treatment could upregulate the expression of connective tissue growth factor (CTGF) in both triple‐negative breast cancer (TNBC) cells and endothelial cells (ECs). Extracellular ATP stimulated the migration of TNBC cells and ECs, and angiogenesis of ECs via the P2Y2––YAP‐CTGF axis. Furthermore, we demonstrated that adenosine triphosphate (ATP) stimulated TNBC cell adhesion to ECs and transmigration through the EC layer via CTGF by upregulation of integrin β1 on TNBC cells and VCAM‐1 on ECs. Both apyrase (ATP‐diphosphohydrolase) and CTGF shRNA treatments could inhibit the metastasis of inoculated tumors to lung and liver in a mouse model, and these treated tumors had fewer blood vessels. Collectively, our data indicated that extracellular ATP promotes tumor angiogenesis and the interactions between TNBC cells and ECs through upregulation of CTGF, thereby stimulating TNBC metastasis. The pleiotropic effects of ATP in angiogenesis and cell adhesion suggest that extracellular ATP or CTGF could be an effective target for TNBC therapy.
The proposed model for the ATP–CTGF axis in TNBC invasion and metastasis. ATP upregulates CTGF expression and secretion in TNBC cells and ECs. For TNBC cells, secreted CTGF enhanced their migration and integrin β1 expression. For EC cells, secreted CTGF enhanced their migration and angiogenesis, as well as VCAM‐1 expression. The upregulated integrin β1 and VCAM‐1 promoted TNBC cell adhesion to ECs and transmigration through the ECs layer.
Summary
Plant defence is multilayered and is essential for surviving in a changing environment. The discovery of long noncoding RNAs (lncRNAs) has dramatically extended our understanding of ...post‐transcriptional gene regulation in diverse biological processes. However, the expression profile and function of lncRNAs in disease resistance are still largely unknown, especially in monocots. Here, we performed strand‐specific RNA sequencing of rice leaves infected by Xanthomonas oryzae pv. Oryzae (Xoo) in different time courses and systematically identified 567 disease‐responsive rice lncRNAs. Target analyses of these lncRNAs showed that jasmonate (JA) pathway was significantly enriched. To reveal the interaction between lncRNAs and JA‐related genes, we studied the coexpression of them and found 39 JA‐related protein‐coding genes to be interplayed with 73 lncRNAs, highlighting the potential modulation of lncRNAs in JA pathway. We subsequently identified an lncRNA, ALEX1, whose expression is highly induced by Xoo infection. A T‐DNA insertion line constructed using enhancer trap system showed a higher expression of ALEX1 and exerted a significant resistance to rice bacterial blight. Functional study revealed that JA signalling is activated and the endogenous content of JA and JA‐Ile is increased. Overexpressing ALEX1 in rice further confirmed the activation of JA pathway and resistance to bacterial blight. Our findings reveal the expression of pathogen‐responsive lncRNAs in rice and provide novel insights into the connection between lncRNAs and JA pathway in the regulation of plant disease resistance.
The dynamics, duration, and nature of immunity produced during SARS-CoV-2 infection are still unclear. Here, we longitudinally measured virus-neutralising antibody, specific antibodies against the ...spike (S) protein, receptor-binding domain (RBD), and the nucleoprotein (N) of SARS-CoV-2, as well as T cell responses, in 25 SARS-CoV-2-infected patients up to 121 days post-symptom onset (PSO). All patients seroconvert for IgG against N, S, or RBD, as well as IgM against RBD, and produce neutralising antibodies (NAb) by 14 days PSO, with the peak levels attained by 15-30 days PSO. Anti-SARS-CoV-2 IgG and NAb remain detectable and relatively stable 3-4 months PSO, whereas IgM antibody rapidly decay. Approximately 65% of patients have detectable SARS-CoV-2-specific CD4
or CD8
T cell responses 3-4 months PSO. Our results thus provide critical evidence that IgG, NAb, and T cell responses persist in the majority of patients for at least 3-4 months after infection.
H2O2 is a significant chemical widely utilized in the environmental and industrial fields, with growing global demand. Without sacrificial agents, simultaneously photocatalyzing H2O2 synthesis ...through the oxygen reduction reaction (ORR) and water oxidation reaction (WOR) dual channels from seawater is green and sustainable but still challenging. Herein, two novel thiophene-containing covalent organic frameworks (TD-COF and TT-COF) were first constructed and served as catalysts for H2O2 synthesis via indirect 2e- ORR and direct 2e- WOR channels. The photocatalytic H2O2 production performance can be regulated by adjusting the N-heterocycle modules (pyridine and triazine) in COFs. Notably, with no sacrificial agents, just using air and water as raw materials, TD-COF exhibited high H2O2 production yields of 4060 μmol h-1 g-1, and 3364 μmol h-1 g-1 in deionized water and natural seawater, respectively. Further computational mechanism studies revealed that the thiophene was the primary photoreduction unit for ORR, while the benzene ring (linked to the thiophene by the imine bond) was the central photooxidation unit for WOR. The current work exploits thiophene-containing COFs for overall photocatalytic H2O2 synthesis via ORR and WOR dual channels and provides fresh insight into creating innovative catalysts for photocatalyzing H2O2 synthesis.
Thrombocytopenia is independently related with increased mortality in severe septic patients. Renin‐angiotensin system (RAS) is elevated in septic subjects; accumulating studies show that angiotensin ...II (Ang II) stimulate the intrinsic apoptosis pathway by promoting reactive oxygen species (ROS) production. However, the mechanisms underlying the relationship of platelet apoptosis and RAS system in sepsis have not been fully elucidated. The present study aimed to elucidate whether the RAS was involved in the pathogenesis of sepsis‐associated thrombocytopenia and explore the underlying mechanisms. We found that elevated plasma Ang II was associated with decreased platelet count in both patients with sepsis and experimental animals exposed to lipopolysaccharide (LPS). Besides, Ang II treatment induced platelet apoptosis in a concentration‐dependent manner in primary isolated platelets, which was blocked by angiotensin II type 1 receptor (AT1R) antagonist losartan, but not by angiotensin II type 2 receptor (AT2R) antagonist PD123319. Moreover, inhibiting AT1R by losartan attenuated LPS‐induced platelet apoptosis and alleviated sepsis‐associated thrombocytopenia. Furthermore, Ang II treatment induced oxidative stress level in a concentration‐dependent manner in primary isolated platelets, which was partially reversed by the AT1R antagonist losartan. The present study demonstrated that elevated Ang II directly stimulated platelet apoptosis through promoting oxidative stress in an AT1R‐dependent manner in sepsis‐associated thrombocytopenia. The results would helpful for understanding the role of RAS system in sepsis‐associated thrombocytopenia.
Ulcerative colitis (UC) is a chronic gastrointestinal disorder characterized by inflammation and ulceration, representing a significant predisposition to colorectal cancer. Recent advances in ...single-cell RNA sequencing (scRNA-seq) technology offer a promising avenue for dissecting the complex cellular inter-actions and molecular signatures driving UC pathology.
To utilize scRNA-seq technology to dissect the complex cellular interactions and molecular signatures that underlie UC pathology.
In this research, we integrated and analyzed the scRNA-seq data from UC patients. Moreover, we conducted mRNA and protein level assays as well as pathology-related staining tests on clinical patient samples.
In this study, we identified the sustained upregulation of inflammatory response pathways during UC progression, characterized the features of damaged endo-thelial cells in colitis. Furthermore, we uncovered the downregulation of phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) has a negative correlation with signal transducer and activator of transcription 3. Significant downregulation of LHPP in UC patient tissues and plasma suggests that LHPP may serve as a potential therapeutic target for UC. This paper highlights the importance of LHPP as a potential key target in UC and unveils its potential role in inflammation regulation.
The findings suggest that LHPP may serve as a potential therapeutic target for UC, emphasizing its importance as a potential key target in UC and unveiling its role in inflammation regulation.
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