ADAR1p150 prevents MDA5 and PKR activation via distinct mechanisms to avert fatal autoinflammation.

Effective immunity requires the innate immune system to distinguish foreign nucleic acids from cellular ones. Cellular double-stranded RNAs (dsRNAs) are edited by the RNA-editing enzyme ADAR1 to evade being recognized as viral dsRNA by cytoplasmic dsRNA sensors, including MDA5 and PKR. The loss of ADAR1-mediated RNA editing of cellular dsRNA activates MDA5. Additional RNA-editing-independent functions of ADAR1 have been proposed, but a specific mechanism has not been delineated. We now demonstrate that the loss of ADAR1-mediated RNA editing specifically activates MDA5, whereas loss of the cytoplasmic ADAR1p150 isoform or its dsRNA-binding activity enabled PKR activation. Deleting both MDA5 and PKR resulted in complete rescue of the embryonic lethality of Adar1p150-/- mice to adulthood, contrasting with the limited or no rescue by removing MDA5 or PKR alone. Our findings demonstrate that MDA5 and PKR are the primary in vivo effectors of fatal autoinflammation following the loss of ADAR1p150.

Solid-state high harmonic spectroscopy for all-optical band structure probing of high-pressure quantum states.

High pressure has triggered various novel states/properties in condensed matter, as the most representative and dramatic example being near-room-temperature superconductivity in highly pressured hydrides (~200 GPa). However, the mechanism of superconductivity is not confirmed, due to the lacking of effective approach to probe the electronic band structure under such high pressures. Here, we theoretically propose that the band structure and electron-phonon coupling (EPC) of high-pressure quantum states can be probed by solid-state high harmonic generation (sHHG). This strategy is investigated in high-pressure Im-3m H3S by the state-of-the-art first-principles time-dependent density-functional theory simulations, where the sHHG is revealed to be strongly dependent on the electronic structures and EPC. The dispersion of multiple bands near the Fermi level is effectively retrieved along different momentum directions. Our study provides unique insights into the potential all-optical route for band structure and EPC probing of high-pressure quantum states, which is expected to be helpful for the experimental exploration of high-pressure superconductivity in the future.

The Verticillium dahliae effector VdPHB1 promotes pathogenicity in cotton and interacts with the immune protein GhMC4.

Verticillium dahliae is a kind of pathogenic fungus that brings about wilt disease and great losses in cotton. The molecular mechanism of the effectors in V. dahliae regulating cotton immunity remains largely unknown. Here we identified an effector of V. dahliae, VdPHB1, whose gene expression is highly induced by infection. VdPHB1 protein is localized in the intercellular space of cotton plants. Knockout VdPHB1 gene in V. dahliae had no effect on pathogen growth, but decreased the virulence in cotton. VdPHB1 ectopically expressed Arabidopsis plants were growth-inhibited and significantly susceptible to V. dahliae. Further, VdPHB1 interacted with the type II metacaspase GhMC4. GhMC4 gene silenced cotton plants were more sensitive to V. dahliae with reduced expressions of pathogen defense-related and programmed cell death genes. The accumulation of GhMC4 protein were concurrently repressed when VdPHB1 protein expressed during infection. In summary, these results revealed a novel molecular mechanism of virulence regulation that the secreted effector VdPHB1 represses the activity of cysteine protease for helping V. dahliae infection in cotton.

Antibacterial, Fatigue-Resistant, and Self-Healing Dressing from Natural-Based Composite Hydrogels for Infected Wound Healing.

The treatment of infected wounds faces substantial challenges due to the high incidence and serious infection-related complications. Natural-based hydrogel dressings with favorable antibacterial properties and strong applicability are urgently needed. Herein, we developed a composite hydrogel by constructing multiple networks and loading ciprofloxacin for infected wound healing. The hydrogel was synthesized via a Schiff base reaction between carboxymethyl chitosan and oxidized sodium alginate, followed by the polymerization of the acrylamide monomer. The resultant hydrogel dressing possessed a good self-healing ability, considerable compression strength, and reliable compression fatigue resistance. In vitro assessment showed that the composite hydrogel effectively eliminated bacteria and exhibited an excellent biocompatibility. In a model of Staphylococcus aureus-infected full-thickness wounds, wound healing was significantly accelerated without scars through the composite hydrogel by reducing wound inflammation. Overall, this study opens up a new way for developing multifunctional hydrogel wound dressings to treat wound infections.

Resolvin and lipoxin metabolism network regulated by Hyssopus Cuspidatus Boriss extract in asthmatic mice.

Resolvin (Rv) and lipoxin (Lx) play important regulative roles in the development of several inflammation-related diseases. The dysregulation of their metabolic network is believed to be closely related to the occurrence and development of asthma. The Hyssopus Cuspidatus Boriss extract (SXCF) has long been used as a treatment for asthma, while the mechanism of anti-inflammatory and anti-asthma action targeting Rv and Lx has not been thoroughly investigated. In this study, we aimed to investigate the effects of SXCF on Rv, Lx in ovalbumin (OVA)-sensitized asthmatic mice. The changes of Rv, Lx before and after drug administration were analyzed based on high sensitivity chromatography-multiple response monitoring (UHPLC-MRM) analysis and multivariate statistics. The pathology exploration included behavioral changes of mice, IgE in serum, cytokines in BALF, and lung tissue sections stained with H&E. It was found that SXCF significantly modulated the metabolic disturbance of Rv, Lx due to asthma. Its modulation effect was significantly better than that of dexamethasone and rosmarinic acid which is the first-line clinical medicine and the main component of Hyssopus Cuspidatus Boriss, respectively. SXCF is demonstrated to be a potential anti-asthmatic drug with significant disease-modifying effects on OVA-induced asthma. The modulation of Rv and Lx is a possible underlying mechanism of the SXCF effects.

Embosphere microspheres size for bronchial artery embolization in patients with hemoptysis caused by bronchiectasis: a retrospective comparative analysis of 500-750 versus 700-900 µm microspheres.

BACKGROUND: Bronchial arterial embolization (BAE) has been accepted as an effective treatment for bronchiectasis-related hemoptysis. However, rare clinical trials compare different sizes of specific embolic agents. This study aims to evaluate whether different Embosphere microsphere sizes change the outcome of BAE. METHODS: A retrospective review was conducted on consecutive patients with bronchiectatic hemoptysis who were scheduled to undergo BAE treatment during a period from January 2018 to December 2022. The patients received BAE using microspheres of different sizes: group A patients were treated with 500-750 µm microspheres, and group B patients were treated with 700-900 µm microspheres. The cost of embolic microspheres (Chinese Yuan, CNY), duration of hospitalization, complications, and hemoptysis-free survival were compared between patients in group A and those in group B. A Cox proportional hazards regression model was used to identify predictors of recurrent hemoptysis. RESULTS: Median follow-up was 30.2 months (range, 20.3-56.5 months). The final analysis included a total of 112 patients (49-77 years of age; 45 men). The patients were divided into two groups: group A (N = 68), which received 500-750 µm Embosphere microspheres, and group B (N = 44), which received 700-900 µm Embosphere microspheres. Except for the cost of embolic microspheres(group A,5314.8 + 1301.5 CNY; group B, 3644.5 + 1192.3 CNY; p = 0.042), there were no statistically significant differences in duration of hospitalization (group A,7.2 + 1.4 days; group B, 8 + 2.4days; p = 0.550), hemoptysis-free survival (group A, 1-year, 2-year, 3-year, 85.9%, 75.8%, 62.9%; group B, 1-year, 2-year, 3-year, 88.4%, 81.2%,59.4%;P = 0.060), and complications(group A,26.5%; group B, 38.6%; p = 0.175) between the two groups. No major complications were observed. The multivariate analysis results revealed that the presence of cystic bronchiectasis (OR 1.61, 95% CI 1.12-2.83; P = 0.001) and systemic arterial-pulmonary shunts (SPSs) (OR 1.52, 95% CI 1.10-2.72; P = 0.028) were independent risk factors for recurrent bleeding. CONCLUSIONS: For the treatment of BAE in patients with bronchiectasis-related hemoptysis, 500-750 µm diameter Embosphere microspheres have a similar efficacy and safety profile compared to 700-900 µm diameter Embosphere microspheres, especially for those without SPSs or cystic bronchiectasis. Furthermore, the utilization of large-sized (700-900 µm) Embosphere microspheres is associated with the reduced cost of an embolic agent.

Mechanism of Mulberry Leaves and Black Sesame in Alleviating Slow Transit Constipation Revealed by Multi-Omics Analysis.

Traditional Chinese medicine (TCM) possesses the potential of providing good curative effects with no side effects for the effective management of slow transit constipation (STC), an intestinal disease characterized by colonic dyskinesia. Mulberry leaves (Morus alba L.) and black sesame (Sesamum indicum L.), referred to as SH, are processed and conditioned as per standardized protocols. SH has applications as food and medicine. Accordingly, we investigated the therapeutic potential of SH in alleviating STC. The analysis of SH composition identified a total of 504 compounds. The intervention with SH significantly improved intestinal motility, reduced the time for the first black stool, increased antioxidant activity, and enhanced water content, thereby effectively alleviating colon damage caused by STC. Transcriptome analysis revealed the SH in the treatment of STC related to SOD1, MUC2, and AQP1. The analysis of 16S rRNA gene sequences indicated notable differences in the abundance of 10 bacteria between the SH and model. Metabolomic analysis further revealed that SH supplementation increased the levels of nine metabolites associated with STC. Integrative analysis revealed that SH modulated amino acid metabolism, balanced intestinal flora, and targeted key genes (i.e., SOD1, MUC2, AQP1) to exert its effects. SH also inhibited the AQP1 expression and promoted SOD1 and MUC2 expression.

Rerouting of the lignin biosynthetic pathway by inhibition of cytosolic shikimate recycling in transgenic hybrid aspen.

Lignin is a phenolic polymer deposited in the plant cell wall, and is mainly polymerized from three canonical monomers (monolignols), i.e. p-coumaryl, coniferyl and sinapyl alcohols. After polymerization, these alcohols form different lignin substructures. In dicotyledons, monolignols are biosynthesized from phenylalanine, an aromatic amino acid. Shikimate acts at two positions in the route to the lignin building blocks. It is part of the shikimate pathway that provides the precursor for the biosynthesis of phenylalanine, and is involved in the transesterification of p-coumaroyl-CoA to p-coumaroyl shikimate, one of the key steps in the biosynthesis of coniferyl and sinapyl alcohols. The shikimate residue in p-coumaroyl shikimate is released in later steps, and the resulting shikimate becomes available again for the biosynthesis of new p-coumaroyl shikimate molecules. In this study, we inhibited cytosolic shikimate recycling in transgenic hybrid aspen by accelerated phosphorylation of shikimate in the cytosol through expression of a bacterial shikimate kinase (SK). This expression elicited an increase in p-hydroxyphenyl units of lignin and, by contrast, a decrease in guaiacyl and syringyl units. Transgenic plants with high SK activity produced a lignin content comparable to that in wild-type plants, and had an increased processability via enzymatic saccharification. Although expression of many genes was altered in the transgenic plants, elevated SK activity did not exert a significant effect on the expression of the majority of genes responsible for lignin biosynthesis. The present results indicate that cytosolic shikimate recycling is crucial to the monomeric composition of lignin rather than for lignin content.

Gender differences in suicidal ideation, suicide attempts, and suicide death among people living with HIV: A systematic review and meta-analysis.

OBJECTIVE: Although excess mortality, especially suicide, is a critical trait in people living with HIV, consensus about gender differences in these areas is lacking. We conducted meta-analyses to examine gender differences in suicidal ideation, suicide attempts, and suicide death among people living with HIV. METHODS: We systematically searched PubMed and Web of Science for studies written in English. In this review, suicide among people living with HIV includes suicide death, suicidal ideation, and suicide attempts. Studies reporting the suicide prevalence among males and females living with HIV were eligible for inclusion in our review. Odds ratios (ORs) and 95% confidence intervals (CIs) served as the effect size index. Fixed-effects or random-effects meta-analyses were chosen based on the size of the heterogeneity. RESULTS: A total of 27 studies comprising 801 017 participants from 11 countries were included in the meta-analysis. The overall prevalence of suicidal ideation was 18.0% (95% CI 13.3%-22.8%) in males and 20.8% (95% CI 16.4%-25.1%) in females, and there was a statistically significant higher risk of suicidal ideation in females living with HIV (OR 1.30; 95% CI 1.09-1.56; p < 0.05). The overall prevalence of suicide attempts was 16.8% (95% CI 9.0%-24.5%) in males and 24.7% (95% CI 12.4%-37.1%) in females, and there was a statistically significant higher risk of suicide attempts in females living with HIV (OR 1.34; 95% CI 1.02-1.75; p < 0.05). The pooled prevalence of suicide death was 1.2% (95% CI 0.5%-1.9%) among males and 0.2% (95% CI 0.1%-0.3%) among females, and the risk of suicide death between genders was not statistically significant (OR 0.78; 95% CI 0.50-1.24; p = 0.298). CONCLUSIONS: There were gender differences in suicidal ideation and suicide attempts among people living with HIV. Females living with HIV were more likely to experience suicidal ideation and make suicide attempts, but there were no statistically significant gender differences in suicide death. Appropriate initiatives to optimize the recognition, treatment, and management suicide behaviours of males and females living with HIV may narrow this gender gap.

Anomalous polarization-sensitive Fabry-Perot resonance in a one-dimensional photonic crystal containing an all-dielectric metamaterial defect.

Owing to polarization-independent property of propagating phases inside isotropic dielectric layers, Fabry-Perot resonances in metal-dielectric-metal sandwich structures and one-dimensional (1-D) photonic crystals (PhCs) with isotropic dielectric defects are polarization-insensitive. Herein, we introduce an all-dielectric elliptical metamaterial (EMM) defect into a 1-D PhC to realize an anomalous polarization-sensitive Fabry-Perot resonance empowered by the polarization-sensitive property of the propagating phase inside the all-dielectric EMM layer. The wavelength difference of the Fabry-Perot resonance between transverse magnetic and transverse electric polarizations is larger than 100 nm at the incident angle of 45 degrees. Enabled by the polarization-sensitive property of the Fabry-Perot resonance, high-performance polarization selectivity can be achieved in a broad angle range. Our work offers a viable recipe, well within the reach of current fabrication technique, to explore polarization-dependent physical phenomena and devices.

Anomalous polarization-sensitive Fabry-Perot resonance in a one-dimensional photonic crystal containing an all-dielectric metamaterial defect: erratum.

This erratum corrects some typing errors of our original paper, Opt. Express31(20), 32669 (2023)10.1364/OE.499830. The correction does not affect the results of the original paper.

Arabidopsis calcium-dependent protein kinase CPK6 regulates drought tolerance under high nitrogen by the phosphorylation of NRT1.1.

Nitrogen (N) is an essential macronutrient for plant growth and development, and its availability is regulated to some extent by drought stress. Calcium-dependent protein kinases (CPKs) are a unique family of Ca2+ sensors with diverse functions in N uptake and drought-tolerance signaling pathways; however, how CPKs are involved in the crosstalk between drought stress and N transportation remains largely unknown. Here, we identify the drought-tolerance function of Arabidopsis CPK6 under high N conditions. CPK6 expression was induced by ABA and drought treatments. The mutant cpk6 was insensitive to ABA treatment and low N, but was sensitive to drought only under high N conditions. CPK6 interacted with the NRT1.1 (CHL1) protein and phosphorylated the Thr447 residue, which then repressed the NO3- transporting activity of Arabidopsis under high N and drought stress. Taken together, our results show that CPK6 regulates Arabidopsis drought tolerance through changing the phosphorylation state of NRT1.1, and improve our knowledge of N uptake in plants during drought stress.

Angle-insensitive topological interface states in hybrid one-dimensional photonic crystal heterostructures containing all-dielectric metamaterials.

Topological interface states (TISs) in conventional one-dimensional (1D) photonic crystal (PhC) heterostructures strongly shift toward higher frequencies as the incident angle increases. This strong blueshift property of TISs intensively limits the operating angle ranges of TISs. Herein, we design two angle-insensitive photonic bandgaps (PBGs) in two hybrid 1D PhCs containing all-dielectric metamaterials. By cascading these two hybrid 1D PhCs to construct a hybrid 1D PhC heterostructure, we achieve an angle-insensitive TIS under transverse magnetic polarization. Empowered by the angle-insensitive property of the PBGs, the angular tolerance of the TIS reaches 69.65°, which is much higher than those of the TISs in conventional 1D PhC heterostructures. In addition, the angle-insensitive property of the TIS is robust against the layer thickness. Our work provides a viable route to achieving TISs with high angular tolerances and would facilitate the applications of photonic topological states.

Spinal cord astrocyte P2X7Rs mediate the inhibitory effect of electroacupuncture on visceral hypersensitivity of rat with irritable bowel syndrome.

This study explored the role of P2X7 receptors in spinal cord astrocytes in the electroacupuncture-induced inhibition of visceral hypersensitivity (VH) in rats with irritable bowel syndrome (IBS). Visceral hypersensitivity of IBS was intracolonically induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). Visceromotor responses to colorectal distension (CRD-20,40,60,80 mmHg) and abdominal withdrawal reflex scoring (AWRs) were recorded after electroacupuncture at bilateral Zusanli (ST36) and Sanyinjiao (SP6) acupoints to evaluate the analgesic effect of electroacupuncture on visceral pain in rats with IBS. Fluorocitric acid (FCA), an astrocyte activity inhibitor, was injected intrathecally before electroacupuncture intervention and AWRs were recorded. Western blot and real-time qPCR were used to detect the expression of NMDA and P2X7 receptor to observe the regulation effect of electroacupuncture on NMDA receptor in the spinal cord of rats with visceral hypersensitivity. Intrathecal injection of P2X7 agonist or antagonist was administered before electroacupuncture treatment. To observe the effect of P2X7 receptor in spinal astrocytes on the inhibition of visceral hyperalgesia by electroacupuncture, the changes of AWR score, NMDA receptor in the spinal cord, and GFAP expression in astrocytes were detected. Inflammation of the colon had basically subsided at day 21 post-TNBS; persistent visceral hypersensitivity could be suppressed by electroacupuncture. This analgesic effect could be inhibited by FCA. The analgesic effect, downregulation of NMDA receptor NR1 subunit, and P2X7 protein of electroacupuncture were all reversed by FCA. P2X7 receptor antagonist A740003 can cooperate with EA to carry out analgesic effect in rats with visceral pain and downregulate the expression of NR1, NR2B, and GFAP in spinal dorsal horn. However, the P2X7 receptor agonist BzATP could partially reverse the analgesic effect of EA, inhibiting the downregulatory effect of EA on the expression of NR1, NR2B, and GFAP. These results indicate that EA may downregulate the expression of the NMDA receptor by inhibiting the P2X7 receptor in the spinal cord, thereby inhibiting spinal cord sensitization in IBS rats with visceral pain, in which astrocytes are an important medium.

Disturbance of suprachiasmatic nucleus function improves cardiac repair after myocardial infarction by IGF2-mediated macrophage transition.

Suprachiasmatic nucleus (SCN) in mammals functions as the master circadian pacemaker that coordinates temporal organization of physiological processes with the environmental light/dark cycles. But the causative links between SCN and cardiovascular diseases, specifically the reparative responses after myocardial infarction (MI), remain largely unknown. In this study we disrupted mouse SCN function to investigate the role of SCN in cardiac dysfunction post-MI. Bilateral ablation of the SCN (SCNx) was generated in mice by electrical lesion; myocardial infarction was induced via ligation of the mid-left anterior descending artery (LAD); cardiac function was assessed using echocardiography. We showed that SCN ablation significantly alleviated MI-induced cardiac dysfunction and cardiac fibrosis, and promoted angiogenesis. RNA sequencing revealed differentially expressed genes in the heart of SCNx mice from D0 to D3 post-MI, which were functionally associated with the inflammatory response and cytokine-cytokine receptor interaction. Notably, the expression levels of insulin-like growth factor 2 (Igf2) in the heart and serum IGF2 concentration were significantly elevated in SCNx mice on D3 post-MI. Stimulation of murine peritoneal macrophages in vitro with serum isolated from SCNx mice on D3 post-MI accelerated the transition of anti-inflammatory macrophages, while antibody-mediated neutralization of IGF2 receptor blocked the macrophage transition toward the anti-inflammatory phenotype in vitro as well as the corresponding cardioprotective effects observed in SCNx mice post-MI. In addition, disruption of mouse SCN function by exposure to a desynchronizing condition (constant light) caused similar protective effects accompanied by elevated IGF2 expression on D3 post-MI. Finally, mice deficient in the circadian core clock genes (Ckm-cre; Bmal1f/f mice or Per1/2 double knockout) did not lead to increased serum IGF2 concentration and showed no protective roles in post-MI, suggesting that the cardioprotective effect observed in this study was mediated particularly by the SCN itself, but not by self-sustained molecular clock. Together, we demonstrate that inhibition of SCN function promotes Igf2 expression, which leads to macrophage transition and improves cardiac repair post-MI.

Investigation of the conversion mechanism of endogenous semicarbazide in shrimp on the amino acid level.

Semicarbazide (SEM), the metabolite of antibiotic nitrofurazone, is often used as the biomarker to determine the use of nitrofurazone. Frequent false-positive events of SEM have brought great trouble to the aquatic industry in international trade. In this paper, the situation of endogenous SEM in aquatic products was investigated, and the possible mechanism of amino acid conversion into SEM was studied by establishing a simulated oxidation system and a urea system. The results revealed the presence of endogenous SEM in the muscle tissue of shrimps, and the content of SEM ranged from 0.56 to 5.28 ng/g, which presented as Macrobrachium nipponense>Macrobrachium rosenbergii>Procambarus clarkii. The increase in SEM production of control lysine under natural oxidation conditions suggests that oxidation has an effect on the conversion of SEM. Under the action of the simulated oxidation system, the SEM of Arginine, Lysine, Citrulline and Glutamine among the 21 amino acids were increased, and the polymer azine was formed. In combination with the structure of four amino acids, it was presumed that the group of amide is a key intermediate structure for the formation of endogenous SEM. In addition, under the urea system, the content of SEM produced by amino acids increased after the addition of urea, and the concentration of urea had a significant correlation with the content of SEM. Taken together, the production of endogenous SEM in shrimps is related to amino acids and urea, and the urea cycle and other substances containing amide structures should also be considered in future explorations.

Palliative care for cancer patients during the COVID-19 pandemic: A narrative synthesis from 36 studies of 16 countries.

BACKGROUND: During the COVID-19 epidemic, palliative care has become even more indispensable for cancer patients. AIM: To identify the changes in palliative care for cancer patients and improvements in palliative care quality during the COVID-19 pandemic. DESIGN: A systematic review and narrative synthesis was conducted in PubMed, Embase and Web of Science. An evaluation tool using mixed methods was used to assess the quality of the study. The main relevant themes identified were used to group qualitative and quantitative findings. RESULTS: A total of 36 studies were identified, primarily from different countries, with a total of 14,427 patients, 238 caregivers and 354 health care providers. Cancer palliative care has been experiencing several difficulties following the COVID-19 pandemic, including increased mortality and infection rates as well as delays in patient treatment that have resulted in poorer prognoses. Treatment providers are seeking solutions such as electronic management of patients and integration of resources to care for the mental health of patients and staff. Telemedicine plays an important role in many ways but cannot completely replace traditional treatment. Clinicians strive to meet patients' palliative care needs during special times and improve their quality of life. CONCLUSIONS: Palliative care faces unique challenges during the COVID-19 epidemic. With adequate support to alleviate care-related challenges, patients in the home versus hospital setting will be able to receive better palliative care. In addition, this review highlights the importance of multiparty collaboration to achieve personal and societal benefits of palliative care. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution.

Calibrating Out-of-Equilibrium Electron-Phonon Couplings in Photoexcited MoS2.

Nonequilibrium electron-phonon coupling (EPC) serves as a dominant interaction in a multitude of transient processes, including photoinduced phase transitions, coherent phonon generation, and possible light-induced superconductivity. Here we use monolayer MoS2 as a prototype to investigate the variation in electron-phonon couplings under laser excitation, on the basis of real-time time-dependent density functional theory simulations. Phonon softening, anisotropic modification of the deformation potential, and enhancement of EPC are observed, which are attributed to the reduced electronic screening and modulated potential energy surfaces by photoexcitation. Furthermore, by tracking the transient deformation potential and nonthermal electronic population, we can monitor the ultrafast time evolution of the energy exchange rate between electrons and phonons upon laser excitation. This work provides an effective strategy to investigate the nonequilibrium EPC and constructs a scaffold for understanding nonequilibrium states beyond the multitemperature models.

Protein arginine methyltransferase CARM1 attenuates the paraspeckle-mediated nuclear retention of mRNAs containing IRAlus.

In many cells, mRNAs containing inverted repeated Alu elements (IRAlus) in their 3' untranslated regions (UTRs) are inefficiently exported to the cytoplasm. Such nuclear retention correlates with paraspeckle-associated protein complexes containing p54(nrb). However, nuclear retention of mRNAs containing IRAlus is variable, and how regulation of retention and export is achieved is poorly understood. Here we show one mechanism of such regulation via the arginine methyltransferase CARM1 (coactivator-associated arginine methyltransferase 1). We demonstrate that disruption of CARM1 enhances the nuclear retention of mRNAs containing IRAlus. CARM1 regulates this nuclear retention pathway at two levels: CARM1 methylates the coiled-coil domain of p54(nrb), resulting in reduced binding of p54(nrb) to mRNAs containing IRAlus, and also acts as a transcription regulator to suppress NEAT1 transcription, leading to reduced paraspeckle formation. These actions of CARM1 work together synergistically to regulate the export of transcripts containing IRAlus from paraspeckles under certain cellular stresses, such as poly(I:C) treatment. This work demonstrates how a post-translational modification of an RNA-binding protein affects protein-RNA interaction and also uncovers a mechanism of transcriptional regulation of the long noncoding RNA NEAT1.

Effect of matrix metalloproteinases on the healing of diabetic foot ulcer: A systematic review.

BACKGROUND: This study aims to discuss the expression of matrix metalloproteinase in wound healing of diabetic foot ulcers and further summarize the strategies of targeted matrix metalloproteinase and its inhibitors in the treatment of diabetic foot ulcers. METHODS: Following PRISMA-SCR guidelines, databases (PubMed, Home-PMC-NCBI, CINAHL, Web of Science) were systematically searched from inception to 19 June 2022. Newcastle-Ottawa Scale (NOS) was used to evaluate the bias risk of the included studies. RESULTS: Eight studies are finally eligible for our systematic review. The combined data analysis of 8 studies showed that there were no significant difference in age(p = 0.110), duration of diabetes(p = 0.197), glycosylated hemoglobin content(p = 0.489), size(p = 0.133) and depth(p＞0.05) of initial ulcer between the ulcer wound healing group and the non-healing group. MMP-1, 2, 8, 9, and TIMP-1, 2 affected the healing of DFUs. In the DFUs healing group, the concentrations of MMP (MMP-1, 2, 8, 9) decreased, and the concentration of TIMP-1 increased. CONCLUSION: Our study showed that high levels of MMP-1, 2, 9 delayed the healing of diabetic foot ulcers, and high expression of MMP-8 in tissues improved wound healing. This study also summarized the effective intervention strategies for the treatment of diabetic foot ulcers.