STING-dependent interferon signatures restrict osteoclast differentiation and bone loss in mice.

Stimulator of interferon genes (STING) is a key mediator of type-I interferon (IFN-I) signaling in response to a variety of stimuli, but the contribution of STING to homeostatic processes is not fully characterized. Previous studies showed that ligand activation of STING limits osteoclast differentiation in vitro through the induction of IFNß and IFN-I interferon-stimulated genes (ISGs). In a disease model (SAVI) driven by the V154M gain-of-function mutation in STING, fewer osteoclasts form from SAVI precursors in response to receptor activator of NF-kappaB ligand (RANKL) in an IFN-I-dependent manner. Due to the described role of STING-mediated regulation of osteoclastogenesis in activation settings, we sought to determine whether basal STING signaling contributes to bone homeostasis, an unexplored area. Using whole-body and myeloid-specific deficiency, we show that STING signaling prevents trabecular bone loss in mice over time and that myeloid-restricted STING activity is sufficient for this effect. STING-deficient osteoclast precursors differentiate with greater efficiency than wild types. RNA sequencing of wild-type and STING-deficient osteoclast precursor cells and differentiating osteoclasts reveals unique clusters of ISGs including a previously undescribed ISG set expressed in RANKL naïve precursors (tonic expression) and down-regulated during differentiation. We identify a 50 gene tonic ISG signature that is STING dependent and shapes osteoclast differentiation. From this list, we identify interferon-stimulated gene 15 (ISG15) as a tonic STING-regulated ISG that limits osteoclast formation. Thus, STING is an important upstream regulator of tonic IFN-I signatures shaping the commitment to osteoclast fates, providing evidence for a nuanced and unique role for this pathway in bone homeostasis.

Far-red light-enhanced apical dominance stimulates flower and fruit abortion in sweet pepper.

Far-red radiation affects many plant processes, including reproductive organ abortion. Our research aimed to determine the role of apical dominance in far-red light-induced flower and fruit abortion in sweet pepper (Capsicum annuum L.). We conducted several climate room experiments where plants were grown under white- or red-rich LED light, with or without additional far-red light. Additional far-red light enhanced apical dominance: it increased auxin levels in the apices of dominant shoots, and caused a greater difference in internode length and apical auxin levels between dominant and subordinate shoots. Additional far-red light stimulated fruit abortion in intact plants but not in decapitated plants, suggesting a crucial role of shoot apices in this effect. However, reducing basipetal auxin transport in the stems with N-1-naphthylphthalamic acid did not influence far-red light-stimulated fruit abortion, although auxin levels in the stem were largely reduced. Applying the synthetic auxin 1-naphthaleneacetic acid on decapitated apices did not influence fruit abortion. However, applying the auxin biosynthesis inhibitor yucasin to shoot apices reduced fruit abortion regardless of the light conditions, accompanied by slight shoot growth retardation. These findings suggest that the basipetal auxin stream does not mediate far-red light-stimulated fruit abortion. Far-red light-stimulated fruit abortion was associated with reduced sucrose accumulation and lower invertase activities in flowers. We suggest that under additional far-red light conditions, increased auxin levels in shoot apices promote fruit abortion probably through enhanced competition for assimilates between apices and flowers, which limits assimilate import into flowers.

Molecular basis for the selective G protein signaling of somatostatin receptors.

G protein-coupled receptors (GPCRs) modulate every aspect of physiological functions mainly through activating heterotrimeric G proteins. A majority of GPCRs promiscuously couple to multiple G protein subtypes. Here we validate that in addition to the well-known Gi/o pathway, somatostatin receptor 2 and 5 (SSTR2 and SSTR5) couple to the Gq/11 pathway and show that smaller ligands preferentially activate the Gi/o pathway. We further determined cryo-electron microscopy structures of the SSTR2‒Go and SSTR2‒Gq complexes bound to octreotide and SST-14. Structural and functional analysis revealed that G protein selectivity of SSTRs is not only determined by structural elements in the receptor-G protein interface, but also by the conformation of the agonist-binding pocket. Accordingly, smaller ligands fail to stabilize a broader agonist-binding pocket of SSTRs that is required for efficient Gq/11 coupling but not Gi/o coupling. Our studies facilitate the design of drugs with selective G protein signaling to improve therapeutic efficacy.

On the Key Influence of Amino Acid Ionic Liquid Anions on CO2 Capture.

Amino acid ionic liquids (AAILs) are promising green materials for CO2 capture and conversion due to their large chemical structural tunability. However, the structural understanding of the AAILs underlying the CO2 reaction dynamics remains uncertain. Herein, we examine the steric effects of AAIL anions with various chemical structures on CO2 capture behavior. Based on ab initio free-energy sampling, we assess reaction mechanisms for carbamate formation via a two-step reaction pathway with a zwitterion intermediate undergoing dynamic proton transfer. Our results show that free-energy barriers for carbamate formation can be significantly reduced as the degree of steric hindrance of the anions decreases. Further analyses reveal that reduced steric hindrance of anions causes markedly stronger intermolecular interactions between zwitterion and anions, leading to an increased kinetically favorable intermolecular proton transfer for carbamate production. We also describe the correlation strength between intramolecular interactions within the zwitterion and intermolecular interactions between the zwitterion and anions. We conclude that the favored structural flexibility due to the less steric hindrance of the zwitterion leads to enhanced intermolecular interactions, facilitating proton transfer to nearby AAIL anions for carbamate formation. Our study provides invaluable insight into the influence of various degrees of steric hindrance of the AAIL anions governing CO2 chemisorption. These findings may aid in the design of optimal AAIL solvents for the CO2 capture process.

A Shape Memory Hydrogel with Excellent Mechanical Properties, Water Retention Capacity, and Tunable Fluorescence for Dual Encryption.

Information encryption platforms with reliable encryption performance, excellent mechanical performance, and high water retention capacity are highly desired. In this study, a tough double-network hydrogel is designed using the first network of a polyion complex containing lanthanide complexes via one-pot polymerization and the second network of a poly (N-hydroxyethyl acrylamide) (PHEAA) obtained by deep eutectic solvent (DES)-assisted introduction and subsequent photopolymerization. In this system, the pH-induced shape memory function and pH-/wavelength-dependent fluorescence allow the use of the prepared hydrogel as a dual-encryption platform. Owing to its high response reversibility, the hydrogel-based platform exhibits both a high security level and the advantages of rewritability, reprogrammability, and reusability. Additionally, the excellent mechanical properties and water retention capacity owing to the solvent exchange process involving the low-volatility solvent DES and the resulting introduction of the second network of PHEAA offer high practical application value for the hydrogel-based dual encryption platform, demonstrating its potential for information security protection.

A revised airway epithelial hierarchy includes CFTR-expressing ionocytes.

The airways of the lung are the primary sites of disease in asthma and cystic fibrosis. Here we study the cellular composition and hierarchy of the mouse tracheal epithelium by single-cell RNA-sequencing (scRNA-seq) and in vivo lineage tracing. We identify a rare cell type, the Foxi1+ pulmonary ionocyte; functional variations in club cells based on their location; a distinct cell type in high turnover squamous epithelial structures that we term 'hillocks'; and disease-relevant subsets of tuft and goblet cells. We developed 'pulse-seq', combining scRNA-seq and lineage tracing, to show that tuft, neuroendocrine and ionocyte cells are continually and directly replenished by basal progenitor cells. Ionocytes are the major source of transcripts of the cystic fibrosis transmembrane conductance regulator in both mouse (Cftr) and human (CFTR). Knockout of Foxi1 in mouse ionocytes causes loss of Cftr expression and disrupts airway fluid and mucus physiology, phenotypes that are characteristic of cystic fibrosis. By associating cell-type-specific expression programs with key disease genes, we establish a new cellular narrative for airways disease.

Prenatal dexamethasone exposure impairs rat blood-testis barrier function and sperm quality in adult offspring via GR/KDM1B/FSTL3/TGFß signaling.

Both epidemiological and animal studies suggest that adverse environment during pregnancy can change the offspring development programming, but it is difficult to achieve prenatal early warning. In this study we investigated the impact of prenatal dexamethasone exposure (PDE) on sperm quality and function of blood-testis barrier (BTB) in adult offspring and the underlying mechanisms. Pregnant rats were injected with dexamethasone (0.1, 0.2 and 0.4 mg·kg-1·d-1, s.c.) from GD9 to GD20. After weaning (PW4), the pups were fed with lab chow. At PW12 and PW28, the male offspring were euthanized to collect blood and testes samples. We showed that PDE significantly decreased sperm quality (including quantity and motility) in male offspring, which was associated with impaired BTB and decreased CX43/E-cadherin expression in the testis. We demonstrated that PDE induced morphological abnormalities of fetal testicle and Sertoli cell development originated from intrauterine. By tracing to fetal testicular Sertoli cells, we found that PDE dose-dependently increased expression of histone lysine demethylases (KDM1B), decreasing histone 3 lysine 9 dimethylation (H3K9me2) levels of follistatin-like-3 (FSTL3) promoter region and increased FSTL3 expression, and inhibited TGFß signaling and CX43/E-cadherin expression in offspring before and after birth. These results were validated in TM4 Sertoli cells following dexamethasone treatment. Meanwhile, the H3K9me2 levels of FSTL3 promoter in maternal peripheral blood mononuclear cell (PBMC) and placenta were decreased and its expression increased, which was positively correlated with the changes in offspring testis. Based on analysis of human samples, we found that the H3K9me2 levels of FSTL3 promoter in maternal blood PBMC and placenta were positively correlated with fetal blood testosterone levels after prenatal dexamethasone exposure. We conclude that PDE can reduce sperm quality in adult offspring rats, which is related to the damage of testis BTB via epigenetic modification and change of FSTL3 expression in Sertoli cells. The H3K9me2 levels of the FSTL3 promoter and its expression in the maternal blood PBMC can be used as a prenatal warning marker for fetal testicular dysplasia.

Effect of suspended particulate matter on physiological, biochemical and photosynthetic characteristics of Chlorella pyrenoidosa in the Jinjiang Estuary (Fujian, China).

Suspended particulate matter (SPM), an important component of the natural water environment, can act as a carrier of many pollutants that affect aquatic organisms. In the present study, the effect of SPM obtained from Jinjiang Estuary on the physiological, biochemical, and photosynthetic properties of typical freshwater algae (Chlorella pyrenoidosa) was investigated. The results showed that under different concentrations of SPM treatment, the superoxide dismutase (SOD), catalase (CAT) activities, and malondialdehyde (MDA) content of C. pyrenoidosa increased, but the soluble protein content decreased. SPM with different particle sizes had less effect on SOD of C. pyrenoidosa, but showed a promoting effect on CAT and MDA as well as soluble protein content. In terms of photosynthetic activity, high concentrations (70, 90 mg/L) and small particle sizes (0-75, 75-120 µm) of SPM had a greater effect on the chlorophyll a content of C. pyrenoidosa. In addition, different concentrations of SPM had no significant effect on the potential photosynthetic activity of PS II (Fv/F0) and the maximum quantum yield of PS II (Fv/Fm), but the inhibition of the initial slope (alpha), the maximum photosynthetic rate (ETRmax) and the semi-light saturation point (Ik) increased with the increase of SPM concentration. Fv/F0, ETRmax, and Ik of C. pyrenoidosa showed some degree of recovery after inhibition in the presence of SPM of different particle sizes.

Influence of Anodal tDCS on the Brain Functional Networks and Muscle Synergy of Hand Movements.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a non-invasive technique that has demonstrated potential in modulating cortical neuron excitability. The objective of this paper is to investigate the effects of tDCS on characteristic parameters of brain functional networks and muscle synergy, as well as to explore its potential for enhancing motor performance. METHODS: By applying different durations of tDCS on the motor cortex of the brain, the 32-lead electroencephalogram (EEG) of the cerebral cortex and 4-lead electromyography (EMG) signals of the right forearm were collected for 4 typical hand movements which are commonly used in rehabilitation training, including right-hand finger flexion, finger extension, wrist flexion, and wrist extension. RESULTS: The study showed that tDCS can enhance the brain's electrical activity in the beta band of the C3 node of the cerebral cortex during hand movements. Furthermore, the structure of muscle synergy remains unaltered; however, the associated muscle activity is amplified (p < 0.05). CONCLUSIONS: Based on the study results, it can be inferred that tDCS enhances the control strength between the motor area of the cerebral cortex and the muscles during hand movements.

Transcriptome analysis revealed the existence of family-specific regulation of growth traits in grass carp.

The grass carp (Ctenopharyngodon idella) is the world's most prolific freshwater fish. Little is known, however, about the functional genes and genetic regulatory networks that govern its growth traits. We created three grass carp families in this study by using two grass carp parents with fast-growing offspring and two grass carp parents with slow-growing offspring, namely the fast-growing × fast-growing family (FF), the slow-growing × slow-growing family (SS), and the fast-growing × slow-growing family (FS). Under the satiation and starvation feeding modes, the average body weight of these families' offspring exhibited a consistent ordering (FF > FS > SS). The transcriptomes of grass carp whole brain and hepatopancreas were then acquired for each family, and it was discovered that the number of differentially expressed genes (DEGs) in the different organs demonstrated family specificity. DEGs were mostly identified in the hepatopancreas of FF and the whole brain of SS, but they were more evenly distributed in FS. There were 14 DEGs that were found in all three families, including three that were negatively correlated in hepatopancreas (ahsg2, lect2) or in brain (drd5), and 11 that were positively connected in hepatopancreas (sycn, pabpc4, zgc:112294, cel, endou, ela2, prss3, zbtb41, ela3) or in brain (fabp7, endod1). The deletion of ahsg2 boosted the growth rate only in certain zebrafish, suggesting that the growth-promoting effects of ahsg2 varies among individuals. Furthermore, we examined the SNP in each family and conducted preliminary research on the probable genetic pathways of family-specific control of growth traits. The family specificity of the growth regulation mechanism of grass carp at the transcriptional level was revealed for the first time in this study, and it was discovered that growth differences among individuals in the FF family were primarily due to differences in nutrient metabolism, whereas growth differences among individuals in the SS family may be primarily due to differences in foraging ability caused by differences in brain development. This research adds to our understanding of the genetic regulatory mechanism of grass carp growth.

Effects of the Chinese heart-healthy diet (Sichuan cuisine) on lowering blood pressure in adults with hypertension: a randomized controlled feeding trial.

BACKGROUND AND OBJECTIVES: Sichuan cuisine is characterized by high salt and oil content. We aimed to evaluate the effects of the Sichuan cuisine version of Chinese heart-healthy diet (CHH diet-SC) on blood pressure reduction among hypertensive adults. METHODS AND STUDY DESIGN: The Chinese heart-healthy diet (CHH) trial was a multicenter randomized controlled feeding trial among Chinese hypertensive people. We conducted a secondary analysis of the CHH trial using data from the Sichuan center in Southwest China. Fifty-three people aged 25 to 75 years with a mean systolic blood pressure (SBP) between 130 and 159 mmHg were enrolled. Eligible participants underwent a 1-week run-in period with the typical local diet and were randomized 1:1 to consume the CHH diet-SC (n=27) or typical local diet (n=26) for the next 4-week. The primary outcome was the net change in SBP, the secondary outcomes included diastolic blood pressure (DBP), mean arterial pressure (MAP), and the rate of BP control. RESULTS: Compared with the control group, the CHH diet-SC decreased cooking salt, oil, and red meat content and increased inclusion of whole grains, fruits, seafood, low-fat dairy, soybean, and nuts; the SBP experienced reductions of 7.54, 8.60, 9.14, and 10.1 mmHg at the end of weeks 1 through 4; the DBP was reduced 4.01 mmHg at week 4; the MAP was significantly reduced 6.02 mmHg finally; and rate of BP control significantly increased (p<0.05). CONCLUSIONS: Adoption of the CHH diet-SC for 4 weeks can significantly reduce BP and increase the rate of BP control in hypertensive adults.

A Fluorous Peptide Amphiphile with Potent Antimicrobial Activity for the Treatment of MRSA-induced Sepsis and Chronic Wound Infection.

The rising prevalence of global antibiotic resistance evokes the urgent need for novel antimicrobial candidates. Cationic lipopeptides have attracted much attention due to their strong antimicrobial activity, broad-spectrum and low resistance tendency. Herein, a library of fluoro-lipopeptide amphiphiles was synthesized by tagging a series of cationic oligopeptides with a fluoroalkyl tail via a disulfide spacer. Among the lipopeptide candidates, R6F bearing six arginine moieties and a fluorous tag shows the highest antibacterial activity, and it exhibits an interesting fluorine effect as compared to the non-fluorinated lipopeptides. The high antibacterial activity of R6F is attributed to its excellent bacterial membrane permeability, which further disrupts the respiratory chain redox stress and cell wall biosynthesis of the bacteria. By co-assembling with lipid nanoparticles, R6F showed high therapeutic efficacy and minimal adverse effects in the treatment of MRSA-induced sepsis and chronic wound infection. This work provides a novel strategy to design highly potent antibacterial peptide amphiphiles for the treatment of drug-resistant bacterial infections.

Phosphoglycerate mutase 5 initiates inflammation in acute kidney injury by triggering mitochondrial DNA release by dephosphorylating the pro-apoptotic protein Bax.

Acute kidney injury (AKI) is a worldwide public health problem characterized by excessive inflammation with no specific therapy in clinic. Inflammation is not only a feature of AKI but also an essential promoter for kidney deterioration. Phosphoglycerate mutase 5 (PGAM5) was up-regulated and positively correlated with kidney dysfunction in human biopsy samples and mouse kidneys with AKI. PGAM5 knockout in mice significantly alleviated ischemia/reperfusion-induced kidney injury, mitochondrial abnormality and production of inflammatory cytokines. Elevated PGAM5 was found to be mainly located in kidney tubular epithelial cells and was also related to inflammatory response. Knockdown of PGAM5 inhibited the hypoxia/reoxygenation-induced cytosolic release of mitochondrial DNA (mtDNA) and binding of mtDNA with the cellular DNA receptor cGAS in cultured cells. cGAS deficiency also attenuated the inflammation and kidney injury in AKI. Mechanistically, as a protein phosphatase, PGAM5 was able to dephosphorylate the pro-apoptotic protein Bax and facilitate its translocation to mitochondrial membranes, and then initiate increased mitochondrial membrane permeability and release of mtDNA. Leaked mtDNA recognized by cGAS then initiated its downstream-coupled STING pathway, a component of the innate immune system that functions to detect the presence of cytosolic DNA. Thus, our results demonstrated mtDNA release induced by PGAM5-mediated Bax dephosphorylation and the activation of cGAS-STING pathway as critical determinants of inflammation and kidney injury. Hence, targeting this axis may be useful for treating AKI.

Brahma-related gene 1 acts as a profibrotic mediator and targeting it by micheliolide ameliorates peritoneal fibrosis.

BACKGROUND: Progressive peritoneal fibrosis is a worldwide public health concern impacting patients undergoing peritoneal dialysis (PD), yet there is no effective treatment. Our previous study revealed that a novel compound, micheliolide (MCL) inhibited peritoneal fibrosis in mice. However, its mechanism remains unclear. Brahma-related gene 1 (BRG1) is a key contributor to organ fibrosis, but its potential function in PD-related peritoneal fibrosis and the relationship between MCL and BRG1 remain unknown. METHODS: The effects of MCL on BRG1-induced fibrotic responses and TGF-ß1-Smads pathway were examined in a mouse PD model and in vitro peritoneal mesothelial cells. To investigate the targeting mechanism of MCL on BRG1, coimmunoprecipitation, MCL-biotin pulldown, molecular docking and cellular thermal shift assay were performed. RESULTS: BRG1 was markedly elevated in a mouse PD model and in peritoneal mesothelial cells cultured in TGF-ß1 or PD fluid condition. BRG1 overexpression in vitro augmented fibrotic responses and promoted TGF-ß1-increased-phosphorylation of Smad2 and Smad3. Meanwhile, knockdown of BRG1 diminished TGF-ß1-induced fibrotic responses and blocked TGF-ß1-Smad2/3 pathway. MCL ameliorated BRG1 overexpression-induced peritoneal fibrosis and impeded TGF-ß1-Smad2/3 signaling pathway both in a mouse PD model and in vitro. Mechanically, MCL impeded BRG1 from recognizing and attaching to histone H3 lysine 14 acetylation by binding to the asparagine (N1540) of BRG1, in thus restraining fibrotic responses and TGF-ß1-Smad2/3 signaling pathway. After the mutation of N1540 to alanine (N1540A), MCL was unable to bind to BRG1 and thus, unsuccessful in suppressing BRG1-induced fibrotic responses and TGF-ß1-Smad2/3 signaling pathway. CONCLUSION: Our research indicates that BRG1 may be a crucial mediator in peritoneal fibrosis and MCL targeting N1540 residue of BRG1 may be a novel therapeutic strategy to combat PD-related peritoneal fibrosis.

KRT18 regulates trophoblast cell migration and invasion which are essential for embryo implantation.

Female infertility is a worldwide concern that impacts the quality of life and well-being of affected couples. Failure of embryo implantation is a major cause of early pregnancy loss and is precisely regulated by a programmed molecular mechanism. Recent studies have shown that proper trophoblast adhesion and invasion are essential for embryo implantation. However, the potential regulatory mechanism involved in trophoblast adhesion and invasion has yet to be fully elucidated. KRT18 has been reported to play a critical role in early embryonic development, but its physiological function in embryo implantation remains unclear. In the present study, we revealed that KRT18 was highly expressed in trophoblast cells and that knockdown of KRT18 in mouse embryos inhibited embryo adhesion and implantation. In vitro experiments further showed that silencing KRT18 disturbed trophoblast migration and invasion. More importantly, we provide evidence that KRT18 directly binds to and stabilizes cell surface E-cadherin in trophoblast cells through microscale thermophoresis (MST) analysis and molecular biology experiments. In brief, our data reveal that KRT18, which is highly expressed in trophoblast cells, plays an important role in the regulation of trophoblast invasion and adhesion during embryo implantation by directly binding to E-cadherin.

B lymphocytes ameliorate Alzheimer's disease-like neuropathology via interleukin-35.

Increasing evidence supports the involvement of the peripheral immune system in the pathogenesis of Alzheimer's disease (AD). In the present study, we found that B lymphocytes could mitigate beta-Amyloid (Aß) pathology and memory impairments in a transgenic AD mouse model. Specifically, in young 5 × FAD mice, we evidenced increased B cells in the frontal cortex and meningeal tissues; depletion of mature B cells aggravated these mice's Aß load and memory deficits. The increased B cells produced more interleukin-35 (IL-35) in the front cortex. We further found IL-35 neutralization exacerbated Aß pathology, while injecting IL-35 mitigated Aß load and cognitive dysfunction in 5 × FAD mice with or without mature B cell deficiency. Mechanistically, IL-35 inhibited neuronal BACE1 transcription through modulating the SOCS1/STAT1 pathway, and reduced Aß production accordingly. Reanalysis of the single-cell RNA sequencing data from blood samples of AD patients suggested an increased population of IL-35-producing B cells. Together, the present study revealed a novel effect of B lymphocyte-derived IL-35 on inhibiting Aß production in the frontal cortex, which may serve as a potential target for future AD treatment.

Dexamethasone Liposomes Alleviate Osteoarthritis in miR-204/-211-Deficient Mice by Repolarizing Synovial Macrophages to M2 Phenotypes.

We undertook this study to investigate the effects and mechanisms of dexamethasone liposome (Dex-Lips) on alleviating destabilization of the medial meniscus (DMM)-induced osteoarthritis (OA) in miR-204/-211-deficient mice. Dex-Lips was prepared by the thin-film hydration method. The characterization of Dex-Lips was identified by the mean size, zeta potential, drug loading, and encapsulation efficiencies. Experimental OA was established by DMM surgery in miR-204/-211-deficient mice, and then Dex-Lips was treated once a week for 3 months. Von Frey filaments was used to perform the pain test. The inflammation level was evaluated with quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Polarization of macrophages was evaluated by immunofluorescent staining. X-ray, micro-CT scanning, and histological observations were conducted in vivo on DMM mice to describe the OA phenotype. We found that miR-204/-211-deficient mice displayed more severe OA symptoms than WT mice after DMM surgery. Dex-Lips ameliorated DMM-induced OA phenotype and suppressed pain and inflammatory cytokine expressions. Dex-Lips could attenuate pain by regulating PGE2. Dex-Lips treatments reduced the expression of TNF-α, IL-1ß, and IL-6 in DRG. Moreover, Dex-Lips could reduce inflammation in the cartilage and serum. Additionally, Dex-Lips repolarize synovial macrophages to M2 phenotypes in miR-204/-211-deficient mice. In conclusion, Dex-Lips inhibited the inflammatory response and alleviated the pain symptoms of OA by affecting the polarization of macrophages.

MicroRNA-122-5p alleviates endometrial fibrosis via inhibiting the TGF-ß/SMAD pathway in Asherman's syndrome.

RESEARCH QUESTION: What is the effect of miR-122 on the progression and recovery of fibrosis in Asherman's syndrome? DESIGN: Endometrial tissue was collected from 21 patients, 11 with intrauterine adhesion (IUA) and 10 without IUA. Quantitative real-time polymerase chain reaction, immunofluorescence and Western blot were applied to observe the expression of mRNAs/miRNAs and protein, respectively. The endometrial physical injury was carried out in C57BL/6 mice to create an endometrial fibrosis model, with intrauterine injection of adenovirus to compare the antifibrosis and repair function of miR-122 on endometrium. The morphology of the uterus was observed using haematoxylin and eosin staining, and fibrosis markers were detected by immunohistochemistry. RESULTS: miR-122 expression was reduced in patients with IUAs, accompanied by fibrosis. MiR-122 overexpression reduced the degree of fibrosis in endometrial stromal cells. Further molecular analyses demonstrated that miR-122 inhibited fibrosis through the TGF-ß/SMAD pathway by directly targeting the 3' untranslated region of SMAD family member 3, suppressing its expression. Notably, miR-122 promoted endometrial regeneration and recovery of pregnancy capacity in a mouse endometrial injury model. CONCLUSIONS: miR-122 is a critical regulator for repair of endometrial fibrosis and provided new insight for the clinical treatment of intrauterine adhesions.

Surface plasmon resonance detection of UV irradiation-induced DNA damage and photoenzymatic repair processes through specific interaction between consensus double-stranded DNA and p53 protein.

DNA damage, such as DNA lesions and strand breaks, impairs normal cell functions and failure in the DNA repair process could lead to gene mutation, cell apoptosis and disease occurrence. p53 is a tumor suppressor and DNA-binding protein, and DNA damage might affect their interaction and the subsequent p53 function. Herein, real-time monitoring of DNA damage and repair processes through DNA-p53 protein interaction was performed by surface plasmon resonance (SPR). The target DNA with consecutive pyrimidine nucleobases was first damaged upon UVC (254 nm) irradiation and then photoenzymatically repaired under UVA (365 nm) irradiation. The as-formed double-stranded (ds) DNA between probe DNA and normal, damaged or repaired target DNA was immobilized on the sensor chips, followed by the injection of p53 protein. By measuring the SPR signals under different cases, the DNA damage and repair processes could be conveniently monitored. The SPR signals were inversely proportional to the UVC doses ranging from 0.021 to 1.26 kJ m-2, providing a viable means for the quantification of the DNA damage level. The binding affinity between p53 and the dsDNA formed upon the hybridization of probe DNA and normal, damaged, or photoenzymatically repaired target DNA was estimated. This is the first report on measuring the equilibrium dissociation constant (KD) between the p53 protein and the dsDNA with photodamaged or repaired target sequences. The sensing strategy by SPR thus opens a new avenue for real-time measurement of the DNA damage and the repair processes.

Efficient NOx Reduction against Alkali Poisoning over a Self-Protection Armor by Fabricating Surface Ce2(SO4)3 Species: Comparison to Commercial Vanadia Catalysts.

Resolving severe deactivation by alkali metals for selective catalytic reduction of NOx with NH3 (NH3-SCR) is challenging. Herein, surface Ce2(SO4)3 species as a self-protection armor originally exhibited antipoisoning of potassium over ceria-based catalysts. The self-protection armor was also effective for other alkali (Na), alkali-earth (Ca), and heavy (Pb) metals, considerably resolving the deactivation of ceria-based SCR catalysts in practical applications. The catalytic activity tests indicated that the presence of ∼0.8 wt % potassium did not deactivate sulfated CeO2 catalysts, yet commercial V2O5-WO3/TiO2 catalysts almost lost the NOx conversions. Potassium preferably bonded with surface sulfates to form K2SO4 accompanied with the majority of surface Ce2(SO4)3 over sulfated CeO2 catalysts, but preferably coupled with active vanadia to generate inactive KVO3 species over V2O5-WO3/TiO2 catalysts. Such an active Ce2(SO4)3 species facilitated the adsorption and reactivity of NH3 and NOx, enabling ceria catalysts to maintain high catalytic efficiency in the presence of potassium. Conversely, the introduction of potassium into V2O5-WO3/TiO2 catalysts caused a considerable loss of surface acidity, hindering catalyst reactivity during the SCR reaction. The self-protection armor of Ce2(SO4)3 species may open a promising pathway to develop efficient ceria-based SCR catalysts with strong antipoisoning ability.