Exogenous melatonin improves germination rate in buckwheat under high temperature stress by regulating seed physiological and biochemical characteristics.

The germinations of three common buckwheat (Fagopyrum esculentum) varieties and two Tartary buckwheat (Fagopyrum tataricum) varieties seeds are known to be affected by high temperature. However, little is known about the physiological mechanism affecting germination and the effect of melatonin (MT) on buckwheat seed germination under high temperature. This work studied the effects of exogenous MT on buckwheat seed germination under high temperature. MT was sprayed. The parameters, including growth, and physiological factors, were examined. The results showed that exogenous MT significantly increased the germination rate (GR), germination potential (GP), radicle length (RL), and fresh weight (FW) of these buckwheat seeds under high-temperature stress and enhanced the content of osmotic adjustment substances and enzyme activity. Comprehensive analysis revealed that under high-temperature stress during germination, antioxidant enzymes play a predominant role, while osmotic adjustment substances work synergistically to reduce the extent of damage to the membrane structure, serving as the primary key indicators for studying high-temperature resistance. Consequently, our results showed that MT had a positive protective effect on buckwheat seeds exposed to high temperature stress, providing a theoretical basis for improving the ability to adapt to high temperature environments.

Inhibition of neuronal pentraxin 2 relieved epileptic seizure via reducing GluA1 phosphorylation.

Neuronal pentraxin 2 (Nptx2), a member of the synaptic protein family linked to excitatory synaptic formation, is found to be upregulated in epileptic mice, yet its role in epilepsy has been unclear. In vivo, we constructed a mouse model of epilepsy by using kainic acid induction. In vitro experiments, a Mg2+-free medium was used to induce epileptiform discharges in neurons. The results showed that the Nptx2 was upregulated in epileptic mice. Moreover, Nptx2 knockdown reduced the number of seizures and seizure duration. Knocking down Nptx2 not only reduced the number and duration of seizures but also showed a decrease in electroencephalogram amplitude. Behavioral tests indicated improvements in learning and memory abilities after Nptx2 knockdown. The Nissl staining and Timms staining revealed that Nptx2 silencing mitigated epilepsy-induced brain damage. The immunofluorescence staining revealed that Nptx2 absence resulted in a reduction of apoptosis. Nptx2 knockdown reduced Bax, cleaved caspase3, and cleaved caspase9 expression, while increased Bcl-2 expression. Notably, Nptx2 knockdown inhibited GluA1 phosphorylation at the S831 site and reduced the GluA1 membrane expression. The PSD95 expression declined in the epilepsy model, while the Nptx2 knockdown reversed it. Collectively, our study indicated that Nptx2 silencing not only alleviated brain damage and neuron apoptosis but also improved learning and memory ability in epileptic mice, suggesting Nptx2 as a promising target for epilepsy treatment.

Integrated transcriptomic and metabolomic analyses reveals anthocyanin biosynthesis in leaf coloration of quinoa (Chenopodium quinoa Willd.).

BACKGROUND: Quinoa leaves demonstrate a diverse array of colors, offering a potential enhancement to landscape aesthetics and the development of leisure-oriented sightseeing agriculture in semi-arid regions. This study utilized integrated transcriptomic and metabolomic analyses to investigate the mechanisms underlying anthocyanin synthesis in both emerald green and pink quinoa leaves. RESULTS: Integrated transcriptomic and metabolomic analyses indicated that both flavonoid biosynthesis pathway (ko00941) and anthocyanin biosynthesis pathway (ko00942) were significantly associated with anthocyanin biosynthesis. Differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) were analyzed between the two germplasms during different developmental periods. Ten DEGs were verified using qRT-PCR, and the results were consistent with those of the transcriptomic sequencing. The elevated expression of phenylalanine ammonia-lyase (PAL), chalcone synthase (CHS), 4-coumarate CoA ligase (4CL) and Hydroxycinnamoyltransferase (HCT), as well as the reduced expression of flavanone 3-hydroxylase (F3H) and Flavonol synthase (FLS), likely cause pink leaf formation. In addition, bHLH14, WRKY46, and TGA indirectly affected the activities of CHS and 4CL, collectively regulating the levels of cyanidin 3-O-(3'', 6''-O-dimalonyl) glucoside and naringenin. The diminished expression of PAL, 4CL, and HCT decreased the formation of cyanidin-3-O-(6"-O-malonyl-2"-O-glucuronyl) glucoside, leading to the emergence of emerald green leaves. Moreover, the lowered expression of TGA and WRKY46 indirectly regulated 4CL activity, serving as another important factor in maintaining the emerald green hue in leaves N1, N2, and N3. CONCLUSION: These findings establish a foundation for elucidating the molecular regulatory mechanisms governing anthocyanin biosynthesis in quinoa leaves, and also provide some theoretical basis for the development of leisure and sightseeing agriculture.

Mechanochemical evolution of coal microscopic groups: A new pathway for mechanical forces acting on coal spontaneous combustion.

Coal spontaneous combustion (CSC) remains a significant threat to regional ecological environments. As coal mining operations extend deeper into the earth, the increasingly complex mechanical force conditions in deep-seated mines escalate the potential risk of CSC. Mechanical forces such as ground stress and mechanical cutting are traditionally believed to be linked to CSC through the following pathway: mechanical forces act → mechanical energy is input → mechanical crushing and pulverization occur → coal-oxygen contact area increases → CSC accelerates. Noteworthily, these forces do more than just physically break coal; they also trigger a mechanochemical effect (MCE) that alters coal's microscopic chemistry. However, an independent evaluation of its influence on CSC was lacking. This study characterized coal's microscopic chemical group responses to the MCE. It was found that the MCE led to the degradation of aliphatic side chains while enhancing the polycondensation of aromatic ring structures, indicating a synergistic effect. Additionally, an increase in oxygen-containing functional groups, such as alkyl/aryl ethers, suggested enhanced interactions of the coal microscopic groups with oxygen due to mechanical forces. Based on these findings, an MCE-modified coal macromolecular model was developed and molecular quantum mechanical calculations were conducted. The results indicated that the MCE boosted coal macromolecule reactivity, thus facilitating easier activation. These conclusions were validated through modern thermal analysis tests. Finally, this study proposed a new pathway of mechanical forces acting on CSC: mechanical forces act → mechanical energy is input → the MCE occurs → evolutions of the microscopic groups within coal are induced → Activity of coal molecules is enhanced → CSC accelerates.

The association between smoking and family health with the mediation role of personality among Chinese people: nationwide cross-sectional study.

BACKGROUND: There may be unexplored interactions between family health, personality, and smoking that could help provide new perspectives on tobacco control. OBJECTIVE: To examine the relationship between the health of one's family and their smoking habits, as well as investigate the potential influence of personality on this relationship. METHODS: For this cross-sectional investigation, a national survey conducted in China in 2022 recruited a total of 21,916 individuals. The Family Health Scale was utilized to assess the health of the family. The 10-item Big Five Inventory scale was utilized to assess the Big five personality traits. The relationship between big five personality, family health, and smoking were investigated using binary and linear logistic regression. The indirect effects mediated by Big five personality were analyzed using mediation analysis with Sobel tests, and the indirect effects were composited using the Karlson-Holm-Breen method. RESULTS: The overall prevalence of smoking in the study population was 14.87%, 26.19% for males and 3.54% for females. Urban and rural smoking prevalence was 13.81% and 16.10% respectively. Binary logistic regression analysis revealed a significant negative relationship between smoking and family health (odds ratio 0.964, 95% CI 0.959, 0.970, P < 0.001) with covariates controlled. The Karlson-Holm-Breen composition facilitated the connection between extraversion (47.81%) and nervousness (52.19%). CONCLUSIONS: Preventive interventions for smoking behavior should prioritize family health and the Big five personality as significant areas to focus on. According to this study, in addition to implementing various interventions for different personalities, family health should be strengthened to reduce smoking behavior.

Value of magnetic resonance imaging radiomics features in predicting histologic grade of invasive ductal carcinoma of the breast.

BACKGROUND: Breast cancer has the second highest mortality rate of all cancers and occurs mainly in women. OBJECTIVE: To investigate the relationship between magnetic resonance imaging (MRI) radiomics features and histological grade of invasive ductal carcinoma (IDC) of the breast and to evaluate its diagnostic efficacy. METHODS: The two conventional MRI quantitative indicators, i.e. the apparent diffusion coefficient (ADC) and the initial enhancement rate, were collected from 112 patients with breast cancer. The breast cancer lesions were manually segmented in dynamic contrast-enhanced MRI (DCE-MRI) and ADC images, the differences in radiomics features between Grades I, II and III IDCs were compared and the diagnostic efficacy was evaluated. RESULTS: The ADC values (0.77 ± 0.22 vs 0.91 ± 0.22 vs 0.92 ± 0.20, F= 4.204, p< 0.01), as well as the B_sum_variance (188.51 ± 67.803 vs 265.37 ± 77.86 vs 263.74 ± 82.58, F= 6.040, p< 0.01), L_energy (0.03 ± 0.02 vs 0.13 ± 0.11 vs 0.12 ± 0.14, F= 7.118, p< 0.01) and L_sum_average (0.78 ± 0.32 vs 16.34 ± 4.23 vs 015.45 ± 3.74, F= 21.860, p< 0.001) values of patients with Grade III IDC were significantly lower than those of patients with Grades I and II IDC. The B_uniform (0.15 ± 0.12 vs 0.11 ± 0.04 vs 0.12 ± 0.03, F= 3.797, p< 0.01) and L_SRE (0.85 ± 0.07 vs 0.78 ± 0.03 vs 0.79 ± 0.32, F= 3.024, p< 0.01) values of patients with Grade III IDC were significantly higher than those of patients with Grades I and II IDC. All differences were statistically significant (p< 0.05). The ADC radiomics signature model had a higher area-under-the-curve value in identifying different grades of IDC than the ADC value model and the DCE radiomics signature model (0.869 vs 0.711 vs 0.682). The accuracy (0.812 vs 0.647 vs 0.710), specificity (0.731 vs 0.435 vs 0.342), positive predictive value (0.815 vs 0.663 vs 0.669) and negative predictive value (0.753 vs 0.570 vs 0.718) of the ADC radiomics signature model were all significantly better than the ADC value model and the DCE radiomics signature model. CONCLUSION: ADC values and breast MRI radiomics signatures are significant in identifying the histological grades of IDC, with the ADC radiomics signatures having greater value.

High lipoprotein(a) concentration is associated with moyamoya disease.

BACKGROUND: Moyamoya disease (MMD) has attracted the attention of scholars because of its rarity and unknown etiology. METHODS: Data for this study were sourced from the Second Affiliated Hospital of Nanchang University. Regression analyses were conducted to examine the association in Lipoprotein [Lp(a)] and MMD. R and IBM SPSS were conducted. RESULTS: A cohort comprising 1012 MMD patients and 2024 controls was established through the propensity score matching method. Compared with controls, MMD patients showed higher median Lp(a) concentrations [18.5 (9.6-37.8) mg/dL vs. 14.9 (7.8-30.5) mg/dL, P < 0.001]. The odds ratios and 95% confidence intervals for Lp(a) were calculated in three models: unadjusted model, model 1 (adjusted for body mass index and systolic blood pressure), and model 2 (adjusted for model 1 plus triglyceride, C-reactive protein, homocysteine, and low-density lipoprotein cholesterol). Results were [1.613 (1.299-2.002), P < 0.001], [1.598 (1.286-1.986), P < 0.001], and [1.661 (1.330-2.074), P < 0.001], respectively. Furthermore, age, sex, or hypertension status had nothing to do with this relationship. CONCLUSIONS: Positive relationship exists between Lp(a) and MMD.

Simultaneous separation and analysis of multiple doxorubicin hydrochloride liposomes forms in serum by circular nonuniform electric field gel electrophoresis.

BACKGROUND: Liposomal formulations have traditionally been considered the most therapeutically effective drug delivery systems (DDS). However, their pharmacokinetics study and efficacy assessment are still challenging given size heterogeneity and unknown forms in vivo. The pharmacodynamic evaluation that solely analyzes total drug concentration is unfit for the liposomal formulation study. Hence, it is crucial to develop effective strategies for the separation and analysis of different forms of liposomal formulations in order to contribute to the study of pharmacokinetic profiles associated with both liposome-incorporated and non-liposomal drugs. (84) RESULTS: A laboratory-built circular nonuniform electric field gel electrophoresis (CNEFGE) system was developed in this study for simultaneous separation and analysis of various forms of doxorubicin hydrochloride (DOX•HCl) liposomes. Liposomes were effectively fractionized based on their size and higher concentration in situ in the concentration zone, obtaining liposome recovery >95 % and a 3.04 concentration factor. It was found that the technique could be used to evaluate not only the size distribution of liposomes but also the drug loading capacity related to size. The charge-to-size-based separation mechanism has also allowed the simultaneous separation of liposome-entrapped drugs, protein-bound drugs, and free drugs in various forms, and the technique has been successfully employed in serum. Moreover, the quantification analysis of liposomes incubated with serum for 72 h showed that the proportion of the ratio of DOX•HCl in liposome-entrapped drugs, protein-bound drugs, and free drugs is approximately 97:2:1. (143) SIGNIFICANCE: Using the separation principle of gel electrophoresis and the electrification characteristics of drug carriers, this study developed and implemented an efficient approach for the simultaneous separation and concentration of multiple forms of drug liposomes in vivo. This approach offers a wide range of applications in the pharmacokinetics, efficacy, and safety evaluation of drug carriers and liposomes. (56).

Mapping Quantitative Trait Loci (QTLs) for Hundred-Pod and Hundred-Seed Weight under Seven Environments in a Recombinant Inbred Line Population of Cultivated Peanut (Arachis hypogaea L.).

The cultivated peanut (Arachis hypogaea L.) is a significant oil and cash crop globally. Hundred-pod and -seed weight are important components for peanut yield. To unravel the genetic basis of hundred-pod weight (HPW) and hundred-seed weight (HSW), in the current study, a recombinant inbred line (RIL) population with 188 individuals was developed from a cross between JH5 (JH5, large pod and seed weight) and M130 (small pod and seed weight), and was utilized to identify QTLs for HPW and HSW. An integrated genetic linkage map was constructed by using SSR, AhTE, SRAP, TRAP and SNP markers. This map consisted of 3130 genetic markers, which were assigned to 20 chromosomes, and covered 1998.95 cM with an average distance 0.64 cM. On this basis, 31 QTLs for HPW and HSW were located on seven chromosomes, with each QTL accounting for 3.7-10.8% of phenotypic variance explained (PVE). Among these, seven QTLs were detected under multiple environments, and two major QTLs were found on B04 and B08. Notably, a QTL hotspot on chromosome A08 contained seven QTLs over a 2.74 cM genetic interval with an 0.36 Mb physical map, including 18 candidate genes. Of these, Arahy.D52S1Z, Arahy.IBM9RL, Arahy.W18Y25, Arahy.CPLC2W and Arahy.14EF4H might play a role in modulating peanut pod and seed weight. These findings could facilitate further research into the genetic mechanisms influencing pod and seed weight in cultivated peanut.

Circular RNA SMARCA5 Promotes a Poor Prognosis and Radiotherapy Resistance for Patients with Hepatocellular Carcinoma.

OBJECTIVE: The involvement of Circular RNA SMARCA5 (cSMARCA5) in several types of cancer has been reported; however, its role in hepatocellular carcinoma (HCC) is unclear. The presented research aimed to explore the expression level of cSMARCA5 in HCC tissues and evaluate the association between cSMARCA5, prognosis, and radiotherapy resistance for patients with HCC. METHODS: This study was designed as a case controlled study and enrolled 106 HCC patients. HCC and paired non-tumor samples were collected from HCC patients. Gene expression was analyzed by RT-qPCR. The association between the expression level of cSMARCA5 and prognosis value and radiotherapy resistance for patients with HCC was analyzed by Kaplan-Meier survival curve and Multivariate Cox analysis. RESULTS: Compared to paracancerous tissue, cSMARCA5 demonstrated higher expression in the tumor tissues (p<0.0001).Higher expression of cSMARCA5 is a risk factor in 3-year overall survival (OS) for HCC patients (HR=1.798, 95%CI: 1.165~3.231, p=0.0321). Multivariate analysis showed that higher expression of cSMARCA5 was related to PVTT (HR=2.136, 95%CI: 1.130~5.218), AFP (>400ng/ml) (HR=2.335, 95%CI: 1.247~5.661), tumor size (>5cm) (HR=3.017, 95%CI: 1.477~5.659), poor histopathologic grading (HR=3.344, 95%CI: 2.175~6.143), and multiple tumor number (HR=2.875, 95%CI: 1.453~3.884). We also found that radiotherapy resistance was related to AFP (>400ng/ml) (OR=2.125, 95%CI: 1.015~3.348), tumor size (>5cm) (OR=2.857, 95%CI: 1.665~4.978), poor histopathologic grading (OR=2.463, 95%CI: 1.389~4.446), multiple tumor number (OR=2.332, 95%CI: 1.538~3.887), and high expression of cSMARCA5 (OR=3.574, 95%CI: 1.663~5.932). CONCLUSION: CircRNA-SMARCA5 is significantly increased in HCC tissues and promotes radiotherapy resistance. More importantly, higher expression level of cSMARCA5 is related to a poorer 3-year OS for patients with HCC.

Genetic mapping of AhVt1, a novel genetic locus that confers the variegated testa color in cultivated peanut (Arachis hypogaea L.) and its utilization for marker-assisted selection.

Introduction: Peanut (Arachis hypogaea L.) is an important cash crop worldwide. Compared with the ordinary peanut with pure pink testa, peanut with variegated testa color has attractive appearance and a higher market value. In addition, the variegated testa represents a distinct regulation pattern of anthocyanin accumulation in integument cells. Methods: In order to identify the genetic locus underlying variegated testa color in peanut, two populations were constructed from the crosses between Fuhua 8 (pure-pink testa) and Wucai (red on white variegated testa), Quanhonghua 1 (pure-red testa) and Wucai, respectively. Genetic analysis and bulked sergeant analysis sequencing were applied to detect and identify the genetic locus for variegated testa color. Marker-assisted selection was used to develop new variegated testa peanut lines. Results: As a result, all the seeds harvested from the F1 individuals of both populations showed the variegated testa type with white trace. Genetic analysis revealed that the pigmentation of colored region in red on white variegated testa was controlled by a previous reported gene AhRt1, while the formation of white region (un-pigmented region) in variegated testa was controlled by another single genetic locus. This locus, named as AhVt1 (Arachis hypogaea Variegated Testa 1), was preliminary mapped on chromosome 08 through bulked sergeant analysis sequencing. Using a secondary mapping population derived from the cross between Fuhua 8 and Wucai, AhVt1 was further mapped to a 1.89-Mb genomic interval by linkage analysis, and several potential genes associated with the uneven distribution of anthocyanin, such as MADS-box, MYB, and Chalcone synthase-like protein, were harbored in the region. Moreover, the molecular markers closely linked to the AhVt1 were developed, and the new variegated testa peanut lines were obtained with the help of marker-assisted selection. Conclusion: Our findings will accelerate the breeding program for developing new peanut varieties with "colorful" testa colors and laid a foundation for map-based cloning of gene responsible for variegated testa.

Fe-MOF with U-Shaped Channels for C2H2/CO2 and C2H2/C2H4 Separation.

The development of high-performance adsorbents is critical for the low-energy separation of acetylene. Herein, we synthesized an Fe-MOF (MOF, metal-organic framework) with U-shaped channels. The adsorption isotherms of C2H2, C2H4, and CO2 show that the adsorption capacity of acetylene is significantly larger than that of the other two gases. Meanwhile, the actual separation performance was verified by breakthrough experiments, indicating the potential to separate C2H2/CO2 and C2H2/C2H4 mixtures at normal temperatures. Grand Canonical Monte Carlo (GCMC) simulation demonstrates that the framework with U-shaped channels interacts more strongly with C2H2 than with C2H4 and CO2. The high C2H2 uptake and low adsorption enthalpy highlight Fe-MOF as a promising candidate for C2H2/CO2 separation with a low regeneration energy.

Effect of Surgical Clipping versus Endovascular Coiling on the Incidence of Delayed Cerebral Ischemia in Patients with Aneurysmal Subarachnoid Hemorrhage: A Multicenter Observational Cohort Study with Propensity Score Matching.

OBJECTIVE: The effect of surgical clipping (SC) and endovascular coiling (EC) on the incidence of delayed cerebral ischemia (DCI) in patients with aneurysmal subarachnoid hemorrhage (aSAH) has always been a controversial topic. Hence, it is necessary to reanalyze the effects of the 2 surgical methods on DCI, which determines the choice of the most favorable method for patients who are suitable for both surgical modalities. METHODS: A multicenter retrospective observational cohort study was performed to evaluate all consecutive patients with aSAH admitted to 5 medical centers in China between April 2019 and June 2021. Univariable and multivariable analyses were used to confirm risk factors of DCI after aSAH. A 1:1 propensity score matching model was generated in the EC and SC groups to reduce the influence of all confounding factors on DCI. RESULTS: A total of 412 patients were included, and 115 patients (27.9%) developed DCI. After propensity score matching for controlling demographic information, past medical history, admission clinical status, aneurysm characteristics, and inflammatory factors associated with DCI, 133 patients with SC and 133 patients with EC treatment were matched. The results of the matched cohorts indicate a significantly lower incidence of DCI when patients received EC than SC (31.9% vs. 20%; adjusted odds ratio, 1.87; 95% confidence interval, 1.08-3.29; P = 0.027). CONCLUSIONS: The study found that the patients who received SC treatment had a higher incidence of DCI than did those who received EC and suggested that ruptured intracerebral aneurysm is preferentially coiled rather than clipped if the aneurysm is suitable for both surgical modalities.

Low lipoprotein(a) concentration is associated with atrial fibrillation: a large retrospective cohort study.

BACKGROUND AND AIMS: The role of serum lipoprotein(a) [Lp(a)] levels in atrial fibrillation (AF) is still uncertain, especially in the Chinese population. Here, we aimed to elucidate the potential relationship between Lp(a) quantiles and AF. METHODS: All data were collected through inpatients with electronic health records from the Second Affiliated Hospital of Nanchang University, Jiangxi Province, China. The propensity score matching (PSM) method was used to match control and case groups. Interactions between AF, Lp(a) quantiles, and other clinical indices were analyzed by logistic regression and stratified analysis. Statistical analyses were performed with IBM SPSS statistical software and R software. RESULTS: From 2017 to 2021, 4,511 patients with AF and 9,022 patients without AF were 1:2 matched by the propensity score matching method. A total of 46.9% of the study group was women, and the baseline mean age was 65 years. The AF group exhibited lower median Lp(a) than the non-AF group (15.95 vs. 16.90 mg/dL; P < 0.001). Based on the Lp(a) quantiles, the study population was divided into four groups: Q1 (≤ 8.71 mg/dL), Q2 (8.71-16.54 mg/dL), Q3 (16.54-32.42 mg/dL) and Q4 (> 32.42 mg/dL). The AF prevalence of each group decreased from 34.2% (Q1) to 30.9% (Q4) (P < 0.001). Lp(a) quantiles 1-3 significantly increased AF to 1.162-fold (1.049-1.286), 1.198-fold (1.083-1.327), and 1.111-fold (1.003-1.231) in the unadjusted logistic regression model, respectively. In the adjusted model, Lp(a) < 32.42 mg/dL still showed a significant inverse association with AF. In the stratified analysis, Lp(a) levels in female patients exhibited a significant negative correlation with AF (OR of Q1: 1.394[1.194-1.626], P = 0.001). Age and hypertension did not affect the adverse correlation. CONCLUSION: Low circulating Lp(a) levels were associated with AF, especially in the female Han population, suggesting that Lp(a) may be useful for risk stratification of AF in female individuals.

Partially Reduced MIL-100(Fe) as a CO Carrier for Sustained CO Release and Regulation of Macrophage Phenotypic Polarization.

Carbon monoxide (CO) is a bioactive molecule with high potential as it shows promising efficacy for regulating inflammation. Materials capable of storing and delivering CO are of great potential therapeutic value. Although CO-releasing molecules (CORMs) have been developed to deliver CO, the short CO duration of minutes to 2 h confines their practical use. In this study, partially reduced MIL-100(Fe) as a new CO-releasing nanoMOF was developed and used for sustained CO release and macrophage (MA) phenotypic polarization regulation. MIL-100(Fe) was synthesized and mildly annealed in vacuum for partial reduction. When the annealing temperature was lower than 250 °C, less Fe(II) present in MIL-100(Fe) and the subsequent CO adsorption and desorption profiles displayed typical features of physisorption. While it was annealed at 250 °C, it showed about 20% of Fe(III) was reduced, which resulted in chemisorption of CO due to the high coordination affinity of Fe(II) to CO. The loading amount of CO was increased, and the CO release was prolonged for about 24 h. Furthermore, the CO release from this nanoMOF could alter the lipopolysaccharide (LPS)-induced macrophage from M1 to the alternative M2 phenotype and promoted the growth of endothelial cells (ECs) by paracrine regulation of MA. It can be envisioned as a promising CO-releasing solid for biomedical application.

Endoplasmic reticulum stress triggered autophagy and regulated the phenotype transformation of rheumatoid arthritis synovial fibroblasts via the IRE1/JNK pathway.

Background: Previous studies have indicated that endoplasmic reticulum (ER) stress may actively promote the pathogenesis of rheumatoid arthritis (RA) by evoking autophagy. However, the underlying mechanism remains largely unknown. This study aimed to explore the mechanism of the ER stress-autophagy pathway in regulating the phenotype transformation of rheumatoid arthritis synovial fibroblasts (RASFs). Methods: Synovial tissue was obtained from RA and osteoarthritis (OA) patients during joint replacement surgery. ER stress/autophagy signature markers were examined in synovial tissue by real-time quantitative polymerase chain reaction (RT-PCR), western blot, and immunohistochemistry. Phenotype transformation of RASFs, including increased cell proliferation and invasion capability, was measured by CCK-8 assay and transwell invasion assay. Signaling pathways were further investigated and inositol requiring enzyme 1 (IRE1) was down-regulated in RASFs by transfecting specific short hairpin RNA-ERN1 (shRNA-ERN1) carried by lentiviral vectors. Results: The expression of ER stress/autophagy pathway-associated proteins, including GRP78, IRE1, protein kinase R-like endoplasmic reticulum kinase (PERK), and LC3, was significantly increased in RA synovium compared with OA synovium. After stimulation with tumor necrosis factor alpha (TNF-α) in vitro, the proliferation and invasion ability of RASFs were upregulated, while this phenomenon could be inhibited by 4-PBA (ER stress inhibitor) or 3-MA (autophagy inhibitor). The expression of IRE1 and p-JNK in particular, occurred in an obviously time-dependent manner after stimulation with TNF-α. Moreover, the proliferation and invasion of RASFs were inhibited after transfection with sh-RNA-ERN1 to downregulate IRE1 expression. Conclusions: ER stress triggered autophagy via the IRE1/JNK pathway to regulate the phenotype transformation of RASFs, indicating an important role of the ER stress-autophagy pathway in the pathological process of synovitis in RA.

NETosis in Psoriatic Arthritis: Serum MPO-DNA Complex Level Correlates With Its Disease Activity.

Background: Neutrophil extracellular trap formation (NETosis) has been rarely reported in psoriatic arthritis (PsA). We aimed to explore the involvement of NETosis in the inflammation of PsA. Methods: Serum myeloperoxidase-DNA (MPO-DNA) complex was detected by a modified enzyme-linked immunosorbent assay and compared among 74 patients with PsA, 58 patients with psoriasis (PsO), and 20 healthy controls. The association of MPO-DNA level with disease activity index at baseline and follow-up was analyzed in patients with PsA. Receiver operating characteristic curve was used to evaluate the predictive value of MPO-DNA for treatment response. Results: MPO-DNA complex level in serum was significantly increased in patients with PsA/PsO compared to healthy controls (p < 0.001). The level of MPO-DNA was positively associated with DAPSA score and its components (including TJC, SJC, PGA, VAS-pain and CRP, r = 0.25-0.409, all p-values < 0.05). Serum MPO-DNA level was downregualted at 12 weeks after treatment compared to baseline (p = 0.022). The decrease of MPO-DNA level was more dramatic in patients with PsA who achieved both ACR50 and PASI50 response than those achieving neither of them at 12 weeks (p = 0.023). ROC analysis revealed that the serum MPO-DNA level predicted both ACR50 and PASI50 achievement at week 12 (p = 0.04; 95% CIs, 0.56-0.94). Moreover, the baseline MPO-DNA level (p = 0.009; 95% CIs, 0.748-1) and change of MPO-DNA at week 12 from baseline (p = 0.004; 95% CIs, 0.802-1) were associated with the achievement of both ACR70 and PASI75 response at week 24. Conclusions: NETosis plays an important role in psoriatic diseases. The level of MPO-DNA complex in serum reflects disease activity. Serum MPO-DNA complex may be a useful biomarker to predict the therapeutic response in PsA.

Corrigendum: Multi-Omics and miRNA Interaction Joint Analysis Highlight New Insights Into Anthocyanin Biosynthesis in Peanuts (Arachis hypogaea L.).

[This corrects the article DOI: 10.3389/fpls.2022.818345.].