Characterization and expression profiles of the ZmLBD gene family in Zea mays.

BACKGROUND: The Lateral Organ Boundaries Domain (LBD) gene family is a family of plant-specific transcription factors (TFs) that are widely involved in processes such as lateral organ formation, stress response, and nutrient metabolism. However, the function of LBD genes in maize remains poorly understood. METHODS AND RESULTS: In this study, a total of 49 ZmLBD genes were identified at the genome-wide level of maize, they were classified into nine branches based on phylogenetic relationships, and all of them were predicted to be nuclear localized. The 49 ZmLBD genes formed eight pairs of segmental duplicates, and members of the same branches' members had similar gene structure and conserved motif composition. The promoters of ZmLBD genes contain multiple types of cis-acting elements. In addition, by constructing the regulatory network of ZmLBD and other genes and miRNAs, 12 and 22 ZmLBDs were found to be involved in the gene regulatory network and miRNA regulatory network, respectively. The expression pattern analysis suggests that ZmLBD genes may be involved in different biological pathways, and drought stress induced the expressions of two inbred lines. CONCLUSIONS: The findings enhance our comprehension of the potential roles of the ZmLBD gene family in maize growth and development, which is pivotal for genetic enhancement and breeding efforts pertaining to this significant crop.

The impact of caregiver burden on quality of life in family caregivers of patients with advanced cancer: a moderated mediation analysis of the role of psychological distress and family resilience.

BACKGROUND: The caregiver burden frequently experienced by family members tending to advanced cancer patients significantly impacts their psychological well-being and quality of life (QoL). Although family resilience might function as a mitigating factor in this relationship, its specific role remains to be elucidated. This study aims to probe the mediating effect of psychological distress on the relationship between caregiver burden and QoL, as well as the moderating effect of family resilience. METHODS: A cross-sectional study was conducted between June 2020 and March 2021 in five tertiary hospitals in China. Data were collected on caregiver burden, family resilience, psychological distress (including anxiety and depression), and QoL. Moderated mediation analysis was performed. RESULTS: Data analysis included 290 caregivers. It confirmed the mediating role of psychological distress in the caregiver burden-QoL relationship (P < 0.001). Both overall family resilience and the specific dimension of family communication and problem-solving (FCPS) demonstrated significant moderating effects on the "psychological distress/anxiety-QoL" paths (P < 0.05). The utilization of social and economic resources (USER) significantly moderated the association between depression and QoL (P < 0.05). CONCLUSIONS: The study corroborates psychological distress's mediation between caregiver burden and QoL and family resilience's moderation between psychological distress and QoL. It underscores the need for minimizing psychological distress and bolstering family resilience among caregivers of advanced cancer patients. Accordingly, interventions should be tailored, inclusive of psychological assistance and promotion of family resilience, particularly focusing on FCPS and USER, to augment the caregivers' well-being and QoL.

Quercetin Alleviates Pulmonary Fibrosis in Silicotic Mice by Inhibiting Macrophage Transition and TGF-ß-Smad2/3 Pathway.

Silicosis is a pulmonary disease caused by the inhalation of silica. There is a lack of early and effective prevention, diagnosis, and treatment methods, and addressing silicotic fibrosis is crucial. Quercetin, a flavonoid with anti-carcinogenic, anti-inflammatory, and antiviral properties, is known to have a suppressive effect on fibrosis. The present study aimed to determine the therapeutic effect of quercetin on silicotic mice and macrophage polarity. We found that quercetin suppressed silicosis in mice. It was observed that SiO2 activated macrophage polarity and the macrophage-to-myofibroblast transition (MMT) by transforming the growth factor-ß (TGF-ß)-Smad2/3 signaling pathway in silicotic mice and MH-S cells. Quercetin also attenuated the MMT and the TGF-ß-Smad2/3 signaling pathway in vivo and in vitro. The present study demonstrated that quercetin is a potential therapeutic agent for silicosis, which acts by regulating macrophage polarity and the MMT through the TGF-ß-Smad2/3 signaling pathway.

Matrix stiffness regulates α-TAT1-mediated acetylation of α-tubulin and promotes silica-induced epithelial-mesenchymal transition via DNA damage.

Silicosis is characterized by silica exposure-induced lung interstitial fibrosis and formation of silicotic nodules, resulting in lung stiffening. The acetylation of microtubules mediated by α-tubulin N-acetyltransferase 1 (α-TAT1) is a posttranslational modification that promotes microtubule stability in response to mechanical stimulation. α-TAT1 and downstream acetylated α-tubulin (Ac-α-Tub) are decreased in silicosis, promoting the epithelial-mesenchymal transition (EMT); however, the underlying mechanisms are unknown. We found that silica, matrix stiffening or their combination triggered Ac-α-Tub downregulation in alveolar epithelial cells, followed by DNA damage and replication stress. α-TAT1 elevated Ac-α-Tub to limit replication stress and the EMT via trafficking of p53-binding protein 1 (53BP1, also known as TP53BP1). The results provide evidence that α-TAT1 and Ac-α-Tub inhibit the EMT and silicosis fibrosis by preventing 53BP1 mislocalization and relieving DNA damage. This study provides insight into how the cell cycle is regulated during the EMT and why the decrease in α-TAT1 and Ac-α-Tub promotes silicosis fibrosis.This article has an associated First Person interview with the first authors of the paper.

Electronic Modulation of Metal-Organic Frameworks Caused by Atomically Dispersed Ru for Efficient Hydrogen Evolution.

Designing excellent electrocatalysts for the hydrogen evolution reaction (HER) is extremely significant in producing clean and sustainable hydrogen fuel. Herein, a rational strategy is developed to fabricate a promising electrocatalyst by introducing atomically dispersed Ru into a cobalt-based metal-organic framework (MOF), Co-BPDC (Co(bpdc)(H2 O)2 , BPDC: 4,4'-Biphenyldicarboxylic acid). The obtained CoRu-BPDC nanosheet arrays exhibit remarkable HER performance with an overpotential of 37 mV at a current density of 10 mA cm-2 in alkaline media, which is superior to most of the MOF-based electrocatalysts and comparable to the commercial Pt/C. Synchrotron radiation-based X-ray absorption fine structure (XAFS) spectroscopy studies verify that the isolated Ru atoms are dispersed in Co-BPDC nanosheets with the formation of five-coordinated Ru-O5 species. XAFS spectroscopy combined with density functional theory (DFT) calculations unravels that atomically dispersed Ru can modulate the electronic structure of the as-obtained Co-BPDC, contributing to the optimization of binding strength for H* and the enhancement of HER performance. This work opens a new avenue to rationally design highly-active single-atom modified MOF-based HER electrocatalysts via modulating electronic structures of MOF.

Family resilience and its influencing factors among advanced cancer patients and their family caregivers: a multilevel modeling analysis.

BACKGROUND: Cancer is highly prevalent worldwide. Family resilience is a positive variable that helps families burdened by advanced cancer to cope effectively. This study aimed to describe the family resilience of advanced cancer patients and caregivers in dyads and identify its influencing factors at the individual and dyadic levels. METHODS: This multisite cross-sectional study was conducted in oncology units in five tertiary hospitals in China. A total of 270 advanced cancer patient-caregiver dyads were recruited between June 2020 and March 2021. Patients' and caregivers' family resilience was measured by the Family Resilience Assessment Scale. Data on potential influencing factors, including demographic and disease-related characteristics as well as family sense of coherence, psychological resilience, perceived social support, symptom burden, and caregiver burden, were collected. Multilevel modeling analysis was adopted to control for the interdependence of the dyads. RESULTS: A total of 241 dyads were included in the data analysis. The mean ages of patients and caregivers were 53.96 (SD 15.37) and 45.18 (SD 13.79) years, respectively. Most caregivers were spouses and adult children (45.6% and 39.0%, respectively). Patients reported a higher mean family resilience score than caregivers (152.56 vs. 149.87, respectively). Undergoing fewer than two types of treatment and a lower symptom burden of patients predicted higher patient (B = -9.702, -0.134, respectively) and caregiver (B = -5.462, -0.096, respectively) family resilience. Patients also reported higher family resilience under the following conditions: 1) were on a medical insurance plan other than the new rural cooperative medical system (B = 6.089), 2) had a better family sense of coherence (B = 0.415), 3) whose caregivers were unmarried (B = 8.618), perceived lower social support (B = -0.145) and higher psychological resilience (B = 0.313). Caregivers who were ≤ 44 years old (B = -3.221), had similar previous caregiving experience (B = 7.706), and had a stronger family sense of coherence (B = 0.391) reported higher family resilience. CONCLUSIONS: Our findings highlight the importance of adopting a dyadic approach when caring for advanced cancer patients and their caregivers. Dyadic longitudinal research is suggested to discover more modifiable factors of family resilience and tailored interventions are needed to obtain optimal dyadic outcomes.

Self-affirmation increases acceptance of information on COVID-19 vaccines and promotes vaccination intention.

Previous studies have shown that self-affirmation increases acceptance of a message and motivates health behavior change. The present study investigated whether self-affirmation increases the acceptance of persuasive messages on COVID-19 vaccines and promotes vaccination intention. A total of 144 participants were randomly assigned to the self-affirmation (n = 72) or control (n = 72) groups before reading a persuasive message on COVID-19 vaccines. The results revealed that the self-affirmation group showed significantly higher acceptance of persuasive information on COVID-19 vaccines than the control group. Additionally, the self-affirmation group also showed significantly higher post-experiment vaccination intention than the control group. Mediation analysis indicated that increased acceptance of persuasive information significantly mediated the beneficial effects of self-affirmation on post-experiment vaccination intention. The present study demonstrated that self-affirmation could be an effective strategy for increasing the acceptance of persuasive messages on COVID-19 vaccines and promoting vaccination intention.

Inhibition of Oncogenic Src Ameliorates Silica-Induced Pulmonary Fibrosis via PI3K/AKT Pathway.

Silicosis is a refractory disease. Previous studies indicate that damaged alveolar epithelial cells act as a driver in pulmonary fibrosis. Our results show that epithelial cells that acquire the mesenchymal phenotype are associated with the pathogenesis of silicosis. c-Src kinase, a non-receptor tyrosine kinase, has been shown to be a positive regulator of organ fibrosis, but specific mechanisms remain unclear and rarely researched in silicosis. The activated Phosphatidylinositol-3 kinases/AKT(PI3K/AKT) pathway promotes fibrosis. We aimed to determine whether c-Src regulates fibrosis via the PI3K/AKT signaling pathway in the development of silicosis. C57/BL mice were intratracheally perfused with 10 mg silica suspension to establish a model of silicosis. In vivo, silica particles induced lung fibrosis. The profibrotic cytokine transforming growth factor-ß1 (TGF-ß1) exhibited a high expression in pulmonary fibrosis. The phosphorylated c-Src protein was increased and the PI3K/AKT pathway was activated in model lung tissue. In vitro, silica increased the expression of TGF-ß1- and TGF-ß1-induced mesenchymal phenotype and fibrosis in a mouse epithelial cells line. siRNA-Src inhibited the c-Src, the phosphorylation of the PI3K/AKT pathway, and the mesenchymal phenotype induced by TGF-ß1. LY294002, a specific inhibitor of PI3K, suppressed the phosphorylation of PI3K/AKT but did not affect Src activation. SU6656, a selective Src inhibitor, attenuated fibrosis in silicosis model. In summary, c-Src promotes fibrosis via the PI3K/AKT pathway in silica-induced lung fibrosis, and Src kinase inhibitors are potentially effective for silicosis treatment.

E3 ubiquitin ligase MID1 ubiquitinates and degrades type-I interferon receptor 2.

Type I interferon (IFN-I) is a common biological molecule used for the treatment of viral diseases. However, the clinical antiviral efficacy of IFN-I needs to be greatly improved. In this study, IFN-I receptor 2 (IFNAR2) was revealed to undergo degradation at the protein level in cells treated with IFN-I for long periods of time. Further studies found a physical interaction between the E3 ubiquitin ligase midline-1 (MID1) and IFNAR2. As a consequence, MID1 induced both K48- and K63-linked polyubiquitination of IFNAR2, which promoted IFNAR2 protein degradation in a lysosome-dependent manner. Conversely, knockdown of MID1 largely restricted IFN-I-induced degradation of IFNAR2. Importantly, MID1 regulated the strength of IFN-I signalling and IFN-I-induced antiviral activity. These findings reveal a regulatory mechanism of IFNAR2 ubiquitination and protein stability in IFN-I signalling, which could provide a potential target for improving the antiviral efficacy of IFN-I.

Follow-up to a randomized controlled trial of the effect of self-affirmation on anxiety during the COVID-19 pandemic.

A recent study showed that a brief intervention involving reflection on personal values (T1: 2 February 2020) can buffer the anxiety response one week later (T2: Feb. 9) during the COVID-19 pandemic in China. The present study reported the results from a follow-up two weeks (T3: Feb. 16) and one-month later (T4: Mar. 1). Two hundred and twenty participants were recruited via convenience sampling and randomly assigned either to the value-affirmation condition or to a control condition, with 110 participants in each condition. The results revealed that similar to T2, participants who affirmed their values showed a lower anxiety response than those in the control group at T3, despite the pandemic continuing to increase rapidly during that time. Meanwhile, anxiety decreased in both groups at T4 as the pandemic eased. Findings suggest that self-affirmations can help reduce stress in the face of the COVID-19.

Oxamate Attenuates Glycolysis and ER Stress in Silicotic Mice.

Glycolysis and ER stress have been considered important drivers of pulmonary fibrosis. However, it is not clear whether glycolysis and ER stress are interconnected and if those interconnections regulate the development of pulmonary fibrosis. Our previous studies found that the expression of LDHA, a key enzyme involved in glycolysis, was increased in silica-induced macrophages and silicotic models, and it was closely related to silicosis fibrosis by participating in inflammatory response. However, whether pharmacological inhibition of LDHA is beneficial to the amelioration of silicosis fibrosis remains unclear. In this study, we investigated the effects of oxamate, a potent inhibitor of LDHA, on the regulation of glycolysis and ER stress in alveolar macrophages and silicotic mice. We found that silica induced the upregulation of glycolysis and the expression of key enzymes directly involved in ER stress in NR8383 macrophages. However, treatment of the macrophages and silicotic mice with oxamate attenuated glycolysis and ER stress by inhibiting LDHA, causing a decrease in the production of lactate. Therefore, oxamate demonstrated an anti-fibrotic role by reducing glycolysis and ER stress in silicotic mice.

Insight into the performance and mechanism of magnetic Ni0.5Cu0.5Fe2O4 in activating peroxydisulfate for ciprofloxacin degradation.

Magnetic nickel-copper ferrite (NixCuyFe2O4) nano-catalyst was synthesized by co-precipitation method, and it exhibited excellent ability for activating peroxydisulfate (PDS) in the degradation of ciprofloxacin (CIP). As-prepared Ni0.5Cu0.5Fe2O4 properties were characterized by Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscope equipped with an energy-dispersive X-ray (SEM-EDX), transmissions electron microscopy (TEM), N2 adsorption-desorption isotherm plot of Brunauer-Emmett-Teller (BET) and Barrett-Joyner-Halenda (BJH), vibrating sample magnetometer (VSM). The maximum degradation efficiency is 80.2% by using 0.500 g/L of Ni0.5Cu0.5Fe2O4 for activating 5.00 mmol/L of PDS to degrade CIP (20.0 mg/L) at 25 ± 2 °C for 50 min (pH = 6.00). The presence of interfering ions Cl-, NO3-, and HCO3- inhibited the reaction by producing reactive species with low oxidation potential, inducing the degradation efficiency down to 60.0%, 58.1% and 21.5% respectively. Ni0.5Cu0.5Fe2O4 displayed great magnetic separation characteristic for the satisfactory magnetization; saturation value is ∼8.6 emu/g. The degradation efficiency of recycled samples has no significant difference after using three times, which is about 60%, indicating that Ni0.5Cu0.5Fe2O4 is a reusability catalyst in activating PDS for CIP degradation. This work might provide an efficient and promising approach to construct recyclable magnetic materials that can be used for wastewater treatment.

Photocatalysis coupled with adsorption of AC@Ni0.5Cu0.5Fe2O4 in peroxydisulfate assisted system efficiently enhance ciprofloxacin removal.

Nickle-copper ferrite (Ni0.5Cu0.5Fe2O4) supported on activated carbon (AC) (AC@Ni0.5Cu0.5Fe2O4) was synthesized and used as adsorbent, photocatalyst, and activator of peroxydisulfate (PDS) to realize the removal of ciprofloxacin (CIP). AC@Ni0.5Cu0.5Fe2O4 properties were characterized by scanning electron microscope equipped with energy-dispersive X-ray (SEM-EDX), X-ray diffraction (XRD), N2 adsorption-desorption isotherm plot of Brunauer-Emmett-Teller (BET) and Barrett-Joyner-Halenda (BJH), vibrating sample magnetometer (VSM). A rapid removal rate (94.30%) of CIP was achieved on AC@Ni0.5Cu0.5Fe2O4/PDS/UV system with the condition of catalyst dosage 0.30 g/L, initial pH 7.3, PDS addition 0.20 mM, CIP concentration 10 mg/L (200 mL), UV 28 W, in 30 min. Free radical quenching experiments indicate that reactive species of superoxide (·O2-), holes (h+), sulfate radicals (SO4-·) and hydroxyl radicals (·OH) were produced and all worked. The reusability test demonstrated that AC@Ni0.5Cu0.5Fe2O4 could be recycled five times with minimal performance reduction for the removal of CIP. The XRD and SEM of the after used AC@Ni0.5Cu0.5Fe2O4 did not change significantly, which further showed its stability and recyclability. This work might provide new insight into the application of AC@Ni0.5Cu0.5Fe2O4 in photocatalysis coupled with adsorption in peroxydisulfate assisted system and has high potential in CIP removal.

MicroRNA-411-3p inhibits bleomycin-induced skin fibrosis by regulating transforming growth factor-ß/Smad ubiquitin regulatory factor-2 signalling.

Skin fibrosis, which is characterized by fibroblast proliferation and increased extracellular matrix, has no effective treatment. An increasing number of studies have shown that microRNAs (miRNAs/miRs) participate in the mechanism of skin fibrosis, such as in limited cutaneous systemic sclerosis and pathological scarring. The objective of the present study was to determine the role of miR-411-3p in bleomycin (BLM)-induced skin fibrosis and skin fibroblast transformation. Using Western blot analysis and real-time quantitative polymerase chain reaction assess the expression levels of miR-411-3p, collagen (COLI) and transforming growth factor (TGF)-ß/Smad ubiquitin regulatory factor (Smurf)-2/Smad signalling factors both in vitro and in vivo with or without BLM. To explore the regulatory relationship between miR-411-3p and Smurf2, we used the luciferase reporter assay. Furthermore, miR-411-3p overexpression was identified in vitro and in vivo via transfection with Lipofectamine 2000 reagent and injection. Finally, we tested the dermal layer of the skin using haematoxylin and eosin and Van Gieson's staining. We found that miR-411-3p expression was decreased in bleomycin (BLM)-induced skin fibrosis and fibroblasts. However, BLM accelerated transforming growth factor (TGF)-ß signalling and collagen production. Overexpression of miR-411-3p inhibited the expression of collagen, F-actin and the TGF-ß/Smad signalling pathway factors in BLM-induced skin fibrosis and fibroblasts. In addition, miR-411-3p inhibited the target Smad ubiquitin regulatory factor (Smurf)-2. Furthermore, Smurf2 was silenced, which attenuated the expression of collagen via suppression of the TGF-ß/Smad signalling pathway. We demonstrated that miR-411-3p exerts antifibrotic effects by inhibiting the TGF-ß/Smad signalling pathway via targeting of Smurf2 in skin fibrosis.

Repurposing bortezomib for choroidal neovascularization treatment via antagonizing VEGF-A and PDGF-D mediated signaling.

Neovascular age-related macular degeneration (neoAMD) is the leading cause of blindness in AMD and manifests as choroidal neovascularization (CNV). Anti-vascular endothelial growth factor (VEGF) therapies are the mainstay treatments but with limited efficacy and cause detrimental effects on the retina after long-term application. These disadvantages warrant alternative strategy. Herein, we examined the effect on CNV by intravitreal injection of bortezomib, a reversible proteasome inhibitor, and further dissected the mechanism. Krypton red Laser was used to create CNV model in mice. The angiogenesis volume was assessed in choroidal flat-mount with isolectin GS-IB4 labeling and the leakage was examined with fluorescein fundus angiography. Injection of Borsub inhibited angiogenesis in the CNV model which was dose-dependent; the injection significantly inhibited leakage as well. Furthermore, Borsub injection reduced the contents of VEGF-A, macrophage chemotactic factor 1 (MCP-1), and platelet-derived growth factor (PDGF)-D but not PDGF-B, examined by enzyme-linked immunosorbent assay, in choroid/retinal pigment epithelium (RPE) tissue. These injections also reduced phospho-VEGFR-2 and phospho-PDGFRß in choroid/RPE tissue examined by immunoblotting. Moreover, Borsub inhibited the recruitment of mural cells or macrophages to laser-injured spots. Injection of Borsub indicated negative effect on scotopic and photopic responses recorded by electroretinogram. Altogether, intravitreal injection of Borsub significantly reduced CNV by antagonizing VEGF-A/Flk-1 and PDGF-D/PDGFRß pathways without impacting electroretinography parameters. Thus, Borsub may offer an invaluable therapy for the prevention and treatment of neoAMD.

MiR-411-3p alleviates Silica-induced pulmonary fibrosis by regulating Smurf2/TGF-ß signaling.

Occupational exposure to silica dust particles was the major cause of pulmonary fibrosis, and many miRNAs have been demonstrated to regulate target mRNAs in silicosis. In the present study, we found that a decreasing level of miR-411-3p in silicosis rats and lung fibroblasts induced by TGF-ß1. Enlargement of miR-411-3p could inhibit the cell proliferation and migration in lung fibroblasts with TGF-ß1 treatment and attenuate lung fibrosis in silicotic mice. In addition, a mechanistic study showed that miR-411-3p exert its inhibitory effect on Smad ubiquitination regulatory factor 2 (Smurf2) expression and decrease ubiquitination degradation of Smad7 regulated by smurf2, result in blocking of TGF-ß/Smad signaling. We proposed that increased expression of miR-411-3p abrogates silicosis by blocking activation of TGF-ß/Smad signaling through decreasing ubiquitination degradation effect of smurf2 on Smad7.

The role of protein arginine methyltransferase 7 in human developmentally arrested embryos cultured in vitro.

Human embryos of in vitro fertilization (IVF) are often susceptible to developmental arrest, which greatly reduces the efficiency of IVF treatment. In recent years, it has been found that protein arginine methyltransferase 7 (PRMT7) plays an important role in the process of early embryonic development. However, not much is known about the relationship between PRMT7 and developmentally arrested embryos. The role of PRMT7 in developmentally arrested embryos was thus investigated in this study. Discarded human embryos from IVF were collected for experimental materials. Quantitative real-time polymerase chain reaction (qRT-PCR) and confocal analyses were used to identify PRMT7 mRNA and protein levels in early embryos at different developmental stages, as well as changes in the methylation levels of H4R3me2s. Additionally, PRMT7 was knocked down in the developmentally arrested embryos to observe the further development of these embryos. Our results demonstrated that PRMT7 mRNA and protein levels in arrested embryos were significantly increased compared with those in control embryos; meanwhile, the methylation levels of H4R3me2s in arrested embryos were also increased significantly. Knockdown of PRMT7 could rescue partially developmentally arrested embryos, and even individual developmentally arrested embryos could develop into blastocysts. In conclusion, over-expression of PRMT7 disrupts the early embryo development process, leading to early embryos developmental arrest, but these developmentally arrested defects could be partially rescued by knockdown of the PRMT7 protein.

Application of Ultra Narrow Band Modulation in Enhanced Loran System.

The Enhanced Loran (eLoran) system is valued for its important role in the positioning, navigation, and timing fields; however, with its current modulation methods, low data rate restricts its development. Ultra narrow band (UNB) modulation is a modulation method with extremely high spectrum utilization. If UNB modulation can be applied to the eLoran system, it will be very helpful. The extended binary phase shift keying modulation in UNB modulation is selected for a detailed study, parameters and application model are designed according to its unique characteristics of signal time and frequency domains, and it is verified through simulation that the application of this modulation not only meets the design constraints of the eLoran system but also does not affect the reception of the respective signals of both parties. Several feasible schemes are compared, analyzed, and selected. Studies have revealed that application of UNB modulation in the eLoran system is feasible, and it will increase the data rate of the system by dozens of times.

Complexation of arsenate to humic acid with different molecular weight fractions in aqueous solution.

Natural organic matter (NOM) has been considered a critical substance in the transport and transformation of arsenic. NOM is a complex mixture of multifunctional organic components with a wide molecular weight (MW) distribution, and it is necessary to understand the complexation of arsenic with MW-dependent NOM fractions. In this study, humic acid (HA) was chosen as the representative fraction of NOM to investigate the complexation mechanism with arsenic. The bulk HA sample was fractionated to five fractions by ultrafiltration technology, and the complexing property of HA fractions with arsenic was analyzed by the dialysis method. We observed that the acidic and neutral conditions favor the complexation of HA fractions with arsenate (As(V)). The HA fractions with molecular weight > 100 kDa, 1-10 kDa, and <1 kDa have the stronger complexing capacity of As(V) than the other HA fractions. The bound As(V) percentage was positively associated with carboxyl content, phenolic content, and especially total acidity. A two-site ligand-binding model can describe the complexing capacity of arsenic onto HA fractions. The results can provide some fundamental information about the complexation of arsenic with MW-dependent HA fractions quantitatively.

N-Acetyl-Seryl-Asparyl-Lysyl-Proline regulates lung renin angiotensin system to inhibit epithelial-mesenchymal transition in silicotic mice.

Silicosis is a major public health concern with various contributing factors. The renin-angiotensin system (RAS)is a critical regulator in the pathogenesis of this disease. We focused on two key RAS enzymes, angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2), to elucidate the activation of the ACE-angiotensin II (Ang II)-angiotensin II receptor 1 (AT1) axis and the inhibition of the ACE2-angiotensin-(1-7) [Ang-(1-7)]-Mas receptor axis in C57BL/6mice following SiO2 treatment. Silica exposure caused nodule formation, pulmonary interstitial fibrosis, epithelial-mesenchymal transition (EMT), abnormal deposition of extracellular matrix, and impaired lung function in mice. These effects were attenuated by the inhibition of ACE (captopril), blockade of the AT1(losartan), or systemic knockdown of the Ace gene. These effects were exacerbated by the inhibition of ACE2 (MLN-4760), blockade of the Mas (A779), or knockdown of the Ace2 gene. N-Acetyl-Seryl-Asparyl-Lysyl-Proline (Ac-SDKP), an anti-fibrotic peptide, ameliorated the silica-exposure-induced pathological changes by targeting the RAS system by activating the protective ACE2-Ang-(1-7)-Mas axis and inhibiting the deleterious ACE-Ang II-AT1 axis, thereby exerting a protective effect. This was confirmed in mouse lung type II epithelial cells (MLE-12) pretreated with Ang II and/or gene silencing separately targeting Ace and Ace2.The effects of Ac-SDKP were similar to those produced by Ace gene silencing and were partly attenuated by Ace2 deficiency. These findings suggested that RAS plays critical roles in the pathomechanism of silicosis fibrosis and that Ac-SDKP regulates lung RAS to inhibit EMT in silicotic mice and MLE-12 cells.