Hg Treatment Research Articles

Optimal Antihypertensive Systolic Blood Pressure: A Systematic Review and Meta-Analysis.

Systolic blood pressure (SBP) lowering reduces major cardiovascular disease (CVD) and all-cause mortality. However, the optimal target for SBP lowering remains controversial. We included trials with random allocation to an SBP <130 mm Hg treatment target and CVD as the primary outcome. Data were extracted from each study independently and in duplicate using a standardized protocol. Random-effects meta-analysis was used to obtain pooled hazard ratios (HRs) and 95% CIs for CVD and all-cause mortality comparing SBP <130 and ≥130 mm Hg treatment targets. A secondary analysis compared the same outcomes for randomization to an SBP target of <120 or <140 mm Hg. Seven trials, including 72 138 participants, met the eligibility criteria. Compared with an SBP target of ≥130 mm Hg, an SBP target of <130 mm Hg significantly reduced major CVD (HR, 0.78 [95% CI, 0.70-0.87]) and all-cause mortality (HR, 0.89 [95% CI, 0.79-0.99]). Compared with an SBP target of <140 mm Hg, an intensive SBP target of <120 mm Hg significantly reduced major CVD (HR, 0.82 [95% CI, 0.74-0.91]), but all-cause mortality was marginally insignificant (HR, 0.85 [95% CI, 0.71-1.01]). Adverse events were significantly more likely in the intensive SBP target groups, but the absolute risks were low. This study suggests targeting an SBP <130 mm Hg significantly reduces the risks of major CVD and all-cause mortality. The findings also support an SBP target of <120 mm Hg, based on a smaller number of trials. URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42023490693.

Microaxial Flow Pump Hemodynamic and Metabolic Effects in Infarct-Related Cardiogenic Shock

Mechanical circulatory support with a microaxial flow pump (MAFP) has been shown to improve survival in ST-elevation myocardial infarction-induced cardiogenic shock (STEMI-CS). Understanding the impact on hemodynamic stability over time is crucial for optimizing patient treatment. To determine if an MAFP reduces the need for pharmacological circulatory support without compromising hemodynamics compared with standard care in STEMI-CS. This was a substudy of the Danish-German (DanGer) Shock trial, an international, multicenter, open-label randomized clinical trial. Patients from 14 heart centers across Denmark, Germany, and the UK were enrolled. Inclusion criteria for the trial were STEMI and systolic blood pressure less than 100 mm Hg or ongoing vasopressor treatment, left ventricular ejection fraction less than 45%, and arterial lactate level greater than 2.5 mmol/L. Of the enrolled patients, after exclusions from death in the catheterization laboratory or immediately on intensive care unit (ICU) admission, the remaining patients had serial recordings of hemodynamics, arterial lactate, and use of vasoactive drugs. Patients who were in comas after cardiac arrest and patients with mechanical complications or right ventricular failure were excluded. Data were analyzed from May to September 2024. MAFP and standard of care or standard of care alone. Hemodynamic status in terms of heart rate and blood pressure, metabolic status in terms of arterial lactate concentration, and vasoactive-inotropic score (VIS). The clinical events during the first 72 hours were as follows: death from all causes, escalation of mechanical circulatory support, and discharge alive from the ICU. From 355 enrolled patients, 324 (mean [IQR] age, 68 [58-75] years; 259 male [80%]) underwent ICU treatment (169 [52%] in the MAFP group, 155 [48%] in the standard-care group). Baseline characteristics were balanced. There was no difference in heart rate between groups, and mean arterial pressure was above the treatment target of 65 mm Hg in both groups but was achieved with a lower VIS in the MAFP group. No difference in arterial lactate level was found between groups at randomization, but on arrival to the ICU, the MAFP group had significantly lower arterial lactate levels compared with the standard-care group (mean difference, 1.3 mmol/L; 95% CI, 0.7-1.9 mmol/L), a difference that persisted throughout the first 24 hours of observation. The MAFP group achieved lactate normalization (<2 mmol/L) 12 hours (95% CI, 5-18 hours) before the standard-care group. Use of a MAFP reduces the use of vasopressors and inotropic medication while maintaining hemodynamic stability and achieving faster normalization of lactate level in patients with STEMI-CS. ClinicalTrials.gov Identifier: NCT01633502.

The relationships between structure and function of plant communities in the desert steppe

BackgroundAssessing the relationships between spatial and temporal structures and functions of plant communities is an effective way to understand the changing dynamics of plant communities in specific environments. In this study, we investigated the response of structural and functional stabilities of plant communities to stocking rate in the desert steppe over a 16-year grazing period as the research background.MethodsWe used classical statistical methods to investigate the quantitative characteristics of plant communities over time (2014–2019) and space (2017–2019) at four stocking rates (control, CK, 0 sheep·ha–1·month–1; light grazing, LG, 0.15 sheep·ha–1·month–1; moderate grazing, MG, 0.30 sheep·ha–1·month–1; heavy grazing, HG, 0.45 sheep·ha–1·month–1) in the Stipa breviflora desert steppe of Inner Mongolia. We then examined the relationship between structural and functional stability of plant communities.ResultsOn the spatial scale, the structural stability of plant community was the highest in the LG treatment and the lowest in the MG treatment. The functional stability of plant community was the highest in the MG treatment and the lowest in the HG treatment. On the temporal scale, the structural stability of plant community was the highest in the MG treatment and the lowest in the LG treatment. The functional stability of plant community was the highest in the LG treatment and the lowest in the HG treatment. Affected by the stocking rate, the structural stability of plant community fluctuated more widely on the spatial scale and its functional stability varied more widely on the temporal scale. Nonetheless, the functional stability of the plant community is more responsive to the stocking rate.ConclusionsOur findings suggest that influenced by the disturbance of stocking rate, the structural stability of plant community is more significant than the functional stability in the desert grassland ecosystem, which lays a solid foundation for the study of ecosystem stability.

METTL3 mediates m6A modification of hsa_circ_0072380 to regulate the progression of gestational diabetes mellitus

Backgroundm6A modification plays a vital role in gestational diabetes mellitus (GDM) progression. However, the role of METTL3 and differential m6A-modified circRNAs in GDMremainsto be investigated. MethodsPlacental tissue samples from GDM patients and normal controls (NC) were collected to measure changes in m6A modification levels. MeRIP-seq on placental tissue was performed to detect differential m6A-modified circRNAs.High glucose (HG)-treated JEG3 cells were used to establish the GDM cell model. Differentially expressed circRNAs levels in GDM and NC groups were measured by qRT-PCR. We knocked down METTL3 to study its function. Additionally, we conducted functional recovery experiments. Dot blot assay was utilized to assess changes in m6A levels. MeRIP-qPCR was performed to evaluate the effect of knocking down METTL3 on m6A modification of hsa_circ_0072380 in JEG3 cells. ResultsCompared with the NC group, the GDM group exhibited increased levels of m6A modification and METTL3 expression. Differences in m6A modification of circRNAs exist between the GDM and NC groups. Hsa_circ_0000994, hsa_circ_0058733, and hsa_circ_0072380 were significantly down-regulated in the GDM group while hsa_circ_0036376, hsa_circ_0000471, and hsa_circ_0001173 showed no significant differences between two groups. HG treatment promoted METTL3 expression and m6A level of JEG3 cells, and inhibited cell proliferation, migration, and invasion abilities. Knocking down METTL3 reversed these effects. After HG treatment, hsa_circ_0072380 was significantly down-regulated. Knocking down METTL3 led to up-regulation of hsa_circ_0072380, while knocking down hsa_circ_0072380 restored the function of SiMETTL3. Additionally, knocking down METTL3 significantly reduced the m6A modification of hsa_circ_0072380. ConclusionMETTL3 mediated m6A modification of hsa_circ_0072380 to regulate GDM progression.

Liraglutide ameliorates high glucose-induced vascular endothelial injury through TRIB3/NF-κB signaling pathway.

As one of the most commonly used antidiabetic medications clinically, liraglutide is involved in the protection of vascular endothelium, and whether it can relieve high glucose-induced vascular endothelial damage was unknown. This study aims to address the response of liraglutide (LIRA) on human umbilical vein endothelial cells, as well as to elucidate its possible underlying mechanism. We established a vascular endothelial cell injury model by exposing human umbilical vein endothelial cells (HUVECs) to high glucose, and used LIRA pretreatment before HG treatment to address the endothelial protective effect of LIRA. Our results suggest that LIRA prevented HG-induced HUVEC apoptosis, oxidative stress, inflammasome activation, and pyroptosis. Furthermore, silencing of tribbles homolog 3 (TRIB3) could markedly reduce HG-induced HUVEC apoptosis, ROS level, the expressions of TXNIP, cleaved caspase3, NLRP3, and caspase1, indicating TRIB3 inhibition protected HUVECs against HG-induced vascular endothelial injury. In addition, LIRA restrained NF-κB/IκB-α signaling pathway activation in HUVECs. Thus, LIRA appears to mitigate HG-induced apoptosis, oxidative stress, inflammasome activation, and pyroptosis in HUVECs via regulating the TRIB3/NF-κB/IκB-α signaling pathway. Our study provides new insight into the mechanisms underlying the protective activity of LIRA against the vascular endothelial injury in diabetic vascular complication.

Lowering systolic blood pressure to less than 120 mm Hg versus less than 140 mm Hg in patients with high cardiovascular risk with and without diabetes or previous stroke: an open-label, blinded-outcome, randomised trial

Uncertainty exists about whether lowering systolic blood pressure to less than 120 mm Hg is superior to that of less than 140 mm Hg, particularly in patients with diabetes and patients with previous stroke. In this open-label, blinded-outcome, randomised controlled trial, participants with high cardiovascular risk were enrolled from 116 hospitals or communities in China. We used minimised randomisation to assign participants to intensive treatment targeting standard office systolic blood pressure of less than 120 mm Hg or standard treatment targeting less than 140 mm Hg. The primary outcome was a composite of myocardial infarction, revascularisation, hospitalisation for heart failure, stroke, or death from cardiovascular causes, assessed by the intention-to-treat principle. This trial was registered with ClinicalTrials.gov, NCT04030234. Between Sept 17, 2019, and July 13, 2020, 11 255 participants (4359 with diabetes and 3022 with previous stroke) were assigned to intensive treatment (n=5624) or standard treatment (n=5631). Their mean age was 64·6 years (SD 7·1). The mean systolic blood pressure throughout the follow-up (except the first 3 months of titration) was 119·1 mm Hg (SD 11·1) in the intensive treatment group and 134·8 mm Hg (10·5) in the standard treatment group. During a median of 3·4 years of follow-up, the primary outcome event occurred in 547 (9·7%) participants in the intensive treatment group and 623 (11·1%) in the standard treatment group (hazard ratio [HR] 0·88, 95% CI 0·78-0·99; p=0·028). There was no heterogeneity of effects by diabetes status, duration of diabetes, or history of stroke. Serious adverse events of syncope occurred more frequently in the intensive treatment group (24 [0·4%] of 5624) than in standard treatment group (eight [0·1%] of 5631; HR 3·00, 95% CI 1·35-6·68). There was no significant between-group difference in the serious adverse events of hypotension, electrolyte abnormality, injurious fall, or acute kidney injury. For hypertensive patients at high cardiovascular risk, regardless of the status of diabetes or history of stroke, the treatment strategy of targeting systolic blood pressure of less than 120 mm Hg, as compared with that of less than 140 mm Hg, prevents major vascular events, with minor excess risk. The Ministry of Science and Technology of China and Fuwai Hospital. For the Mandarin translation of the abstract see Supplementary Materials section.

Reshaping the root endophytic microbiota in plants to combat mercury-induced stress

Emerging evidence suggests that plants experiencing abiotic stress actively seek help from soil microbes. However, the empirical evidence supporting this strategy is limited, especially in response to heavy metal stress. We used integrated microbial community profiling and culture-based methods to investigate the interaction between mercury (Hg) stress, the entophytic root microbiome, and maize seedlings. The results of the pot experiment showed that soil Hg (20 mg/kg) strongly inhibited maize growth, indicating its strong phytotoxicity. Furthermore, Hg stress significantly altered the structure of the bacterial and fungal communities and enriched the potentially pathogenic Fusarium sp., suggesting that soil Hg stress may enhance the bio-stress induced by Fusarium species in maize. Additionally, soil Hg also led to the enrichment of beneficial bacterial members of Streptomyces, Lysobacter, and Sphingomonas (defined as differential species), which were also identified as keystone species in the Hg treatment by the analysis of co-occurrence networks. Therefore, it can be postulated that the members of Streptomyces, Lysobacter, and Sphingomonas function as stress-alleviating microbes. We successfully isolated the representatives of these stress-alleviating microbes. As expected, these strains mitigated the detrimental effects of Hg stess for the maize seedlings, suggesting that plants recruit the stress-alleviated microbiota to combat Hg stress. This study provides insights into the potential of manipulating the root microbiome to enhance plant growth in polluted environments.

Effect of acute exposure of Hg on physiological parameters and transcriptome expression in silkworms (Bombyx mori).

Mercury (Hg) contamination poses a global threat to the environment, given its elevated ecotoxicity. Herein, we employed the lepidopteran model insect, silkworm (Bombyx mori), to systematically investigate the toxic effects of Hg-stress across its growth and development, histomorphology, antioxidant enzyme activities, and transcriptome responses. High doses of Hg exposure induced evident poisoning symptoms, markedly impeding the growth of silkworm larvae and escalating mortality in a dose-dependent manner. Under Hg exposure, the histomorphology of both the midgut and fat body exhibited impairments. Carboxylesterase (CarE) activity was increased in both midgut and fat body tissues responding to Hg treatment. Conversely, glutathione S-transferase (GST) levels increased in the fat body but decreased in the midgut. The transcriptomic analysis revealed that the response induced by Hg stress involved multiple metabolism processes. Significantly differently expressed genes (DEGs) exhibited strong associations with oxidative phosphorylation, nutrient metabolisms, insect hormone biosynthesis, lysosome, ribosome biogenesis in eukaryotes, and ribosome pathways in the midgut or the fat body. The findings implied that exposure to Hg might induce the oxidative stress response, attempting to compensate for impaired metabolism. Concurrently, disruptions in nutrient metabolism and insect hormone activity might hinder growth and development, leading to immune dysfunction in silkworms. These insights significantly advance our theoretical understanding of the potential mechanisms underlying Hg toxicity in invertebrate organisms.

Bioaccumulation and sub-lethal physiological effects of metal mixtures on mussel, Mytilus edulis: Continuous exposure to a binary mixture of mercury and cadmium

In the natural ecosystem, aquatic organisms are exposed to a cocktail of chemicals that may result in toxicological responses differing from those of individual chemicals. In the present study, mussels were exposed using a semi-static and triplicated design to either control (no added metal), 50 µg l−1 (Hg alone), 50 µg l−1 (Cd alone), or 50 µg l−1 Hg plus 50 µg l−1 Cd (Hg + Cd) mixture for 14 days. Tissues were collected on days 0, 2, 4, 8, and 14 for metal analysis and sub-lethal responses using a suite of assays. Tissue metal concentrations were not significantly different in the single metal (Hg or Cd) compared to the Hg plus Cd mixture treatment for all tissues, apart from the gill of the Cd alone treatment. At the end of the experiment, the gill Cd concentration was significantly increased in the Hg plus Cd mixture compared to the Cd alone treatment, suggesting the influence of Hg on Cd uptake. The percentage increases of the Hg plus Cd mixture compared to the arithmetic sum of the individual metals were ( %): 20.2, 9.3, 25.1, 23.8, 10.7, and 12.4 for adductor muscle, digestive gland, gill, gonad, remaining soft tissue, and haemolymph, respectively. There were no observed treatment effects on total haemocyte count, haemolymph protein, or glucose concentration in the cell-free haemolymph. Neither was there any treatment effect on osmotic pressure, ions in the tissues, or in the cell-free haemolymph. At the end of the experiment, Hg-mediated oxidative damage, as an increase of thiobarbituric reactive substances (TBARS) and apparent depletion of total glutathione. This was observed in the gill and digestive gland of the Hg alone and Hg plus Cd mixture. Histopathology examination showed similar pathology in the Hg alone and the Hg plus Cd treatment. In conclusion, despite some oxidative stress and pathology during metal exposure, the accumulation of metals and effects on mussel health were similar between single exposures and a mixture of Hg plus Cd. In terms of risk assessment, regulations for the individual metals should suffice to protect against the mixture of Hg plus Cd, at least for adult M. edulis in full-strength seawater.

Effects of sulfur nanoparticles on rhizosphere microbial community changes in oilseed rape plantation soil under mercury stress

In the present study, experiments were conducted to assess the influence of nanoscale sulfur in the microbial community structure of metallophytes in Hg-contaminated rhizosphere soil for planting rapeseed. The results showed that the richness and diversity of the rhizobacteria community decreased significantly under Hg stress, but increased slightly after SNPs addition, with a reduction in the loss of Hg-sensitive microorganisms. Moreover, all changes in the relative abundances of the top ten phyla influenced by Hg treatment were reverted when subjected to Hg + SNPs treatment, except for Myxococcota and Bacteroidota. Similarly, the top five genera, whose relative abundance decreased the most under Hg alone compared to CK, increased by 19.05%–54.66% under Hg + SNPs treatment compared with Hg alone. Furthermore, the relative abundance of Sphingomonas, as one of the dominant genera for both CK and Hg + SNPs treatment, was actively correlated with plant growth. Rhizobacteria, like Pedobacter and Massilia, were significantly decreased under Hg + SNPs and were positively linked to Hg accumulation in plants. This study suggested that SNPs could create a healthier soil microecological environment by reversing the effect of Hg on the relative abundance of microorganisms, thereby assisting microorganisms to remediate heavy metal-contaminated soil and reduce the stress of heavy metals on plants.

Down-Regulation Assession of Methyl CpG Binding Protein 2 in Diabetic Nephropathy

Diabetes nephropathy (DN) is the most significant microvascular complication of diabetes worldwide due to hyperglycemiainduced podocyte injury and apoptosis. The role of methyl CpG binding protein 2 (MECP2) has been observed, but its specific involvement in DN remains unclear. In this study, an in vitro DN model was established using human glomerular podocytes exposed to high glucose (HG, 30 mM). MECP2 expression was assessed using qRT-PCR and Western Blot. Proliferation and migration were evaluated through CCK-8 and transwell assays in both the HG group and the HG + MECP2 knockdown group. Apoptosis was assessed by flow cytometry and Western Blot. RNA-Sequencing identified differentially expressed genes (DEGs) between HG and HG+MECP2 knockdown groups, with subsequent enrichment analysis using KEGG and GSEA databases. Our results revealed elevated MECP2 expression in HG-treated podocytes compared to the control group. Podocytes with MECP2 knockdown displayed increased proliferation and migration compared to the HG group. MECP2 knockdown significantly inhibited HG-induced apoptosis in podocytes, with lower expression of pro-apoptotic protein (cleaved-caspase3, Bax, BAD, Desmin) and higher expression of anti-apoptotic protein Bcl-2 in the HG+MECP2 shRNA group. RNA sequencing identified 123 upregulated and 129 downregulated DEGs. Enrichment analysis highlighted apoptosis-related pathways like PPAR, TNF, p53, RELAXIN, WNT, and RAP1 signaling. Podocytes with MECP2 knockdown showed reduced apoptosis upon HG treatment. In summary, downregulation of MECP2 in podocytes effectively mitigated apoptosis caused by high glucose, suggesting a potential strategy to improve diabetes nephropathy outcomes.

In vivo chronic exposure to inorganic mercury worsens hypercholesterolemia, oxidative stress and atherosclerosis in the LDL receptor knockout mice

Heavy metal exposure leads to multiple system dysfunctions. The mechanisms are likely multifactorial and involve inflammation and oxidative stress. The aim of this study was to evaluate markers and risk factors for atherosclerosis in the LDL receptor knockout mouse model chronically exposed to inorganic mercury (Hg) in the drinking water. Results revealed that Hg exposed mice present increased plasma levels of cholesterol, without alterations in glucose. As a major source and target of oxidants, we evaluated mitochondrial function. We found that liver mitochondria from Hg treated mice show worse respiratory control, lower oxidative phosphorylation efficiency and increased H2O2 release. In addition, Hg induced mitochondrial membrane permeability transition. Erythrocytes from Hg treated mice showed a 50% reduction in their ability to take up oxygen, lower levels of reduced glutathione (GSH) and of antioxidant enzymes (SOD, catalase and GPx). The Hg treatment disturbed immune system cells counting and function. While lymphocytes were reduced, monocytes, eosinophils and neutrophils were increased. Peritoneal macrophages from Hg treated mice showed increased phagocytic activity. Hg exposed mice tissues present metal impregnation and parenchymal architecture alterations. In agreement, increased systemic markers of liver and kidney dysfunction were observed. Plasma, liver and kidney oxidative damage indicators (MDA and carbonyl) were increased while GSH and thiol groups were diminished by Hg exposure. Importantly, atherosclerotic lesion size in the aorta root of Hg exposed mice were larger than in controls. In conclusion, in vivo chronic exposure to Hg worsens the hypercholesterolemia, impairs mitochondrial bioenergetics and redox function, alters immune cells profile and function, causes several tissues oxidative damage and accelerates atherosclerosis development.

Protective effect of SERCA2a-SUMOylation by SUMO-1 on diabetes-induced atherosclerosis and aortic vascular injury.

Diabetes is a major risk factor for cardiovascular disease. However, the exact mechanism by which diabetes contributes to vascular damage is not fully understood. The aim of this study was to investigate the role of SUMO-1 mediated SERCA2a SUMOylation in the development of atherosclerotic vascular injury associated with diabetes mellitus.ApoE-/- mice were treated with streptozotocin (STZ) injection combined with high-fat feeding to simulate diabetic atherosclerosis and vascular injury. Human aortic vascular smooth muscle cells (HAVSMCs) were treated with high glucose (HG, 33.3 mM) and palmitic acid (PA, 200 µM) for 24h to mimic a model of diabetes-induced vascular injury in vitro. Aortic vascular function, phenotypic conversion, migration, proliferation, intracellular Ca2+ concentration, the levels of small ubiquitin-like modifier type 1 (SUMO1), SERCA2a and SUMOylated SERCA2a were detected.Diabetes-induced atherosclerotic mice presented obvious atherosclerotic plaques and vascular injury, companied by significantly lower levels of SUMO1 and SERCA2a in aorta. HG and PA treatment in HAVSMCs reduced the expressions of SUMO1, SERCA2a and SUMOylated SERCA2a, facilitated the HAVSMCs phenotypic transformation, proliferation and migration, attenuated the Ca2+ transport, and increased the resting intracellular Ca2+ concentration. We also confirmed that SUMO1 directly bound to SERCA2a in HAVSMCs. Overexpression of SUMO1 restored the function and phenotypic contractile ability of HAVSMCs by upregulating SERCA2a SUMOylation, thereby alleviating HG and PA-induced vascular injury.These observations suggest an essential role of SUMO1 to protect diabetes-induced atherosclerosis and aortic vascular injury by the regulation of SERCA2a-SUMOylation and calcium homeostasis.

SMPDL3B is palmitoylated and stabilized by ZDHHC5, and its silencing aggravates diabetic retinopathy of db/db mice: Activation of NLRP3/NF-κB pathway

Abnormal inflammation of vascular endothelial cells occurs frequently in diabetic retinopathy (DR). Sphingomyelin phosphodiesterase acid-like 3B (SMPDL3B) is a lipid raft enzyme and plays an anti-inflammatory role in various diseases but its function in DR-related vascular endothelial dysfunction remains unknown. We first found that SMPDL3B expression was upregulated from week 10 to 18 in the retinal tissues of db/db mice. Particularly, the high expression of SMPDL3B was mainly observed in retinal vascular endothelium of DR mice. To interfere retinal SMPDL3B expression, adeno-associated viruses 2 (AAV-2) containing SMPDL3B specific shRNA (1233–1253 bp) were injected into the vitreous cavity of db/db mice. SMPDL3B silencing exacerbated the spontaneous DR by further activating the NF-κB/NLRP3 pro-inflammatory pathway. In vitro, human retinal microvascular endothelial cells (HRVECs) were infected with SMPDL3B-shRNA lentiviruses and then stimulated with 30 mM glucose (HG) for 24 h. SMPDL3B-silenced HRVECs secreted more interleukin-1β and had enhanced nuclear p65 translocation. Notably, HG treatment induced the palmitoylation of SMPDL3B. Zinc finger DHHC-type palmitoyltransferase 5 (ZDHHC5) is a palmitoyltransferase that catalyzes the palmitoylation of its substrates, HG exposure increased the interaction between ZDHHC5 and SMPDL3B in HRVECs. 2-BP, a palmitoylation inhibitor, accelerated the protein degradation of SMPDL3B, whereas palmostatin B, a depalmitoylation inhibitor, decreased its turnover rate in HRVECs. Collectively, the present study suggests a compensatory increase of SMPDL3B in HG-treated HRVECs and the retinal tissues of DR mice, indicating that SMPDL3B may be a potential target for DR treatment.

MicroRNA-204-5p Ameliorates Renal Injury via Regulating Keap1/Nrf2 Pathway in Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is characterized by renal fibrosis, and the pathogenesis of renal fibrosis is still not definitely confirmed. MiR-204-5p plays an important role in the regulation of fibrosis, autophagy and oxidative stress. In this study, we aimed to investigate the role of miR-204-5p on renal damage in diabetic kidneys and the underlying mechanisms involved. In vivo, AAV-Ksp-miR-204-5p mimics were injected into mice via tail vein. In vitro, high glucose-induced HK-2 cells were treated with miR-204-5p inhibitor, miR-204-5p mimics, ATG5 siRNA, tertiary butyl hydroquinone (TBHQ), ML385, or 3-Methyladenine (3-MA). FISH and qRT-PCR were used to detect miR-204-5p expression. The expressions of protein and mRNA were detected by Western blotting, immunofluorescence, immunohistochemistry and qRT-PCR. The concentration of fibronectin in HK-2 cells culture medium was detected by ELISA. The expression of miR-204-5p in diabetic kidneys was significantly inhibited than that in control group. Delivering miR-204-5p mimics increased miR-204-5p expression, improved renal function, inhibited renal fibrosis and oxidative stress, and restored autophagy in db/db mice. In vitro, the expression of miR-204-5p was inhibited by HG treatment in HK-2 cells. MiR-204-5p mimics effectively increased miR-204-5p expression and reduced fibronectin and collagen I expression, restored autophagy dysfunction, and increased Nrf2 expression, whereas these alterations were abrogated by Nrf2 inhibitor ML385, autophagy inhibitor 3-methyladenine (3-MA, 5 mM) treatment or ATG5 siRNA transfection in HG-induced HK-2 cells. In addition, miR-204-5p inhibitor significantly inhibited miR-204-5p expression and aggravated HG-induced fibronectin and collagen I expression, autophagy dysfunction, and decreased Nrf2 expression, while these alterations were abolished by Nrf2 activator TBHQ. Furthermore, the binding of miR-204-5p with Keap1 was confirmed by luciferase reporter assay and miR-204-5p negatively regulated Keap1 expression, resulting in the activation of Nrf2 pathway. MicroRNA-204-5p protects against the progression of diabetic renal fibrosis by restoring autophagy via regulating Keap1/Nrf2 pathway.

Alisol A inhibits the circ_0001831/miR-346/LIN28B pathway to ameliorate high glucose-induced injury of human renal mesangial cells.

Alisol A can ameliorate glucose metabolism disorders, however, there is no data regarding its role in diabetic nephropathy (DN). The present work evaluates the role of Alisol A in DN and the underlying mechanism. RNA expression of circ_0001831, miR-346, and lin-28 homolog B (LIN28B) was detected by qRT-PCR. Cell viability and proliferation were investigated by MTT assay and EdU assay, respectively. The inflammatory cytokines were examined by ELISAs. Oxidative stress was evaluated by the commercial kits. Protein expression was detected by western blotting. The interactions among circ_0001831, miR-346, and LIN28B were identified by dual-luciferase reporter assay and RIP assay. DN mouse model assay was used to analyse the effect of Alisol A on renal injury of diabetic mice. HG treatment promoted HRMC proliferation, fibrosis, inflammation, and oxidative stress; however, these effects were reversed after Alisol A treatment. Alisol A treatment ameliorated STZ-induced renal injury of diabetic mice. Additionally, circ_0001831 or LIN28B overexpression or miR-346 downregulation relieved Alisol A-induced effects under HG conditions. Mechanistically, circ_0001831 acted as a miR-346 sponge, and LIN28B was identified as a target gene of miR-346. Further, the regulation of circ_0001831 in HG-induced HRMC dysfunction involved LIN28B. Alisol A ameliorated HG-induced HRMC fibrosis, inflammation, and oxidative stress and STZ-induced renal injury of diabetic mice by regulating the circ_0001831/miR-346/LIN28B pathway.

Tuning Chemical Interface Damping: Competition between Surface Damping Pathways in Amalgamated Gold Nanorods Coated with Mesoporous Silica Shells.

The mechanism of mercury (Hg) amalgamation in gold nanorods coated with a mesoporous silica shell (AuNRs@mSiO2) and the effect of chemical treatments on the localized surface plasmon resonance (LSPR) spectral changes in single amalgamated AuNRs@mSiO2 remains unclear. In this study, we investigated Hg amalgamation and inward Hg diffusion in single AuNRs@mSiO2 without structural deformation via dark-field scattering spectroscopy and X-ray photoelectron spectroscopy. Then, we investigated the chemisorption of thiol molecules on single amalgamated AuNRs@Hg-mSiO2. Unlike previous studies on single AuNRs, the thiolation on single AuNRs@Hg-mSiO2 resulted in a redshift and line width narrowing of the LSPR peak within 1 h. To determine the chemical effect, we investigated the competition between two surface damping pathways: metal interface damping (MID) and chemical interface damping (CID). When we exposed amalgamated AuNRs@Hg-mSiO2 to 1-alkanethiols with three different carbon chain lengths for 1 h, we observed an increase in the line width broadening with longer chain lengths owing to enhanced CID, demonstrating the tunability of CID and LSPR properties upon chemical treatments. We also investigated the competition between the two surface damping pathways as a function of the time-dependent Au-Hg surface properties in AuNRs@Hg-mSiO2. The 24-h Hg treatment resulted in increased line width broadening compared to the 1-h treatment for the same thiols, which was attributed to the predominance of CID. This was in contrast to the predominance of MID under the 1-h treatment, which formed a core-shell structure. Therefore, this study provides new insights into the Hg amalgamation process, the effect of chemical treatments, competition between surface decay pathways, and LSPR control in AuNRs@mSiO2.

Retention properties and mechanism of agricultural waste maize whisker on atmospheric mercury

Mercury (Hg) is a global pollutant transmitted mainly through the atmosphere, posing a serious threat to biological survival and human health. Porous materials, with high specific surface area, high porosity, and high adsorption, are particularly suitable for the purification of atmospheric Hg mixtures. However, plant porous materials are rarely directly used for atmospheric Hg purification. In this study, the properties and mechanism of maize whisker in removing atmospheric Hg were analyzed. The results show that the Hg content in the whiskers increases significantly as the initial Hg concentration increases, and 79.38% Hg can be removed by 0.2 g maize whiskers after 1 h exposure when the initial Hg concentration is 0.1 μg m−3, indicating that maize whiskers can accumulate atmospheric Hg rapidly and effectively. The hole diameter of the maize whisker is between 0.83 and 3.06 μm, which is suitable for the adsorption of small substances. Correlation analysis shows that maize whiskers have a significant correlation between atmospheric Hg retention and its specific surface area, pore size, medium pore ratio, and micropore ratio, suggesting that the maize whisker hole feature has a significant influence on its ability to retain atmospheric Hg. Compared with the energy profiles before and after Hg treatment, the peak of Mg decreased after Hg adsorption. Fourier infrared spectrometer analysis suggests that functional groups such as -OH, -COOH, and -O- are involved in the adsorption process. The change in pH value shows an obvious effect on the overall change in zeta potential in the adsorption process. Therefore, a variety of mechanisms, including physical adsorption, electrostatic adsorption, complexation, chelation, and ion exchange, are involved in Hg retention with the maize whisker. This study reveals the important potential value of agricultural waste maize whiskers in the purification of atmospheric heavy metal Hg.Graphical

DNA hypomethylation-associated transcriptional rewiring enables resistance to heavy metal mercury (Hg) stress in rice

Mercury (Hg) is an important hazardous pollutant that can cause phytotoxicity and harm human health through the food chain. Recently, rice (Oryza sativa L.) has been confirmed as a potential Hg bioaccumulator. Although the genetic and molecular mechanisms involved in heavy metal absorption and translocation in rice have been investigated for several heavy metals, Hg is largely neglected. Here, we analyzed one Hg-resistant line in rice (RHg) derived from a DNA methyltransferase-coding gene, OsMET1–2 heterozygous mutant. Compared with its isogenic wild-type (WT), RHg exhibited a significantly higher survival rate after Hg treatment, ameliorated oxidative damage, and lower Hg uptake and translocation. RNAseq-based comparative transcriptomic analysis identified 34 potential Hg resistance-related genes involved in phytohormone signaling, abiotic stress response, and zinc (Zn) transport. Importantly, the elevated expression of Hg resistance-related genes in RHg was highly correlated with DNA hypomethylation in their putative promoter regions. An ionomic analysis unraveled a negative correlation between Zn and Hg in roots. Moreover, Hg concentration was effectively decreased by exogenous application of Zn in Hg-stressed rice plants. Our findings indicate an epigenetic basis of Hg resistance and reveal an antagonistic relationship between Hg and Zn, providing new hints towards Hg detoxification in plants. Environmental implicationMercury (Hg) as an important hazardous pollutant adversely impacts the environment and jeopardizes human health, due to its chronicity, transferability, persistence, bioaccumulation and toxicity. In this paper, we identified 34 potential genes that may significantly contribute to Hg resistance in rice. We find the expression of Hg resistance-related genes was highly correlated with DNA hypomethylation in their putative promoter regions. Our results also revealed an antagonistic relationship between Hg and Zinc (Zn), providing new hints towards Hg detoxification in plants. Together, findings of this study extend our current understanding of Hg tolerance in rice and are informative to breed seed non–accumulating rice cultivars.

Long Non-coding RNA ZFAS1 Regulates Fibrosis and Scortosis in the Cell Model of Diabetic Nephropathy Through miR-525-5p/SGK1 Axis.

Diabetic nephropathy (DN) is a common clinical syndrome in diabetic patients. Functional characterization of non-coding (ncRNAs) involved in the progression of DN can provide insights into the diagnosis and therapeutic management of DN. Human kidney proximal tubular epithelial cells (HK-2) were challenged by high glucose (HG, 50mM) as a cell model of DN. The expression level of long non-coding RNA (lncRNA) ZFAS1 was quantified by qRT-PCR. The proteins and cytokines related to fibrosis and scortosis in DN (NLRP3, GSDMD-N, IL-1β and Caspase 1, fibronectin, collagen I, collagen III, IL-1β, and IL-18) were examined by western blot or ELISA. RNA precipitation and luciferase reporter activity experiments were conducted to assess the molecular associations. ZFAS1 and SGK1 were highly induced in HK-2 cells challenged with HG, while miR-525-5p downregulated upon HG treatment. ZFAS1 knockdown attenuated HG-induced fibrosis and scortosis in HK-2 cells by reducing the levels of NLRP3, GSDMD-N, Caspase 1, fibronectin, collagen I/III, IL-1β, and IL-18. Mechanically, ZFAS1 knockdown protected HK-2 cells from HG-induced injury by upregulating miR-525-5p and repressing SGK1 expression. Overall, our results suggest that knocking down ZFAS1 may be formulated as a protective strategy in ameliorating DN progression through regulating miR-525-5p/SGK1 pathway. Targeting ZFAS1 could be further explored as a potential approach for the management of DN.