Casual effects of telomere length on sarcoidosis: a bidirectional Mendelian randomization analysis.

Background: Telomere length, crucial for genomic stability, have been implicated in various inflamm-aging diseases, but their role in sarcoidosis remains unexplored. Objective: This study aims to explore the casual effects between TL and sarcoidosis via a bidirectional Mendelian Randomization (MR) study. Methods: We examined single nucleotide polymorphisms (SNPs) associated with TL and sarcoidosis, utilizing available open-access genome-wide association study (GWAS) databases from the UK Biobank and FinnGen. We employed five MR techniques, including Inverse Variance Weighted (IVW), MR Egger, weighted median (WM), Robust adjusted profile score (RAPS), and Maximum likelihood, to assess causal relationships and explore pleiotropy. Results: Summary data extracted from GWAS datasets of TL (n = 472,174) and (n = 217,758) of European ancestry. Employing 130 SNPs with genome-wide significance as instrumental factors for TL, we detect a significant negative correlation between TL and sarcoidosis (OR: 0.682, 95% confidence interval: 0.524-0.888, p : 0.0045). Similarly, utilizing 6 SNPs with genome-wide significance as instrumental factors for sarcoidosis, we fail to identify a noteworthy association between sarcoidosis and TL (OR: 0.992, 95% confidence interval: 0.979-1.005, p : 0.2424). Conclusion: Our results suggest that longer telomeres may reduce the risk of sarcoidosis, highlighting TL as a potential biomarker for diagnosis and long-term monitoring. Understanding the critical role of telomere shortening enables more effective focus on diagnosing, treating, and curing sarcoidosis linked to telomeres. Clinical investigations into treatments that enhance TL are warranted.

Activation of peroxydisulfate by zero valent iron-carbon composites prepared by carbothermal reduction: Enhanced non-radical and radical synergies.

Since its application in environmental remediation, nano zero-valent iron (nZVI) has gained wide attention for its environmental friendliness, strong reducing ability, and wide range of raw materials. However, its high preparation cost and difficulty in preservation remain the bottlenecks for their application. Carbothermal reduction is a promising method for the industrial preparation of nZVI. Micronized zero-valent iron/carbon materials (Fe0/CB) were produced in one step by co-pyrolysis of carbon and iron. The performance of the Fe0/CB is comparable to that of nZVI. In addition, Fe0/CB overcomed the disadvantages of agglomeration and oxidative deactivation of nZVI. Experiments on the Fenton-like reaction of its activated PDS showed that metronidazole (MNZ) was efficiently removed through the synergistic action of radicals and non-radicals, which were mainly superoxide radicals (·O2-), monoclinic oxygen (1O2), and high-valent iron (FeIVO). Moreover, the degradation process showed better generalization, making it suitable for a wide range of applications in the degradation of antibiotics.

Evolutionary trajectory of TRPM2 channel activation by adenosine diphosphate ribose and calcium.

Ion channel activation upon ligand gating triggers a myriad of biological events and, therefore, evolution of ligand gating mechanism is of fundamental importance. TRPM2, a typical ancient ion channel, is activated by adenosine diphosphate ribose (ADPR) and calcium and its activation has evolved from a simple mode in invertebrates to a more complex one in vertebrates, but the evolutionary process is still unknown. Molecular evolutionary analysis of TRPM2s from more than 280 different animal species has revealed that, the C-terminal NUDT9-H domain has evolved from an enzyme to a ligand binding site for activation, while the N-terminal MHR domain maintains a conserved ligand binding site. Calcium gating pattern has also evolved, from one Ca2+-binding site as in sea anemones to three sites as in human. Importantly, we identified a new group represented by olTRPM2, which has a novel gating mode and fills the missing link of the channel gating evolution. We conclude that the TRPM2 ligand binding or activation mode evolved through at least three identifiable stages in the past billion years from simple to complicated and coordinated. Such findings benefit the evolutionary investigations of other channels and proteins.

Hollow Mesoporous Silica Nanoparticles as a New Nanoscale Resistance Inducer for Fusarium Wilt Control: Size Effects and Mechanism of Action.

In agriculture, soil-borne fungal pathogens, especially Fusarium oxysporum strains, are posing a serious threat to efforts to achieve global food security. In the search for safer agrochemicals, silica nanoparticles (SiO2NPs) have recently been proposed as a new tool to alleviate pathogen damage including Fusarium wilt. Hollow mesoporous silica nanoparticles (HMSNs), a unique class of SiO2NPs, have been widely accepted as desirable carriers for pesticides. However, their roles in enhancing disease resistance in plants and the specific mechanism remain unknown. In this study, three sizes of HMSNs (19, 96, and 406 nm as HMSNs-19, HMSNs-96, and HMSNs-406, respectively) were synthesized and characterized to determine their effects on seed germination, seedling growth, and Fusarium oxysporum f. sp. phaseoli (FOP) suppression. The three HMSNs exhibited no side effects on cowpea seed germination and seedling growth at concentrations ranging from 100 to 1500 mg/L. The inhibitory effects of the three HMSNs on FOP mycelial growth were very weak, showing inhibition ratios of less than 20% even at 2000 mg/L. Foliar application of HMSNs, however, was demonstrated to reduce the FOP severity in cowpea roots in a size- and concentration-dependent manner. The three HMSNs at a low concentration of 100 mg/L, as well as HMSNs-19 at a high concentration of 1000 mg/L, were observed to have little effect on alleviating the disease incidence. HMSNs-406 were most effective at a concentration of 1000 mg/L, showing an up to 40.00% decline in the disease severity with significant growth-promoting effects on cowpea plants. Moreover, foliar application of HMSNs-406 (1000 mg/L) increased the salicylic acid (SA) content in cowpea roots by 4.3-fold, as well as the expression levels of SA marker genes of PR-1 (by 1.97-fold) and PR-5 (by 9.38-fold), and its receptor gene of NPR-1 (by 1.62-fold), as compared with the FOP infected control plants. Meanwhile, another resistance-related gene of PAL was also upregulated by 8.54-fold. Three defense-responsive enzymes of POD, PAL, and PPO were also involved in the HMSNs-enhanced disease resistance in cowpea roots, with varying degrees of reduction in activity. These results provide substantial evidence that HMSNs exert their Fusarium wilt suppression in cowpea plants by activating SA-dependent SAR (systemic acquired resistance) responses rather than directly suppressing FOP growth. Overall, for the first time, our results indicate a new role of HMSNs as a potent resistance inducer to serve as a low-cost, highly efficient, safe and sustainable alternative for plant disease protection.

Photoactivated 9-methylacridine destroys midgut tissues of Aedes aegypti larvae by targeting ROS-mediated apoptosis in the mitochondrial pathway of midgut cells.

An aromatic ring-containing compound with a wide range of biological activities, 9-methylacridine (AD-9-Me) is a precursor for the synthesis of various drugs. However, its photoactivation properties and mechanism of damage as a photo activator against Aedes aegypti are unknown. The toxic effects of AD-9-Me on Aedes aegypti mosquitoes were determined under light and non-light conditions. The results showed that the toxicity of AD-9-Me to mosquito larvae was significantly higher than that of the dark treatment after 24 h of light exposure; AD-9-Me was mainly distributed in the midgut of larvae, after 24 h of treatment, it can cause an increase in calcium ion concentration, reactive oxygen species (ROS) eruption and ROS accumulation by blocking the ROS elimination pathway in midgut cells. This in turn caused an increase in protein carbonyl and malondialdehyde (MDA) content, a decrease in mitochondrial membrane potential (MMP), a disruption of the barrier function of midgut tissues, a significant decrease in midgut weight and chitin content, which induced the up-regulation of AeDronc, AeCaspase8 and AeCaspase7 genes, leading to apoptotic cell death. In this study, we confirmed that AD-9-Me has photoactivation activity and mainly acts on the midgut of mosquito larvae, which can generate a large amount of ROS in the cells of the midgut and induce apoptosis to occur, resulting in the disruption of the function of the tissues of mosquito larvae, accelerating the death and delaying the development of the mosquito larvae.

Structures and ion transport mechanisms of plant high-affinity potassium transporters.

Plant high-affinity K+ transporters (HKTs) mediate Na+ and K+ uptake, maintain Na+/K+ homeostasis, and therefore play crucial roles in plant salt tolerance. In this study, we present cryoelectron microscopy structures of HKTs from two classes, class I HKT1;1 from Arabidopsis thaliana (AtHKT1;1) and class II HKT2;1 from Triticum aestivum (TaHKT2;1), in both Na+- and K+-bound states at 2.6- to 3.0-Å resolutions. Both AtHKT1;1 and TaHKT2;1 function as homodimers. Each HKT subunit consists of four tandem domain units (D1-D4) with a repeated K+-channel-like M-P-M topology. In each subunit, D1-D4 assemble into an ion conduction pore with a pseudo-four-fold symmetry. Although both TaHKT2;1 and AtHKT1;1 have only one putative Na+ ion bound in the selectivity filter with a similar coordination pattern, the two HKTs display different K+ binding modes in the filter. TaHKT2;1 has three K+ ions bound in the selectivity filter, but AtHKT1;1 has only two K+ ions bound in the filter, which has a narrowed external entrance due to the presence of a Ser residue in the first filter motif. These structures, along with computational, mutational, and electrophysiological analyses, enable us to pinpoint key residues that are critical for the ion selectivity of HKTs. The findings provide new insights into the ion selectivity and ion transport mechanisms of plant HKTs and improve our understanding about how HKTs mediate plant salt tolerance and enhance crop growth.

Toxicity and Behavior-Altering Effects of Three Nanomaterials on Red Imported Fire Ants and Their Effectiveness in Combination with Indoxacarb.

The red imported fire ant (Solenopsis invicta Buren) is one of the 100 worst invasive alien species in the world. At present, the control of red imported fire ants is still mainly based on chemical control, and the most commonly used is indoxacarb bait. In this study, the contact and feeding toxicity of 16 kinds of nanomaterials to workers, larvae, and reproductive ants were evaluated after 24 h, 48 h, and 72 h. The results showed that the mortality of diatomite, Silica (raspberry-shaped), and multi-walled carbon nanotubes among workers reached 98.67%, 97.33%, and 68%, respectively, after contact treatment of 72 h. The mortality of both larval and reproductive ants was less than 20% after 72 h of treatment. All mortality rates in the fed treatment group were below 20% after 72 h. Subsequently, we evaluated the digging, corpse-removal, and foraging behaviors of workers after feeding with diatomite, Silica (raspberry-shaped), and multi-walled carbon nanotubes for 24 h, which yielded inhibitory effects on the behavior of red imported fire ants. The most effective was diatomite, which dramatically decreased the number of workers that dug, extended the time needed for worker ant corpse removal and foraging activities, decreased the number of workers that foraged, and decreased the weight of the food carried by the workers. In addition, we also evaluated the contact and feeding toxicity of these three nanomaterials in combination with indoxacarb on red imported fire ants. According to contact toxicity, after 12 h of contact treatment, the death rate among the red imported fire ants exposed to the three materials combined with indoxacarb reached more than 97%. After 72 h of exposure treatment, the mortality rate of larvae was more than 73% when the nanomaterial content was above 1% and 83% when the diatomite content was 0.5%, which was significantly higher than the 50% recorded in the indoxacarb control group. After 72 h of feeding treatment, the mortality of diatomite, Silica (raspberry-shaped), and multi-walled carbon nanotubes combined with indoxacarb reached 92%, 87%, and 98%, respectively. The death rates of the three kinds of composite ants reached 97%, 67%, and 87%, respectively. The three kinds of composite food had significant inhibitory effects on the behavior of workers, and the trend was largely consistent with the effect of nanomaterials alone. This study provides technical support for the application of nanomaterials in red imported fire ant control.

lncRNA-MIAT rs9625066 polymorphism could be a potential biomarker for ischemic stroke.

BACKGROUND: Ischemic stroke (IS) is a common and serious neurological condition that is highly fatal but so far no early diagnostic markers are available. Myocardial infarction-associated transcript (MIAT) is a long non-coding RNA (lncRNA) that could lead to IS by inducing autophagy and apoptosis in neuronal cells. However, there has been no report on the link between susceptibility to IS and the single-nucleotide polymorphisms (SNPs) of MIAT. This study aimed to investigate the association between MIAT gene polymorphisms and IS risk. METHODS: A total of 320 IS patients and 310 age-, sex- and race-matched controls were included in this study. Four polymorphisms (rs2157598, rs5761664, rs1894720, and rs9625066) were genotyped by using SNPscan technique. RESULTS: Among the 4 polymorphisms of MIAT, only rs9625066 was associated with IS risk (CA vs. CC: adjusted OR = 0.55, 95% CI, 0.37-0.85, P = 0.006; AA vs. CC: adjusted OR = 0.39, 95% CI, 0.16-0.94, P = 0.036; (AA + CA vs. CC: adjusted OR = 0.53, 95% CI, 0.35-0.80, P = 0.002; A vs. C adjusted OR = 0.59, 95% CI, 0.42-0.82, P = 0.002). Haplotype analysis showed a 1.32-fold increase (95% CI, 1.05-1.67, P = 0.017) in IS risk for rs2157598-rs5761664-rs1894720-rs9625066 (A-C-G-C). Logistic regression analysis identified some independent impact factors for IS including rs9625066 AA/AC, TC, TG, HDL-C (P < 0.05). CONCLUSION: The rs9625066 polymorphism of MIAT might be associated with IS susceptibility in Chinese population, in which AA/CA plays a protective role in IS, whereas the CC genotype increases the risk of developing IS, suggesting it might be a marker predictive of IS risk.

Synovial microenvironment-influenced mast cells promote the progression of rheumatoid arthritis.

Mast cells are phenotypically and functionally heterogeneous, and their state is possibly controlled by local microenvironment. Therefore, specific analyses are needed to understand whether mast cells function as powerful participants or dispensable bystanders in specific diseases. Here, we show that degranulation of mast cells in inflammatory synovial tissues of patients with rheumatoid arthritis (RA) is induced via MAS-related G protein-coupled receptor X2 (MRGPRX2), and the expression of MHC class II and costimulatory molecules on mast cells are upregulated. Collagen-induced arthritis mice treated with a combination of anti-IL-17A and cromolyn sodium, a mast cell membrane stabilizer, show significantly reduced clinical severity and decreased bone erosion. The findings of the present study suggest that synovial microenvironment-influenced mast cells contribute to disease progression and may provide a further mast cell-targeting therapy for RA.

Toxicity and Behavioral Effects of Amending Soils with Biochar on Red Imported Fire Ants, Solenopsis invicta.

Solenopsis invicta, often known as the red imported fire ants (RIFAs), is a well-known global invasive ant species that can be found in agricultural, urban, and natural environments worldwide. Simultaneously, it also inhabits the soil. Biochar is generated by the pyrolysis of organic matter under high-temperature anoxic environments and widely used in agricultural ecosystems and soil amendment. However, to date, it remains unknown as to whether soil application of biochar has a negative effect on RIFAs. In our study, we investigated the toxicity and irritability effects of different amounts of biochar (0%, 1%, 2%, 5%, 10%, and 20%) introduced into the soil on red fire ants; upon comparison with the control soil (0% biochar), the application of 1%, 2%, and 5% biochar did not result in significantly different results. But the utilization of biochar at a concentration over 10% effectively repelled the RIFAs, resulting in their departure from the treated soils. High doses of biochar were able to cause death of red fire ants; the mortality rate of red fire ants reached 55.56% after 11 days of 20% biochar treatment. We also evaluated the effects of biochar on four behaviors of red fire ants, namely aggregation, walking, grasping, and attacking; 20% of the biochar treatment group reduced aggregation by 64.22% and this value was 55.22%, 68.44%, and 62.36% for walking, grasping, and attacking. Finally, we measured the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) enzyme activity and malondialdehyde (MDA) content in red fire ants; the results showed that the activities of the three enzymes increased with the increase in biochar addition, which indicated that a high dose of biochar induced oxidative stress in red fire ants. Our results indicate that biochar has the potential to cause toxicity and repel red imported fire ants (RIFAs) in a manner that is dependent on the concentration. We propose that biochar could be utilized in the control and manufacturing of baits for red fire ant management. This work establishes a foundation for the prevention and management of red fire ants and the logical utilization of biochar.

Efficacy of lure mixtures in baited traps to attract different fruit fly species in guava and vegetable fields.

Fruit flies (Diptera: Tephritidae) are major pests of fruits and vegetables worldwide. We measured the efficacy of attractive lure mixtures in baited traps on naturally-occurring fruit flies in commercial mosaic guava and vegetables fields in Pakistan. We tested three mixtures (methyl-eugenol [ME] and cue lure [CL]; GF-120 and methyl eugenol; and GF-120 and cue lure) in eleven ratios: 0:100, 10:90, 20:80, 30:70, 40:60, 50:50, 60:40, 70:30, 80:20, 90:10, and 100:0. We recorded three fruit fly species: Bactrocera zonata was the most abundant in baited traps, followed by Bactrocera dorsalis, while Zeugodacus cucurbitae was significantly less attracted to baited traps. We also found that the most attractive mixture and ratio varied among species: B. dorsalis was most attracted by 40CL:60ME, while B. zonata was most and equally attracted by 100ME, 10CL:90ME, 20CL:80ME, 30CL:70ME, and 40CL:60ME. Finally, Z. cucurbitae was most attracted by 10CL:90ME, which resulted in the highest total number of flies counted in 10CL:90ME-baited traps. Mixtures with GF-120 were less attractive to all three species. Our results suggest that lure mixtures in baited traps influence the attraction of fruit flies in a species-specific way. This needs to be considered in the integrated pest management of multiple species of fruit flies simultaneously. If Bactrocera species are most damaging and abundant, a 40CL:60ME mixture in baited traps will likely be most effective to reduce pest abundance and crop damage. However, if Z. cucurbitae is the main pest target causing most crop damage and yield loss, 10CL:90ME-baited traps will be a more effective in their monitoring and management.