Extravascular administration of IGF1R antagonists protects against aortic aneurysm in rodent and porcine models.

An abdominal aortic aneurysm (AAA) is a life-threatening cardiovascular disease. We identified plasma insulin-like growth factor 1 (IGF1) as an independent risk factor in patients with AAA by correlating plasma IGF1 with risk. Smooth muscle cell- or fibroblast-specific knockout of Igf1r, the gene encoding the IGF1 receptor (IGF1R), attenuated AAA formation in two mouse models of AAA induced by angiotensin II infusion or CaCl2 treatment. IGF1R was activated in aortic aneurysm samples from human patients and mice with AAA. Systemic administration of IGF1C, a peptide fragment of IGF1, 2 weeks after disease development inhibited AAA progression in mice. Decreased AAA formation was linked to competitive inhibition of IGF1 binding to its receptor by IGF1C and modulation of downstream alpha serine/threonine protein kinase (AKT)/mammalian target of rapamycin signaling. Localized application of an IGF1C-loaded hydrogel was developed to reduce the side effects observed after systemic administration of IGF1C or IGF1R antagonists in the CaCl2-induced AAA mouse model. The inhibitory effect of the IGF1C-loaded hydrogel administered at disease onset on AAA formation was further evaluated in a guinea pig-to-rat xenograft model and in a sheep-to-minipig xenograft model of AAA formation. The therapeutic efficacy of IGF1C for treating AAA was tested through extravascular delivery in the sheep-to-minipig model with AAA established for 2 weeks. Percutaneous injection of the IGF1C-loaded hydrogel around the AAA resulted in improved vessel flow dynamics in the minipig aorta. These findings suggest that extravascular administration of IGF1R antagonists may have translational potential for treating AAA.

Effectors and environment modulating rice blast disease: from understanding to effective control.

Rice blast is a highly destructive crop disease that requires the interplay of three essential factors: the virulent blast fungus, the susceptible rice plant, and favorable environmental conditions. Although previous studies have focused mainly on the pathogen and rice, recent research has shed light on the molecular mechanisms by which the blast fungus and environmental conditions regulate host resistance and contribute to blast disease outbreaks. This review summarizes significant achievements in understanding the sophisticated modulation of blast resistance by Magnaporthe oryzae effectors and the dual regulatory mechanisms by which environmental conditions influence rice resistance and virulence of the blast fungus. Furthermore, it emphasizes potential strategies for developing blast-resistant rice varieties to effectively control blast disease.

Growth Process of Fe-O Nanoclusters with Different Sizes Biosynthesized by Protein Nanocages.

All protein-directed syntheses of metal nanoclusters (NCs) and nanoparticles (NPs) have attracted considerable attention because protein scaffolds provide a unique metal coordination environment and can adjust the shape and morphology of NCs and NPs. However, the detailed formation mechanisms of NCs or NPs directed by protein templates remain unclear. In this study, by taking advantage of the ferritin nanocage as a biotemplate to monitor the growth of Fe-O NCs as a function of time, we synthesized a series of iron NCs with different sizes and shapes and subsequently solved their corresponding three-dimensional atomic-scale structures by X-ray protein crystallography and cryo-electron microscopy. The time-dependent structure analyses revealed the growth process of these Fe-O NCs with the 4-fold channel of ferritin as nucleation sites. To our knowledge, the newly biosynthesized Fe35O23Glu12 represents the largest Fe-O NCs with a definite atomic structure. This study contributes to our understanding of the formation mechanism of iron NCs and provides an effective method for metal NC synthesis.

Myriophyllum Biochar-Supported Mn/Mg Nano-Composites as Efficient Periodate Activators to Enhance Triphenyl Phosphate Removal from Wastewater.

Transition metals and their oxide compounds exhibit excellent chemical reactivity; however, their easy agglomeration and high cost limit their catalysis applications. In this study, an interpolation structure of a Myriophyllum verticillatum L. biochar-supported Mn/Mg composite (Mn/Mg@MV) was prepared to degrade triphenyl phosphate (TPhP) from wastewater through the activating periodate (PI) process. Interestingly, the Mn/Mg@MV composite showed strong radical self-producing capacities. The Mn/Mg@MV system degraded 93.34% TPhP (pH 5, 10 µM) within 150 min. The experimental results confirmed that the predominant role of IO3· and the auxiliary ·OH jointly contributed to the TPhP degradation. In addition, the TPhP pollutants were degraded to various intermediates and subsequent Mg mineral phase mineralization via mechanisms like interfacial processes and radical oxidation. DFT theoretical calculations further indicated that the synergy between Mn and Mg induced the charge transfer of the carbon-based surface, leading to the formation of an ·OH radical-enriched surface and enhancing the multivariate interface process of ·OH, IO3, and Mn(VII) to TPhP degradation, resulting in the further formation of Mg PO4 mineralization.

Rice false smut virulence protein subverts host chitin perception and signaling at lemma and palea for floral infection.

The flower-infecting fungus Ustilaginoidea virens causes rice false smut, which is a severe emerging disease threatening rice (Oryza sativa) production worldwide. False smut not only reduces yield, but more importantly produces toxins on grains, posing a great threat to food safety. U. virens invades spikelets via the gap between the 2 bracts (lemma and palea) enclosing the floret and specifically infects the stamen and pistil. Molecular mechanisms for the U. virens-rice interaction are largely unknown. Here, we demonstrate that rice flowers predominantly employ chitin-triggered immunity against U. virens in the lemma and palea, rather than in the stamen and pistil. We identify a crucial U. virens virulence factor, named UvGH18.1, which carries glycoside hydrolase activity. Mechanistically, UvGH18.1 functions by binding to and hydrolyzing immune elicitor chitin and interacting with the chitin receptor CHITIN ELICITOR BINDING PROTEIN (OsCEBiP) and co-receptor CHITIN ELICITOR RECEPTOR KINASE1 (OsCERK1) to impair their chitin-induced dimerization, suppressing host immunity exerted at the lemma and palea for gaining access to the stamen and pistil. Conversely, pretreatment on spikelets with chitin induces a defense response in the lemma and palea, promoting resistance against U. virens. Collectively, our data uncover a mechanism for a U. virens virulence factor and the critical location of the host-pathogen interaction in flowers and provide a potential strategy to control rice false smut disease.

Insight into the anti-proliferation activity and photoinduced NO release of four nitrosylruthenium isomeric complexes and their HSA complex adducts.

Four Ru(II)-centered isomeric complexes [RuCl(5cqn)(Val)(NO)] (1-4) were synthesized with 5cqn (5-chloro-8-hydroxyquinoline) and chiral Val (Val = L- or D-valine) as co-ligand, and their structures were confirmed using the X-ray diffraction method. The cytotoxicity and photodynamic activity of the isomeric complexes and their human serum albumin (HSA) complex adducts were evaluated. Both the isomeric complexes and their HSA complex adducts significantly affected HeLa cell proliferation, with an IC50 value in the range of 0.3-0.5 µM. The photo-controlled release of nitric oxide (NO) in solution was confirmed using time-resolved Fourier transform infrared and electron paramagnetic resonance spectroscopy techniques. Furthermore, photoinduced NO release in living cells was observed using a selective fluorescent probe for NO. Moreover, the binding constants (Kb) of the complexes with HSA were calculated to be 0.17-1.98 × 104 M-1 and the average number of binding sites (n) was found to be close to 1, it can serve as a crucial carrier for delivering metal complexes. The crystal structure of the HSA complex adduct revealed that one [RuCl(H2O)(NO)(Val)]+ molecule binds to a pocket in domain I. This study provides insight into possible mechanism of metabolism and potential applications for nitrosylruthenium complexes.

Are microplastics in livestock and poultry manure an emerging threat to agricultural soil safety?

Microplastics (MPs) have attracted much attention in recent years, due to the difficulty of degradation and threats to ecological systems and humans. Based on the analysis of 1429 articles on MPs in soil, we found that we know little about the behavior and fate of manure-born MPs from the livestock and poultry production systems to agriculture soils. This review summarizes the analytical methods for sampling, separation, and identification and the occurrence of MPs in livestock and poultry manure, mainly based on 7 surveys related to manure-born MPs. Then, the sources, fate, and environmental risks of MPs in livestock and poultry manure are discussed. MPs, heavy metals, pathogens, antibiotic resistance genes, and persistent organic pollutants are common pollutants in livestock and poultry manure. Worse, manure-born MPs will become smaller, rougher, and more numerous and could easily form more toxic compound pollution after complicated processes of manure treatment, which seriously threatens agricultural soil safety. Finally, an outlook is offered for future research. We hope this article to attract attention to the risks of MPs in livestock and poultry manure and provide a reference for future research.

Liver toxicity in rats after subchronic exposure to HTP aerosol and cigarette smoke.

Background: Heated tobacco product (HTP) considered to be a novel tobacco product which was reported safer than traditional cigarettes evidenced by lower potential harmful components released. Liver is an important detoxification organ of the body, the chemical components in aerosols are metabolized in the liver after absorbed, so it is necessary to explore the effect of HTP on the liver. Materials and Methods: The potential effect of HTP and cigarette smoke (CS) on SD rats was explored according to OECD 413 subchronic inhalation. The rats were randomly divided into Sham (air), different dosage of HTP groups (HTP_10, 23 and 50 µg nicotine/L aerosol) and Cig_23 (23 µg nicotine/L aerosol) group. After exposure, the clinical pathology, inflammation and oxidative stress were measured. Results: The clinical pathology results showed that both HTP_50 and Cig_23 led to abnormality of ALT for male rats. CS and HTP exposure reduced the expression of IL-1ß, IL-6 and TNF-α and mitochondrial medicated oxidative stress. In addition, the ATP production was reduced in Cig_23 group. Although inflammation and oxidative stress were displayed, no apoptosis were observed by TUNEL assay and these existed obvious pathological changes only in HTP_50 group, while in CS group with equivalent nicotine, hepatocytes swelling were observed in liver. Conclusion: CS exposure induced liver damage through mitochondrial mediated oxidative stress and inflammation, which was also observed in high concentration of HTP exposure group. For the same equivalent nicotine, HTP may show lower toxic effect on liver than CS.

Identification of NADPH Oxidase Genes Crucial for Rice Multiple Disease Resistance and Yield Traits.

Reactive oxygen species (ROS) act as a group of signaling molecules in rice functioning in regulation of development and stress responses. Respiratory burst oxidase homologues (Rbohs) are key enzymes in generation of ROS. However, the role of the nine Rboh family members was not fully understood in rice multiple disease resistance and yield traits. In this study, we constructed mutants of each Rboh genes and detected their requirement in rice multiple disease resistance and yield traits. Our results revealed that mutations of five Rboh genes (RbohA, RbohB, RbohE, RbohH, and RbohI) lead to compromised rice blast disease resistance in a disease nursery and lab conditions; mutations of five Rbohs (RbohA, RbohB, RbohC, RbohE, and RbohH) result in suppressed rice sheath blight resistance in a disease nursery and lab conditions; mutations of six Rbohs (RbohA, RbohB, RbohC, RbohE, RbohH and RbohI) lead to decreased rice leaf blight resistance in a paddy yard and ROS production induced by PAMPs and pathogen. Moreover, all Rboh genes participate in the regulation of rice yield traits, for all rboh mutants display one or more compromised yield traits, such as panicle number, grain number per panicle, seed setting rate, and grain weight, resulting in reduced yield per plant except rbohb and rbohf. Our results identified the Rboh family members involved in the regulation of rice resistance against multiple pathogens that caused the most serious diseases worldwide and provide theoretical supporting for breeding application of these Rbohs to coordinate rice disease resistance and yield traits.

Broad-spectrum resistance gene RPW8.1 balances immunity and growth via feedback regulation of WRKYs.

Arabidopsis RESISTANCE TO POWDERY MILDEW 8.1 (RPW8.1) is an important tool for engineering broad-spectrum disease resistance against multiple pathogens. Ectopic expression of RPW8.1 leads to enhanced disease resistance with cell death at leaves and compromised plant growth, implying a regulatory mechanism balancing RPW8.1-mediated resistance and growth. Here, we show that RPW8.1 constitutively enhances the expression of transcription factor WRKY51 and activates salicylic acid and ethylene signalling pathways; WRKY51 in turn suppresses RPW8.1 expression, forming a feedback regulation loop. RPW8.1 and WRKY51 are both induced by pathogen infection and pathogen-/microbe-associated molecular patterns. In ectopic expression of RPW8.1 background (R1Y4), overexpression of WRKY51 not only rescues the growth suppression and cell death caused by RPW8.1, but also suppresses RPW8.1-mediated broad-spectrum disease resistance and pattern-triggered immunity. Mechanistically, WRKY51 directly binds to and represses RPW8.1 promoter, thus limiting the expression amplitude of RPW8.1. Moreover, WRKY6, WRKY28 and WRKY41 play a role redundant to WRKY51 in the suppression of RPW8.1 expression and are constitutively upregulated in R1Y4 plants with WRKY51 being knocked out (wrky51 R1Y4) plants. Notably, WRKY51 has no significant effects on disease resistance or plant growth in wild type without RPW8.1, indicating a specific role in RPW8.1-mediated disease resistance. Altogether, our results reveal a regulatory circuit controlling the accumulation of RPW8.1 to an appropriate level to precisely balance growth and disease resistance during pathogen invasion.

Efficient removal of tetracycline hydrochloride through novel Fe/BiOBr/Bi2WO6 photocatalyst prepared by dual-strategy under visible-light irradiation.

It is important to investigate whether combining two modification strategies has a synergistic effect on the activity of photocatalysts. In this manuscript, Fe-doped BiOBr/Bi2WO6 heterojunctions were synthesized by a one-pot solvothermal method, and excellent photocatalytic performance was obtained for the degradation of tetracycline hydrochloride (TCH) in water without the addition of surfactant. Combining experiments and characterization, the synergistic effect between Fe ion doping and the BiOBr/Bi2WO6 heterojunction was elucidated. The Fe/BiOBr/Bi2WO6 composite photocatalyst had a beneficial void structure, enhanced visible light response, and could inhibit the recombination of photogenerated support well, which improved the photocatalytic activity. The presented experiments demonstrate that Fe/BiOBr/Bi2WO6 removes 97% of TCH from aqueous solution, while pure BiOBr and Bi2WO6 only remove 56% and 65% of TCH, respectively. Finally, the separation and transfer mechanisms of photoexcited carriers were determined in conjunction with the experimental results. This study provides a new direction for the design of efficient photocatalysts through the use of a dual co-modification strategy.

Red and Blue Light Induce Soybean Resistance to Soybean Mosaic Virus Infection through the Coordination of Salicylic Acid and Jasmonic Acid Defense Pathways.

Soybean mosaic virus (SMV) seriously harms soybean quality and yield. In order to understand the effect of a heterogeneous light environment on the disease resistance of intercropped soybeans, we simulated three kinds of light environments to learn the effects of white light, blue light, and far-red light on the SMV resistance of soybeans. The results showed that compared with the control, SMV-infected soybeans showed dwarfing and enhanced defense. The symptoms of leaves under red and blue light were less severe than those under white light, the virus content of infected plants was about 90% lower than under white light, the activity of antioxidant enzymes increased, and the accumulation of reactive oxygen species decreased. The oxidation damage in SMV-infected soybeans was serious under far-red light. Transcriptome data showed that the biostimulatory response, plant-pathogen interaction, and plant hormone signaling pathway gene expression of SMV-infected soybeans were significantly up-regulated under red light compared with the control. Compared with the control, the genes in the biostimulatory response, calcium ion binding, carbohydrate-binding, mitogen-activated protein kinase (MAPK) signaling, and plant-pathogen interaction pathways, were significantly up-regulated in SMV-infected soybeans under blue light. In far-red light, only 39 genes were differentially expressed in SMV-infected soybeans compared with the control, and most of the genes were down-regulated. Compared with the control, the up-regulation of the salicylic acid (SA) pathway defense gene in SMV-infected soybeans under red light was higher than under other light treatments. Compared with the control, the up-regulation of the jasmonic acid (JA) and ethylene (ET) pathway defense genes in SMV-infected soybeans under blue light was higher than under other light treatments. Compared with the control, most defense-related genes in the SA and JA pathways were inhibited in SMV-infected soybeans under far-red light, while genes in the ET pathway were significantly up-regulated. These results will advance our understanding of the disease resistance mechanism of intercropping soybeans in a heterogeneous light environment and provide new ideas for the prevention and control of viral diseases.

Testicular tissue response following a 90-day subchronic exposure to HTP aerosols and cigarette smoke in rats.

Background: Researches have shown that chronic inhalation of cigarette smoke (CS) disrupts male reproductive system, but it is unclear about the mechanisms behind reproductive damages by tobacco toxicants in male rats. This study was designed to explore the effects of heated tobacco products (HTP) aerosols and CS exposure on the testicular health of rats. Materials and Methods: Experiments were performed on male SD rats exposed to filtered air, HTP aerosols at 10 µg/L, 23 µg/L, and 50 µg/L nicotine-equivalent contents, and also CS at 23 µg/L nicotine-equivalent content for 90 days in five exposure groups (coded as sham, HTP_10, HTP_23, HTP_50 and Cig_23). The expression of serum testosterone, testicular tissue inflammatory cytokines (IL-1ß, IL-6, IL-10, TNF-α), reactive oxygen species (ROS), superoxide dismutase (SOD) and malondialdehyde (MDA), NLRP3 inflammasome-related mRNAs and proteins (NLRP3, ASC, and Caspase-1), the degree of pyroptosis and histopathology were investigated. Results: The results demonstrated that HTP_50 and Cig_23 caused varying degrees of oxidative damage to rat testis, resulting in a decrease of sperm quantity and serum testosterone contents, an increase in the deformity rate, expression levels of proinflammatory cytokines, and NLRP3 inflammasome-related mRNA, and an increase in the NLRP3, ASC, and Caspase-1-immunopositive cells, pyroptosis cell indices, and histopathological damage in the testes of rats. Responses from the HTP_10 and HTP_23 groups were less than those found in the above two exposure groups. Conclusion: These findings indicate that HTP_50 and Cig_23 induced oxidative stress in rat testes, induced inflammation and pyroptosis through the ROS/NLRP3/Caspase-1 pathway, and destroyed the integrity of thetesticular tissue structure.

Life and death: the destiny of Phytophthora sojae determined by a receptor-like kinase.

Leucine-rich repeat receptor-like kinases (LRR-RLKs) are well known to act in plant growth, development, and defense responses. Plant LRR-RLKs locate on cell surface to sense and initiate responsive signals to a variety of extracellular stimuli, such as microbe-associated molecular patterns (MAMPs) released from microorganisms. LRR-RLKs are also present in microbes and function in microbial growth and development, but their roles in communicating with hosts are largely unknown. A recent study published in Nature Communications uncovered that a microbial LRR-RLK, PsRLK6, is required for oospore development in the sexual reproduction of Phytophthora sojae, an oomycete pathogen that causes root and stem rot in soybean. Meanwhile, PsRLK6 is recognized as a novel type of MAMP by an unknown plant LRR receptor-like protein and triggers immune responses in soybean, tomato, and Nicotiana benthamiana. The findings reveal dual roles of a pathogen LRR-RLK in determining both life through sexual reproduction and death through triggering plant immunity.

Preliminary application of three-dimensional venography and fusion navigation technique in May-Thurner syndrome.

OBJECTIVE: The purpose of this study was to report a technique for intraprocedural guidance of endovascular iliac vein stenting procedures using three-dimensional (3D) venography images as an overlay on live biplanar fluoroscopy. METHODS: Using 3D venography and a fusion navigation technique, percutaneous transluminal angioplasty and stent placement were performed to evaluate the feasibility of using 3D venography images and the fusion navigation technique to treat MTS compared with traditional digital subtraction angiography. The general epidemiologic data (ie, age, gender), clinical manifestations (ie, major symptoms, affected extremity, CEAP [clinical, etiology, anatomy, pathophysiology] classification, comorbidity, stenosis rate), intraoperative findings (ie, stent type, stent count, stent to inferior vena cava distance, procedure time, radiation dose, contrast agent dosage), and postoperative recovery were obtained and analyzed. RESULTS: A total of 30 consecutive patients with symptomatic MTS from our institution were enrolled in the present study. Of the 30 patients, 12 (group A) were treated using 3D venography images and fusion navigation and 18 (group B) were treated with two-dimensional venography images during endovascular management. Significant differences were observed between the two groups with respect to the procedure time (64.42 ± 4.35 minutes vs 76.61 ± 3.47 minutes; P = .04), radiation dose (2152 ± 124.7 mGy vs 2561 ± 105.6 mGy; P = .02), and contrast agent dosage (71.42 ± 4.87 mL vs 86.17 ± 4.14 mL; P = .03). CONCLUSIONS: 3D venography and its fusion navigation technique can improve prediction of the coverage area of the stent. Its use can also shorten the procedure time and reduce the contrast agent dose and radiation exposure, making it a valuable tool for both the diagnosis and the treatment of symptomatic MTS.

Knockdown of ELF4 aggravates renal injury in ischemia/reperfusion mice through promotion of pyroptosis, inflammation, oxidative stress, and endoplasmic reticulum stress.

BACKGROUND: Renal ischemia/reperfusion (I/R) injury is a major cause of acute kidney injury (AKI). Dysfunction of E74-like ETS transcription factor 4 (ELF4) leads to inflammation. This research intended to look into the function and mechanisms of ELF4 in I/R and oxygen-glucose deprivation/reperfusion (OGD/R) model. RESULTS: In I/R and OGD/R model, ELF4 expression was downregulated. ELF4 knockout aggravated I/R-induced kidney injury, oxidative stress (OS), endoplasmic reticulum stress (ERS), apoptosis, inflammation, and pyroptosis in mice. In HK-2 cells treated with OGD/R, suppression of ELF4 expression inhibited cell proliferation and promoted cell apoptosis, OS, ERS, inflammation, and pyroptosis. Moreover, ELF4 overexpression led to the opposite results. CONCLUSION: ELF4 deficiency aggravated I/R induced AKI, which was involved in apoptosis, OS, ERS, inflammation, and pyroptosis. Targeting ELF4 may be a promising new therapeutic strategy for preventing inflammation after IR-AKI.

Enhancing acidogenic fermentation of waste activated sludge via urea hydrogen peroxide pretreatment: Performance and mechanisms.

Improving the anaerobic treatment performance of waste activated sludge (WAS) to achieve resource recovery is an indispensable requirement to reduce carbon emissions, minimize and stabilize biosolids. In this study, a novel strategy by using urea hydrogen peroxide (UHP) to enhance SCFAs production through accelerating WAS disintegration, degrading recalcitrant substances and alleviating competitive suppression of methanogens. The SCFAs production and acetate proportion rose from 436.9 mg COD/L and 31.3% to 3102.6 mg COD/L and 54.1%, respectively, when UHP grew from 0 to 80 mg/g TSS. Mechanism investigation revealed that OH, O2 and urea were the major contributors to accelerate WAS disintegration with the sequence of OH> O2 > urea. Function microbes related to acidification and genes associated with acetate production ([EC:2.3.1.8] and [EC:2.7.2.1]) were upregulated while genes encoding propionic acid production ([EC:6.4.1.3] and [EC:6.2.1.1]) were downregulated. These results raised the application prospects of UHP in WAS resource utilization.

Discovery and characterization of potent pan-variant SARS-CoV-2 neutralizing antibodies from individuals with Omicron breakthrough infection.

The SARS-CoV-2 Omicron variant evades most currently approved neutralizing antibodies (nAbs) and caused drastic decrease of plasma neutralizing activity elicited by vaccination or prior infection, urging the need for the development of pan-variant antivirals. Breakthrough infection induces a hybrid immunological response with potentially broad, potent and durable protection against variants, therefore, convalescent plasma from breakthrough infection may provide a broadened repertoire for identifying elite nAbs. We performed single-cell RNA sequencing (scRNA-seq) and BCR sequencing (scBCR-seq) of B cells from BA.1 breakthrough-infected patients who received 2 or 3 previous doses of inactivated vaccine. Elite nAbs, mainly derived from the IGHV2-5 and IGHV3-66/53 germlines, showed potent neutralizing activity across Wuhan-Hu-1, Delta, Omicron sublineages BA.1 and BA.2 at picomolar NT50 values. Cryo-EM analysis revealed diverse modes of spike recognition and guides the design of cocktail therapy. A single injection of paired antibodies cocktail provided potent protection in the K18-hACE2 transgenic female mouse model of SARS-CoV-2 infection.