Targeting the transmembrane cytokine co-receptor neuropilin-1 in distal tubules improves renal injury and fibrosis.

Neuropilin-1 (NRP1), a co-receptor for various cytokines, including TGF-ß, has been identified as a potential therapeutic target for fibrosis. However, its role and mechanism in renal fibrosis remains elusive. Here, we show that NRP1 is upregulated in distal tubular (DT) cells of patients with transplant renal insufficiency and mice with renal ischemia-reperfusion (I-R) injury. Knockout of Nrp1 reduces multiple endpoints of renal injury and fibrosis. We find that Nrp1 facilitates the binding of TNF-α to its receptor in DT cells after renal injury. This signaling results in a downregulation of lysine crotonylation of the metabolic enzyme Cox4i1, decreases cellular energetics and exacerbation of renal injury. Furthermore, by single-cell RNA-sequencing we find that Nrp1-positive DT cells secrete collagen and communicate with myofibroblasts, exacerbating acute kidney injury (AKI)-induced renal fibrosis by activating Smad3. Dual genetic deletion of Nrp1 and Tgfbr1 in DT cells better improves renal injury and fibrosis than either single knockout. Together, these results reveal that targeting of NRP1 represents a promising strategy for the treatment of AKI and subsequent chronic kidney disease.

Graves' disease and the risk of five autoimmune diseases: A Mendelian randomization and colocalization study.

BACKGROUND: Epidemiological studies have consistently demonstrated a high prevalence of concurrent autoimmune diseases in individuals with Graves' disease (GD). OBJECTIVE: The objective of this study is to establish a causal association between GD and autoimmune diseases. METHODS: We employed a two-sample Mendelian randomization (MR) to infer a causal association between GD and five autoimmune diseases, namely rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Crohn's disease (CD), ulcerative colitis (UC), and amyotrophic lateral sclerosis (ALS), in the East Asian and European population. Genetic correlations were explored through linkage disequilibrium score regression analysis (LDSC). Finally, colocalization analyses were performed to investigate possible genetic foundations. RESULTS: Bidirectional MR analysis indicated that genetically predicted GD increased the risk of RA (Odds Ratio (OR): 1.34, 95 % Confidence Interval (CI): 1.21 to 1.47, P < 0.001) and SLE (OR: 1.21, 95%CI: 1.08 to 1.35, P < 0.001) in the East Asian population. In contrast, we found that genetically predicted RA (OR: 1.14, 95%CI: 1.05 to 1.24, P = 0.002) and SLE (OR: 1.10, 95%CI: 1.03 to 1.17, P = 0.003) were associated with a higher risk of GD. The results have been partially validated in European cohorts. Colocalization analysis suggested the potential existence of shared causal variants between GD and other autoimmune diseases. In particular, gene ARID5B may play an important role in the incidence of autoimmune diseases. CONCLUSION: This study has confirmed that GD was associated with RA and SLE and found a possible key gene ARID5B. It may be necessary to strengthen detection to prevent the occurrence of comorbidities in clinical practice.

Gclc as a Marker for Injured Distal Nephron in Ischemia-Reperfusion Induced Acute Kidney Injury.

Purpose: The distal nephron of kidney plays a pivotal role in advancing acute kidney injury (AKI). Understanding the role of distal nephrons in AKI and identifying markers of injured distal nephrons are critical to comprehending the mechanism of renal injury and identifying novel therapeutic targets. Methods: We analyzed single-cell RNA sequencing (scRNA-seq) data from mice with AKI induced by ischemia-reperfusion (IR), unilateral ureteral obstruction (UUO), cisplatin (CP), sodium oxalate (SO) and lipopolysaccharide (LPS). Additionally, we analyzed renal transcriptomics samples for AKI. Subsequently, we validated the effectiveness of targeting the biomarker Gclc in vitro and in vivo through metabolomics and immunofluorescence. Results: The LOH-Inj and DCT-Inj subtypes were identified through scRNA-seq. Compared to normal distal nephrons, the injured distal nephrons exhibited higher levels of ferroptosis, pro-inflammation, and fibrosis. The expression of ferroptosis-related gene Gclc were high in various AKI models. Furthermore, Gclc was exclusively expressed in the distal nephron and upregulated in the injury subtype. To confirm our findings, we suppressed GCLC expression in the kidneys, resulting to aggravated IR-induced AKI. Inhibition of Gclc promoted damage to primarily renal tubular epithelial cells by promoting inflammatory infiltration, inhibiting glutathione metabolism and exacerbating oxidative stress. Conclusion: Our research findings suggest that Gclc is a potential marker for injured distal nephron.

Expression of Cry1Ab/2Aj Protein in Genetically Engineered Maize Plants and Its Transfer in the Arthropod Food Web.

While transgenic Bacillus thuringiensis (Bt) maize provides pest resistance and a reduced application of chemical pesticides, a comprehensive environmental risk assessment is mandatory before its field release. This research determined the concentrations of Bt protein in plant tissue and in arthropods under field conditions in Gongzhuling City, northeastern China, to provide guidance for the selection of indicator species for non-target risk assessment studies. Bt maize expressing Cry1Ab/2Aj and non-transformed near-isoline were grown under identical environmental and agricultural conditions. Cry1Ab/2Aj was detected in plant tissues and arthropods collected from Bt maize plots during pre-flowering, flowering, and post-flowering. The expression of Cry1Ab/2Aj varied across growth stages and maize tissues, as well as in the collected arthropods at the three growth stages. Therefore, representative species should be chosen to cover the whole growing season and to represent different habitats and ecological functions. Dalbulus maidis (Hemiptera: Cicadellidae), Rhopalosiphum padi (Hemiptera: Aphididae), Heteronychus arator (Coleoptera: Scarabaeidae), and Somaticus angulatus (Coleoptera: Tenebrionidae) are suitable non-target herbivores. Propylea japonica (Coleoptera: Coccinellidae), Paederus fuscipes (Coleoptera: Staphylinidae), Chrysoperla nipponensis (Neuroptera: Chrysopidae), and spiders are suggested predators. Apis cerana and Apis mellifera ligustica (both Hymenoptera: Apidae) represent pollinators and Folsomia candida (Collembola: Isotomidae) decomposers.

Effects of Circadian Rhythm and Feeding Modes on Rumen Fermentation and Microorganisms in Hu Sheep.

All organisms have a biological clock system which is strongly tied to how well an organism digests food and develops. This study aimed to understand the effects of circadian rhythm and feeding modes on rumen fermentation and microorganisms in Hu sheep. Forty-five healthy Hu sheep were randomly divided into three treatment groups of 15 sheep in each group, wherein they were fed the same concentrate and roughage. Under the condition that the nutrient-feeding amount was consistent throughout the day, the concentrate-to-forage ratio was dynamically adjusted during the day and night. Rumen fluid collected after the feeding experiment was used to determine the study parameters; the results showed a connection between rumen fermentation and the circadian clock. Volatile fatty acids (VFAs), pH, and NH3-N were significantly influenced by the fermentation duration (p < 0.05). The activities of digestive enzymes also showed a relationship with nutrition and circadian rhythm, and there were differences in the digestive enzyme activities of amylase, lipase, and cellulase (p < 0.05). Dominant microorganisms, such as Saccharomycetes and Mucor, were more abundant in the daytime of the high-concentrate fed group. The correlation among the study objectives was evident from the differences in enzyme activity and microbial diversity among the treatment groups. On the basis of the circadian rhythm characteristics of Hu sheep, changes in the feeding mode of Hu sheep and only adjusting the proportion of concentrate and forage in the morning and evening showed that feeding diets with the high-concentrate ratio in the day significantly reduced rumen PH and increased NH3-N concentration (p < 0.05). Under this feeding pattern, the activities of major digestive enzymes in the rumen, such as amylase and lipase, were significantly increased (p < 0.05), and the microbial diversity was also improved.

Diagnostic Significance of 18F-FDG PET/CT Imaging Coupled with Magnetic Resonance Imaging of the Entire Body for Bone Metastases.

Objective: To see if 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) imaging paired with MR diffusion imaging can help doctors diagnose bone metastases. Methods: From September 2020 to December 2021, a total of 30 individuals with probable bone metastases were recruited for the trial. With an average interval of four days, MAGNETIC resonance whole-body diffusion imaging (MR whole-body diffusion imaging) was performed on each of the 30 patients who had 18F-FDG PET/CT. The SUVmax values of the group with bone metastases were compared to those of the group without bone metastases. In this study, 18F-FDG PET/CT imaging, MR whole-body diffusion imaging, and their combination were examined. The researchers compared the results when 18F-FDG PET/CT imaging, whole-body MRI diffusion scans, and their combination indicated abnormal bone lesions. By comparing the diagnostic efficacy of 18F-FDG PET/CT imaging, MR whole-body diffusion imaging, and their combination, as well as accuracy, sensitivity, and specificity, the three techniques for diagnosing bone metastases will be evaluated for diagnostic usefulness. Results: the SUV max values of patients with bone metastases were significantly different from those of patients without bone metastases, as determined by 18F-FDG PET/CT imaging (P < 0.05). Using 18F-FDG PET/CT imaging, MR whole-body diffusion imaging, and their combined detection of aberrant bone lesions in various areas, we found statistically significant differences. Conclusion: The use of 18F-FDG PET/CT imaging in conjunction with MR whole-body diffusion imaging in the diagnosis of bone metastases can be very helpful.

Upregulation of antioxidant and autophagy pathways via NRF2 activation protects spinal cord neurons from ozone damage.

Ozone therapy can relieve multiple types of pain but exhibits potential neurotoxicity, the mechanism of which is unclear. The present study aimed to identify the role of nuclear factor (erythroid­derived­2)­related 2 (NRF2) in preventing spinal cord injury caused by ozone overdose. Primary neuronal cells were extracted from newborn Wistar rats and authenticated by immunofluorescence using anti­microtubule­associated protein 2 as a cell type­specific marker. Cell viability assay with different ozone concentrations (0, 10, 20, 30 and 40 µg/ml) was used to determine the concentration that caused primary neuron injury; 30 min of 40 µg/ml ozone therapy notably decreased cell viability to 71%. In order to test the effects of ozone, the cells were divided into five treatment groups [0­, 30­ and 40 µg/ml ozone, tert­butylhydroquinone (tBHQ) + 40 µg/ml ozone (T40) and tBHQ (T0)]. Cells in the T40 and T0 groups received 40 µmol/l tBHQ on the fifth day of SCN cultivation. Reverse transcription­quantitative PCR and western blotting showed that protein expression levels of heme oxygenase­1 (HO­1) and mRNA expression levels of HO­1 and NRF2 were decreased. NRF2, ubiquitin­binding protein p62 and microtubule­associated proteins 1A/1B light chain 3B expression levels were decreased following treatment with 40 µg/ml ozone. Immunofluorescence showed that NRF2 nuclear expression levels also decreased following 40 µg/ml ozone treatment. However, cells in the T40 group did not display decreased NRF2 nuclear expression levels. Normal/Apoptotic/Necrotic Cell Detection kit revealed that necrosis rate increased following treatment with 40 µg/ml ozone; however, the T40 group did not exhibit this increased necrosis. At 40 µg/ml, ozone increased spinal cord neuron (SCN) death in vitro. Moreover, treatment with 40 µg/ml ozone damaged SCNs. The p62/NRF2/antioxidant response element pathway prevented such injury. tBHQ activated this pathway, upregulated autophagy and increased local nuclear NRF2 concentration, thus enhancing the antioxidant system to protect SCNs from injury caused by high concentrations of ozone.

Ozone Exposure Induces Metabolic Disorders and NAD+ Depletion Through PARP1 Activation in Spinal Cord Neurons.

Background and Objective: Ozone therapy has shown therapeutic efficacy in different disorders particularly low back pain (LBP). However, ozone therapy has been associated with toxic effects on the respiratory, endocrine, cardiovascular systems as well as nervous system because of its strong oxidizing capacity. Recent studies have reported possible associations between ozone exposure and metabolic disorders, but the findings are controversial and little is known on the mechanisms of action. This study aims to investigate the cytotoxic effects of ozone exposure and possible mechanism of action in the animal model. Methods: Wistar neonate rats with the age of 24 h after birth were sacrificed by cervical dislocation under general anesthesia, then immersed in 75% alcohol and iodophor for 5 min, respectively. The spinal cord was isolated and cut to samples of ~1 mm3 and prepared for further experiments. The spinal cord neurons (SCNs) were exposed to ozone at different concentrations and then cultured in 96-well plates with glass bottom for 7 days. The cell viability, ATP levels and the NAD+ concentration were determined and compared between the different experimental groups and the control group. Results: Analyses of the data by non-targeted liquid chromatography-mass spectrometry (LC-MS) analysis determined the metabolic disorder in SCNs following the ozone exposure. Moreover, our assessments showed that ozone exposure resulted in DNA damage, poly (ADP)-ribose polymerase-1 (PARP1) excessive activation, nicotinamide adenine dinucleotide (NAD+) depletion and decrease of ATP level in SCNs. The PARP1 inhibitor can inhibit the cytotoxic effect of ozone to SCNs without inhibiting the activation of AMP-activated protein kinase (AMPK). Our findings revealed that the cytotoxic effects of ozone to SCNs might be mediated by excessive PARP1 activation and subsequent NAD+ depletion. Moreover, using PARP1 inhibitor can protect SCNs from cytotoxic effects of ozone by preventing NAD+ depletion during ozone exposure. Conclusion: Ozone exposure seems to induce metabolic disorders and NAD+ depletion through excessive PARP1 activation in SCNs.

Species-specific abundant retrotransposons elucidate the genomic composition of modern sugarcane cultivars.

Modern sugarcane cultivars are highly polyploid and derived from the hybridization of Saccharum officinarum and S. spontaneum, thus leading to singularly complex genomes. The complex genome has hindered the study of genomic structures. Here, we adopted a computational strategy to isolate highly repetitive and abundant sequences in either S. officinarum or S. spontaneum and isolated four S. spontaneum-enriched retrotransposons. Fluorescence in situ hybridization (FISH) assays with these repetitive DNA sequences generated whole-genome painting signals for S. spontaneum but not for S. officinarum. We demonstrated that these repetitive sequence-based probes distinguish the parental S. spontaneum genome in hybrids derived from crosses between it and S. officinarum. A cytological analysis of 14 modern sugarcane cultivars revealed that the percentages of chromosomes with introgressive S. spontaneum fragments ranged from 11.9 to 40.9% and substantially exceeded those determined for previously investigated cultivars (5-13%). The comparatively higher percentages of introgressive S. spontaneum fragments detected in the aforementioned cultivars indicate frequent recombination between parental genomes. Here, we present the application of our strategy to isolate species-specific cytological markers. This information may help to elucidate complex plant genomic structures and trace their evolutionary histories.

Direct exfoliation of graphite in water with addition of ammonia solution.

To bring graphene closer to its real-world applications, finding a green, low-cost, environment-friendly and less toxic solvent for production of high-quality graphene is highly demanded. However, water, the most widely used green solvent, is generally considered to be a poor solvent for hydrophobic graphene. In this study, we exfoliate graphene nanosheets directly in basic water without surfactants, polymers or organic solvents. The addition of a small amount of ammonia solution achieves the exfoliation of few-layer graphene nanosheets from pristine graphite. Diverse characterization methods are employed to investigate the morphology and quality of as-prepared graphene sheets. The release of gaseous ammonia plays the key role in exfoliation of graphene. The concentration of stable graphene dispersions can reach 0.058mg/mL.

Stable Aqueous Dispersion of Exfoliated Graphene for Tribological Applications.

In this study, the directly exfoliated graphene prepared by a jet cavitation method was tested as additive in pure water toward tribological applications. Reductions of friction coefficient and wear volume up to 22.8% and 44.4% respectively were achieved by addition of the graphene flakes. The as-prepared aqueous graphene dispersions exhibited high stability against sedimentation, and concurrently maintained their tribological properties after deposited for 15 days. The improvement in lubricating and anti-wear performances can be attributed to the graphene network formed on the sliding surfaces during the test.

Effects of Processing Parameters on Massive Production of Graphene by Jet Cavitation.

The massive production of graphene by jet cavitation method with high productivity is demonstrated. Effects of the critical processing parameters on the product dispersions are studied systematically. Experimental results show that high yield of graphene flakes relies on appropriate initial concentration of graphite, high jet pressure, and long treating time. By processing a large batch (10 L) of graphite dispersion for 8 h under 20 MPa in the jet cavitation device, an exfoliation fraction of up to ~12 wt% was achieved. Based on statistical analysis of atomic force microscopy, the as-produced graphene flakes were proved to be highly exfoliated, while the distributions of flake thickness and area became narrower with the increase of treating time. Raman spectra confirm that few defects on the graphene basal planes were induced. In general, the presented approach shows advantages in comparison with peer liquid phase exfoliation methods and thus provides a new route in efficiently producing high-quality graphene in large scale.

Co-recycling of acrylonitrile-butadiene-styrene waste plastic and nonmetal particles from waste printed circuit boards to manufacture reproduction composites.

This study investigated the feasibility of using acrylonitrile-butadiene-styrene (ABS) waste plastic and nonmetal particles from waste printed circuit boards (WPCB) to manufacture reproduction composites (RC), with the aim of co-recycling these two waste resources. The composites were prepared in a twin-crew extruder and investigated by means of mechanical testing, in situ flexural observation, thermogravimatric analysis, and dimensional stability evaluation. The results showed that the presence of nonmetal particles significantly improved the mechanical properties and the physical performance of the RC. A loading of 30 wt% nonmetal particles could achieve a flexural strength of 72.6 MPa, a flexural modulus of 3.57 GPa, and an impact strength of 15.5 kJ/m2. Moreover, it was found that the application of maleic anhydride-grafted ABS as compatilizer could effectively promote the interfacial adhesion between the ABS plastic and the nonmetal particles. This research provides a novel method to reuse waste ABS and WPCB nonmetals for manufacturing high value-added product, which represents a promising way for waste recycling and resolving the environmental problem.

Investigating the nature of graphene-based films prepared by vacuum filtration of graphene dispersions.

Though the graphene-based films prepared by vacuum filtration of graphene dispersions can be well and easily prepared so far and show great prospects in conductive, transparent, and flexible devices and coatings, the nature of these films has been rarely investigated. In order to reveal how graphene flakes constitute these films, herein we prepared a thin graphene-based film by vacuum filtering graphene dispersions and characterized the film by diverse techniques. Microscopic analyses evidenced the layer structure nature of the film. Raman spectra, transmission electron microscopy, and X-ray diffraction results indicate that the film is neither graphene nor graphite, but intrinsically a graphene block constituted by numerous graphene flakes which are randomly stacked. Though aggregation of graphene flakes happens in the filtration process, the aggregation is not a process to drive graphene flakes stacked in Bernal AB style to form bulk graphite. The adjoining graphene flakes are poorly coupled, likely due to the interlayer adventitious impurities introduced from liquid-phase processing.

Novel recycling of nonmetal particles from waste printed wiring boards to produce porous composite for sound absorbing application.

Nonmetal materials take up about 70 wt% of waste printed wiring boards (WPWB), which are usually recycled as low-value fillers or even directly disposed by landfill dumping and incineration. In this research, a novel reuse ofthe nonmetals to produce porous composites for sound absorbing application was demonstrated. The manufacturing process, absorbing performance and mechanical properties of the composites were studied. The results show that the high porous structure of the composites leads to an excellent sound absorption ability in broad-band frequency range. Average absorption coefficient of above 0.4 can be achievedby the composite in the frequency range from 100 to 6400 Hz. When the particle size is larger than 0.2 mm, the absorption ability of the composite is comparable to that of commercial wood-fibre board and urea-formaldehyde foam. Mechanical analysis indicates that the porous composites possess sufficient structural strength for self-sustaining applications. All the results indicate that producing sound absorbing composite with nonmetal particles from WPWB provides an efficient and profitable way for recycling this waste resource and can resolve both the environment pollution and noise pollution problems.

Water can stably disperse liquid-exfoliated graphene.

Liquid-exfoliated graphene can be stably dispersed in water and concurrently maintain its high quality (average 1 nm thick, low content of defects and oxides). The high stability is attributed to the reduction of flake size and thus the enhanced edge effects. This work opens up a whole new vista on how to disperse graphene.

Hydrodynamics-assisted scalable production of boron nitride nanosheets and their application in improving oxygen-atom erosion resistance of polymeric composites.

Searching for a method for low-cost, easily manageable, and scalable production of boron nitride nanosheets (BNNSs) and exploring their novel applications are highly important. For the first time we demonstrate that a novel and effective hydrodynamics method, which involves multiple exfoliation mechanisms and thus leads to much higher yield and efficiency, can realize large-scale production of BNNSs. The exfoliation mechanisms that multiple fluid dynamics events contribute towards normal and lateral exfoliation processes could be applied to other layered materials. Up to ~95% of the prepared BNNSs are less than 3.5 nm thick with a monolayer fraction of ~37%. Compared to the conventional sonication and ball milling-based methods, the hydrodynamics method has the advantages of possessing multiple efficient ways for exfoliating BN, being low-cost and environmentally-friendly, producing high quality BNNSs in high yield and efficiency, and achieving concentrated BNNSs dispersions even in mediocre solvents. It is also shown for the first time that BNNSs can be utilized as fillers to improve the oxygen-atom erosion resistance of epoxy composites which are widely used for spacecraft in low earth orbit (LEO) where atom oxygen abounds. An addition of only 0.5 wt% BNNSs can result in a 70% decrease in the mass loss of epoxy composites after atom oxygen exposure equivalent to 160 days in an orbit of ~300 km. Overall, the demonstrated hydrodynamics method shows great potential in large-scale production of BNNSs in industry in terms of yield, efficiency, and environmental friendliness; and the innovative application of BNNSs to enhancing oxygen-atom erosion resistance of polymeric composites in space may provide a novel route for designing light spacecraft in LEO.

Controllable functionalization and wettability transition of graphene-based films by an atomic oxygen strategy.

Though chemical modification of graphene based on Hummers method has been most widely used to tailor its properties and interfacial characteristics, a method which could achieve definitive and controllable groups and properties is still highly required. Here, we demonstrate a high-vacuum oxidation strategy by atomic oxygen (AO) and investigate the AO induced functionalization and wettability transition in films made from basal-defect- and oxide-free graphene dispersions. These graphene-based films are neither graphene nor graphite, but graphene blocks constituted by numerous randomly stacked graphene flakes. It is found that AO induced functionalization of these films through the formation of epoxy groups, sp3 configuration, ether, and double and triple C-O groups. The films turn to be hydrophilic after exposed to AO. The contact angle increases with AO exposure time. This phenomenon is attributed to the lower surface roughness induced by collision and/or edge erosion of energetic ions to the film surface and is further explained by the Wenzel model. The demonstrated strategy can overcome limitations of Hummers method, provide possibility to gain functionalization and wettability transition in liquid-phase exfoliated basal-defect- and oxide-free graphene in the dry environment, and may extend the study and application of this material in spacecraft in low earth orbit.

Preparation of graphene by jet cavitation.

Despite its bright prospects, graphene faces challenges including issues concerning mass production. Here we present a totally green approach whereby common crystal graphite can be exfoliated into graphene sheets in aqueous solution by jet cavitation. This is possible mainly because the tensile stress caused by graphite-solution interfacial reflection of compressive waves acts an intensive 'suction disk' on the graphite flakes. We confirm the presence of graphene sheets by diverse characterizations. The graphene yield by our method is estimated as ∼ 4 wt%, which could potentially be improved by further processing. The method, of a mechanical nature, is powerful compared to the traditional low-throughput micromechanical cleavage. Our work here illustrates jet cavitation as a facile, low cost, timesaving and laborsaving route, which can potentially be scaled up to mass production of graphene.

A novel approach to recycling of glass fibers from nonmetal materials of waste printed circuit boards.

The printed circuit boards (PCBs) contain nearly 70% nonmetal materials, which usually are abandoned as an industrial solid-waste byproduct during the recycling of waste PCBs. However those materials have abundant high-value glass fibers. In this study, a novel fluidized bed process technology for recycling glass fibers from nonmetal materials of waste PCBs is studied. The recycled glass fibers (RGF) are analyzed by determination of their purity, morphology and surface chemical composition. This process technology is shown to be effective and robust in treating with nonmetal materials of waste PCBs. The thermoset resins in the nonmetal materials are decomposed in the temperature range from 400 degrees C to 600 degrees C. And the glass fibers are collected at high purity and recovery rate by the cyclone separators without violating the environmental regulation. This novel fluidized bed technology for recycling high-value glass fibers from nonmetal materials of waste PCBs represents a promising way for recycling resources and resolving the environmental pollutions during recycling of waste PCBs.