Superconductivity in Monolayer Carbon Allotropes with High Thermal Stability.

Intrinsic superconductivity is rarely discovered in sp2-hybridized monolayer carbon allotropes. Here we design a carbon monolayer configured of pentagon, heptagon, and hexagon rings with p2 plane group symmetry. Full-sp2 hybridization is proposed to favor thermal metastability on a low Gibbs free energy. The extremely small thermal expansion coefficient is predicted to the turn negative value to positive with elevating temperature. Carbon polygon structures remain intact at a high thermal temperature of 3,000 K. The high specific surface area is found to approach 2,700 m2/g, with O2-adsorption being advantageous over pristine graphene. We reveal electronic Fermi surfaces mediated by phonon modes of carbon out-of-plane vibrations. By calculating the Eliashberg equation, we evaluate intrinsic superconductivity with a large electron-phonon coupling coefficient. The superconducting transition temperature is estimated to reach 20 K under a high logarithmic average frequency. These first-principles calculations shall stimulate experimentalists' interest in exploring low-dimensional carbon superconductors with gas sensitivity.

SENP1 reduces oxidative stress and apoptosis in renal ischaemia-reperfusion injury by deSUMOylation of HIF-1α.

Renal ischaemia-reperfusion injury (RIRI) is a primary cause of acute kidney damage, occurring frequently in situations like renal transplantation, yet the underlying mechanisms were not fully understood. Sentrin-specific protease 1 (SENP1) is an important member of the SENP family, which is widely involved in various diseases. However, the role of SENP1 in RIRI has been unclear. In our study, we discovered that SENP1 was involved in RIRI and reduced renal cell apoptosis and oxidative stress at elevated levels. Further mechanistic studies showed that hypoxia-inducible factor-1α (HIF-1α) was identified as a substrate of SENP1. Furthermore, SENP1 deSUMOylated HIF-1α, which reduced the degradation of HIF-1α, and exerted a renoprotective function. In addition, the protective function was lost after application of the HIF-1α specific inhibitor KC7F2. Briefly, our results fully demonstrated that SENP1 reduced the degradation of HIF-1α and attenuated oxidative stress and apoptosis in RIRI by regulating the deSUMOylation of HIF-1α, suggesting that SENP1 may serve as a potential therapeutic target for the treatment of RIRI.

Hedyotis diffusa Willd inhibits inflammation and oxidative stress to protect against chronic prostatitis via the NRF2/ARE signaling pathway.

Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a common and serious disease with unclear pathogenesis and recurrent symptoms. Hedyotis diffusa Willd (HDW) has been recognized for its potential in managing various chronic inflammatory diseases. This research aimed to interrogate the mechanism of HDW in treating CP/CPPS. Complete Freund Adjuvant (CFA) and LPS were utilized to establish the rat and cell models of CP/CPPS. Results showed that HDW decreased levels of inflammation-related factors in CP rat prostate tissue and LPS-elicited RWPE-1 cell injury model. Moreover, HDW administration impaired oxidative stress in the prostate and RWPE-1 cells. In addition, HDW treatment activated the NRF2/ARE signaling in rat prostate tissue and cell models. Interestingly, NRF2/ARE pathway inhibitor ML385 reversed the inhibition effects of cell apoptosis, inflammation, and oxidative stress triggered by HDW. In summary, HDW alleviated inflammation and oxidative stress by activating NRF2/ARE signaling in CP/CPPS rat model and human prostate epithelial cell injury model.

The impact of donor diabetes on recipient postoperative complications, renal function, and survival rate in deceased donor kidney transplantation: a single-center analysis.

As the global incidence of diabetes rises and diagnoses among younger patients increase, transplant centers worldwide are encountering more organ donors with diabetes. This study examined 80 donors and 160 recipients, including 30 donors with diabetes (DD) and their 60 recipients (DDR). The control group comprised 50 non-diabetic donors (ND) and 100 recipients (NDR). We analyzed clinical, biochemical, and pathological data for both diabetic and control groups, using logistic regression to identify risk factors for delayed graft function (DGF) after kidney transplantation. Results showed that pre-procurement blood urea nitrogen levels were significantly higher in DD [18.20 ± 10.63 vs. 10.86 ± 6.92, p = 0.002] compared to ND. Renal pathological damage in DD was notably more severe, likely contributing to the higher DGF incidence in DDR compared to NDR. Although DDR had poorer renal function during the first three months post-transplant, both groups showed similar renal function thereafter. No significant differences were observed in 1-year or 3-year mortality rates or graft failure rates between DDR and NDR. Notably, according to the Renal Pathology Society (RPS) grading system, kidneys from diabetic donors with a grade > IIb are associated with significantly lower postoperative survival rates. Recipient gender [OR: 5.452 (1.330-22.353), p = 0.013] and pre-transplant PRA positivity [OR: 34.879 (7.698-158.030), p < 0.001] were identified as independent predictors of DGF in DDR. In conclusion, transplant centers may consider utilizing kidneys from diabetic donors, provided they are evaluated pathologically, without adversely impacting recipient survival and graft failure rates.

Recent Advances in Hybrid Materials of Metal Nanoparticles and Polyoxometalates.

Polyoxometalates (POMs), anionic metal-oxygen nanoclusters that possess various composition-dependent properties, are widely used to modify the existing properties of metal nanoparticles and to endow them with new ones. Herein, we present an overview of recent advances in hybrid materials that consist of metal nanoparticles and POMs. Following a brief introduction on the inception of this area and its development, representative properties and applications of these materials in various fields such as electrochemistry, photochemistry, and catalysis are introduced. We discuss how the combination of two classic inorganic materials facilitates cooperative and synergistic behavior, and we also give personal perspectives on the future development of this field.

CCL7 playing a dominant role in recruiting early OCPs to facilitate osteolysis at metastatic site of colorectal cancer.

BACKGROUND: Chemoattractant is critical to recruitment of osteoclast precursors and stimulates tumor bone metastasis. However, the role of chemoattractant in bone metastasis of colorectal cancer (CRC) is still unclear. METHODS: Histochemistry analysis and TRAP staining were utilized to detect the bone resorption and activation of osteoclasts (OCs) after administration of CCL7 neutralizing antibody or CCR1 siRNA. qRT-PCR analysis and ELISA assay were performed to detect the mRNA level and protein level of chemoattractant. BrdU assay and Tunel assay were used to detect the proliferation and apoptosis of osteoclast precursors (OCPs). The migration of OCPs was detected by Transwell assay. Western blots assay was performed to examine the protein levels of pathways regulating the expression of CCL7 or CCR1. RESULTS: OCPs-derived CCL7 was significantly upregulated in bone marrow after bone metastasis of CRC. Blockage of CCL7 efficiently prevented bone resorption. Administration of CCL7 promoted the migration of OCPs. Lactate promoted the expression of CCL7 through JNK pathway. In addition, CCR1 was the most important receptor of CCL7. CONCLUSION: Our study indicates the essential role of CCL7-CCR1 signaling for recruitment of OCPs in early bone metastasis of CRC. Targeting CCL7 or CCR1 could restore the bone volume, which could be a potential therapeutical target. Video Abstract.

Atomic-Scale Pentagraphene Ribbons Stabilized with Alkali Metals under Moderate Pressures.

Pentagraphene frameworks with sp2 carbon atoms have significance in fundamental research studies and material science. Here, we find pentagon ribbons stacked in an AB sequence at the atomic scale within alkali metal atoms. A Pnma phase is favored on the Gibbs free energy landscape at moderate pressures and finite temperatures. Strong electron localization, covalent interactions, weak van der Waals interactions, and electronic repulsive interactions coexist in this ionic structure. Electronic bands with narrow direct gaps are flattened with double degeneracy to produce a small effective mass and van Hove singularity for the density of states, which enhances visible-light absorption and produces a thermoelectric power factor on crystals. Alkali metal atoms strongly scatter acoustic-optical phonons to reduce the lattice thermal conductivity to an ultralow level. These characteristics introduce potential thermoelectric effects into Pnma crystals. In addition, the alkali metal ions exhibit high delocalizations with superionic properties at high temperatures.

Subsurface Manure Injection Reduces Surface Transport of Antibiotic Resistance Genes but May Create Antibiotic Resistance Hotspots in Soils.

Compared to surface application, manure subsurface injection reduces surface runoff of nutrients, antibiotic resistant microorganisms, and emerging contaminants. Less is known regarding the impact of both manure application methods on surface transport of antibiotic resistance genes (ARGs) in manure-amended fields. We applied liquid dairy manure to field plots by surface application and subsurface injection and simulated rainfall on the first or seventh day following application. The ARG richness, relative abundance (normalized to 16s rRNA), and ARG profiles in soil and surface runoff were monitored using shotgun metagenomic sequencing. Within 1 day of manure application, compared to unamended soils, soils treated with manure had 32.5-70.5% greater ARG richness and higher relative abundances of sulfonamide (6.5-129%) and tetracycline (752-3766%) resistance genes (p ≤ 0.05). On day 7, soil ARG profiles in the surface-applied plots were similar to, whereas subsurface injection profiles were different from, that of the unamended soils. Forty-six days after manure application, the soil ARG profiles in manure injection slits were 37% more diverse than that of the unamended plots. The abundance of manure-associated ARGs were lower in surface runoff from manure subsurface injected plots and carried a lower resistome risk score in comparison to surface-applied plots. This study demonstrated, for the first time, that although manure subsurface injection reduces ARGs in the runoff, it can create potential long-term hotspots for elevated ARGs within injection slits.

Supported Anionic Gold Nanoparticle Catalysts Modified Using Highly Negatively Charged Multivacant Polyoxometalates.

Although supported anionic gold nanoparticle catalysts have been theoretically investigated for their efficacy in activating O2 in aerobic oxidation reactions, limited studies have been reported due to the difficulty of designing these catalysts. Herein, we developed a feasible method for preparing supported anionic gold nanoparticle catalysts using multivacant lacunary polyoxometalates with high negative charges. We confirmed the strong and robust electronic interaction between gold nanoparticles and multivacant lacunary polyoxometalates, and the electronic states of the supported gold nanoparticle catalysts can be sequentially modulated. Particularly, the catalyst prepared using [SiW9 O34 ]10- acted as an efficient reusable heterogeneous catalyst, showing superior catalytic performance for the oxidative dehydrogenation of piperidone derivatives to the corresponding enaminones and remarkably higher stability than supported gold nanoparticle catalysts without this modification.

AgroSeek: a system for computational analysis of environmental metagenomic data and associated metadata.

BACKGROUND: Metagenomics is gaining attention as a powerful tool for identifying how agricultural management practices influence human and animal health, especially in terms of potential to contribute to the spread of antibiotic resistance. However, the ability to compare the distribution and prevalence of antibiotic resistance genes (ARGs) across multiple studies and environments is currently impossible without a complete re-analysis of published datasets. This challenge must be addressed for metagenomics to realize its potential for helping guide effective policy and practice measures relevant to agricultural ecosystems, for example, identifying critical control points for mitigating the spread of antibiotic resistance. RESULTS: Here we introduce AgroSeek, a centralized web-based system that provides computational tools for analysis and comparison of metagenomic data sets tailored specifically to researchers and other users in the agricultural sector interested in tracking and mitigating the spread of ARGs. AgroSeek draws from rich, user-provided metagenomic data and metadata to facilitate analysis, comparison, and prediction in a user-friendly fashion. Further, AgroSeek draws from publicly-contributed data sets to provide a point of comparison and context for data analysis. To incorporate metadata into our analysis and comparison procedures, we provide flexible metadata templates, including user-customized metadata attributes to facilitate data sharing, while maintaining the metadata in a comparable fashion for the broader user community and to support large-scale comparative and predictive analysis. CONCLUSION: AgroSeek provides an easy-to-use tool for environmental metagenomic analysis and comparison, based on both gene annotations and associated metadata, with this initial demonstration focusing on control of antibiotic resistance in agricultural ecosystems. Agroseek creates a space for metagenomic data sharing and collaboration to assist policy makers, stakeholders, and the public in decision-making. AgroSeek is publicly-available at https://agroseek.cs.vt.edu/ .

IL4/IL4R signaling promotes the osteolysis in metastatic bone of CRC through regulating the proliferation of osteoclast precursors.

BACKGROUND: Bone metastasis of colorectal cancer (CRC) often indicates a poor prognosis. Osteolysis can be observed in metastatic sites, implying an aberrant activation of osteoclasts. However, how osteoclastogenesis is regulated in metastatic microenvironment caused by colorectal cancer is still unclear. METHODS: In this study, mice bone metastatic model of CRC was established through injection of MC-38 or CT-26 cells. BrdU assays showed primary CD115 ( +) osteoclast precursors (OCPs) proliferated at the first 2 weeks. Transcriptomic profiling was performed to identify differentially expressing genes and pathways in OCPs indirectly co-cultured with CRC cells RESULTS: The expression of IL4Rα was found to be significantly upregulated in OCPs stimulated by tumor conditioned medium (CM). Further investigation indicated that IL-4 signaling regulated proliferation of OPCs through interacting with type I IL4 receptor, and neutrophils were the main source of IL-4 in bone marrow. The proliferation of OCPs can be inhibited in IL4 deficiency mice. In addition, ERK pathway was activated by IL4/IL4R signaling. Ravoxertinib, an ERK antagonists, could significantly prevent bone destruction through inhibiting the proliferation of OCPs. CONCLUSION: Our study indicates the essential role of IL4/IL4R signaling for the proliferation of OCPs in early metastasis of CRC predominantly through activating ERK pathway, which remarkedly impacts the number of osteoclasts in later stage and leads to osteolytic lesions. Moreover, Ravoxertinib could be a new therapeutical target for bone metastasis of CRC.

Tungsten Hexanitride with Single-Bonded Armchairlike Hexazine Structure at High Pressure.

WN_{6} phase discovered at 126-165 GPa after heating of W in nitrogen. XRD refinements reveal a unit cell in space group R3[over ¯]m which is consistent with the WN_{6} structure with armchairlike hexazine (N_{6}) rings, while strong A_{1g} Raman mode confirms its N─N single bonds. Density functional theory (DFT) calculations reveal balanced contributions of attractive interactions between W and covalent N_{6} rings, and repulsions between N_{6} rings that make WN_{6} ultrastiff and tough. The WN_{6} phase displays long bond lengths in the nearest N-N and pressure-enhanced electronic band gap, which pave the way for finding novel nitrides.

Short communication: Increasing temperature and pH can facilitate reductions of cephapirin and antibiotic resistance genes in dairy manure slurries.

Quantifying antibiotics and antibiotic resistance genes (ARG) in manure exposed to various temperature and pH treatments could guide the development of cost-effective manure handling methods to minimize the spread of antibiotic resistance following land application of manure. This study aimed to investigate the effect of various temperatures and initial pH shocks on the persistence of a cephalosporin antibiotic and ARG in dairy manure slurries. Feces and urine were collected from 5 healthy dairy cows administered with cephapirin (cephalosporin antibiotic) at dry-off via intramammary infusion and were mixed with sterile water to generate manure slurries. In a 28-d incubation study, dairy manure slurries either were continuously exposed to 1 of 3 temperatures (10, 35, and 55°C) or received various initial pH (5, 7, 9, and 12) shocks. Cephapirin was detected in the initial samples and on d 1 following all treatments, but it was undetectable thereafter. This indicates that cephapirin can be rapidly degraded irrespective of temperature and pH treatments. However, degradation was greater on d 1 with the mesophilic (35°C) and thermophilic (55°C) environments compared with the psychrophilic environment (10°C). Increasing pH beyond neutral also accelerated degradation as cephapirin concentrations were lower on d 1 after initial alkaline adjustments (pH 9 and 12) than after neutral and acidic adjustments (pH 7 and 5). No significant effect of temperature or initial pH was observed on abundances of a ß-lactam ARG, cfxA, and a tetracycline ARG, tet(W), implying that bacteria that encoded cfxA or tet(W) genes were not sensitive to temperature or pH in dairy manure slurries. However, abundances of a macrolide ARG, mefA, were decreased in the psychrophilic and thermophilic environments and also following exposure to a strong alkaline shock (pH 12). Our results suggest that increasing temperature or pH during storage of dairy manure slurries could be used together with other on-farm practices that are tailored to reduce the transfer of ARG from manure to the environment following land application.

A smart and portable micropump for stable liquid delivery.

Precise and reliable liquid delivery is vital for microfluidic applications. Here, we illustrate the design, fabrication, characterization, and application of a portable, low cost, and robust micropump, which brings solution to stable liquid delivery in microfluidic environment. The pump is designed with three optional speeds of different pumping flow rates, and it can be simply actuated by spring-driven mechanism. The different flow rates of the pump are realized via passive microvalves in a compact microfluidic chip, which is installed in the pump. Importantly, the membrane structures of the microvalves allow accurate liquid control, and stable flow rates can be achieved via a spring setup. The proposed pump is applied to continuously and stably infuse microbead suspension into an inertial microfluidic chip, and good particle focusing is realized in the spiral channel of the inertial microfluidic chip. The proposed portable, self-powered, and cost-efficient pump is crucial for microfluidic lab-on-a-chip system integration, which may facilitate microfluidic application for precise liquid delivery, control, measurement, and analysis.

DNA Facilitates the Sorption of Polycyclic Aromatic Hydrocarbons on Montmorillonites.

The sorption of polycyclic aromatic hydrocarbons (PAHs) to montmorillonites is largely influenced by their interactions with dissolved organic matter (DOM). However, the role of DOM rather than humic and fulvic acids (e.g., extracellular DNA) in the PAH sorption to soil clays is little known. Here, we demonstrate that extracellular double-stranded salmon testes DNA substantially increased the sorption of phenanthrene and pyrene to Na-, Ca-, and Fe-modified montmorillonites. All PAH sorption isotherms fitted the linear and Freundlich models reasonably well ( R2 = 0.918-0.999). Distribution coefficients were increased from 0.0458-0.103 and 0.0493-0.141 L/g at 0 mg/L DNA to 0.413-0.589 and 0.385-0.560 L/g at 10 mg/L DNA for phenanthrene and pyrene, respectively. Spectroscopic and computational chemistry analyses confirmed that PAHs were first inserted into DNA by binding with the nucleobases via van der Waals and π-π electron donor-acceptor interactions. Compared to PAHs, the DNA-PAH complex can be more easily sorbed to cation-modified montmorillonites by complexation between DNA phosphate and exchangeable cations in addition to intercalation into clay interlayers. This work highlights the importance of understanding the control on contaminant sorption by many organic compounds that are ubiquitous in soils but not represented by humic and fulvic acids.

Metagenomic Characterization of Antibiotic Resistance Genes in Full-Scale Reclaimed Water Distribution Systems and Corresponding Potable Systems.

Water reclamation provides a valuable resource for meeting nonpotable water demands. However, little is known about the potential for wastewater reuse to disseminate antibiotic resistance genes (ARGs). Here, samples were collected seasonally in 2014-2015 from four U.S. utilities' reclaimed and potable water distribution systems before treatment, after treatment, and at five points of use (POU). Shotgun metagenomic sequencing was used to profile the resistome (i.e., full contingent of ARGs) of a subset ( n = 38) of samples. Four ARGs ( qnrA, blaTEM, vanA, sul1) were quantified by quantitative polymerase chain reaction. Bacterial community composition (via 16S rRNA gene amplicon sequencing), horizontal gene transfer (via quantification of intI1 integrase and plasmid genes), and selection pressure (via detection of metals and antibiotics) were investigated as potential factors governing the presence of ARGs. Certain ARGs were elevated in all ( sul1; p ≤ 0.0011) or some ( blaTEM, qnrA; p ≤ 0.0145) reclaimed POU samples compared to corresponding potable samples. Bacterial community composition was weakly correlated with ARGs (Adonis, R2 = 0.1424-0.1734) and associations were noted between 193 ARGs and plasmid-associated genes. This study establishes that reclaimed water could convey greater abundances of certain ARGs than potable waters and provides observations regarding factors that likely control ARG occurrence in reclaimed water systems.

Method of Dairy Manure Application and Time before Rainfall Affect Antibiotics in Surface Runoff.

Although research has shown that manure soil subsurface injection reduces nutrient input to the aquatic environment, it is less known if it also reduces antibiotic surface runoff from manure-applied fields. Surface runoff of four dairy production antibiotics was monitored comparing (i) surface application and subsurface injection of manure and (ii) time gaps between manure application and a subsequent rain event. Liquid dairy manure spiked with pirlimycin, tylosin, chlortetracycline, and sulfamerazine was applied to 1.5-m × 2-m test plots at an agronomic N rate via surface application and subsurface injection. On the day of application (Day 0), and 3 and 7 d after manure application, a simulated rainfall (70 mm h) was conducted to collect 30 min runoff. Target antibiotics in runoff water and sediment were quantified using ultra-performance liquid chromatography tandem mass spectrometry. Results demonstrated that runoff was a significant route for transporting antibiotics off manure-applied fields, amounting to 0.45 to 2.62% of their initial input with manure. However, compared with manure surface application, subsurface injection reduced sulfamerazine, chlortetracycline, pirlimycin, and tylosin losses in runoff by at least 47, 50, 57, and 88%, respectively. Antibiotic distribution between aqueous and solid phases of runoff was largely determined by water solubility and partition capacity of antibiotics to soil particles. Masses in the aqueous phase were 99 ± 0.5, 94 ± 4, 91 ± 7, and 22 ± 15% of pirlimycin, sulfamerazine, tylosin, and chlortetracycline, respectively. Manure application 3 d or longer before a subsequent rain event reduced antibiotic runoff by 9 to 45 times. Therefore, using subsurface injection and avoiding manure application <3 d before rain would be a recommended manure land management best practice.

Antibiotics and Antibiotic Resistance Genes in Bulk and Rhizosphere Soils Subject to Manure Amendment and Vegetable Cultivation.

There is interest in understanding effects of amending soil with manure in a cultivation setting and if composting can provide benefits. Raw or composted manure from cattle administered with and without sulfamethazine, chlortetracycline, and tylosin was amended to loamy sand and silty clay loam soils, where lettuce ( L.), radish ( L.), and broccoli ( L. var. ) were cultivated and compared with those grown in soil amended with fertilizer as a control. Upon plant maturation, rhizosphere and bulk soils were analyzed for antibiotics, and 1, B, (W), and I1 genes were quantified. Antibiotic concentrations in compost-amended soils were below detection limits. For soils amended with manure containing antibiotics, sulfamethazine ranged from 1.1 to 3.1 µg kg in the bulk soils but was below detection limits in the rhizosphere soils. Chlortetracycline (2.8-9.3 µg kg) was two times lower in the rhizosphere than in the bulk soil. Levels of tylosin in the rhizosphere soil were similar to the bulk soil. Soil texture or vegetable type did not have significant influence on antibiotic concentration differences between the bulk and rhizosphere soils. Relative abundances of (W) and I1 in the fertilizer-amended soil were significantly lower than in those amended with manure or compost ( < 0.05), whereas B was not detected in any soils. Rhizosphere zone has no significant effect on the detected antibiotic resistance genes. It is suggested that plant roots may have a substantial effect on the fate of certain antibiotics in manure-amended fields, but less of an effect on antibiotic resistance and mobility genes.

Fate of Pirlimycin and Antibiotic-Resistant Fecal Coliforms in Field Plots Amended with Dairy Manure or Compost during Vegetable Cultivation.

Identification of agricultural practices that mitigate the environmental dissemination of antibiotics is a key need in reducing the prevalence of antibiotic-resistant bacteria of human health concern. Here, we aimed to compare the effects of crop (lettuce [ L.] or radish [ L.]), soil amendment type (inorganic fertilizer, raw dairy manure, composted dairy manure, or no amendment), and prior antibiotic use history (no antibiotics during previous lactation cycles vs. manure mixed from cows administered pirlimycin or cephapirin) of manure-derived amendments on the incidence of culturable antibiotic-resistant fecal coliforms in agricultural soils through a controlled field-plot experiment. Antibiotic-resistant culturable fecal coliforms were recoverable from soils across all treatments immediately after application, although persistence throughout the experiment varied by antibiotic class and time. The magnitude of observed coliform counts differed by soil amendment type. Compost-amended soils had the highest levels of cephalosporin-resistant fecal coliforms, regardless of whether the cows from which the manure was derived were administered antibiotics. Samples from control plots or those treated with inorganic fertilizer trended toward lower counts of resistant coliforms, although these differences were not statistically significant. No statistical differences were observed between soils that grew leafy (lettuce) versus rooted (radish) crops. Only pirlimycin was detectable past amendment application in raw manure-amended soils, dissipating 12 to 25% by Day 28. Consequently, no quantifiable correlations between coliform count and antibiotic magnitude could be identified. This study demonstrates that antibiotic-resistant fecal coliforms can become elevated in soils receiving manure-derived amendments, but that a variety of factors likely contribute to their long-term persistence under typical field conditions.

GADD45α is involved in the apoptosis of lymphocytes induced by riboflavin and ultraviolet light.

BACKGROUND: Riboflavin plus ultraviolet (UV) pathogen reduction technology (RF-PRT) is an effective method for inactivating the residual white blood cells (WBCs) in blood components. The RF-PRT system for platelets is known to activate many signaling pathways, including p38 and NF-κB. Nevertheless, proteomic studies in WBCs after riboflavin plus UV treatment requires further analysis. STUDY DESIGN AND METHODS: ABO/D-matched lymphocytes were pooled, split, and treated with RF-PRT or UV light or left untreated. After treatment, cell apoptosis was measured. In addition, cell proliferation and the cycle distribution were evaluated upon stimulation with phytohemagglutinin. The changes in the protein expression levels of growth arrest and DNA damage-inducible (GADD)45α, p38, and c-Jun N-terminal kinase (JNK) were determined by Western blotting. The effect of GADD45α, p38, and JNK on apoptosis was assessed. RESULTS: RF-PRT significantly inhibited proliferation and induced G1 arrest in lymphocytes. Furthermore, the percentage of apoptotic cells was increased in RF-PRT-treated lymphocytes compared to UV-treated cells or untreated cells, associated with the up regulation of GADD45α expression. Consistent with these observations, the inhibition of GADD45α expression partially counteracted the effects of riboflavin plus UV treatment. The p38 and JNK signaling pathways were activated by GADD45α in RF-PRT-treated lymphocytes. CONCLUSIONS: These data revealed that RF-PRT effectively inhibited proliferation and induced apoptosis of lymphocytes by promoting GADD45α expression, which subsequently activates p38 and JNK signaling pathways.