PKM2 induces mitophagy through the AMPK-mTOR pathway promoting CSFV proliferation.

Viruses exploit the host cell's energy metabolism system to support their replication. Mitochondria, known as the powerhouse of the cell, play a critical role in regulating cell survival and virus replication. Our prior research indicated that the classical swine fever virus (CSFV) alters mitochondrial dynamics and triggers glycolytic metabolic reprogramming. However, the role and mechanism of PKM2, a key regulatory enzyme of glycolytic metabolism, in CSFV replication remain unclear. In this study, we discovered that CSFV enhances PKM2 expression and utilizes PKM2 to inhibit pyruvate production. Using an affinity purification coupled mass spectrometry system, we successfully identified PKM as a novel interaction partner of the CSFV non-structural protein NS4A. Furthermore, we validated the interaction between PKM2 and both CSFV NS4A and NS5A through co-immunoprecipitation and confocal analysis. PKM2 was found to promote the expression of both NS4A and NS5A. Moreover, we observed that PKM2 induces mitophagy by activating the AMPK-mTOR signaling pathway, thereby facilitating CSFV proliferation. In summary, our data reveal a novel mechanism whereby PKM2, a metabolic enzyme, promotes CSFV proliferation by inducing mitophagy. These findings offer a new avenue for developing antiviral strategies. IMPORTANCE: Viruses rely on the host cell's material-energy metabolic system for replication, inducing host metabolic disorders and subsequent immunosuppression-a major contributor to persistent viral infections. Classical swine fever virus (CSFV) is no exception. Classical swine fever is a severe acute infectious disease caused by CSFV, resulting in significant economic losses to the global pig industry. While the role of the metabolic enzyme PKM2 (pyruvate dehydrogenase) in the glycolytic pathway of tumor cells has been extensively studied, its involvement in viral infection remains relatively unknown. Our data unveil a new mechanism by which the metabolic enzyme PKM2 mediates CSFV infection, offering novel avenues for the development of antiviral strategies.

IDO1 promotes CSFV replication by mediating tryptophan metabolism to inhibit NF-κB signaling.

Tryptophan metabolism plays a crucial role in facilitating various cellular processes essential for maintaining normal cellular function. Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzes the conversion of tryptophan (Trp) into kynurenine (Kyn), thereby initiating the degradation of Trp. The resulting Kyn metabolites have been implicated in the modulation of immune responses. Currently, the role of IDO1-mediated tryptophan metabolism in the process of viral infection remains relatively unknown. In this study, we discovered that classical swine fever virus (CSFV) infection of PK-15 cells can induce the expression of IDO1, thereby promoting tryptophan metabolism. IDO1 can negatively regulate the NF-κB signaling by mediating tryptophan metabolism, thereby facilitating CSFV replication. We found that silencing the IDO1 gene enhances the expression of IFN-α, IFN-ß, and IL-6 by activating the NF-κB signaling pathway. Furthermore, our observations indicate that both silencing the IDO1 gene and administering exogenous tryptophan can inhibit CSFV replication by counteracting the cellular autophagy induced by Rapamycin. This study reveals a novel mechanism of IDO1-mediated tryptophan metabolism in CSFV infection, providing new insights and a theoretical basis for the treatment and control of CSFV.IMPORTANCEIt is well known that due to the widespread use of vaccines, the prevalence of classical swine fever (CSF) is shifting towards atypical and invisible infections. CSF can disrupt host metabolism, leading to persistent immune suppression in the host and causing significant harm when co-infected with other diseases. Changes in the host's metabolic profiles, such as increased catabolic metabolism of amino acids and the production of immunoregulatory metabolites and their derivatives, can also influence virus replication. Mammals utilize various pathways to modulate immune responses through amino acid utilization, including increased catabolic metabolism of amino acids and the production of immunoregulatory metabolites and their derivatives, thereby limiting viral replication. Therefore, this study proposes that targeting the modulation of tryptophan metabolism may represent an effective approach to control the progression of CSF.

Fluorosulfate as a Latent Sulfate in Peptides and Proteins.

Sulfation widely exists in the eukaryotic proteome. However, understanding the biological functions of sulfation in peptides and proteins has been hampered by the lack of methods to control its spatial or temporal distribution in the proteome. Herein, we report that fluorosulfate can serve as a latent precursor of sulfate in peptides and proteins, which can be efficiently converted to sulfate by hydroxamic acid reagents under physiologically relevant conditions. Photocaging the hydroxamic acid reagents further allowed for the light-controlled activation of functional sulfopeptides. This work provides a valuable tool for probing the functional roles of sulfation in peptides and proteins.

A Robust Switchable Oil-In-Water Emulsion Stabilized by Electrostatic Repulsions between Surfactant and Similarly Charged Carbon Dots.

How to control the stability of oil-in-water (O/W) emulsions is one of the main topics for scientists working in colloidal systems. Recently, carbon dots (CDs) have received great interest as smart materials because of their excellent physicochemical properties and versatile applications. Herein, for the first time, advanced and switchable O/W emulsions are presented that are stabilized by the synergistic effect of cationic surfactant cetyltrimethylammonium bromide CTAB (emulsifier) and similarly charged CDs (stabilizer). In the formulated emulsion, the cationic surfactant molecules are adsorbed at the oil and water interface to decrease the interfacial tension and enrich the drops with a positive charge to ensure intensive electrostatic repulsions among them. On the contrary, cationic CDs are distributed in the water phase among the droplets to reduce the water secretion and prevent flocculation and droplet coalescence. The stabilizing effect is found to be universal for emulsions of a range of oil phases. Furthermore, the formulated emulsion is found to be switchable between "stable" and "unstable" modes by adding an equivalent of anionic surfactant sodium dodecyl benzene sulphonate (SDBS). The stabilized and switchable O/W emulsions are believed to have wide practical applications in water purification, pharmaceuticals, protein recognition, as well as catalysis.

Histidine-Specific Peptide Modification via Visible-Light-Promoted C-H Alkylation.

Histidine (His) carries a unique heteroaromatic imidazole side chain and plays irreplaceable functional roles in peptides and proteins. Existing strategies for site-selective histidine modification predominantly rely on the N-substitution reactions of the moderately nucleophilic imidazole group, which inherently suffers from the interferences from lysine and cysteine residues. Chemoselective modification of histidine remains one of the most difficult challenges in peptide chemistry. Herein, we report peptide modification via radical-mediated chemoselective C-H alkylation of histidine using C4-alkyl-1,4-dihydropyridine (DHP) reagents under visible-light-promoted conditions. The method exploits the electrophilic reactivity of the imidazole ring via a Minisci-type reaction pathway. This method exhibits an exceptionally broad scope for both peptides and DHP alkylation reagents. Its utility has been demonstrated in a series of important peptide drugs, complex natural products, and a small protein. Distinct from N-substitution reactions, the unsubstituted nitrogen groups of the modified imidazole ring are conserved in the C-H alkylated products.

Socioeconomic disparities in prevalence, awareness, treatment, and control of hypertension over the life course in China.

BACKGROUND: The socioeconomically disadvantaged populations are more likely to suffer from hypertension, and few have effectively treated and controlled their hypertension. Research on socioeconomic disparities in prevalence, awareness, treatment, and control of hypertension is warranted to inform the development of new strategies for reducing such health inequities. METHODS: The China Health and Nutrition Survey (CHNS) followed up 20,174 individuals over a 20-year period. We added seven key socioeconomic indicators with age and age-squared into the mixed-effects models to explicitly assess the effect of socioeconomic determinants on hypertension throughout the adult life course. RESULTS: Prevalence of hypertension was at a higher level in the younger birth cohorts than that in the older generations. Age-related increases in prevalence, awareness, treatment, and control of hypertension were observed over the adult life course. Males, insured and ethnic Han were more likely to suffer from hypertension than their counterparts [coefficient (95% confidence intervals): 0.07(0.04, 0.09), 0.02(0.01, 0.03) and 0.05(0.03, 0.07), respectively]. Hypertension was more prevalent among individuals with higher income who lived in urbanized communities, and less among those with higher education attainment [coefficient (95% confidence intervals): -0.07(-0.12, -0.016)] across adulthood. High-level urbanization and education increased the probabilities of awareness, treatment, and control of hypertension, while household income decreased them [coefficient (95% confidence intervals): 0.28(0.17, 0.39), 0.27(0.17, 0.37) and 0.14(0.08, 0.21), respectively] over the adult life course. CONCLUSIONS: Community urbanicity brought the raise in awareness, treatment, and control of hypertension, but also led to an increase in prevalence of hypertension. People with fewer educational years or higher income may be the disadvantaged population of hypertension over the adult life course in China.

A Bioactive Injectable Hydrogel Regulates Tumor Metastasis and Wound Healing for Melanoma via NIR-Light Triggered Hyperthermia.

Surgical resection remains the mainstream treatment for malignant melanoma. However, challenges in wound healing and residual tumor metastasis pose significant hurdles, resulting in high recurrence rates in patients. Herein, a bioactive injectable hydrogel (BG-Mngel) formed by crosslinking sodium alginate (SA) with manganese-doped bioactive glass (BG-Mn) is developed as a versatile platform for anti-tumor immunotherapy and postoperative wound healing for melanoma. The incorporation of Mn2+ within bioactive glass (BG) can activate the cGAS-STING immune pathway to elicit robust immune response for cancer immunotherapy. Furthermore, doping Mn2+ in BG endows system with excellent photothermal properties, hence facilitating STING activation and reversing the tumor immune-suppressive microenvironment. BG exhibits favorable angiogenic capacity and tissue regenerative potential, and Mn2+ promotes cell migration in vitro. When combining BG-Mngel with anti-PD-1 antibody (α-PD-1) for the treatment of malignant melanoma, it shows enhanced anti-tumor immune response and long-term immune memory response. Remarkably, BG-Mngel can upregulate the expression of genes related to blood vessel formation and promote skin tissue regeneration when treating full-thickness wounds. Overall, BG-MnGel serves as an effective adjuvant therapy to regulate tumor metastasis and wound healing for malignant melanoma.

Unveiling a pH-Responsive Dual-Androgen-Blocking Magnetic Molecularly Imprinted Polymer for Enhanced Synergistic Therapy of Prostate Cancer.

Prostate cancer is the most common malignancy diagnosed in men. Androgens are directly related to its pathogenesis. Inhibition of the androgen receptor (AR) is considered to be the most promising therapeutic approach for the treatment of prostate cancer. In this study, a new type of pH-responsive dual androgen-blocking nanodrug (FASC MIPs) based on a molecularly imprinted polymer has been designed and synthesized. The nanodrug could selectively sequester testosterone from the prostate tumor through specific molecular imprinting sites and simultaneously deliver the AR inhibitory drug bicalutamide, which ultimately leads to enhanced synergistic therapy of prostate cancer. FASC MIPs demonstrate excellent pH responsiveness in a simulated tumor microenvironment due to the presence of chitosan and significantly inhibit the growth of prostate cancer cells (LNCaP cells) by blocking the G1 phase of cytokinesis. Additionally, the nanodrug also displayed excellent antitumor properties in a xenograft mouse model of prostate cancer without any sign of detrimental effects on healthy tissues and organs. Both in vitro and in vivo studies verified the augmented and synergistic therapeutic effects of FASC MIPs, and the proposed dual-androgen-blocking strategy could explore novel avenues in prostate cancer treatment.

Changes in α-Dicarbonyl Compound Contents during Storage of Various Fruits and Juices.

α-Dicarbonyl compounds (α-DCs) are commonly present in various foods. We conducted the investigation into concentration changes of α-DCs including 3-deoxyglucosone (3-DG), glyoxal (GO), and methylglyoxal (MGO) in fresh fruits and decapped commercial juices during storage at room temperature and 4 °C, as well as in homemade juices during storage at 4 °C. The studies indicate the presence of α-DCs in all samples. The initial contents of 3-DG in the commercial juices (6.74 to 65.61 µg/mL) are higher than those in the homemade ones (1.97 to 4.65 µg/mL) as well as fruits (1.58 to 3.33 µg/g). The initial concentrations of GO and MGO are normally less than 1 µg/mL in all samples. During storage, the α-DC levels in the fruits exhibit an initial increase followed by a subsequent decrease, whereas, in all juices, they tend to accumulate continuously over time. As expected, 4 °C storage reduces the increase rates of the α-DC concentrations in most samples. From the viewpoint of the α-DC contents, fruits and homemade juices should always be the first choice for daily intake of nutrients and commercial juices ought to be mostly avoided.

CSFV restricts necroptosis to sustain infection by inducing autophagy/mitophagy-targeted degradation of RIPK3.

IMPORTANCE: CSFV infection in pigs causes persistent high fever, hemorrhagic necrotizing multi-organ inflammation, and high mortality, which seriously threatens the global swine industry. Cell death is an essential immune response of the host against pathogen invasion, and lymphopenia is the most typical clinical feature in the acute phase of CSFV infection, which affects the initial host antiviral immunity. As an "old" virus, CSFV has evolved mechanisms to evade host immune response after a long genetic evolution. Here, we show that necroptosis is a limiting host factor for CSFV infection and that CSFV-induced autophagy can subvert this host defense mechanism to promote its sustained replication. Our findings reveal a complex link between necroptosis and autophagy in the process of cell death, provide evidence supporting the important role for CSFV in counteracting host cell necrosis, and enrich our knowledge of pathogens that may subvert and evade this host defense.

Determination of α-Dicarbonyl compounds in traditional Chinese herbal medicines.

α-DCs (α-dicarbonyls) have been proven to be closely related to aging and the onset and development of many chronic diseases. The wide presence of this kind of components in various foods and beverages has been unambiguously determined, but their occurrence in various phytomedicines remains in obscurity. In this study, we established and evaluated an HPLC-UV method and used it to measure the contents of four α-DCs including 3-deoxyglucosone (3-DG), glyoxal (GO), methylglyoxal (MGO), and diacetyl (DA) in 35 Chinese herbs after they have been derivatized with 4-nitro-1,2-phenylenediamine. The results uncover that 3-DG is the major component among the α-DCs, being detectable in all the selected herbs in concentrations ranging from 22.80 µg/g in the seeds of Alpinia katsumadai to 7032.75 µg/g in the fruit of Siraitia grosuenorii. The contents of the other three compounds are much lower than those of 3-DG, with GO being up to 22.65 µg/g, MGO being up to 55.50 µg/g, and DA to 18.75 µg/g, respectively. The data show as well the contents of the total four α-DCs in the herbs are generally in a comparable level to those in various foods, implying that herb medicines may have potential risks on human heath in view of the α-DCs.

CLK2 mediates IκBα-independent early termination of NF-κB activation by inducing cytoplasmic redistribution and degradation.

Activation of the NF-κB pathway is strictly regulated to prevent excessive inflammatory and immune responses. In a well-known negative feedback model, IκBα-dependent NF-κB termination is a delayed response pattern in the later stage of activation, and the mechanisms mediating the rapid termination of active NF-κB remain unclear. Here, we showed IκBα-independent rapid termination of nuclear NF-κB mediated by CLK2, which negatively regulated active NF-κB by phosphorylating the RelA/p65 subunit of NF-κB at Ser180 in the nucleus to limit its transcriptional activation through degradation and nuclear export. Depletion of CLK2 increased the production of inflammatory cytokines, reduced viral replication and increased the survival of the mice. Mechanistically, CLK2 phosphorylated RelA/p65 at Ser180 in the nucleus, leading to ubiquitin‒proteasome-mediated degradation and cytoplasmic redistribution. Importantly, a CLK2 inhibitor promoted cytokine production, reduced viral replication, and accelerated murine psoriasis. This study revealed an IκBα-independent mechanism of early-stage termination of NF-κB in which phosphorylated Ser180 RelA/p65 turned off posttranslational modifications associated with transcriptional activation, ultimately resulting in the degradation and nuclear export of RelA/p65 to inhibit excessive inflammatory activation. Our findings showed that the phosphorylation of RelA/p65 at Ser180 in the nucleus inhibits early-stage NF-κB activation, thereby mediating the negative regulation of NF-κB.

[Impact factors analysis of standardized perioperative antibiotic application on nosocomial infection and drug-resistance bacteria].

OBJECTIVE: To investigate the impact factors and clinical significance of standardized perioperative antibiotic application on nosocomial infection and drug-resistant bacteria strains in eye hospital. METHODS: It was a retrospective series case study. The inpatients underwent ophthalmologic operation of one year before standardized application (from Sep. 2009 to Aug. 2010) and one year after standardized application (from Sep. 2010 to Aug. 2011) in Tianjin Eye Hospital were selected and the incidence rate of nosocomial infection and types of drug-resistant strains in these two years were analyzed. RESULTS: From Sep. 2009 to Aug. 2010, the prophylactic antibiotics application rate for type I incisional surgeries was 80.29% (12937/16 111), the nosocomial infection rate was 0.011% (2/17 563). From Sep. 2010 to Aug. 2011, the same values were 44.50% (7968/17 905) and 0.005% (1/19 441). There was a significant decrease of prophylactic antibiotics application comparing these two years (χ(2) = 4587.78, P < 0.05). However, there was no significant difference in nosocomial infection rate (χ(2) = 0.44, P > 0.05). Average antibiotics application rate for inpatient (type I-IV incisional surgeries) was 76.69% (13 469/17 563) from Sep. 2009 to Aug. 2010, and 49.40% (9604/19 441) from Sep. 2010 to Aug. 2011. There was a significant decrease over these two years (χ(2) = 2927.19, P < 0.05). The results of isolation and cultivation of bacteria in these two years showed that staphylococcus epidermidis predominated in gram-positive bacteria, pseudomonas aeruginosa predominated in gram-negative bacteria. Drug resistance rate of staphylococcus was 42.86% (33/77) from Sep. 2009 to Aug. 2010 and 39.19% (39/74) from Sep. 2010 to Aug. 2011. Drug resistance rate of pseudomonas aeruginosa was 2/11 from Sep. 2009 to Aug. 2010 and 2/13 from Sep. 2010 to Aug. 2011. There were no significant differences in drug resistance rate of staphylococcus and pseudomonas aeruginosa between these two years (χ(2) = 0.09, P > 0.05, χ(2) = 0.03, P > 0.05). CONCLUSIONS: By standardizing the perioperative antibiotics application in eye hospital, the rate of systemic administration of antibiotics declined gradually. The Choices and the administrative mode of antibiotics were more rational than before. In the meanwhile, the rate of nosocomial infection and drug-resistance did not increase. Therefore, avoiding the drug abuse ensured the medical safety, which was worthy of further study.

Recombinant Porcine Interferon-α Decreases Pseudorabies Virus Infection.

Interferon (IFN) is a cell-secreted cytokine possessing biological activities including antiviral functioning, immune regulation, and others. Interferon-alpha (IFN-α) mainly derives from plasmacytoid dendritic cells, which activate natural killer cells and regulate immune responses. IFN-α responds to the primary antiviral mechanism in the innate immune system, which can effectively cure acute infectious diseases. Pseudorabies (PR) is an acute infectious disease caused by pseudorabies virus (PRV). The clinical symptoms of PRV are as follows: reproductive dysfunction among pregnant sows and high mortality rates among piglets. These pose a severe threat to the swine industry. Related studies show that IFN-α has broad applications in preventing and treating viral diseases. Therefore, a PRV mouse model using artificial infection was established in this study to explore the pathogenic effect of IFN-α on PRV. We designed a sequence with IFN-α4 (M28623, Genbank) and cloned it on the lentiviral vector. CHO-K1 cells were infected and identified using WB and RT-PCR; a CHO-K1 cell line with a stable expression of the recombinant protein PoIFN-α was successfully constructed. H&E staining and virus titer detection were used to investigate the recombinant protein PoIFN-α's effect on PR in BALB/c mice. The results show that the PoIFN-α has a preventive and therapeutic impact on PR. In conclusion, the recombinant protein can alleviate symptoms and reduce the replication of PRV in vivo.

USP14 promotes colorectal cancer progression by targeting JNK for stabilization.

MAPK/JNK signaling is pivotal in carcinogenesis. However, ubiquitin-mediated homeostasis of JNK remains to be verified. Here, with results from RNA sequencing (RNA-seq) and luciferase reporter pathway identification, we show that USP14 orchestrates MAPK/JNK signaling and identify USP14 as a deubiquitinase that interacts and stabilizes JNK. USP14 is elevated in colorectal cancer patients and is positively associated with JNK protein and downstream gene expression. USP14 ablation reduces cancer cell proliferation in vitro and colorectal tumorigenesis in vivo by downregulating MAPK/JNK pathway activation. Moreover, USP14 expression is induced by TNF-α, forming a feedback loop with JNK and leading to tumor amplification. Our study suggests that elevated expression of USP14 promotes MAPK/JNK signaling by stabilizing JNK, which in turn augments colorectal carcinogenesis, indicating a potential therapeutic target for colorectal cancer patients with increased USP14 expression.

Virus-like particle vaccines with epitopes from porcine epidemic virus and transmissible gastroenteritis virus incorporated into self-assembling ADDomer platform provide clinical immune responses in piglets.

Introduction: Porcine epidemic diarrhea virus (PEDV) and transmissible gastroenteritis virus (TGEV) are major intestinal coronaviruses that cause vomiting, diarrhea, dehydration, and mortality in piglets. These viruses coexist and lead to significant economic losses in the swine industry. Virus-like particles (VLPs) have emerged as promising alternatives to conventional inactivated vaccines due to their exceptional safety, efficacy, and ability to provide multi-disease protection with a single dose. Methods: Our study focused on specific antigenic epitopes from the PEDV S protein (SS2 and 2C10 regions) and the TGEV S protein (A and D sites) as target candidates. These epitopes were integrated into the ADDomer framework, and we successfully generated recombinant proteins AD, AD-P, AD-T, and AD-PT using the baculovirus expression vector system (BEVS). By meticulously optimizing conditions in High Five cells, we successfully expressed and purified the recombinant proteins. Subsequently, we developed the recombinant ADDomer-VLP vaccine and conducted a comprehensive evaluation of its efficacy in piglets. Results: Following ultrafiltration concentration and sucrose gradient centrifugation purification, the recombinant proteins self-assembled into VLPs as observed by transmission electron microscopy (TEM). Administration of the vaccine did not result in any adverse reactions in the immunized piglets. Additionally, no significant instances of fever were detected in any of the experimental groups, and there were no notable changes in average daily weight gain compared to the control group that received PBS. The recombinant ADDomer-VLP vaccines demonstrated strong immunogenicity, effectively stimulating the production of neutralizing antibodies against both PEDV and TGEV. Moreover, the recombinant ADDomer-VLP vaccine induced elevated levels of IFN-γ, IL-2, and IL-4, and enhanced cytotoxic T lymphocyte (CTL) activity in the peripheral blood of piglets. Discussion: These recombinant VLPs have demonstrated the ability to induce strong cellular and humoral immune responses in piglets, making them an incredibly promising platform for the rapid and simplified development of epitope vaccines.

Evolutionary dynamics and adaptive analysis of Seneca Valley virus.

Over the past 20 years, the Seneca Valley virus (SVV) has emerged in various countries and regions around the world. Infected pigs display symptoms similar to foot-and-mouth disease and other vesicular diseases, causing severe economic losses to affected countries. In recent years, the number of SVV infections has been increasing in Brazil, China, and the United States. In this study, we comprehensively analyzed SVV genomic sequence data from the perspectives of evolutionary dynamics, phylogeography, and codon usage bias. We aimed to gain further insights into SVV's genetic diversity, spatiotemporal distribution patterns, and evolutionary adaptations. Phylogenetic analysis revealed that SVV has evolved into eight distinct lineages. Based on the results of phylogeographic analysis, it is speculated that the United States might have been the source of SVV, from where it subsequently spread to different countries and regions. Moreover, our analysis of positive selection sites in SVV capsid proteins suggests their potential importance in the process of receptor recognition. Finally, codon preference analysis indicates that natural selection has been a primary evolutionary driver influencing SVV codon usage bias. In conclusion, our in-depth investigation into SVV's origin, dissemination, evolution, and adaptation emphasizes the significance of SVV surveillance and control measures.

Progranulin Promotes the Formation and Development of Capsules Caused by Silicone in Sprague-Dawley Rats.

Background: Silicone implants are currently the most widely used artificial materials in plastic surgery. Capsule formation following implant application is unavoidable. When the capsule is excessively thick and strongly contracted, it can lead to obvious symptoms, clinically known as capsular contracture. Biological factors have always been the focus of research on the capsule formation. As a growth factor, progranulin (PGRN) plays an important regulatory role in wound healing, tissue fibrosis, tumor proliferation and invasion, and inflammation regulation. At present, the research on the capsule mainly involves the regulation of tissue healing and fibrosis under the influence of inflammation. Because PGRN has a regulatory role in these processes, we believe that the study of both can provide a new theoretical basis and intervention sites for monitoring and inhibiting the development of the capsule. Methods: In this experiment, the effects of different surgical operations on the content of PGRN in the surgical site and plasma of rats were detected. Sprague-Dawley (SD) rat dermal fibroblasts were co-cultured by recombinant PGRN. The effects of r-PGRN on fibroblasts were detected by 5-ethynyl-2'-deoxyuridine (EdU) assay, wound healing assay and Western blot assay. Finally, the effect of PGRN on capsule formation and contracture was studied by changing the content of PGRN in the prosthesis in rats after operation. Results: Surgical trauma and silicone implant increased plasma and local PGRN levels in SD rats. PGRN can activate the TGF-ß/SMAD signaling pathway in a dose-dependent manner, thereby promoting fibroblast proliferation, differentiation and migration and inhibiting apoptosis and enhancing cell function, thereby promoting capsule formation and contracture. Conclusion: PGRN promotes the formation and contracture of the silicone implant capsule in SD rats by activating the TGF-ß/SMAD signaling pathway. This discovery may provide new therapeutic targets and detection indicators.

Efficient decolorization of azo dye wastewater with polyaniline/graphene modified anode in microbial electrochemical systems.

Azo dye pollution has become a worldwide issue, and the current treatment methods can hardly meet the expected emission standards. Microbial electrochemical systems (MESs) show promising applications for decolorization, but their performance critically depends on the microorganisms. Electrode modification is an interesting method of improving decolorization performance. However, the mechanisms of how the modification can affect microbial communities and the decolorization process remain unclear. Here, a modified anode with polyaniline (PANI) and graphene was fabricated via electro-deposition. Consequently, the highest decolorization efficiency was obtained. The Congo red (CR) decolorization rate of the MESs with the PANI/graphene-modified electrode (PG) reached 90% at 54 h. By contrast, the CR decolorization rates of the MESs with the PANI-modified electrode (P) and those of the MESs with the unmodified electrode (C) only reached 68% and 79%, respectively. Results of the microbial community analysis showed abundant Methanobrevibacter arboriphilus in PG (11%), which was 5.5 times that in C (2%) at 18 h. This phenomenon may be related to the rapid decolorization. The upregulated metabolism pathways, including arginine and proline metabolism, purine metabolism, arginine biosynthesis, and riboflavin metabolism, provided more electron shuttles and redox mediators that facilitated the extracellular electron transfer. Therefore, the PG-modified electrode facilitated the decolorization by altering certain metabolic pathways. This study can help to improve the guideline on the potential application of MESs for wastewater treatment.