Identification of Key lncRNAs in Gout Under Copper Death and Iron Death Mechanisms: A Study Based on ceRNA Network Analysis and Random Forest Algorithm.

This study focused on identifying potential key lncRNAs associated with gout under the mechanisms of copper death and iron death through ceRNA network analysis and Random Forest (RF) algorithm, which aimed to provide new insights into the molecular mechanisms of gout, and potential molecular targets for future therapeutic strategies of gout. Initially, we conducted an in-depth bioinformatics analysis of gout microarray chips to screen the key cuproptosis-related genes (CRGs) and key ferroptosis-related genes (FRGs). Using these data, we constructed a key ceRNA network for gout. Finally, key lncRNAs associated with gout were identified through the RF algorithm combined with ROC curves, and validated using the Comparative Toxicogenomics Database (CTD). We successfully identified NLRP3, LIPT1, and DBT as key CRGs associated with gout, and G6PD, PRKAA1, LIG3, PHF21A, KLF2, PGRMC1, JUN, PANX2, and AR as key FRGs associated with gout. The key ceRNA network identified four downregulated key lncRNAs (SEPSECS-AS1, LINC01054, REV3L-IT1, and ZNF883) along with three downregulated mRNAs (DBT, AR, and PRKAA1) based on the ceRNA theory. According to CTD validation inference scores and biological functions of target mRNAs, we identified a potential gout-associated lncRNA ZNF883/hsa-miR-539-5p/PRKAA1 regulatory axis. This study identified the key lncRNA ZNF883 in the context of copper death and iron death mechanisms related to gout for the first time through the application of ceRNA network analysis and the RF algorithm, thereby filling a research gap in this field and providing new insights into the molecular mechanisms of gout. We further found that lncRNA ZNF883 might function in gout patients by regulating PRKAA1, the mechanism of which was potentially related to uric acid reabsorption in the proximal renal tubules and inflammation regulation. The proposed lncRNA ZNF883/hsa-miR-539-5p/PRKAA1 regulatory axis might represent a potential RNA regulatory pathway for controlling the progression of gout disease. This discovery offered new molecular targets for the treatment of gout, and had significant implications for future therapeutic strategies in managing the gout.

Clinical Trial Inclusion and Impact on Early Adoption of Medical Innovation in Diverse Populations.

BACKGROUND: Inadequate inclusion in clinical trial enrollment may contribute to health inequities by evaluating interventions in cohorts that do not fully represent target populations. OBJECTIVES: The aim of this study was to determine if characteristics of patients with heart failure (HF) enrolled in a pivotal trial are associated with who receives an intervention after approval. METHODS: Demographics from 2,017,107 Medicare patients hospitalized for HF were compared with those of the first 10,631 Medicare beneficiaries who received implantable pulmonary artery pressure sensors. Characteristics of the population studied in the pivotal CHAMPION (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients) clinical trial (n = 550) were compared with those of both groups. All demographic data were analyzed nationally and in 4 U.S. regions. RESULTS: The Medicare HF cohort included 80.9% White, 13.3% African American, 1.9% Hispanic, 1.3% Asian, and 51.5% female patients. Medicare patients <65 years of age were more likely to be African American (33%) and male (58%), whereas older patients were mostly White (84%) and female (53%). Forty-one percent of U.S. HF hospitalizations occurred in the South; demographic characteristics varied significantly across all U.S. regions. The CHAMPION trial adequately represented African Americans (23% overall, 35% <65 years of age), Hispanic Americans (2%), and Asian Americans (1%) but underrepresented women (27%). The trial's population characteristics were similar to those of the first patients who received pulmonary artery sensors (82% White, 13% African American, 1% Asian, 1% Hispanic, and 29% female). CONCLUSIONS: Demographics of Centers for Medicare and Medicaid Services beneficiaries hospitalized with HF vary regionally and by age, which should be considered when defining "adequate" representation in clinical studies. Enrollment diversity in clinical trials may affect who receives early application of recently approved innovations.

Efficacy comparison between acupuncture and other modalities in the treatment of rotator cuff diseases: meta-analysis of randomized controlled trials.

OBJECTIVE: This study aimed to analyze the efficacy of acupuncture alone or combined with physical therapy compared to other treatment interventions for relieving pain and improving function in rotator cuff diseases. METHODS: Our study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. After PROSPERO (CRD42023396740) registration, all randomized controlled trials (RCTs) published from the inception of the databases to October 10, 2023, evaluating the efficacy of acupuncture either alone or in combination with physical therapy for treating rotator cuff diseases, were extracted from seven databases, including PubMed, Embase, the Web of Science, the Cochrane Library, the China National Knowledge Infrastructure (CNKI), the VIP Database for Chinese Technical Periodicals (VIP), and the Wanfang Date. Two independent researchers assessed the quality of the included studies and extracted relevant data. Furthermore, a meta-analysis was conducted using Stata 14 software. RESULTS: We included 13 RCTs - 12 published in English and 1 in Chinese - that enrolled 1,371 patients. The meta-analysis results demonstrated that acupuncture alone or in combination with physical therapy was superior to other interventions for short-term shoulder joint function improvement (standardized mean difference [SMD] = -0.82, 95% confidence interval [95% CI]: -1.28 to -0.35, P = 0.001), medium-term shoulder joint function improvement (SMD = -1.00, 95% CI: -1.62 to -0.38, P = 0.002), short-term pain relief (weighted mean difference [WMD] = -1.37, 95% CI: -2.39 to -0.38, P = 0.006), medium-term pain relief (WMD = -1.66, 95% CI: -2.70 to -0.63, P = 0.002), and post-treatment shoulder joint abduction improvements (SMD = 0.68, 95% CI: 0.20 to 1.16, P = 0.005), external rotation (SMD = 0.62, 95% CI: 0.13 to 1.11, P = 0.012), and forward flexion (SMD = 0.71, 95% CI: 0.44 to 0.97, P < 0.001), with significant differences (P < 0.05). CONCLUSION: Based on the current clinical data, meta-analysis showed that acupuncture alone or combined with physical therapy is efficacious for short- and medium-term (< 3 months) pain relief and functional improvements. However, compared to other interventions, the efficacy of the long-term (3 to 12 months) period did not significantly differ. After treatment, these modalities displayed advantages such as improved shoulder joint abduction, external rotation, and forward flexion movements. However, no significant difference was noted in internal rotation movement. Thus, future studies might further investigate whether different acupuncture methods affect the efficacy of treating rotator cuff diseases and improving long-term outcome.

METTL3 knockdown suppresses RA-FLS activation through m6A-YTHDC2-mediated regulation of AMIGO2.

The dysregulation of N6-methyladenosine (m6A) on mRNAs is involved in the pathogenesis of rheumatoid arthritis (RA). Methyltransferase-like 3 (METTL3), serving as a central m6A methyltransferase, is highly expressed in macrophages, synovial tissues and RA fibroblast-like synoviocytes (RA-FLS) of RA patients. However, METTL3-mediated m6A modification on target mRNAs and the molecular mechanisms involved in RA-FLS remain poorly defined. Our research demonstrated that METTL3 knockdown decreased the proliferation, migratory and invasive abilities of RA-FLS. Notably, we identified the adhesion molecule with Ig like domain 2 (AMIGO2) as a probable downstream target of both METTL3 and YTH Domain Containing 2 (YTHDC2) in RA-FLS. We revealed that AMIGO2 augmented the activation of RA-FLS and can potentially reverse the phenotypic effects induced by the knockdown of either METTL3 or YTHDC2. Mechanistically, METTL3 knockdown decreased m6A modification in the 5'-untranslated region (5'UTR) of AMIGO2 mRNA, which diminished its interaction with YTHDC2 in RA-FLS. Our findings unveiled that silencing of METTL3 inhibited the proliferation and aggressive behaviors of RA-FLS by downregulating AMIGO2 expression in an m6A-YTHDC2 dependent mechanism, thereby underscoring the pivotal role of the METTL3-m6A-YTHDC2-AMIGO2 axis in modulating RA-FLS phenotypes.

Engineered Saccharomyces cerevisiae harbors xylose isomerase and xylose transporter improves co-fermentation of xylose and glucose for ethanol production.

Saccharomyces cerevisiae cannot assimilate xylose, second to glucose derived from lignocellulosic biomass. Here, the engineered S. cerevisiae strains INVSc-XI and INVSc-XI/XT were constructed using xylA and Xltr1p to co-utilize xylose and glucose, achieving economic viability and sustainable production of fuels. The xylose utilization rate of INVSc-XI/XT was 2.3-fold higher than that of INVSc-XI, indicating that overexpressing Xltr1p could further enhance xylose utilization. In mixed sugar media, a small amount of glucose enhanced the consumption of xylose by INVSc-XI/XT. Transcriptome analysis showed that glucose increased the upregulation of acetate of coenzyme A synthetase (ACS), alcohol dehydrogenase (ADH), and transketolase (TKL) gene expression in INVSc-XI/XT, further promoting xylose utilization and ethanol yield. The highest ethanol titer of 2.91 g/L with a yield of 0.29 g/g at 96 h by INVSc-XI/XT was 56.9% and 63.0% of the theoretical ethanol yield from glucose and xylose, respectively. These results showed overexpression of xylA and Xltr1p is a promising strategy for improving xylose and glucose conversion to ethanol. Although the ability of strain INVSc-XI/XT to produce ethanol was not very satisfactory, glucose was discovered to influence xylose utilization in strain INVSc-XI/XT. Altering the glucose concentration is a promising strategy to improve the xylose and glucose co-utilization.

INVSc-XI and INVSc-XI/XT strains were newly constructed to utilize xylose and glucose.XylA, in combination with xylose transporter Xltr1p, enhances xylose consumption.A small amount of glucose enhanced xylose utilization in INVSc-XI/XT strain.The expression of ACS, ADH, and TKL genes is upregulated in the media containing mixed sugars.The highest ethanol yield of 0.29 g/g was produced in a 2-L scale-up fermenter.

The role of basic leucine zipper transcription factor E4BP4 in cancer: a review and update.

Mutations in the genes of tumor cells and the disorder of immune microenvironment are the main factors of tumor development. The sensitivity of tumor cells to chemotherapy drugs affect the treatment of tumor. Nuclear transcription factor E4BP4 is dysregulated in a variety of malignant tumors. It can suppress the transcription of NFKBIA, RASSF8, SOSTDC1, FOXO-induced genes (TRAIL, FAS, GADD45a and GADD45b) and Hepcidin, up-regulate RCAN1-1 and PRNP, activate mTOR and p38 in cancer cells. Also, E4BP4 can regulate tumor immune microenvironment. TGFb1/Smad3/E4BP4/ IFNγ axis in NK cells plays an important role in antitumor immunotherapy. Over expression of E4BP4 inhibited the development of Th17 cells by directly binding to the RORγt promoter. Moreover, recent studies have shown that E4BP4 inhibited the expression of multidrug resistance genes. In this review, we summarize the molecular mechanism of E4BP4 in cancer cellular process, the effects of E4BP4 in cancer immunotherapy and antitumor drug resistance, to provide theoretical basis for tumor treatment strategies targeting E4BP4.

Proteomic investigation reveals the role of bacterial laccase from Bacillus pumilus in oxidative stress defense.

The wide distribution of laccases in nature makes them involved in different biological processes. However, little information is known about how laccase participates in the defense machinery of bacteria against oxidative stress. The present study aimed to elucidate the oxidative stress response mechanism of Bacillus pumilus ZB1 and the functional role of bacterial laccase in stress defense. The oxidative stress caused by methyl methanesulfonate (MMS) significantly induced laccase activity and its transcript level. The morphological analysis revealed that the defense of B. pumilus ZB1 against oxidative stress was activated. Based on the proteomic study, 114 differentially expressed proteins (DEPs) were up-regulated and 79 DEPs were down-regulated. In COG analysis, 66.40% DEPs were classified into the category "Metabolism". We confirmed that laccase was up-regulated in response to MMS stress and its functional annotation was related to "Secondary metabolites biosynthesis, transport and catabolism". Based on protein-protein interaction prediction, two up-regulated DEPs (YcnJ and GabP) showed interaction with laccase and contributed to the formation of laccase stability and adaptability. The overexpressed laccase might improve the antioxidative property of B. pumilus ZB1. These findings provide an insight and the guidelines for better exploitation of bioremediation using bacterial laccase. SIGNIFICANCE: Bacillus pumilus is a gram-positive bacterium that has the potential for many applications, such as bioremediation. The expression of bacterial laccase is significantly influenced by oxidative stress, while the underlying mechanism of laccase overexpression in bacteria has not been fully studied. Elucidation of the biological process may benefit the bioremediation using bacteria in the future. In this study, the differentially expressed proteins were analyzed using a TMT-labeling proteomic approach when B. pumilus was treated with methyl methanesulfonate (MMS). Reactive oxygen species induced by MMS activated the secondary metabolites biosynthesis, transport, and catabolism in B. pumilus, including laccase overexpression. Moreover, the simultaneously up-regulated YcnJ and GabP may benefit the synthesis and the stability of laccase, then improve the antioxidative property of B. pumilus against environmental stress. Our findings advance the understanding of the adaptive mechanism of B. pumilus to environmental conditions.

Metal-Organic Framework-Mediated Synergistic Hypoxia-Activated Chemo-Immunotherapy Induced by High Intensity Focused Ultrasound for Enhanced Cancer Theranostics.

High intensity focused ultrasound (HIFU) has attracted considerable attention as a noninvasive, efficient, and economic therapeutic modality for solid tumors. However, HIFU surgery has its intrinsic limitation in completely ablating tumors, leading to residual tumor tissue. Furthermore, the severely hypoxic environment ensuring after surgery can exacerbate the unrestricted proliferation and metabolism of residual tumor cells, leading to tumor recurrence and metastasis. To address these limitations, a versatile HIFU-specific metal-organic framework nanosystem (called ADMOFs) is developed by coordinating hypoxia-activated prodrug AQ4N, Mn2+ , and DOX based on the postoperative response to changes in the tumor microenvironment. ADMOFs loaded with AQ4N/Mn2+ exhibited remarkable tumor-targeting behavior in vivo and enhanced photoacoustic/magnetic resonance imaging effects, enabling more accurate guidance for HIFU surgery. After surgery, the ADMOFs exploited the severely hypoxic tumor environment induced by HIFU, overcoming hypoxia-associated drug resistance, and inducing immunogenic cell death. Finally, it effectively inhibited tumor growth and eliminated lung metastasis. Transcriptome studies revealed that this strategy significantly up-regulated genes involved in apoptosis, cell cycle, and HIF-1 signaling pathway while downregulating genes related to tumor proliferation and metastasis. These findings suggest that combining hypoxia-activated chemo-immunotherapy with HIFU is a promising strategy for enhancing cancer theranostics.

Celastrol suppresses human pancreatic cancer via m6A-YTHDF3-mediated downregulation of Claspin and Bcl-2.

BACKGROUND: Celastrol has been revealed to exhibit anticancer pharmacological activity, however, the molecular mechanisms of celastrol involved in pancreatic cancer remain to be further elucidated. The present study was to illustrate whether celastrol suppresses pancreatic cancer through modulating RNA m6A modification. METHODS: Effect of celastrol treatment on the malignant phenotypes of pancreatic cancer cells was evaluated by CCK-8 assay, EdU assay, colony formation assay, flow cytometry analysis and subcutaneous xenograft experiments. RNA sequencing (RNA-seq) analysis was carried out to analyze the genes differentially expressed in celastrol-treated pancreatic cancer cells. RT-qPCR, Western blotting and immunohistochemistry were employed to evaluate the expression of the indicated genes. RNA dot blot and quantification of total RNA m6A modification assays, MeRIP-qPCR assay, RIP-qPCR assay, RNA stability and protein stability assays were applied to evaluate the regulatory mechanism of celastrol treatment in pancreatic cancer cells. RESULTS: We demonstrated that celastrol suppressed cell proliferation and induced cell cycle arrest and apoptosis of pancreatic cancer cells in vitro, and decreased tumor growth in vivo. Specifically, Bcl-2, Claspin, METTL3 and YTHDF3 were identified as the potential targets of celastrol treatment in pancreatic cancer cells. Moreover, our results indicated that celastrol treatment downregulated METTL3 and decreased m6A levels of Claspin and Bcl-2 mRNA, leading to the degradation of Claspin and Bcl-2 mRNA in pancreatic cancer cells. Furthermore, we revealed that celastrol treatment downregulated Claspin and Bcl-2, at least in part, in an m6A-YTHDF3-mediated manner in pancreatic cancer cells. CONCLUSION: Our study highlighted a novel mechanism underlying celastrol-induced cellular proliferation inhibition and apoptosis in pancreatic cancer cells via m6A-YTHDF3-mediated downregulation of Claspin and Bcl-2.

Pediatric tuina for recurrent respiratory tract infection in children: A systematic review and meta-analysis.

BACKGROUND: To evaluate the effects and safety of pediatric tuina for recurrent respiratory tract infections (RRTIs). METHODS: Web of Science, PubMed, Cochrane Library, Embase, CNKI, Wanfang Data, VIP, and CBM databases were searched from inception to September 20 2023. Two authors independently selected studies, collected data, and evaluated methodological quality using the Cochrane Risk of Bias tool. Revman 5.4 was used for the meta-analysis. RESULTS: Fifteen randomized controlled trials involving 1420 pediatric patients were included in this meta-analysis. The meta-analysis indicated that pediatric tuina significantly reduced the incidence of RRTIs [MD -1.11, 95% confidence interval (CI) (-1.77, -0.46)], decreased infection duration (MD -1.16 days, 95% CI [- 1.66, - 0.66]), improved IgA (MD 0.25 g/L, 95% CI [0.09, 0.41]), IgG (MD 1.64 g/L; 95% CI [0.82, 2.45]), CD3+ (MD 3.33%, 95% CI [0.74, 5.92]), CD4+ (MD 4.78%, 95% CI [2.08, 7.48]), CD4+/CD8+ ratio (MD 0.27%, 95% CI [0.08, 0.47]), and total effective rate (RR 1.19, 95% CI [1.13, 1.25]). However, IgM levels (MD 0.26 g/L, 95% CI [-0.26, 0.81]) and CD8+ (MD -1.36%, 95% CI [- 3.12, 0.41]) were not significantly different between the groups. Moreover, no Tuina-linked adverse reactions were observed. CONCLUSION: Pediatric tuina has shown positive effects in RRTIs treatment. However, these results should be interpreted with caution owing to study quality. Further large-scale and high-quality randomized controlled trials are warranted to confirm these findings.

Progress of Conjugated Linoleic Acid on Milk Fat Metabolism in Ruminants and Humans.

As a valuable nutrient in milk, fat accounts for a significant proportion of the energy requirements of ruminants and is largely responsible for determining milk quality. Fatty acids (FAs) are a pivotal component of milk fat. Conjugated linoleic acid (CLA) is one of the naturally occurring FAs prevalent in ruminant dairy products and meat. Increasing attention has been given to CLA because of its anti-cancer, anti-inflammatory, immune regulation, and lipid metabolism regulation properties, and these benefits potentially contribute to the growth and health of infants. In breast milk, CLA is present in trace amounts, mainly in the form of cis-9, trans-11 CLA. Notably, cis-9, trans-11 CLA improves the milk fat rate while trans-10, cis-12 CLA inhibits it. Apart from having multiple physiological functions, CLA is also a pivotal factor in determining the milk quality of ruminants, especially milk fat rate. In response to growing interest in green and healthy functional foods, more and more researchers are exploring the potential of CLA to improve the production performance of animals and the nutritional value of livestock products. Taken together, it is novel and worthwhile to investigate how CLA regulates milk fat synthesis. It is the purpose of this review to clarify the necessity for studying CLA in ruminant milk fat and breast milk fat.

Mutational antigenic landscape of prevailing H9N2 influenza virus hemagglutinin spectrum.

H9N2 influenza viruses are globally endemic in birds, and a sharp increase in human infections with H9N2 occurred during 2021 to 2022. In this study, we assess the antigenic and pathogenic impact of 23 hemagglutinin (HA) amino acid mutations. Our study reveals that three specific mutations, labeled R164Q, N166D, and I220T, are responsible for the binding of antibodies with escape mutations. Variants containing R164Q and I220T mutations increase viral replication in avian and mammalian cells. Furthermore, T150A and I220T mutations are found to enhance viral replication in mice, indicating that these mutations may have the potential to adapt mammals. Structure analysis reveals that residues 164 and 220 bearing R164Q and I220T mutations increase interactions with the surrounding residues. Our findings enrich current knowledge about the risk assessment regarding which predominant HA immune-escape mutations of H9N2 viruses may pose the greatest threat to the emergence of pandemics in birds and humans.

Effective biosynthesis of 2,5-furandicarboxylic acid from 5-hydroxymethylfurfural via a bi-enzymatic cascade system using bacterial laccase and fungal alcohol oxidase.

BACKGROUND: As a cost-effective and eco-friendly approach, biocatalysis has great potential for the transformation of 5-hydroxymethylfurfural (HMF) into 2,5-furandicarboxylic acid (FDCA). However, the compatibility of each enzyme in the cascade reaction limits the transformation efficiency of HMF to FDCA. RESULTS: Coupled with an alcohol oxidase from Colletotrichum gloeosporioides (CglAlcOx), this study aims to study the potential of bacterial laccase from Bacillus pumilus (BpLac) in an enzymatic cascade for 2,5-furandicarboxylic acid (FDCA) biosynthesis from 5-hydroxymethylfurfural (HMF). BpLac showed 100% selectivity for HMF oxidation and generated 5-hydroxymethyl-2-furancarboxylic acid (HMFCA). CglAlcOx was capable of oxidizing HMFCA to 2-formyl-5-furancarboxylic acid (FFCA). Both BpLac and CglAlcOx could oxidize FFCA to FDCA. At the 5 mM scale, a complete transformation of HMF with a 97.5% yield of FDCA was achieved by coupling BpLac with CglAlcOx in the cascade reaction. The FDCA productivity in the reaction was 5.3 mg/L/h. Notably, BpLac could alleviate the inhibitory effect of FFCA on CglAlcOx activity and boost the transformation efficiency of HMF to FDCA. Moreover, the reaction was scaled up to 40 times the volume, and FDCA titer reached 2.6 mM with a yield of 58.77% at 168 h. CONCLUSIONS: This work provides a candidate and novel insight for better design of an enzymatic cascade in FDCA production.

Mechanism of transforming growth factor-ß1 induce renal fibrosis based on transcriptome sequencing analysis. / åŸºäºŽè½¬å½•ç»„æµ‹åºåˆ†æžè½¬åŒ–ç”Ÿé•¿å› å­-ß1诱导肾纤维化机制.

OBJECTIVES: To explore the mechanism of transforming growth factor-ß1 (TGF-ß1) induce renal fibrosis. METHODS: Renal fibroblast NRK-49F cells treated with and without TGF-ß1 were subjected to RNA-seq analysis. DESeq2 was used for analysis. Differentially expressed genes were screened with the criteria of false discovery rate<0.05 and l o g 2 F C >1. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for differentially expressed genes. Genes encoding transcription factors were further screened for differential expression genes. Then, the expression of these genes during renal fibrosis was verified using unilateral ureteral obstruction (UUO)-induced mouse renal fibrosis model and a public gene expression dataset (GSE104954). RESULTS: After TGF-ß1 treatment for 6, 12 and 24 h, 552, 1209 and 1028 differentially expressed genes were identified, respectively. GO analysis indicated that these genes were significantly enriched in development, cell death, and cell migration. KEGG pathway analysis showed that in the early stage of TGF-ß1 induction (TGF-ß1 treatment for 6 h), the changes in Hippo, TGF-ß and Wnt signaling pathways were observed, while in the late stage of TGF-ß1 induction (TGF-ß1 treatment for 24 h), the changes of extracellular matrix-receptor interaction, focal adhesion and adherens junction were mainly enriched. Among the 291 up-regulated differentially expressed genes treated with TGF-ß1 for 6 h, 13 genes (Snai1, Irf8, Bhlhe40, Junb, Arid5a, Vdr, Lef1, Ahr, Foxo1, Myc, Tcf7, Foxc2, Glis1) encoded transcription factors. Validation in a cell model showed that TGF-ß1 induced expression of 9 transcription factors (encoded by Snai1, Irf8, Bhlhe40, Junb, Arid5a, Vdr, Lef1, Myc, Tcf7), while the expression levels of the other 4 genes did not significantly change after TGF-ß1 treatment. Validation results in UUO-induced mouse renal fibrosis model showed that Snai1, Irf8, Bhlhe40, Junb, Arid5a, Myc and Tcf7 were up-regulated after UUO, Vdr was down-regulated and there was no significant change in Lef1. Validation based on the GSE104954 dataset showed that IRF8 was significantly overexpressed in the renal tubulointerstitium of patients with diabetic nephropathy or IgA nephropathy, MYC was highly expressed in diabetic nephropathy, and the expressions of the other 7 genes were not significantly different compared with the control group. CONCLUSIONS: TGF-ß1 induces differentially expressed genes in renal fibroblasts, among which Irf8 and Myc were identified as potential targets of chronic kidney disease and renal fibrosis.

Phase coupling of acoustic and optical modes in antiferromagnetic materials CrCl3.

In layered antiferromagnetic material CrCl3, due to the antiferromagnetic coupling between two magnetic sublattices, there are two antiferromagnetic resonance modes, called acoustic mode with in-phase precession and optical mode with out-of-phase precession. By using Landau-Lifshitz-Gilbert equation, we study the magnetization dynamics of the two sublattices in CrCl3. A coupling resonance mode appears at the coupling point when the acoustic and optical magnon modes are tuned by an applied magnetic field, which is called 'coupling mode'. In this paper, we present an explanation for the coupling of the acoustic and the optical mode. Our calculation shows that the coupling of the acoustic and optical mode is accomplished by change of the precession phase-difference between two magnetic sublattices.

Effective biodegradation of chlorophenols, sulfonamides, and their mixtures by bacterial laccase immobilized on chitin.

Coexisting multi-pollutants like sulfonamides (SAs) and chlorophenols (CPs) in the ecological environment pose a potential risk to living organisms. The development of a strategy for the effective removal of multiple pollutants has become an urgent need. Herein, we systematically investigated the potential of immobilized bacterial laccase to remove chlorophenols (CPs), sulfonamides (SAs), and their mixtures. Laccase from Bacillus pumilus ZB1 was efficiently immobilized on chitin and its thermal stability, pH stability, and affinity to substrates were improved. Reusability assessment showed the immobilized laccase retained 75.5% of its initial activity after five cycles. The removal efficiency of CPs and SAs by immobilized laccase was significantly improved compared with that of free laccase. In particular, the removal of 2,4-dichlorophenol and 2,4,6-trichlorophenol reached 96.9% and 89.3% respectively within 8 h. The immobilized laccase could remove 63.70% of 2,4-dichlorophenol after four cycles. The degradation pathways of 2,4-dichlorophenol and sulfamethazine were proposed via LC/MS analysis. When the co-pollutants containing 2,4,6-trichlorophenol and sulfamethoxazole, immobilized laccase showed 100% removal of 2,4,6-trichlorophenol and 38.71% removal of sulfamethoxazole simultaneously. Cytotoxicity and phytotoxicity tests indicated that immobilized laccase can alleviate the toxicity of co-pollutants. The results demonstrate that chitin-based laccase immobilization can be an effective strategy for the removal of SAs, CPs, and their co-pollutants.

Stationary Charge Radiation in Anisotropic Photonic Time Crystals.

Time metamaterials offer a great potential for wave manipulation, drawing increasing attention in recent years. Here, we explore the exotic wave dynamics of an anisotropic photonic time crystal (APTC) formed by an anisotropic medium whose optical properties are uniformly and periodically changed in time. Based on a temporal transfer matrix formalism, we show that a stationary charge embedded in an APTC emits radiation, in contrast to the case of isotropic photonic time crystals, and its distribution in momentum space is controlled by the APTC band structure. Our approach extends the functionalities of time metamaterials, offering new opportunities for radiation generation and control, with implications for both classical and quantum applications.

USP1-Associated Factor 1 Modulates Japanese Encephalitis Virus Replication by Governing Autophagy and Interferon-Stimulated Genes.

Japanese encephalitis virus (JEV) is a typical mosquito-borne flavivirus that can cause central nervous system diseases in humans and animals. Host factors attempt to limit virus replication when the viruses invade the host by using various strategies for replication. It is essential to clarify the host factors that affect the life cycle of JEV and explore its underlying mechanism. Here, we found that USP1-associated factor 1 (UAF1; also known as WD repeat-containing protein 48) modulated JEV replication. We found that JEV propagation significantly increased in UAF1-depleted Huh7 cells. Moreover, we found that knockdown of UAF1 activated cell autophagic flux in further functional analysis. Subsequently, we demonstrated that autophagy can be induced by JEV, which promotes viral replication by inhibiting interferon-stimulated gene (ISG) expression in Huh7 cells. The knockdown of UAF1 reduced ISG expression during JEV infection. To explore the possible roles of autophagy in UAF1-mediated inhibition of JEV propagation, we knocked out ATG7 to generate autophagy-deficient cells and found that depletion of UAF1 failed to promote JEV replication in ATG7 knockout cells. Moreover, in ATG7-deficient Huh7 cells, interference with UAF1 expression did not lead to the induction of autophagy. Taken together, these findings indicate that UAF1 is a critical regulator of autophagy and reveal a mechanism by which UAF1 knockdown activates autophagy to promote JEV replication. IMPORTANCE Host factors play an essential role in virus replication and pathogenesis. Although UAF1 is well known to form complexes with ubiquitin-specific proteases, little is known about the function of the UAF1 protein itself. In this study, we confirmed that UAF1 is involved in JEV replication. Notably, we discovered a novel function for UAF1 in regulating autophagy. Furthermore, we demonstrated that UAF1 modulated JEV replication through its autophagy regulation. This study is the first description of the novel function of UAF1 in regulating autophagy, and it clarifies the underlying mechanism of the antiviral effect of UAF1 against JEV. These results provide a new mechanistic insight into the functional annotation of UAF1 and provide a potential target for increasing virus production during vaccine production.

DnRCNN: Deep Recurrent Convolutional Neural Network for HSI Destriping.

In spite of achieving promising results in hyperspectral image (HSI) restoration, deep-learning-based methodologies still face the problem of spectral or spatial information loss due to neglecting the inner correlation of HSI. To address this issue, we propose an innovative deep recurrent convolution neural network (DnRCNN) model for HSI destriping. To the best of our knowledge, this is the first study on HSI destriping from the perspective of inner band and interband correlation explorations with the recurrent convolution neural network. In the novel DnRCNN, a selective recurrent memory unit (SRMU) is designed to respectively extract the correlative features involved in spectral and spatial domains. Moreover, an innovative recurrent fusion (RF) strategy incorporated with group concatenation is further proposed to remove strip noise and preserve scene details using the complementary features from SRMU. Experimental results on extensive HSI datasets validated that the proposed method achieves a new state-of-the-art (SOTA) HSI destriping performance.

Deciphering the alkaline stable mechanism of bacterial laccase from Bacillus pumilus by molecular dynamics simulation can improve the decolorization of textile dyes.

Laccases are considered promising tools for removing synthetic dyes from textile and tannery effluents. However, the alkaline pH in the effluents causes laccase instability, inactivation, and difficulty in its bioremediation. Based on a Bacillus pumilus ZB1 (BpLac) derived alkaline stable laccase, this study aimed to elucidate its alkaline stable mechanism at molecular level using molecular dynamics simulation. The effects of metal ions, organic solvents, and inhibitors on BpLac activity were assessed. BpLac formed more salt bridges and negatively charged surface in alkaline environment. Thereafter, pH-induced conformation changes were analyzed using GROMACS at pH 5.0 and 10.0. Among the identified residues with high fluctuation, the distance between Pro359 and Thr414 was stable at pH 10.0 but highly variable at pH 5.0. DSSP analysis suggested that BpLac formed more ß-sheet and less coil at pH 10.0. Principal component analysis and free energy landscape indicated that irregular coils formed at pH 5.0 benefit for activity, while rigid α-helix and ß-sheet structures formed at pH 10.0 contributed to alkaline stability. Breaking the α-helix near T1 copper center would not reduce alkaline stability but could improve dye decolorization by BpLac. Overall, these findings would advance the potential application of bacterial laccase in alkaline effluent treatment.