The nuclear receptor subfamily 4 group A1 in human disease.

Nuclear receptor 4A1 (NR4A1), a member of the NR4A subfamily, acts as a gene regulator in a wide range of signaling pathways and responses to human diseases. Here, we provide a brief overview of the current functions of NR4A1 in human diseases and the factors involved in its function. A deeper understanding of these mechanisms can potentially improve drug development and disease therapy.

Histone acetyltransferases MystA and MystB contribute to morphogenesis and aflatoxin biosynthesis by regulating acetylation in fungus Aspergillus flavus.

Myst family is highly conserved histone acetyltransferases in eukaryotic cells and is known to play crucial roles in various cellular processes; however, acetylation catalysed by acetyltransferases is unclear in filamentous fungi. Here, we identified two classical nonessential Myst enzymes and analysed their functions in Aspergillus flavus, which generates aflatoxin B1, one of the most carcinogenic secondary metabolites. MystA and MystB located in nuclei and cytoplasm, and mystA could acetylate H4K16ac, while mystB acetylates H3K14ac, H3K18ac and H3K23ac. Deletion mystA resulted in decreased conidiation, increased sclerotia formation and aflatoxin production. Deletion of mystB leads to significant defects in conidiation, sclerotia formation and aflatoxin production. Additionally, double-knockout mutant (ΔmystA/mystB) display a stronger and similar defect to ΔmystB mutant, indicating that mystB plays a major role in regulating development and aflatoxin production. Both mystA and mystB play important role in crop colonization. Moreover, catalytic domain MOZ and the catalytic site E199/E243 were important for the acetyltransferase function of Myst. Notably, chromatin immunoprecipitation results indicated that mystB participated in oxidative detoxification by regulating the acetylation level of H3K14, and further regulated nsdD to affect sclerotia formation and aflatoxin production. This study provides new evidences to discover the biological functions of histone acetyltransferase in A. flavus.

Risk Factors and Pathogen Spectrum in Continuous Ambulatory Peritoneal Dialysis-Associated Peritonitis: A Single Center Retrospective Study.

BACKGROUND To investigate the incidence, risk factors, pathogen distribution, and drug resistance patterns in continuous ambulatory peritoneal dialysis-associated peritonitis (CAPDP). MATERIAL AND METHODS Clinical data for 248 patients who underwent continuous ambulatory peritoneal dialysis (CAPD) treatment in a single center in China from March 2018 to January 2021 were retrospectively collected. The patients were divided into the CAPDP group (n=40) and the non-CAPDP group (n=208) according to whether peritonitis occurred. The incidence rate, risk factors, bacterial distribution, and drug sensitivity of CAPDP were analyzed. RESULTS The incidence of CAPDP was 16.13%, and 87.5% of patients with CAPDP continued CAPDP treatment after anti-infection treatment. Patients with and without CAPDP were clearly distinguished, on the basis of their clinical characteristics, by using principal component analysis (PCA) methods. Logistic regression analysis found that body mass index (BMI; P=0.0095), albumin (P=0.016), albumin/globulin ratio (P=0.018), C-reactive protein (P=0.0001), and rapid transport (P=0.034) were independent risk factors for CAPDP. The main pathogens causing the CAPDP were Staphylococcus epidermidis (50.00%), Staphylococcus capitis (13.33%), and Escherichia coli (10.00%). Among the pathogenic bacteria, the main drugs to which gram-negative cocci were sensitive were imipenem, meropenem, piperacillin/tazobactam, cefoperazone/sulbactam, ceftazidime, and tigecycline. The main drugs to which gram-positive cocci were sensitive were vancomycin, teicoplanin, and linezolid. The drug resistance rate of pathogenic bacteria to penicillin G, ampicillin, compound trimethoprim, cefepime, ceftriaxone, and amoxicillin-clavulanic acid drugs was 36.26-100%. CONCLUSIONS BMI, albumin, albumin/globulin ratio, C-reactive protein, and rapid transport are independent risk factors for CAPDP. Gram-positive bacteria are the main pathogens of CAPDP and are sensitive to vancomycin, teicoplanin, and linezolid.

Yiqi Huoxue Tongluo recipe regulates NR4A1 to improve renal mitochondrial function in unilateral ureteral obstruction (UUO) rats.

CONTEXT: Yiqi Huoxue Tongluo recipe (YHTR) is a traditional Chinese medicine for the treatment of chronic kidney disease, but its exact mechanism is not clear. OBJECTIVES: To monitor the potential improvement of renal mitochondrial function in unilateral ureteral obstruction (UUO) rats by regulating NR4A1 using the YHTR. MATERIALS AND METHODS: Wistar rats were randomly divided into four groups: sham, UUO (left ureteral ligation for 14 days), eplerenone (EPL) (UUO + EPL), and YHTR (UUO + YHTR). UUO rats were established and intragastrically administered EPL (100 mg/day/kg) or YHTR (11.7 g/day/kg) for 14 days. The expression of related proteins in kidneys was detected by immunohistochemistry, western blot, RT-PCR, and chemical colorimetric assay, respectively. RESULTS: In vivo, YHTR treatment reduced the levels of BUN and Scr (by 17.9% and 23.5%) in UUO rats. Moreover, YHTR improved the renal mitochondrial function via increasing key enzymes of the tricarboxylic acid (TCA) cycle (p < 0.05) and activity of the mitochondrial complex (I-V) (by 30.8%, 29.1%, 19.7%, 35.9%, and 22.4%) in UUO rats. Compared with the UUO group, the expression of NR4A1 and Bcl-2 were significantly increased (p < 0.05), the expression of caspase-3 and caspase-9 were significantly decreased (p < 0.05) in the YHTR group. YHTR could upregulate key enzymes of the TCA cycle via promoting NR4A1 expression in HK2 cells, leading to inhibition of TGF-ß1 induced cell apoptosis. CONCLUSIONS: YHTR significantly improved the development of CKD; this study may provide new ideas for the pathogenesis of CKD and new strategies for the development of new drugs against CKD.

NAC Transcription Factor PwNAC11 Activates ERD1 by Interaction with ABF3 and DREB2A to Enhance Drought Tolerance in Transgenic Arabidopsis.

NAC (NAM, ATAF1/2, and CUC2) transcription factors are ubiquitously distributed in eukaryotes and play significant roles in stress response. However, the functional verifications of NACs in Picea (P.) wilsonii remain largely uncharacterized. Here, we identified the NAC transcription factor PwNAC11 as a mediator of drought stress, which was significantly upregulated in P. wilsonii under drought and abscisic acid (ABA) treatments. Yeast two-hybrid assays showed that both the full length and C-terminal of PwNAC11 had transcriptional activation activity and PwNAC11 protein cannot form a homodimer by itself. Subcellular observation demonstrated that PwNAC11 protein was located in nucleus. The overexpression of PwNAC11 in Arabidopsis obviously improved the tolerance to drought stress but delayed flowering time under nonstress conditions. The steady-state level of antioxidant enzymes' activities and light energy conversion efficiency were significantly increased in PwNAC11 transgenic lines under dehydration compared to wild plants. PwNAC11 transgenic lines showed hypersensitivity to ABA and PwNAC11 activated the expression of the downstream gene ERD1 by binding to ABA-responsive elements (ABREs) instead of drought-responsive elements (DREs). Genetic evidence demonstrated that PwNAC11 physically interacted with an ABA-induced protein-ABRE Binding Factor3 (ABF3)-and promoted the activation of ERD1 promoter, which implied an ABA-dependent signaling cascade controlled by PwNAC11. In addition, qRT-PCR and yeast assays showed that an ABA-independent gene-DREB2A-was also probably involved in PwNAC11-mediated drought stress response. Taken together, our results provide the evidence that PwNAC11 plays a dominant role in plants positively responding to early drought stress and ABF3 and DREB2A synergistically regulate the expression of ERD1.

Expression of Fusarium pseudograminearum FpNPS9 in wheat plant and its function in pathogenicity.

Fusarium pseudograminearum-induced crown rot causes significant reduction to wheat production worldwide. To date, efforts to develop effective resistance to this disease have been hampered by the quantitative nature of resistance trait and a lack of understanding of the molecular pathogenesis. Non-ribosomal peptides have important roles in development, pathogenicity, and toxins in many plant pathogens, while less is known in F. pseudograminearum. In this work, we studied the expression and function of a nonribosomal peptide gene FpNPS9 in F. pseudograminearum. We determined the expression of FpNPS9 which was significantly up regulated during the infection of wheat. A deletion mutant Δfpnps9 produced in this study displayed a normal growth and conidiation phenotype, however, hyphae polar growth was obviously affected. Deoxynivalenol production in this mutant was significantly reduced and the infection of wheat coleoptiles and wheat spikelet was attenuated. The Δfpnps9 showed serious defects on the extension of infectious hyphae in plant and inhibition of roots elongation compared with the wild type. The complementation assay using a FpNPS9-GFP fusion construct fully restored the defects of the mutant. GFP signal was detected in the germinating conidia and infectious hyphae in coleoptiles of the infected plants. Interestingly, the signal was not observed when it was grown on culture medium, suggesting that the expression of FpNPS9 was regulated by an unknown host factor. This observation was supported by the result of qRT-PCR. In summary, we provided new knowledge on FpNPS9 expression in F. pseudograminearum and its function in F. pseudograminearum pathogenicity in wheat.

FpDep1, a component of Rpd3L histone deacetylase complex, is important for vegetative development, ROS accumulation, and pathogenesis in Fusarium pseudograminearum.

Histone deacetylases (HDACs) play essential roles in modulating chromatin structure to provide accessibility to gene regulators. Increasing evidence has linked HADCs to pathogenesis control in the filamentous plant fungi. However, its function remains unclear in Fusarium pseudograminearum, which has led to the emergence of the disease Fusarium crown rot in China. Here we identified the FpDEP1 gene, an orthologue of Saccharomyces cerevisiae DEP1 encoding a component of the Rpd3 histone deacetylase complex in F. pseudograminearum. The gene deletion mutant, ΔFpdep1, showed significantly retarded growth on PDA plates with reduced aerial hyphae formation. Pathogenicity tests displayed no typical leaf lesions and limited expansion capability of coleoptiles. Histopathological analysis indicated the ΔFpdep1 deletion mutant differentiated infectious hyphae and triggered massive reactive oxygen species (ROS) accumulation during the early infection stage, resulting in limited expansion to neighbor cells which was concurring with sensitivity to H2O2 and SDS tests in vitro. FM4-64 staining revealed that the ΔFpdep1 deletion mutant was delayed in endocytosis. The FpDEP1-GFP transgene complemented the mutant phenotypes and the fusion protein co-localized with DAPI staining, indicating that the FpDEP1 gene product is localized to the nucleus in spores and mycelia. Immunoprecipitation coupled with LC-MS/MS and yeast two-hybrid screening identified the Rpd3L-like HDAC complex containing at least FpDep1, FpSds3, FpSin3, FpRpd3, FpRxt3, FpCti6, FpRho23, and FpUme6. These results suggest that FpDep1 is involved in a HDAC complex functioning on fungal development and pathogenesis in F. pseudograminearum.

Reaction condition controlled nickel(ii)-catalyzed C-C cross-coupling of alcohols.

The challenge in the C-C cross-coupling of secondary and primary alcohols using acceptorless dehydrogenation coupling (ADC) is the difficulty in accurately controlling product selectivities. Herein, we report a controlled approach to a diverse range of ß-alkylated secondary alcohols, α-alkylated ketones and α,ß-unsaturated ketones using the ADC methodology employing a Ni(ii) 4,6-dimethylpyrimidine-2-thiolate cluster catalyst under different reaction conditions. This catalyst could tolerate a wide range of substrates and exhibited a high activity for the annulation reaction of secondary alcohols with 2-aminobenzyl alcohols to yield quinolines. This work is an example of precise chemoselectivity control by careful choice of reaction conditions.

Switchable Chemoselective Transfer Hydrogenations of Unsaturated Carbonyls Using Copper(I) N-Donor Thiolate Clusters.

Unsaturated alcohols and saturated carbonyls are important chemical, pharmaceutical, and biochemical intermediates. We herein report an efficient transfer hydrogenation protocol in which conversion of unsaturated carbonyl compounds to either unsaturated alcohols or saturated carbonyls was catalyzed by Cu(I) N-donor thiolate clusters along with changing hydrogen source (isopropanol or butanol) and base (NaOH or K2CO3). Mechanistic studies supported by DFT transition state modeling indicate that such a chemoselectivity can be explained by the relative concentrations of Cu(I) monohydride and protonated Cu(I) hydride complexes in each catalytic system.

RUVBL1-ITFG1 interaction is required for collective invasion in breast cancer.

BACKGROUND: The mechanisms of breast cancer collective invasion are poorly understood limiting the metastasis therapy. The ATPase RUVBL1 is frequently overexpressed in various cancers and plays a crucial role in oncogenic process. We further investigated the role of RUVBL1 in promoting collective invasion and uncovered that targeting RUVBL1 could inhibit metastatic progression. METHODS: The expression levels of RUVBL1 and ITFG1 were examined by Western blot and qRT-PCR. Co-localization and interaction of RUVBL1 and ITFG1 were determined by immunofluorescence and co-immunoprecipitation. The invasive ability was examined by transwell assay and microfluidic assay. The metastatic and tumorigenic abilities of breast cancer cells were revealed in BALB/c nude mice by xenograft and tail vein injection. RESULTS: ATPase RUVBL1 is highly expressed in breast cancer and predicts the poor prognosis. Elevated expression of RUVBL1 is found in high metastatic breast cancer cells. Silencing RUVBL1 suppresses cancer cell expansion and invasion in vitro and in vivo. RUVBL1 interacts with a conserved transmembrane protein ITFG1 in cytoplasm and plasma membrane to promote the collective invasion. Using a microfluidic model, we demonstrated that silencing RUVBL1 or ITFG1 individually compromises collective invasion of breast cancer cells. CONCLUSION: RUVBL1 is a vital regulator for collective invasion. The interaction between RUVBL1 and ITFG1 is required for breast cancer cell collective invasion and progression. GENERAL SIGNIFICANCE: Targeting collective invasion promoted by RUVBL1-ITFG1 complex provides a novel therapeutic strategy to improve the prognosis of invasive breast cancer.

Physicochemical and microbial responses of Streptomyces natalensis HW-2 to fungal elicitor.

The effects of fungal elicitor on the physicochemical and microbial responses of Streptomyces natalensis HW-2 were investigated. The results showed that the elicitor could decrease dry cell weight (DCW) by 17.7% and increase the utilization of glucose, while the curve of pH was not obviously altered. The elicitor enhanced the yield of natamycin from 1.33 to 2.49 g/L. The morphology of the colony and the mycelium treated with elicitor showed significant differences from that of control. The level of intracellular reactive oxygen species (ROS) increased to 333.8 ng/L, which was a twofold increase comparing with the control. The concentration of Ca2+ reached 421.1 nmol/L, which increased by 32.8% after the addition of the elicitor. The activities of pyruvic carboxylase and phosphoenol pyruvate carboxylase were enhanced by 27.8 and 11.9%, respectively, while citrate synthase activity decreased by 23.1% in comparison with the control.

Fractional Excretion of Urate is Positively Associated with Type 2 Diabetes in HUA Patients: A Cross-Sectional Study.

Purpose: People with hyperuricemia (HUA) are often related to metabolic disorders such as diabetes, metabolic syndrome (MetS), and obesity. However, the correlation between excretion of uric acid and these diseases is unclear. Our study aimed to explore the relationship between uric acid excretion and type 2 diabetes (T2D). Methods: A total of 228 HUA patients from Tianjin Medical University General Hospital from 2022 to 2023 were included in this study. We collected demographic, biochemical, and anthropometric data on each subject. Urine uric acid excretion (UUAE) was calculated enzymatically from a single urine collection that lasted 24 hours. And fractional excretion of uric acid (FEUA) was calculated from serum uric acid and creatinine and uric acid and creatinine. Binary logistic regression modeling assessed the association between uric acid excretion and T2D. Results: Of the 228 subjects, 13.4% had T2D and 48.7% had obesity. The obesity group had a lower FEUA (p<0.05) and a higher UUAE compared to the control group (p<0.05). And FEUA had a stronger correlation with the risk of T2D (p<0.001). Also, there was a negative association between BMI and FEUA and a positive link between BMI and UUAE in the outpatients. Conclusion: Increased FEUA levels were significantly associated with T2D in HUA patients. Therefore, routine calculating of FEUA is essential for proper diagnosis and appropriate treatment T2D of in HUA patients.

Inhibitory effects of Eplerenone on angiogenesis via modulating SGK1/TGF-ß pathway in contralateral kidney of CKD pregnancy rats.

BACKGROUND: Eplerenone is a selective aldosterone receptor blocker that is effective in preventing the progression of chroinic kidney disease (CKD). However, its mechanism and role in CKD pregnancy still remain uncertain. The aim of this study was to evaluate whether eplerenone could attenuated the fibrosis of unilateral ureteral obstruction (UUO) pregnant rats' contralateral kidney, improved pregnancy outcome and explore its therapeutic mechanisms. METHODS: A pregnancy rat model of UUO established, female Wistar rats were randomly assigned into sham-operated group (Sham group),sham-operated combined pregnancy group (SP group), unilateral ureteral obstruction combined pregnancy group (UUO + Pregnancy group), unilateral ureteral obstruction combined pregnancy, administered eplerenone (UUO + Pregnancy+Eplerenone group). On the 18th day of pregnancy, the rats were placed in a metabolic cage, 24 h urine was collected and stored at -80 °C. Next day, all animals were euthanized, and serum was collected by centrifugation and stored at -20 °C. Then the right kidney was extracted, a part of the kidney was placed in 4% paraformaldehyde for morphology, immunohistochemical staining, and immunofluorescence staining, and the other part was placed in a - 80 °C refrigerator for RNA and protein extraction. In vitro, HUVECs was treated with aldosterone, progesterone and estradiol, VEGFA and its receptor blocker bevacizumab. The ability of proliferation, migration and tubularization of HUVECs was detected by CCK-8, scratch wound assay and endothelial tube formation assay. And the co-expression of CD34 and α-SMA of HUVECs was detected by Flow cytometry. RESULTS: Immunofluorescence results showed that the co-expression of CD34 and α-SMA increased in the UUO + Pregnancy group was significantly increased. The expression of SGK-1, TGFß-1, Smad2, Smad3, VEGF-A, VEGFR2, CD34, α-SMA and Collagen I was significantly higher in the kidneys of the UUO + Pregnancy group compared to the Sham group and SP group. Eplerenone inhibited the expression of those results. In vitro, the ability of proliferation, migration and tubularization was increased after treated with aldosterone, aldosterone with progesterone and estradiol or VEGFA. Similarly, the expression of α-SMA on the surface of HUVECs treated with aldosterone, aldosterone with progesterone and estradiol were increased, while eplerenone supressed its expression. CONCLUSION: Eplerenone inhibits renal angiogenesis by blocking the SGK-1/TGFß signal transduction pathway, thereby inhibiting the phenotypic transformation of endothelial cells, slowing down renal fibrosis, and reducing kidney damage caused by pregnancy.

Clinical evaluation of a novel digital microfluidic based point-of-care test platform for detection of SARS-Cov-2 and influenza A/B.

Respiratory pathogens, such as SARS-CoV-2 and influenza A/B, can cause severe illnesses in susceptible individuals. This research evaluated a novel digital microfluidic point-of-care testing platform designed to detect 23 pathogens, comparing its performance to conventional laboratory-based nucleic acid tests. The platform integrates nucleic acid extraction and amplification processes for rapid detection with only 2 min of hands-on time. Performance assays demonstrated that the platform has high sensitivity (87 %-100 %) and specificity (99 %-100 %) for the detection of the evaluated 3 viruses. Additionally, the platform can be adapted for the detection of other respiratory pathogens, aiding in the early diagnosis of respiratory diseases, identifying the source of an outbreak or epidemic, and curbing the spread of the disease.

Nuclear receptor 4A1 ameliorates renal fibrosis by inhibiting vascular endothelial growth factor A induced angiogenesis in UUO rats.

INTRODUCTION: Angiogenesis is closely related to renal fibrosis; however, its basic mechanism remains unclear. In our study, we found that nuclear receptor 4A1 (NR4A1) inhibits vascular endothelial growth factor A (VEGFA)-induced angiogenesis, ameliorating renal fibrosis. METHODS: We prepared a renal fibrosis animal model with unilateral ureteral obstruction (UUO) and NR4A1 knockdown UUO mice model, Using Human umbilical vein endothelial cells (HUVECs) to conduct all in vitro experiments. We then detected and analyzed the expression levels of NR4A1 and other genes related to angiogenesis and fibrosis. RESULTS: The angiogenesis related genes, such as VEGFA, vascular endothelial growth factor receptor-2 (VEGFR-2), endoglin (CD105), as well as the expression of fibrosis related genes that included, α-smooth muscle actin (α-SMA), Vimentin, and Collagen I are all significantly increased in the UUO rat model. In addition, the expression of NR4A1 of the kidney tissue of UUO rats was significantly reduced. Therefore, according to the above results, we speculated that angiogenesis may exacerbate renal fibrosis and NR4A1 may repress renal fibrosis by inhibiting angiogenesis. To further verify the above results, we used VEGFA to stimulate HUVECs with (or without) overexpression or knockdown of NR4A1. The results showed that with prolonged stimulation using VEGFA, the expression of NR4A1 decreases. Overexpression of NR4A1 significantly inhibits the expression of related indicators of angiogenesis and renal fibrosis. Furthermore, knockdown of NR4A1 induces endothelial cell proliferation and migration; therefore, exacerbating angiogenesis and fibrosis. Finally, the results of NR4A1 knockdown UUO mice showed that knockdown of NR4A1 can aggravating kidney damage and induce the expression of angiogenesis and renal fibrosis related indicators, while UUO can significantly induce kidney damage, angiogenesis and renal fibrosis. When knockdown of NR4A1, renal kidney damage, angiogenesis and fibrosis becomes more severe than UUO. Thus, all of these results indicate that NR4A1 can ameliorate renal fibrosis by inhibiting angiogenesis. CONCLUSIONS: NR4A1 can inhibit angiogenesis to ameliorate renal fibrosis.

Janus liposozyme for the modulation of redox and immune homeostasis in infected diabetic wounds.

Diabetic foot ulcers often become infected, leading to treatment complications and increased risk of loss of limb. Therapeutics to manage infection and simultaneously promote healing are needed. Here we report on the development of a Janus liposozyme that treats infections and promotes wound closure and re-epithelialization. The Janus liposozyme consists of liposome-like selenoenzymes for reactive oxygen species (ROS) scavenging to restore tissue redox and immune homeostasis. The liposozymes are used to encapsulate photosensitizers for photodynamic therapy of infections. We demonstrate application in methicillin-resistant Staphylococcus aureus-infected diabetic wounds showing high ROS levels for antibacterial function from the photosensitizer and nanozyme ROS scavenging from the liposozyme to restore redox and immune homeostasis. We demonstrate that the liposozyme can directly regulate macrophage polarization and induce a pro-regenerative response. By employing single-cell RNA sequencing, T cell-deficient Rag1-/- mice and skin-infiltrated immune cell analysis, we further reveal that IL-17-producing γδ T cells are critical for mediating M1/M2 macrophage transition. Manipulating the local immune homeostasis using the liposozyme is shown to be effective for skin wound repair and tissue regeneration in mice and mini pigs.

The relationship and clinical significance of serum cytokine expression level and skin pruritus in patients with Hodgkin lymphoma and angioimmunoblastic T-cell lymphoma.

Pruritus of lymphoma is commonly associated with both Hodgkin lymphoma (HL) and angioimmunoblastic T cell lymphoma (AITL) and critically affects the life quality of patient. Recent evidence suggests that the pruritogenic cytokines seem to play a significant role in the genesis of chronic. This study aims to investigate the cytokines associated with itching in lymphoma patients and provide the basis for potential therapeutic targets. Serum samples were collected from 60 lymphoma patients, including 47 with Hodgkin lymphoma (HL) and 13 with angioimmunoblastic T-cell lymphoma (AITL), serving as the observation group (lymphoma group, LP group, n = 60). Additionally, serum samples from 8 healthy donors (HD group, n = 8) were collected for comparison. Within the lymphoma group, patients were stratified into those with pruritus (LWP group, n = 30) and those without pruritus (LWOP group, n = 30) based on the presence of skin pruritus symptoms. Elevated levels of multiple cytokines were significantly observed in the LP group in comparison to the HD group (p < 0.01). Patients in LWP group exhibited higher serum levels of IL-31 (p < 0.001), IL-1ß (P = 0.039), and IL-1α (P = 0.037) compared to LWOP group. Notably, serum IL-31 levels were higher in advanced AITL patients (stage IV) than in early AITL patients (stage I-Ⅲ, P < 0.05). In subgroup analysis, patients with pruritus in the AITL group exhibited higher serum levels of MIG and CTACK compared to HL group, whereas PDGF-BB levels were significantly lower (p < 0.05). Elevated serum levels of IL-31, IL-1ß, and IL-1α are linked to lymphoma-associated pruritus. Differences in serum cytokine profiles between HL and AITL subgroups are also highlighted. These findings offer valuable insights for clinical intervention in managing lymphoma-related pruritus.

Foxo1 Drives the TGFß1-Dependent Dichotomy of Th17 Cell Fates.

T-helper 17 (Th17) cells play a dual role in immunological responses, serving as essential components in tissue homeostasis and host defense against microbial pathogens while also contributing to pro-inflammatory conditions and autoimmunity. While Transforming Growth Factor-beta 1 (TGFß1) is pivotal for the differentiation of non-pathogenic Th17 cells, the role of TGFß3 and Activin in steering Th17 cells toward a pathogenic phenotype has been acknowledged. However, the molecular mechanisms governing this dichotomy remain elusive. In this study, we demonstrate that the transcription factor Foxo1 is upregulated in a TGFß1 dose-dependent manner, serving as a critical regulator that specifically modulates the fate of pathogenic Th17 cells. Analyses in both uveitis patients and an Experimental Autoimmune Uveitis (EAU) mouse model reveal a strong correlation between disease severity and diminished Foxo1 expression levels. Ectopic expression of Foxo1 selectively attenuates IL-17A production under pathogenic Th17-inducing conditions. Moreover, enhanced Foxo1 expression, triggered by TGFß1 signaling, is implicated in fatty acid metabolism pathways that favor non-pathogenic Th17 differentiation. Our drug screening identifies several FDA-approved compounds can upregulate Foxo1. Collectively, our findings offer evidence that Foxo1 serves as a molecular switch to specifically control pathogenic versus non-pathogenic Th17 differentiation in a TGFß1-dependent manner. Suggest that targeting Foxo1 could be a promising therapeutic strategy for autoimmune diseases.

RNA Seq and ceRNA Network Analysis of the Rat Model of Chronic Kidney Disease.

BACKGROUND: Long non-coding RNAs (lncRNAs) containing microRNA (miRNA) response elements (MREs) can be used as competitive endogenous RNAs (ceRNAs) to regulate gene expression. OBJECTIVE: The purpose of this study was to investigate the expression profile and role of mRNAs and lncRNAs in unilateral ureteral obstruction (UUO) model rats and to explore any associated competing endogenous (ceRNA) network. METHODS: Using the UUO model, the obstructed kidney was collected on the 15th day after surgery. RNA Seq analysis was performed on renal tissues of four UUO rats and four sham rats. Four mRNAs and four lncRNAs of differentially expressed genes were randomly selected for real-time quantitative PCR (RT qPCR) analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed, and bioinformatics was used to predict MREs. By screening for ceRNAs combined with target gene prediction, a related ceRNA network was constructed and verified by RT-qPCR. RESULTS: We identified 649 up-regulated lncRNAs, 518 down-regulated lncRNAs, 924 downregulated mRNAs and 2029 up-regulated mRNAs. We identified 30 pathways with the highest enrichment in GO and KEGG. According to the RNA Seq results and the expression of Nr4a1, the network was constructed based on Nr4a1 and included two MREs and ten lncRNAs. Furthermore, lncNONRATT011668.2/miR-361-3p/Nr4a1 was identified and verified according to ceRNA sequencing and target gene prediction. CONCLUSION: mRNAs and lncRNAs are differentially expressed in UUO model rats, which may be related to the pathogenesis of chronic kidney disease. The lncNONRATT011668.2/miR-361- 3p/Nr4a1 ceRNA network may be involved in the pathogenesis of chronic kidney disease.

The spillover effect of green finance development on rural revitalization: an empirical analysis based on China's provincial panel data.

With the overall victory of poverty alleviation in China, the focus of rural work has been transformed into rural revitalization. Therefore, based on the panel data of 30 provinces and cities in China spanning 2011 to 2019, this research used the entropy-TOPSIS method to calculate the weights of each index of the two rural revitalization and green finance systems. This research also constructs the spatial Dubin model to empirically analyze the direct effects and spatial spillover effects of green finance development on the level of rural revitalization. Additionally, this research calculates the weight of each indicator of rural revitalization and green finance using entropy-weighted TOPSIS. This research reveals that the current state of green finance is not conducive to increasing local rural revitalization and does not significantly affect all provinces. Further, the number of human resources can improve the local level of rural revitalization, not the entire province. These dynamics benefit the growth of local rural revitalization in the surrounding areas if employment and technology levels are developed domestically. Moreover, this research reveals that education level and air quality have a spatial crowding effect on rural revitalization. Thus, when developing rural revitalization and development policies, it is vital to prioritize the high-quality development of finance to be closely monitored by local governments at the respective levels. Furthermore, the stakeholders must pay critical attention to the connection between supply and demand and between financial institutions and agricultural enterprises in the provinces. Again, the policymakers must also increase policy preference, deepen regional economic cooperation, and improve the supply of essential rural elements to play a more significant role in green finance and support rural revitalization.