The extensin protein SAE1 plays a role in leaf senescence and is targeted by the ubiquitin ligase SINA4 in tomato.

Extensins are hydroxyproline-rich glycoproteins and generally play a structural role in cell wall integrity. In this study, we determined a novel role of tomato (Solanum lycopersicum) SENESCENCE-ASSOCIATED EXTENSIN1 (SAE1) in leaf senescence. Both gain- and loss-of-function analyses suggest that SAE1 plays a positive role in leaf senescence in tomato. Transgenic plants overexpressing SAE1 (SAE1-OX) exhibited premature leaf senescence and enhanced dark-induced senescence, whereas SAE1 knockout (SAE1-KO) plants displayed delayed development-dependent and dark-induced leaf senescence. Heterologous overexpression of SlSAE1 in Arabidopsis also led to premature leaf senescence and enhanced dark-induced senescence. In addition, the SAE1 protein was found to interact with the tomato ubiquitin ligase SlSINA4, and SlSINA4 promoted SAE1 degradation in a ligase-dependent manner when co-expressed in Nicotiana benthamiana leaves, suggesting that SlSINA4 controls SAE1 protein levels via the ubiquitin-proteasome pathway. Introduction of an SlSINA4-overexpression construct into the SAE1-OX tomato plants consistently completely eliminated accumulation of the SAE1 protein and suppressed the phenotypes conferred by overexpression of SAE1. Taken together, our results suggest that the tomato extensin SAE1 plays a positive role in leaf senescence and is regulated by the ubiquitin ligase SINA4.

Study on the Application Value of the Content of Prostatic Exosomal Protein in the Treatment of Chronic Prostatitis.

BACKGROUND: To evaluate the application value of urinary prostatic exosomal protein (PSEP) in the treatment of chronic prostatitis (CP). METHODS: We evaluated 174 patients with chronic prostatitis (44 cases of NIH-II, 65 cases of NIH-IIIa, and 65 cases of NIH-IIIb) who had obvious symptoms of chronic prostatitis syndrome and met the diagnostic criteria of National Institutes of Health Prostatitis from May 2018 to February 2021. They were also evaluated according to the clinical treatment's effect after six weeks of treatment. Urine samples of CP patients were collected before treatment and after six weeks of treatment, and the level of PSEP in the urine samples of all patients, before and after treatment, was detected by the ELISA method to evaluate the application value of PSEP in the end of CP curative effect. RESULTS: After six weeks of treatment, the total CPSI score of CP patients decreased significantly, compared to patients before treatment. After six weeks of treatment, the PSEP content in the patients' urine was compared to before treatment. The PSEP levels of CP subgroups decreased significantly (p < 0.05): NIH-II group (1.55 ± 1.39 ng/mL vs. 3.09 ± 2.66 ng/mL); NIH-IIIa group (1.68 ± 1.06 ng/mL vs. 3.34 ± 2.69 ng/mL); and NIH-IIIb group (1.57 ± 1.17 ng/mL vs. 3.14 ± 2.81 ng/mL). CONCLUSIONS: The concentration of PSEP in the urine of CP patients has a good application value for evaluating clinical treatment's effect on chronic prostatitis, and its concentration level may affect the development and outcome of prostatitis.

Manipulation of the transcription factor SlNAC1 for improved tolerance to abiotic stress in tomato.

The tomato transcription factor SlNAC1 plays an important role in abiotic stress response and is fine-tuned at both transcriptional and posttranslational levels. The SlNAC1 gene is strongly induced by multiple abiotic stresses and the SlNAC1 protein is subjected to ubiquitin proteasome-mediated degradation. We found here that SlNAC1 possesses two distinct transactivation domains (TADs), TAD1 and TAD2. Significantly, the instability of SlNAC1 was attributed to the acidic amino acid-rich TAD1, in which the instability and transcriptional potential of TAD1 functionally overlapped; whereas the glutamine-rich TAD2 was stable and accounted for the abiotic stress signalling mediated by SlNAC1. Towards the goal of enhanced tolerance to abiotic stress in tomatoes, we manipulated SlNAC1 at both gene and protein levels: we generated a stable and functional SlNAC1 mutant SlNAC1∆191-270 by removing TAD1 and further engineered it to be stress-controllable by fusing the corresponding cDNA with the abiotic stress-inducible promoter ProStNAC1 . Transgenic tomato plants expressing the ProStNAC1 ::SlNAC1∆191-270 transgene did not display any undesired traits and exhibited enhanced tolerance to cold, drought and salt stresses. Taken together, our manipulation of the stress-related transcription factor via conditional expression of its derived stable and functional mutant provides a successful example for developing crops dynamically adapted to abiotic stress.

A comparison of clinical pathologic characteristics between alpha-fetoprotein negative and positive hepatocellular carcinoma patients from Eastern and Southern China.

BACKGROUND: Alpha-fetoprotein (AFP) is a biomarker used in clinical management of hepatocellular carcinoma (HCC), however, approximately 40% of HCC patients do not present with elevated serum AFP levels. This study aimed to investigate the clinical and pathologic characteristics between AFP positive and negative HCC patients to allow for improved clinical management and prognostication of the disease. METHODS: This study observed a cohort of HCC patients from Eastern and Southern China with comparisons of the clinical and pathologic features between serum AFP positive and negative patient groups; patients with decompensated hepatic cirrhosis, those with chronic hepatitis B, and hepatitis B virus (HBV) asymptomatic carrier patients were used as controls. Data included the laboratory results, pathology diagnosis, clinical staging and scores were obtained from routine clinical diagnostic methods. RESULTS: Patients with HCC, larger tumor sizes, liver cancer with hepatic cirrhosis, portal vein thrombosis, metastasis, high Child-Pugh score, high Barcelona-Clínic Liver Cancer (BCLC) stage, and advanced clinical stage had significantly higher serum AFP levels. Also, patients with HBsAg and HBeAg positive, high HBV DNA levels had significantly higher serum AFP levels. Patients with high serum AFP levels had higher protein induced by vitamin K absence or antagonist-II (PIVKA-II), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alpha-l-fucosidase (AFU), gamma-glutamyl transpeptidase (γ-GT), γ-GT /ALT, direct bilirubin (DBIL), indirect bilirubin (IDBIL), fibrinogen, and D-dimer levels. Patients with AFP positive had higher white blood cells (WBC), neutrophil, monocyte, and platelet count and neutrophil to lymphocyte ratio (NLR). CONCLUSIONS: The are significant differences in clinical pathologic characteristics between AFP positive and negative HCC patients which may be helpful for the management and prognostication of the disease.

The potato cyst nematode effector RHA1B is a ubiquitin ligase and uses two distinct mechanisms to suppress plant immune signaling.

Plant pathogens, such as bacteria, fungi, oomycetes and nematodes, rely on wide range of virulent effectors delivered into host cells to suppress plant immunity. Although phytobacterial effectors have been intensively investigated, little is known about the function of effectors of plant-parasitic nematodes, such as Globodera pallida, a cyst nematode responsible for vast losses in the potato and tomato industries. Here, we demonstrate using in vivo and in vitro ubiquitination assays the potato cyst nematode (Globodera pallida) effector RHA1B is an E3 ubiquitin ligase that employs multiple host plant E2 ubiquitin conjugation enzymes to catalyze ubiquitination. RHA1B was able to suppress effector-triggered immunity (ETI), as manifested by suppression of hypersensitive response (HR) mediated by a broad range of nucleotide-binding leucine-rich repeat (NB-LRR) immune receptors, presumably via E3-dependent degradation of the NB-LRR receptors. RHA1B also blocked the flg22-triggered expression of Acre31 and WRKY22, marker genes of pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI), but this did not require the E3 activity of RHA1B. Moreover, transgenic potato overexpressing the RHA1B transgene exhibited enhanced susceptibility to G. pallida. Thus, our data suggest RHA1B facilitates nematode parasitism not only by triggering degradation of NB-LRR immune receptors to block ETI signaling but also by suppressing PTI signaling via an as yet unknown E3-independent mechanism.

A novel BSD domain-containing transcription factor controls vegetative growth, leaf senescence, and fruit quality in tomato.

BSD (mammalian BTF2-like transcription factors, synapse-associated proteins, and DOS2-like proteins) is a conserved domain that exists in a variety of organisms, but its function has not been well studied. Here, we identified a novel BSD domain-containing protein (SlBSD1) in tomato (Solanum lycopersicum). Biochemical and microscopy assays indicated that SlBSD1 is a functional transcription factor that is predominantly localized in the nucleus. Loss-of-function and overexpression analyses suggested that SlBSD1 is a novel regulator of vegetative growth and leaf senescence in tomato. SlBSD1-knockdown (-KD) plants exhibited retarded vegetative growth and precocious leaf senescence, whereas SlBSD1-overexpression (-OX) plants displayed the opposite phenotypes. The negative role of SlBSD1 in leaf senescence was also supported by RNA-seq analysis comparing leaf tissues from SlBSD1-KD and wild-type plants. In addition, contents of soluble solids were altered in fruits in the SlBSD1-KD and SlBSD1-OX plants. Taken together, our data suggest that the novel transcription factor SlBSD1 plays important roles in controlling fruit quality and other physiological processes in tomato, including vegetative growth and leaf senescence.

Analysis of serum gastrin-17 and Helicobacter pylori antibody in healthy Chinese population.

BACKGROUND: Gastrin-17 (G-17) and Helicobacter pylori (H pylori) antibody are widely used in the screening of gastric diseases, especially in gastric cancer. In this study, we aimed to evaluate the value of G-17 and H pylori antibody in gastric disease screening. METHODS: Healthy males and females (1368 and 1212, respectively) aged between 21-80 years were recruited for the study. Serum G-17 value was measured using ELISA, and H pylori antibodies were measured using Western blotting. Statistical analyses were performed using the chi-square, Mann-Whitney U, and Kruskal-Wallis H tests. RESULTS: Serum G-17 level was higher in the H pylori-positive group than in the negative group. Serum G-17 level was higher in the type 1 H pylori-positive group than in the type 2 H pylori-positive group. Further, serum G-17 level was higher in females than in males and showed significant differences among different age-groups, with changes in trend proportional to the age. The positive rate of H pylori infection in all the subjects was 58.29% and did not show a significant difference between males and females. However, it showed significant differences among different age-groups, with the changing trend proportional to the age. CONCLUSION: Analysis of serum G-17 level and H pylori antibody typing is valuable in gastric disease screening. Every laboratory should establish its own reference interval for G-17 level.

Serum vascular endothelial growth factor receptor 3 as a potential biomarker in psoriasis.

To discover novel biomarkers of psoriasis, a target-specific antibody array screening of serum samples from psoriasis patients was initially performed. The results revealed that vascular endothelial growth factor receptor 3 (VEGFR-3) was significantly elevated in the sera of psoriasis patients, compared to healthy controls. Next, ELISA validation studies in a larger cohort of psoriasis patients (N = 73) were conducted, which confirmed that serum VEGFR-3 was indeed significantly increased in patients with psoriasis compared to healthy controls (P < 0.001). Furthermore, receiver operating characteristic curve analysis demonstrated that serum VEGFR-3 exhibited potential in distinguishing healthy controls from psoriasis patients: area under the curve = 0.85, P < 0.001. In addition, serum levels of VEGFR-3 were correlated with Psoriasis Area Severity Index scores (R = 0.32, P = 0.008) in psoriasis patients. Interestingly, serum VEGFR-3 levels were significantly elevated in psoriatic arthritis compared to non-psoriatic arthritis (P = 0.026). A pilot longitudinal study demonstrated that serum levels of VEGFR-3 could reflect disease progression in psoriasis. Collectively, serum VEGFR-3 may have a clinical value in monitoring disease activity of psoriasis.

Age and Gender-Specific Reference Intervals for ProGRP in Healthy Chinese Han Ethnic Adults using the Roche Cobas Immunoassay.

BACKGROUND: Pro-gastrin-releasing peptide (ProGRP) is a kind of tumor marker applied more and more commonly in recent years. This study was aimed at determining the age and gender-specific reference intervals (RIs) for ProGRP in healthy Han ethnic adults from Guangxi, China. METHODS: A total of 2,045 apparently healthy males and 1,740 apparently healthy females aged from 21 to 90 years were included in this study. The serum ProGRP values were determined by electrochemiluminescence immunoassay (ECLIA). The one-sided upper 95th percentile of ProGRP concentrations were used to define the RIs. RESULTS: The reference limits in different age groups (21 - 40, 41 - 50, 51 - 60, 61 - 70, and > 70 years) were 37.3, 39.7, 45.7, 47.3, and 61.3 pg/mL for males, and 36.3, 38.1, 42.7, 53.5, and 60.1 pg/mL for females, respectively. There was no significant difference in the levels of ProGRP between males and females. The serum ProGRP levels were positively correlated with age. CONCLUSIONS: We established the age and gender-specific RIs for ProGRP in the adults from Guangxi, China. It will be valuable for future clinical and laboratory studies.

A Fe3O4@Au-basedpseudo-homogeneous electrochemical immunosensor for AFP measurement using AFP antibody-GNPs-HRP as detection probe.

In this study, a Fe3O4@Au-based pseudo-homogeneous electrochemical immunosensor was prepared for detection of alpha fetoprotein (AFP), a well-known hepatocellular carcinoma biomarker. The primary antibody (Ab1) was immobilized on Fe3O4@Au NPs as the capture probe. Horseradish peroxidase (HRP) and secondary antibody (Ab2) were conjugated on gold nanoparticles (GNPs) through electrostatic adsorption to form signal-amplifying labels. In the presence of AFP, a sandwich immunocomplex was formed via specific recognition of antigen-antibody in a Fe3O4@Au-basedpseudo-homogeneousreaction system. After the immunocomplex was captured to the surface of magnetic glassy carbon electrode (MGCE), the labeling HRP catalyzed the decomposition of H2O2, resulting in a substantial current for the quantitative detection of AFP. The amperometric (i-t) method was employed to record the response signal of the immunosensor based on the catalysis of the immobilized HRP toward the reduction of H2O2 with hydroquinone (HQ) as the redox mediator. Under the optimal conditions, the amperometric current response presented a linear relationship with AFP concentration over the range of 20 ng/mL-100 ng/mLwith a correlation coefficient of 0.9940, and the detection limit was 0.64 ng/mL at signal/noise [S/N] = 3. Moreover, the electrochemical immunosensor exhibited higher anti-interference ability, acceptable reproducibility and long-term stability for AFP detection.

Genome analysis of extensively drug-resistant Pseudomonas aeruginosa ST1971 from a patient in China hospitalized for severe pneumonia.

OBJECTIVES: The emergence and outbreak of carbapenem-resistant Pseudomonas aeruginosa are a major global public threat. In this study we aimed to characterize the genome of drug-resistant and virulent genes in an extremely drug-resistant (XDR) P. aeruginosa strain to understand its antimicrobial resistance trends and pathogenicity. METHODS: An XDR P. aeruginosa strain was isolated in China from a patient with severe pneumonia. Antimicrobial susceptibility testing, genome sequencing, and phylogenetic analysis were performed. Predictions were fulfilled using curated bioinformatics tools. RESULTS: Assembly of the strain (CRPA190) comprised 76 contigs with a total length of 7 009 318 bp. CRPA190 belongs to sequence type 1971 (ST1971) and the O11 serogroup. Nine prophage regions, three CRISPR arrays, and two Cas clusters were identified. However, no plasmids were predicted. Antibiotic susceptibility tests showed that CRPA190 was resistant to all the tested antibiotics, including carbapenem, polymyxin B, and ceftazidime-avibactam. Forty antimicrobial resistance genes were predicted in CRPA190, including several carbapenemase genes such as blaPDC-142, blaPME-1, blaNDM-1, and blaOXA-902. The isolate was predicted to be pathogenic and possess strong biofilm-forming ability. It harbours virulence genes that are associated with an arsenal of virulence determinants involved in adherence, motility, exotoxins, exoenzymes, immune modulation, biofilms, nutritional/metabolic factors, and effector delivery systems. CONCLUSIONS: These findings enhance our understanding of the resistance and pathogenicity of the ST1971 P. aeruginosa strain that is unique in China and provide a broader perspective on the global epidemiological landscape, suggesting the emergence of P. aeruginosa ST1971, which requires control measures to limit its dissemination.

Attitude and willingness of biodiversity conservation in Chinese university students: Associated factors and the mediation of social support.

In this cross-sectional study of 1475 Chinese university students, we explored associated factors of attitude and willingness of biodiversity conservation, analyzed the hypothesized mediation by social support in the association between attitude and willingness of biodiversity conservation. Multivariate logistic regression model revealed that major and social support were prominently related to both attitude and willingness of biodiversity conservation. Besides, path model identified a statistically significant mediation by social support, sex, race, and family residence presented noticeable effect modification on the mediation of social support. These major findings suggest that intervention measures which aiming at enhancing social support could be considered for elevating attitude and willingness of biodiversity conservation among Chinese university students.

The SINA1-BSD1 Module Regulates Vegetative Growth Involving Gibberellin Biosynthesis in Tomato.

In plants, vegetative growth is controlled by synergistic and/or antagonistic effects of many regulatory factors. Here, the authors demonstrate that the ubiquitin ligase seven in absentia1 (SINA1) mammalian BTF2-like transcription factors, Drosophila synapse-associated proteins, and yeast DOS2-like proteins (BSD1) function as a regulatory module to control vegetative growth in tomato via regulation of the production of plant growth hormone gibberellin (GA). SINA1 negatively regulates the protein level of BSD1 through ubiquitin-proteasome-mediated degradation, and the transgenic tomato over-expressing SINA1 (SINA1-OX) resembles the dwarfism phenotype of the BSD1-knockout (BSD1-KO) tomato plant. BSD1 directly activates expression of the BSD1-regulated gene 1 (BRG1) via binding to a novel core BBS (standing for BSD1 binding site) binding motif in the BRG1 promoter. Knockout of BRG1 (BRG1-KO) in tomato also results in a dwarfism phenotype, suggesting BRG1 plays a positive role in vegetative growth as BSD1 does. Significantly, GA contents are attenuated in transgenic SINA1-OX, BSD1-KO, and BRG1-KO plants exhibiting dwarfism phenotype and exogenous application of bioactive GA3 restores their vegetative growth. Moreover, BRG1 is required for the expression of multiple GA biosynthesis genes and BSD1 activates three GA biosynthesis genes promoting GA production. Thus, this study suggests that the SINA1-BSD1 module controls vegetative growth via direct and indirect regulation of GA biosynthesis in tomato.

Clinical significance of proliferation, apoptosis and senescence of nasopharyngeal cells by the simultaneously blocking EGF, IGF-1 receptors and Bcl-xl genes.

BACKGROUND: In previous work, we constructed short hairpin RNA (shRNA) expression plasmids that targeted human EGF and IGF-1 receptors messenger RNA, respectively, and demonstrated that these vectors could induce apoptosis of human nasopharyngeal cell lines (CNE2) and inhibit ligand-induced pAkt and pErk activation. METHOD: We have constructed multiple shRNA expression vectors of targeting EGFR, IGF1R and Bcl-xl, which were transfected to the CNE2 cells. The mRNA expression was assessed by RT-PCR. The growth of the cells, cell cycle progression, apoptosis of the cells, senescent tumor cells and the proteins of EGFR, IGF1R and Bcl-xl were analyzed by MTT, flow cytometry, cytochemical therapy or Western blot. RESULTS: In group of simultaneously blocking EGFR, IGF1R and Bcl-xl genes, the mRNA of EGFR, IGF1R and Bcl-xl expression was decreased by (66.66±3.42)%, (73.97±2.83)% and (64.79±2.83)%, and the protein expressions was diminished to (67.69±4.02)%, (74.32±2.30)%, and (60.00±3.34)%, respectively. Meanwhile, the cell apoptosis increased by 65.32±0.18%, 65.16±0.25% and 55.47±0.45%, and senescent cells increased by 1.42±0.15%, 2.26±0.15% and 3.22±0.15% in the second, third and fourth day cultures, respectively. CONCLUSIONS: Simultaneously blocking EGFR, IGF1R and Bcl-xl genes is capable of altering the balance between proliferating versus apoptotic and senescent cells in the favor of both of apoptosis and senescence and, therefore, the tumor cells regression.

The Ratio of Monocyte to Apolipoprotein A1 is an Independent Predictor of Breast Cancer: A Retrospective Study.

Objective: To explore the predictive value of the ratio of monocyte to apolipoprotein A1 (MAR) (a new index related to inflammation and lipid in breast cancer (BC)) and its relationship with clinicopathological staging. Methods: The hematological test results of 394 patients with breast diseases, including 276 cases of BC, 118 cases of benign breast disease (BBD), and 219 healthy volunteers (HV), were retrospectively collected. The clinical value of MAR was analyzed with binary logistic regression. Results: Using statistical software analysis, the results showed that MAR level (P<0.001) was the largest in the BC group, followed by BBD, and the lowest in the HV group, and it was found to be an indicator to distinguish BC from BBD, also an independent risk factor for BC. The increase in MAR level showed that the risk of BC was 3.733 times higher than that of HV (P<0.001). In addition, there was a notable difference in MAR between early, middle and late stages of BC patients (P=0.047), with the highest MAR level in late stage (0.510±0.078) and the lowest MAR level in early stage (0.392±0.011); the MAR level of those with tumor invasion depth of Phase 4 was the highest (0.484±0.072), and that of Phase 1/2 was the lowest (0.379±0.010), with a statistically significant difference (P<0.001). MAR was positively correlated with tumor invasion depth (P<0.001, r=0.210), that's, the size of MAR increased when there was more deeper tumor invasion. Conclusion: MAR is a new indicator for the auxiliary differential diagnosis of benign and malignant breast diseases, and is also an independent risk factor for BC. High-level MAR is closely related to late staging and tumor invasion depth of BC. It can be seen that MAR is a potentially valuable predictor of BC, and this is the first study to explore the clinical value of MAR in BC.

Uncovering the Achilles heel of genetic heterogeneity: machine learning-based classification and immunological properties of necroptosis clusters in Alzheimer's disease.

Background: Alzheimer's disease (AD) is an age-associated neurodegenerative disease, and the currently available diagnostic modalities and therapeutic agents are unsatisfactory due to its high clinical heterogeneity. Necroptosis is a common type of programmed cell death that has been shown to be activated in AD. Methods: In this study, we first investigated the expression profiles of necroptosis-related genes (NRGs) and the immune landscape of AD based on GSE33000 dataset. Next, the AD samples in the GSE33000 dataset were extracted and subjected to consensus clustering based upon the differentially expressed NRGs. Key genes associated with necroptosis clusters were identified using Weighted Gene Co-Expression Network Analysis (WGCNA) algorithm, and then intersected with the key gene related to AD. Finally, we developed a diagnostic model for AD by comparing four different machine learning approaches. The discrimination performance and clinical relevance of the diagnostic model were assessed using various evaluation metrics, including the nomogram, calibration plot, decision curve analysis (DCA), and independent validation datasets. Results: Aberrant expression patterns of NRGs and specific immune landscape were identified in the AD samples. Consensus clustering revealed that patients in the GSE33000 dataset could be classified into two necroptosis clusters, each with distinct immune landscapes and enriched pathways. The Extreme Gradient Boosting (XGB) was found to be the most optimal diagnostic model for the AD based on the predictive ability and reliability of the models constructed by four machine learning approaches. The five most important variables, including ACAA2, BHLHB4, CACNA2D3, NRN1, and TAC1, were used to construct a five-gene diagnostic model. The constructed nomogram, calibration plot, DCA, and external independent validation datasets exhibited outstanding diagnostic performance for AD and were closely related with the pathologic hallmarks of AD. Conclusion: This work presents a novel diagnostic model that may serve as a framework to study disease heterogeneity and provide a plausible mechanism underlying neuronal loss in AD.

Serum LL-37 and inflammatory cytokines levels in psoriasis.

BACKGROUND: Psoriasis (PsO) is a T-cell-associated inflammatory autoimmune dermatitis. Leucine leucine-37 (LL-37) is upregulated in PsO patients and correlated with the area and severity of PsO. However, the exact relation between LL-37 and T cell-associated inflammation is not well understood. It is very important to clarify the relationship between LL-37 and inflammatory response for clinical diagnosis and treatment of PsO. This study investigated the serum levels of LL-37 and inflammatory cytokines, as well as correlations between them in PsO patients, which aimed to provide new ideas for the diagnosis and treatment of PsO. METHODS: PsO patients (n = 50) and healthy volunteers (n = 33) were recruited in this study. Skin specimens were stained with hematoxylin and eosin (H&E). The serum levels of LL-37, T-helper type 1 (Th1, IFN-γ), T-helper type 17 (Th17, IL-17), T-helper type 22 (Th22, IL-22), and T-helper type 2 cytokines (Th2, IL-4) were assessed by enzyme-linked immunosorbent assay. Some of the patients were re-recruited after treatment to evaluate LL-37 and cytokines levels. RESULTS: Pathological changes were observed in PsO skin lesions. LL-37, IFN-γ, IL-17, and IL-22 serum levels were much higher in PsO patients than those in healthy volunteers (p < .001), and posttreatment reduction was observed in five patients. However, no remarkable difference in IL-4 level (p > .05) was found. LL-37 level was positively correlated with IFN-γ, IL-17, and IL-22 levels (p < .001) in PsO patients. CONCLUSION: LL-37 expression was significantly associated with inflammatory response, which may provide us new ideas for diagnosing and monitoring disease activity of PsO.

FBXO30 functions as a tumor suppressor and an E3 ubiquitin ligase for hZIP1­mediated HIF­1α degradation in renal cell carcinoma.

Studies on clear cell renal cell carcinoma (ccRCC) are gaining momentum due to its high malignancy and potential to metastasize. F­box protein 30 (FBXO30) is a member of the F­box protein family; however, its role and mechanism in cancer remains to be fully elucidated. Western blotting, reverse transcription­quantitative PCR and immunohistochemsitry were performed to detect the expression levels of FBXO30 in ccRCC tissues and adjacent normal tissues. Tumor biological function assays and animal experiments were conducted to clarify the inhibitory effect of FBXO30 on the progression and metastasis of ccRCC. Protein half­life assay, MG132 inhibition assay, immunofluorescence assay and co­immunoprecipitation assay were performed to explore the ubiquitination mechanism of FBXO30 and HIF­1α. Zinc supplementation assay was used to verify the regulatory relationship between human ZRT, IRT­like protein 1 (hZIP1), FBXO30 and HIF­1α. The present study revealed that the expression levels of FBXO30 were lower in ccRCC tissues compared with those in normal adjacent tissues. In addition, FBXO30 inhibited the tumorigenesis and metastatic capacity of ccRCC cells in vivo and in vitro. FBXO30 mediated the ubiquitination and degradation of hypoxia­inducible factor­1α (HIF­1α) in ccRCC cells under normoxia, thereby inhibiting the oncogenic effect of HIF­1α. Notably, hZIP1 served as an upstream regulator of FBXO30, regulating the expression of FBXO30 and HIF­1α by recruiting Zn2+. In conclusion, the present data suggested that FBXO30 is a novel E3 ubiquitination ligase that can function as a tumor suppressor in ccRCC, and the hZIP1/Zn2+/FBXO30/HIF­1α axis may provide potential biomarkers or therapeutic targets for ccRCC.

Tomato SlSTK is involved in glucose response and regulated by the ubiquitin ligase SlSINA4.

Glucose signaling plays an essential role in plant growth, development and stress response. Previous studies have shown that STOREKEEPER (STK) is a new class of DNA binding protein that regulates patatin expression in potato tubers and confers elevated sensitivity to glucose response in Arabidopsis thaliana. However, the biological functions of STK gene in tomato (Solanum lycopersicum) have not been studied. Here, we characterized the tomato SlSTK and determined its role in glucose signaling. The SlSTK protein was localized in the nucleus and the expression of the SlSTK gene was induced by the glucose treatment. Overexpression of SlSTK in tomato enhanced glucose sensitivity, as manifested by reduced seed germination rate and arrested growth at the early seedling stage. In contrast, the SlSTK-knockout plants generated via the clustered regularly interspaced short palindromic repeats (CRISPR) - CRISPR-associated protein 9 (CRISPR-Cas9) technique attenuated the sensitivity to glucose. In addition, SlSTK was ubiquitinated in plant cells and interacted with the tomato ubiquitin ligase SEVEN IN ABSENTIA4 (SlSINA4) that degrades SlSTK in a ligase-dependent manner. Taken together, these results suggest that SlSTK is involved in glucose signaling and its stability is regulated by the ubiquitin ligase SlSINA4.

Correction: Silver complexes with substituted terpyridines as promising anticancer metallodrugs and their crystal structure, photoluminescence, and DNA interactions.

Correction for 'Silver complexes with substituted terpyridines as promising anticancer metallodrugs and their crystal structure, photoluminescence, and DNA interactions' by Jiahe Li et al., Dalton Trans., 2023, 52, 9607-9621, https://doi.org/10.1039/D2DT03463H.