DoriC 12.0: an updated database of replication origins in both complete and draft prokaryotic genomes.

DoriC was first launched in 2007 as a database of replication origins (oriCs) in bacterial genomes and has since been constantly updated to integrate the latest research progress in this field. The database was subsequently extended to include the oriCs in archaeal genomes as well as those in plasmids. This latest release, DoriC 12.0, includes the oriCs in both draft and complete prokaryotic genomes. At the same time, the number of oriCs in the database has also increased significantly and currently contains over 200 000 bacterial entries distributed in more than 40 phyla. Among them, a large number are from bacteria in new phyla whose oriCs were not explored before. Additionally, new oriC features and improvements have been introduced, especially in the visualization and analysis of oriCs. Currently, DoriC is considered as an important database in the fields of bioinformatics, microbial genomics, and even synthetic biology, providing a valuable resource as well as a comprehensive platform for the research on oriCs. DoriC 12.0 can be accessed at https://tubic.org/doric/ and http://tubic.tju.edu.cn/doric/.

Pirin Promotes the Progression of Non-Small-Cell Lung Cancer by Increasing ODC1 to Suppress Autophagy.

Non-small-cell lung cancer (NSCLC), a common malignant tumor, requires deeper pathogenesis investigation. Autophagy is an evolutionarily conserved lysosomal degradation process that is frequently blocked during cancer progression. It is an urgent need to determine the novel autophagy-associated regulators in NSCLC. Here, we found that pirin was upregulated in NSCLC, and its expression was positively correlated with poor prognosis. Overexpression of pirin inhibited autophagy and promoted NSCLC proliferation. We then performed data-independent acquisition-based quantitative proteomics to identify the differentially expressed proteins (DEPs) in pirin-overexpression (OE) or pirin-knockdown (KD) cells. Among the pirin-regulated DEPs, ornithine decarboxylase 1 (ODC1) was downregulated in pirin-KD cells while upregulated along with pirin overexpression. ODC1 depletion reversed the pirin-induced autophagy inhibition and pro-proliferation effect in A549 and H460 cells. Immunohistochemistry showed that ODC1 was highly expressed in NSCLC cancer tissues and positively related with pirin. Notably, NSCLC patients with pirinhigh/ODC1high had a higher risk in terms of overall survival. In summary, we identified pirin and ODC1 as a novel cluster of prognostic biomarkers for NSCLC and highlighted the potential oncogenic role of the pirin/ODC1/autophagy axis in this cancer type. Targeting this pathway represents a possible therapeutic approach to treat NSCLC.

Clonal evolution from B-cell acute lymphoblastic leukemia with BCR::ABL1 multilineage involvement to acute myeloid leukemia after multiple anti-CD19 chimeric antigen receptor T-cell therapy.

Not available.

Immune protection of grass carp by oral vaccination with recombinant Bacillus methylotrophicus expressing the heterologous tolC gene.

In the field of aquaculture, the enhancement of animal health and disease prevention is progressively being tackled using alternatives to antibiotics, including vaccines and probiotics. This study was designed to evaluate the potential of a recombinant Bacillus methylotrophicus, engineered to express the outer membrane channel protein TolC of Aeromonas hydrophila AH3 and the green fluorescent protein GFP, as an oral vaccine. Initially, the genes encoding tolC and GFP were cloned into a prokaryotic expression system, and anti-TolC mouse antiserum was generated. Subsequently, the tolC gene was subcloned into a modified pMDGFP plasmid, which was transformed into B. methylotrophicus WM-1 for protein expression. The recombinant B. methylotrophicus BmT was then administered to grass carp via co-feeding, and its efficacy as an oral vaccine was assessed. Our findings demonstrated successful expression of the 55 kDa TolC and 28 kDa GFP proteins, and the preparation of polyclonal antibodies with high specificity. The BmT exhibited stable expression of the GFP-TolC fusion protein and excellent genetic stability. Following oral immunization, significant elevations were observed in serum-specific IgM levels and the activities of acid phosphatase (ACP), alkaline phosphatase (AKP), superoxide dismutase (SOD), and lysozyme (LZM) in grass carp. Concurrently, significant upregulation of immune-related genes, including IFN-I, IL-10, IL-1ß, TNF-α, and IgT, was noted in the intestines, head kidney, and spleen of the grass carp. Colonization tests further revealed that the BmT persisted in the gut of immunized fish even after a fasting period of 7 days. Notably, oral administration of BmT enhanced the survival rate of grass carp following A. hydrophila infection. These results suggest that the oral BmT vaccine developed in this study holds promise for future applications in aquaculture.

Rosmarinic Acid Protects Skin Keratinocytes from Particulate Matter 2.5-Induced Apoptosis.

Background: The exposure of the human skin to particulate matter 2.5 (PM2.5) results in adverse health outcomes, such as skin aging, wrinkle formation, pigment spots, and atopic dermatitis. It has previously been shown that rosmarinic acid (RA) can protect keratinocytes from ultraviolet B radiation by enhancing cellular antioxidant systems and reducing oxidative damage; however, its protective action against the adverse effects of PM2.5 on skin cells remains unclear. Therefore, in this study, we explored the mechanism underlying the protective effects of RA against PM2.5-mediated oxidative stress in HaCaT keratinocytes. Methods: HaCaT keratinocytes were pretreated with RA and exposed to PM2.5. Thereafter, reactive oxygen species (ROS) production, protein carbonylation, lipid peroxidation, DNA damage, and cellular apoptosis were investigated using various methods, including confocal microscopy, western blot analysis, and flow cytometry. Results: RA significantly inhibited PM2.5-induced lipid peroxidation, protein carbonylation, DNA damage, increases in intracellular Ca2+ level, and mitochondrial depolarization. It also significantly attenuated PM2.5-induced apoptosis by downregulating Bcl-2-associated X, cleaved caspase-9, and cleaved caspase-3 protein levels, while upregulating B-cell lymphoma 2 protein level. Further, our results indicated that PM2.5-induced apoptosis was associated with the activation of the mitogen-activated protein kinase (MAPK) signaling pathway and that MAPK inhibitors as well as RA exhibited protective effects against PM2.5-induced apoptosis. Conclusion: RA protected HaCaT cells from PM2.5-induced apoptosis by lowering oxidative stress.

Protective Effect of Fermented Sea Tangle Extract on Skin Cell Damage Caused by Particulate Matter.

The skin is directly exposed to atmospheric pollutants, especially particulate matter 2.5 (PM2.5) in the air, which poses significant harm to skin health. However, limited research has been performed to identify molecules that can confer resistance to such substances. Herein, we analyzed the effect of fermented sea tangle (FST) extract on PM2.5-induced human HaCaT keratinocyte damage. Results showed that FST extract, at concentrations less than 800 µg/mL, exhibited non-significant toxicity to cells and concentration-dependent inhibition of PM2.5-induced reactive oxygen species (ROS) production. PM2.5 induced oxidative stress by stimulating ROS, resulting in DNA damage, lipid peroxidation, and protein carbonylation, which were inhibited by the FST extract. FST extract significantly suppressed the increase in calcium level and apoptosis caused by PM2.5 treatment and significantly restored the reduced cell viability. Mitochondrial membrane depolarization occurred due to PM2.5 treatment, however, FST extract recovered mitochondrial membrane polarization. PM2.5 inhibited the expression of the anti-apoptotic protein Bcl-2, and induced the expression of pro-apoptotic proteins Bax and Bim, the apoptosis initiator caspase-9, as well as the executor caspase-3, however, FST extract effectively protected the changes in the levels of these proteins caused by PM2.5. Interestingly, pan-caspase inhibitor Z-VAD-FMK treatment enhanced the anti-apoptotic effect of FST extract in PM2.5-treated cells. Our results indicate that FST extract prevents PM2.5-induced cell damage via inhibition of mitochondria-mediated apoptosis in human keratinocytes. Accordingly, FST extract could be included in skin care products to protect cells against the harmful effects of PM2.5.

Low concentrations of TNF-α in vitro transform the phenotype of vascular smooth muscle cells and enhance their survival in a three-dimensional culture system.

BACKGROUND: Vascular smooth muscle cells (VSMCs) are commonly used as seed cells in tissue-engineered vascular constructions. However, their variable phenotypes and difficult to control functions pose challenges. This study aimed to overcome these obstacles using a three-dimensional culture system. METHODS: Calf VSMCs were administered tumor necrosis factor-alpha (TNF-α) before culturing in two- and three-dimensional well plates and polyglycolic acid (PGA) scaffolds, respectively. The phenotypic markers of VSMCs were detected by immunofluorescence staining and western blotting, and the proliferation and migration abilities of VSMCs were detected by CCK-8, EDU, cell counting, scratch, and Transwell assays. RESULTS: TNF-α rapidly decreased the contractile phenotypic markers and elevated the synthetic phenotypic markers of VSMCs, as well as markedly increasing the proliferation and migration ability of VSMCs under two- and three-dimensional culture conditions. CONCLUSIONS: TNF-α can rapidly induce a phenotypic shift in VSMCs and change their viability on PGA scaffolds.

Diisoprenyl Cyclohexene-Type Meroterpenoids with Cytotoxic Activity from a Mangrove Endophytic Fungus Aspergillus sp. GXNU-Y85.

Five new diisoprenyl cyclohexene-type meroterpenoids, aspergienynes J-N (1-5), along with three known analogues (6-8), were obtained from the mangrove endophytic fungal strain Aspergillus sp. GXNU-Y85. The chemical structures, including their absolute configurations, were established via spectroscopic data and comparison of experimental and calculated ECD spectra. Cytotoxicity assay results indicated that compound 8 had strong cytotoxicity against HeLa cancer cells, and its IC50 value was 11.8 µM. In addition, flow cytometry analysis revealed that the cytotoxicity of 8 was due to the induction of G1 cell cycle arrest and apoptosis in HeLa cells.

Silver nanoparticle-induced cell damage via impaired mtROS-JNK/MnSOD signaling pathway.

This study investigated the mechanism of silver nanoparticle (AgNP) cytotoxicity from a mitochondrial perspective. The effect of AgNP on manganese superoxide dismutase (MnSOD), a mitochondrial antioxidant enzyme, against oxidative stress has not been studied in detail. We demonstrated that AgNP decreased MnSOD mRNA level, protein expression, and activity in human Chang liver cells in a time-dependent manner. AgNP induced the production of mitochondrial reactive oxygen species (mtROS), particularly superoxide anion. AgNP was found to increase mitochondrial calcium level and disrupt mitochondrial function, leading to reduced ATP level, succinate dehydrogenase activity, and mitochondrial permeability. AgNP induced cytochrome c release from the mitochondria into the cytoplasm, attenuated the expression of the anti-apoptotic proteins phospho Bcl-2 and Mcl-1, and induced the expression of the pro-apoptotic proteins Bim and Bax. In addition, c-Jun N-terminal kinase (JNK) phosphorylation was significantly increased by AgNP. Treatment with elamipretide (a mitochondria-targeted antioxidant) and SP600125 (a JNK inhibitor) showed the involvement of MnSOD and JNK in these processes. These results indicated that AgNP damaged human Chang liver cells by destroying mitochondrial function through the accumulation of mtROS.

Subthreshold micropulse diode laser treatment in diabetic macular edema: biological impact, therapeutic effects, and safety.

PURPOSE: To introduce the treatment of diabetic macular edema (DME) with subthreshold micropulse diode laser (SMPL), to summarize the biological impact, therapeutic effects, and safety of this treatment, and to discuss the response to DME when SMPL is combined with anti-vascular endothelial growth factor (anti-VEGF) or steroid. METHODS: The literature search was performed on the PubMed database, with a selection of English-language articles published from 2000 to 2023 with the following combinations of search terms: diabetes macular (o) edema, micropulse laser or subthreshold micropulse laser, anti-vascular endothelial growth factor, and steroid. RESULTS: SMPL is a popular, invisible retinal laser phototherapy that is inexpensive, safe, and effective in the treatment of DME. It can selectively target the retinal pigment epithelium, reduce the expression of pro-inflammatory factors, promote the absorption of macular edema, and exert a similar and lasting clinical effect to traditional lasers. No significant difference was found in the therapeutic effects of SMPL between different wavelengths. However, HbA1c level and pretreatment central macular thickness (CMT) may affect the therapeutic outcomes of SMPL. CONCLUSION: SMPL has a slow onset and produces lasting clinical effects similar to conventional photocoagulation. It has been reported that SMPL combined with the intravitreal anti-VEGF injection can significantly reduce the number of injections without influencing the therapeutic effect, which is essential for clinical applications and research. Although 577 nm SMPL is widely used clinically, there are no standardized protocols for SMPL. Additionally, some important problems regarding the treatment of SMPL require further discussion and exploration.

Complementary water and nutrient utilization of perianth structural units help maintain long floral lifespan in Dendrobium.

Most orchids have high ornamental value with long-lived flowers. However, the mechanisms by which orchids maintain floral longevity are poorly understood. Here, we hypothesized that floral longevity in Dendrobium is maintained by high resource investment and complementary water and nutrient utilization in different structural units of the perianth. To test this hypothesis, we determined which water- and nutrient-related traits are correlated with flower longevity in 23 Dendrobium species or cultivars, and examined variations of the related traits during flower development of one long-lived cultivar. We found that floral longevity was correlated with dry mass per unit area of perianths and total flower biomass, which indicates that maintaining floral longevity requires increased resource investment. During development of long-lived flowers, labella showed a high capacity for water storage and nutrient reutilization, which could partly remedy high water demand and biomass investment. Sepals and petals, in contrast, had stronger desiccation avoidance and higher metabolic activity with lower biomass investment. These findings indicate that Dendrobium flowers maintain longevity by complementary water and nutrient utilization strategies in the sepals, petals and labella, with labella consuming more water and nutrients to extend flower display, and sepals and petals using a more conservative strategy.

Insights into the Conductive Network of Electrochemical Exfoliation with Graphite Powder as Starting Raw Material for Graphene Production.

Electrochemical exfoliation starting with graphite powder as the raw material for graphene production shows superiority in cost effectiveness over the popular bulk graphite. However, the crucial conductive network inside the graphite powder electrode along with its formation and influence mechanisms remains blank. Here, an adjustable-pressure graphite powder electrode with a sandwich structure was designed for this. Appropriate encapsulation pressure is necessary and conducive to constructing a continuous and stable conductive network, but overloaded encapsulation pressure is detrimental to the exfoliation and graphene quality. With an initial encapsulation pressure (IEP) of 4 kPa, the graphite powders expand rapidly to a final stable expansion pressure of 49 kPa with a final graphene yield of 46.3%, where 84% of the graphene sheets are less than 4 layers with ID/IG values between 0.22 and 1.24. Increasing the IEP to 52 kPa, the expansion pressure increases to 73 kPa, but the graphene yield decreases to 39.3% with a worse graphene quality including higher layers and ID/IG values of 1.68-2.13. In addition, small-size graphite powders are not suitable for the electrochemical exfoliation. With the particle size decreasing from 50 to 325 mesh, the graphene yield decreases almost linearly from 46.3% to 5.5%. Conductive network and electrolyte migration synergize and constrain each other, codetermining the electrochemical exfoliation. Within an encapsulated structure, the electrochemical exfoliation of the graphite powder electrode proceeds from the outside to the inside. The insights revealed here will provide direction for further development of electrochemical exfoliation of graphite powder to produce graphene.

Association between post-stroke smoking and stroke recurrence in first-ever ischemic stroke survivors: based on a 10-year prospective cohort.

BACKGROUND: Whether smoking is a risk factor for ischemic stroke (IS) recurrence in IS survivors is still uncovered, and evidences are sparse. Meanwhile, an add-on effect of clopidogrel was observed in myocardial infarction patients who smoked, but whether the paradox exists in IS patients is still unsolved. The objectives of this study are to explore the association between smoking behavior after index stroke and IS recurrence and to explore whether the paradox exists. METHODS: A prospective cohort of first-ever IS patients was conducted between 2010 and 2019. The prognosis and smoking features of enrolled patients were obtained via telephone follow-up every 3 months. Fine-gray model with interaction terms was applied to measure the relationships between stroke recurrence and smoking behaviors after index stroke and to explore the add-on effect of clopidogrel in smoking patients. RESULTS: There were 171 (24.26%) recurrences and 129 (18.30%) deaths during follow-up in 705 enrolled IS patients. One hundred forty-six (20.71%) patients smoked after index stroke. The hazard ratios (HRs) and 95% confidence intervals (CIs) of interaction terms between antiplatelet drug and follow-up smoking (smoking status and daily smoking amount) were 1.092 (95% CI: 0.524, 2.276) and 0.985 (95% CI: 0.941, 1.031), respectively. A significantly higher risk of recurrence was observed in patients with a higher daily smoking amount during follow-up (per cigarette), with HR being 1.027 (95% CI: 1.003, 1.052). CONCLUSIONS: Smoking could elevate the risk of IS recurrence, and IS survivor should be advised to quit or smoke less. Add-on effect of clopidogrel may not exist in smoking strokers taking clopidogrel.

Widely targeted quantitative lipidomics and prognostic model reveal plasma lipid predictors for nasopharyngeal carcinoma.

BACKGROUND: Dysregulation of lipid metabolism is closely associated with cancer progression. The study aimed to establish a prognostic model to predict distant metastasis-free survival (DMFS) in patients with nasopharyngeal carcinoma (NPC), based on lipidomics. METHODS: The plasma lipid profiles of 179 patients with locoregionally advanced NPC (LANPC) were measured and quantified using widely targeted quantitative lipidomics. Then, patients were randomly split into the training (125 patients, 69.8%) and validation (54 patients, 30.2%) sets. To identify distant metastasis-associated lipids, univariate Cox regression was applied to the training set (P < 0.05). A deep survival method called DeepSurv was employed to develop a proposed model based on significant lipid species (P < 0.01) and clinical biomarkers to predict DMFS. Concordance index and receiver operating curve analyses were performed to assess model effectiveness. The study also explored the potential role of lipid alterations in the prognosis of NPC. RESULTS: Forty lipids were recognized as distant metastasis-associated (P < 0.05) by univariate Cox regression. The concordance indices of the proposed model were 0.764 (95% confidence interval (CI), 0.682-0.846) and 0.760 (95% CI, 0.649-0.871) in the training and validation sets, respectively. High-risk patients had poorer 5-year DMFS compared with low-risk patients (Hazard ratio, 26.18; 95% CI, 3.52-194.80; P < 0.0001). Moreover, the six lipids were significantly correlated with immunity- and inflammation-associated biomarkers and were mainly enriched in metabolic pathways. CONCLUSIONS: Widely targeted quantitative lipidomics reveals plasma lipid predictors for LANPC, the prognostic model based on that demonstrated superior performance in predicting metastasis in LANPC patients.

Evidence for a chromosome origin unwinding system broadly conserved in bacteria.

Genome replication is a fundamental requirement for the proliferation of all cells. Throughout the domains of life, conserved DNA replication initiation proteins assemble at specific chromosomal loci termed replication origins and direct loading of replicative helicases (1). Despite decades of study on bacterial replication, the diversity of bacterial chromosome origin architecture has confounded the search for molecular mechanisms directing the initiation process. Recently a basal system for opening a bacterial chromosome origin (oriC) was proposed (2). In the model organism Bacillus subtilis, a pair of double-stranded DNA (dsDNA) binding sites (DnaA-boxes) guide the replication initiator DnaA onto adjacent single-stranded DNA (ssDNA) binding motifs (DnaA-trios) where the protein assembles into an oligomer that stretches DNA to promote origin unwinding. We report here that these core elements are predicted to be present in the majority of bacterial chromosome origins. Moreover, we find that the principle activities of the origin unwinding system are conserved in vitro and in vivo. The results suggest that this basal mechanism for oriC unwinding is broadly functionally conserved and therefore may represent an ancestral system to open bacterial chromosome origins.

Heterologous expression of a deacetylase and its application in L-glufosinate preparation.

With potent herbicidal activity, biocatalysis synthesis of L-glufosinate has drawn attention. In present research, NAP-Das2.3, a deacetylase capable of stereoselectively resolving N-acetyl-L-glufosinate to L-glufosinate mined from Arenimonas malthae, was heterologously expressed and characterized. In Escherichia coli, NAP-Das2.3 activity only reached 0.25 U/L due to the formation of inclusive bodies. Efficient soluble expression of NAP-Das2.3 was achieved in Pichia pastoris. In shake flask and 5 L bioreactor fermentation, NAP-Das2.3 activity by recombinant P. pastoris reached 107.39 U/L and 1287.52 U/L, respectively. The optimum temperature and pH for N-acetyl-glufosinate hydrolysis by NAP-Das2.3 were 45 °C and pH 8.0, respectively. The Km and Vmax of NAP-Das2.3 towards N-acetyl-glufosinate were 25.32 mM and 19.23 µmol mg-1 min-1, respectively. Within 90 min, 92.71% of L-enantiomer in 100 mM racemic N-acetyl-glufosinate was converted by NAP-Das2.3. L-glufosinate with high optical purity (e.e.P above 99.9%) was obtained. Therefore, the recombinant NAP-Das2.3 might be an alternative for L-glufosinate biosynthesis.

A comprehensive approach to quantify the source identification and human health risk assessment of toxic elements in park dust.

In this research, enrichment factor (EF) and pollution load index were utilized to explore the contamination characteristics of toxic elements (TEs) in park dust. The results exhibited that park dust in the study area was mainly moderately polluted, and the EF values of dust Cd, Zn, Pb, Cu and Sb were all > 1. The concentrations of Cr, Cu, Zn and Pb increased with the decrease of dust particle size. The investigation results of chemical speciation and bioavailability of TEs showed that Zn had the highest bioavailability. Three sources of TEs were determined by positive matrix factorization model, Pearson correlation analysis and geostatistical analysis, comprising factor 1 mixed sources of industrial and transportation activities (46.62%), factor 2 natural source (25.56%) and factor 3 mixed source of agricultural activities and the aging of park infrastructures (27.82%). Potential ecological risk (PER) and human health risk (HHR) models based on source apportionment were exploited to estimate PER and HHR of TEs from different sources. The mean PER value of TEs in the park dust was 114, indicating that ecological risk in the study area was relatively high. Factor 1 contributed the most to PER, and the pollution of Cd was the most serious. There were no significant carcinogenic and non-carcinogenic risks for children and adults in the study area. And factor 3 was the biggest source of non-carcinogenic risk, and As, Cr and Pb were the chief contributor to non-carcinogenic risk. The primary source of carcinogenic risk was factor 2, and Cr was the cardinal cancer risk element.

[Research progress in prevention and treatment of radiation-induced intestinal injury by traditional Chinese medicine active components].

Radiation-induced intestinal injury(RIII), a common complication of radiotherapy for pelvic malignancies, affects the quality of life and the radiotherapy efficacy for cancer. Currently, the main clinical approaches for the prevention and treatment of RIII include drug therapy, hyperbaric oxygen therapy, and surgical treatment. Among these methods, drug therapy is cost-effective. Traditional Chinese medicine(TCM) containing a variety of active components demonstrates mild side effects and good efficacy in preventing and treating RIII. Studies have proven that TCM active components, such as flavonoids, terpenoids, phenylpropanoids, and alkaloids, can protect the intestine against RIII by inhibiting oxidative stress, regulating the expression of inflammatory cytokines, modulating the mitochondrial apoptosis pathway, adjusting intestinal flora, and suppressing cell apoptosis. These mechanisms can help alleviate the symptoms of RIII. The paper aims to provide a theoretical reference for the discovery of new drugs for the prevention and treatment of RIII by reviewing the literature on TCM active components in the last 10 years.

XIST as a valuable biomarker for prognosis and clinical parameters in diverse tumors: a comprehensive meta- and bioinformatics analysis.

Long non-coding RNA (lncRNA) X inactivate-specific transcript (XIST) has been found dysregulated in a variety of human tumors and influenced the clinicopathologic characteristics in cancer patients. Therefore, we systematically searched relevant literature that has identified the correlation of lncRNA XIST expression and clinical outcomes of tumor patients and conducted this meta-analysis to elucidate the clinical prognostic value of long noncoding RNA XIST in human tumors. A comprehensive literature search was performed from PubMed, Web of Science, EMBASE, and Cochrane library databases up to August 1, 2019. Pooled hazard ratios (HRs) or odds ratios (ORs) with a 95% confidence interval (95% Cl) were calculated to evaluate the prognosis, as well as the clinicopathological parameters of XIST, respectively. We also further validated this meta-analysis using The Cancer Genome Atlas (TCGA) dataset. The outcome revealed that XIST overexpression in tumor tissue was interacted to a poor overall survival (OS) (HR=0.52, 95% CI: 0.44-0.61, p<0.0001), disease-free survival (DFS) (HR=0.50; 95% CI: 0.36-0.69, p<0.0001), tumor type (digestive system malignancies, HR=0.53; 95% CI: 0.44-0.63, p<0.0001); nondigestive system malignancies, HR=0.48; 95% CI: 0.34-0.67, p<0.0001), lymph node metastasis(LNM) (OR=0.61, 95% CI: 0.37-1.00; p=0.048), differentiation (OR=1.46; 95% CI: 0.94-2.29; p=0.096), distant metastasis (DM) (OR=0.48, 95% CI: 0.31-0.75; p=0.001), tumor size (OR=0.59, 95% CI: 0.38-0.92; p=0.019), and tumor stage (OR=2.36; 95% CI: 1.62-3.43; p<0.001). XIST could have potential value in early diagnosis and result in prediction and provide a novel view for the therapeutic target in clinical application.

Hesperidin Exhibits Protective Effects against PM2.5-Mediated Mitochondrial Damage, Cell Cycle Arrest, and Cellular Senescence in Human HaCaT Keratinocytes.

Particulate matter 2.5 (PM2.5) exposure can trigger adverse health outcomes in the human skin, such as skin aging, wrinkles, pigment spots, and atopic dermatitis. PM2.5 is associated with mitochondrial damage and the generation of reactive oxygen species (ROS). Hesperidin is a bioflavonoid that exhibits antioxidant and anti-inflammatory properties. This study aimed to determine the mechanism underlying the protective effect of hesperidin on human HaCaT keratinocytes against PM2.5-induced mitochondrial damage, cell cycle arrest, and cellular senescence. Human HaCaT keratinocytes were pre-treated with hesperidin and then treated with PM2.5. Hesperidin attenuated PM2.5-induced mitochondrial and DNA damage, G0/G1 cell cycle arrest, and SA-ßGal activity, the protein levels of cell cycle regulators, and matrix metalloproteinases (MMPs). Moreover, treatment with a specific c-Jun N-terminal kinase (JNK) inhibitor, SP600125, along with hesperidin markedly restored PM2.5-induced cell cycle arrest and cellular senescence. In addition, hesperidin significantly reduced the activation of MMPs, including MMP-1, MMP-2, and MMP-9, by inhibiting the activation of activator protein 1. In conclusion, hesperidin ameliorates PM2.5-induced mitochondrial damage, cell cycle arrest, and cellular senescence in human HaCaT keratinocytes via the ROS/JNK pathway.