[Occurrence and Fate of Steroid Hormones in Sewage Treatment Plants].

Sewage treatment plants (STPs) are one of the crucial barriers for the environmental emission of steroid hormones. Insights into the occurrence and fate of different categories of steroid hormones in STPs could provide theoretical support for improving steroid removal by STPs. The present study investigated 22 steroid hormones in each treatment process of two STPs located in Wuxi via eight monthly sampling campaigns and compared the efficacy of Anaerobic-Anoxic-Aerobic (A2/O) and reversed A2/O treatments. The results showed that the total steroid concentrations in the influent and effluent were 27.7-256.8 ng·L-1 and 5.7-211.0 ng·L-1, respectively, and 36.3-123.6 ng·g-1 in the excess sludge. Androsterone, androstenedione, estrone, estriol, and progesterone were the main species detected in the STPs. The concentrations of most steroids increased with the rise of rainfall and temperature, whereas the removal rates were not significantly different between winter and summer. Secondary and tertiary treatment processes showed better performance in steroid removal compared with that in the primary treatment; however, reversed A2/O did not show advantages over traditional A2/O. The organic-normalized partition coefficients (lg Koc) of steroids ranged between 2 and 4.5. The values of lg Koc in STP A were slightly greater than those in STP B, indicating that the partition behavior of steroids may influence their treatment efficacies.

Effects of Moringa Oleifera Leaf Extract Plus Rosiglitazone on Serum Leptin and Glucose and Lipid Metabolism in Type 2 Diabetic Rats.

Objective: To investigate the effects of Moringa Oleifera Leaf Extract (MOLE) plus rosiglitazone (RSG) on glucose and lipid metabolism, serum leptin, and the Akt/GSK3ß/ß-Catenin signaling pathway in type 2 diabetic (T2D) rats. Methods: Sixty male Sprague-Dawley (SD) rats were randomly divided into six groups: the normal group, the model group, the RSG group, the low- and high-dose MOLE group, and the MOLE+RSG group. The normal group was fed a standard rat diet, while the other groups were given a single intraperitoneal injection of low-dose streptozomycin (STZ) (35 mg/kg) and fed a high-sugar and high-fat diet. After 8 weeks, the treatment outcomes were evaluated by measuring key parameters of blood glucose and lipid metabolism and the protein kinase B (AKT) / Glycogen synthase kinase 3beta (GSK3ß) /ß-Catenin signaling pathway in the T2D rats. Results: Compared with the normal group, the model group showed significantly increased levels of blood glucose, blood lipids, serum leptin, free fatty acid (FFA), and tumor necrosis factor-α (TNF-α). Compared with the model group, the RSG, low-dose MOLE, and high-dose MOLE groups displayed effective control of blood glucose, blood lipids, serum leptin, FFA, and TNF-α. The MOLE+RSG group surpassed the RSG group in regulating glucose, lipid metabolism, and serum leptin levels in T2D rats. In addition, the MOLE+RSG group also had superiority over the RSG group in activating the AKT/GSK3ß/ß-Catenin pathway. Conclusion: MOLE plus RSG can effectively reduce blood glucose and blood lipids in T2DM rats.

Identifying the risk factors and developing a predictive model for postoperative pelvic floor dysfunction in cervical cancer patients.

Background: Pelvic floor dysfunction is a common complication after cervical cancer surgery, and the key to early prevention and treatment is the timely identification of risk factors and high-risk patients. The present study explored the risk factors of pelvic floor dysfunction in cervical cancer patients after surgery and established a predictive model. Methods: A total of 282 cervical cancer patients admitted to Wuhan No.7 Hospital from January 2020 to June 2022 was retrospectively enrolled in this study. All patients underwent surgery and were followed up after surgery. The patients were divided into a pelvic floor dysfunction group (n=92) and a control group (n=190) according to whether they developed pelvic floor dysfunction or not at 6 months post-surgery. The differences in clinical features between the two groups were observed to identify the risk factors of pelvic floor dysfunction after cervical cancer, and a prediction model was established. Results: There were significant differences in age, surgical method, surgical resection range, and radiotherapy between the two groups (P<0.05). Age greater than 65 years, open surgery, total hysterectomy, and radiotherapy were identified as the risk factors of postoperative pelvic floor dysfunction in patients with cervical cancer (P<0.05). The R4.0.3 statistical software was used to randomly divide the dataset into a training dataset (n=141) and a validation dataset (n=141). The area under the curve was 0.755 (95% confidence interval: 0.673-0.837) in the training set and 0.604 (95% confidence interval: 0.502-0.705) in the verification set. In the validation set, the model was tested with a Hosmer-Lemeshow Goodness-of-Fit test, with a chi-square value of 9.017 and a P value of 0.341. Conclusions: Patients with cervical cancer have a high incidence of postoperative pelvic floor dysfunction. Age greater than 65 years, open surgery, total hysterectomy, and radiotherapy are risk factors of postoperative pelvic floor dysfunction in cervical cancer patients, and the present model helps to identify patients at high-risk of pelvic floor dysfunction.

The mitochondrial protein YME1 Like 1 is important for non-small cell lung cancer cell growth.

The expression and biological function of the mitochondrial inner membrane protease YME1L (YME1 Like 1 ATPase) in NSCLC are tested here. Bioinformatical analyses and results from local human tissues show that YME1L expression is elevated in NSCLC tissues. YME1L upregulation was observed in primary and immortalized NSCLC cells. In NSCLC cells, shRNA-mediated silence of YME1L or dCas9/sgRNA-induced knockout (KO) of YME1L robustly suppressed cell growth and migration, and provoking apoptosis. YME1L shRNA/KO resulted in mitochondrial dysfunctions in NSCLC cells, leading to mitochondrial depolarization, ROS accumulation and ATP depletion. Conversely, ectopic YME1L overexpression augmented NSCLC cell proliferation and motility. Akt-S6K1 phosphorylation was reduced after YME1L shRNA/KO in primary NSCLC cells, but augmented after YME1L overexpression. Importantly, YME1L KO-caused anti-NSCLC cell activity was attenuated by a constitutively-activate Akt1 (S473D) construct. In vivo, subcutaneous NSCLC xenograft growth was remarkably slowed following intratumoral YME1L shRNA AAV injection in nude mice. YME1L knockdown, Akt-mTOR inactivation and ATP reduction were detected in YME1L-silenced NSCLC xenografts. Taken together, overexpressed YME1L in NSCLC exerts pro-tumorigenic function.

Serum glycoprotein non-metastatic melanoma protein B (GPNMB) level as a potential biomarker for diabetes mellitus-related cataract: A cross-sectional study.

Background: Diabetes mellitus (DM), a metabolic disease that has attracted significant research and clinical attention over the years, can affect the eye structure and induce cataract in patients diagnosed with DM. Recent studies have indicated the relationship between glycoprotein non-metastatic melanoma protein B (GPNMB) and DM and DM-related renal dysfunction. However, the role of circulating GPNMB in DM-associated cataract is still unknown. In this study, we explored the potential of serum GPNMB as a biomarker for DM and DM-associated cataract. Methods: A total of 406 subjects were enrolled, including 60 and 346 subjects with and without DM, respectively. The presence of cataract was evaluated and serum GPNMB levels were measured using a commercial enzyme-linked immunosorbent assay kit. Results: Serum GPNMB levels were higher in diabetic individuals and subjects with cataract than in those without DM or cataract. Subjects in the highest GPNMB tertile group were more likely to have metabolic disorder, cataract, and DM. Analysis performed in subjects with DM elucidated the correlation between serum GPNMB levels and cataract. Receiver operating characteristic (ROC) curve analysis also indicated that GPNMB could be used to diagnose DM and cataract. Multivariable logistic regression analysis illustrated that GPNMB levels were independently associated with DM and cataract. DM was also found to be an independent risk factor for cataract. Further surveys revealed the combination of serum GPNMB levels and presence of DM was associated with a more precise identification of cataract than either factor alone. Conclusions: Increased circulating GPNMB levels are associated with DM and cataract and can be used as a biomarker of DM-associated cataract.

Chiral dual-emission composite material fluorescein/CCQDs @ZIF-8 for highly efficient recognition of phenylenediamine isomers and their oxidized product.

As a new type of fluorescent nanomaterial, chiral carbon quantum dots (CCQDs) have the advantages of wide source, good water solubility and high chemical stability, and have been widely used in drug detection, bioimaging and chemical sensing. In this work, a chiral dual-emission hybrid material fluorescein/CCQDs@ZIF-8 (1) was synthesized by in-situ encapsulation strategy. Luminescence emission position of CCQDs and fluorescein are almost unchanged after the encapsulation into ZIF-8. The luminescent emissions of CCQDs and fluorescein can be observed to be located at 430 nm and 513 nm, respectively. When 1 is soaked in pure water, ethanol, dimethylsulfoxide, DMF, DMA and targeted substances solution for 24 h, 1 can maintain its structural stability. Photo-luminescent (PL) studies show that 1 can discriminate p-phenylenediamine (PPD) from m-phenylenediamine (MPD) and o-phenylenediamine (OPD), which can detect the presence of PPD with high sensitivity and selectivity (ratiomeric fluorescent probe with KBH: 1.85 × 103 M-1 and detection limit: 8.51 µM). Further, 1 also effectively distinguish the oxidized product of these phenylenediamine(PD) isomers. 1 can be used as a "turn-off" fluorescent probe to detect oxidized product of PPD (ratiomeric fluorescent probe with KSV: 6.82 × 102 M-1 and detection limit: 0.112 mM) and a "turn-on" fluorescent probe to detect oxidized product of MPD (ratiomeric fluorescent probe: KBH: 1.65 × 103 M-1 and detection limit: 35.03 µM) and oxidized product of OPD (ratiomeric fluorescent probe: KBH: 2.40 × 106 M-1 and detection limit: 0.105 µM). Further, for the convenience of practical application, 1 can be developed as fluorescence ink and be prepared into a mixed matrix membrane. When the target substances are gradually added to the membrane, significant luminescence change with obvious color change can be observed.

5-epi-ent-Kaurane diterpenoids from the aerial parts of Isodon eriocalyx and their anti-atherosclerotic potential.

The phytochemical investigation of the EtOAc extract from the aerial parts of Isodon eriocalyx afforded seventeen diterpenoids, including eight undescribed compounds. Eriocalyxins H-L have unique structural characteristics featuring a 5-epi-ent-kaurane diterpenoid scaffold with eriocalyxins H-K also possess an unusual 6,11-epoxyspiro-lactone ring while eriocalyxin L, a 1,7:3,20-diepoxy-ent kaurene, features an 1,7-oxygen linkage. The structures of these compounds were elucidated by spectroscopic data interpretation, and the absolute configurations of eriocalyxins H, I, L, and M were confirmed by single-crystal X-ray diffraction. The isolates were screened for their inhibitory activities against VCAM-1 and ICAM-1 at 5 µM. While eriocalyxin O, coetsoidin A and laxiflorin P were found to significantly inhibit both VCAM-1 and ICAM-1, 8 (17),13-ent-labdadien-15 â†’ 16-lactone-19-oic acid displayed evidently inhibitory effect against ICAM-1.

Association between dietary calcium and depression among American adults: National health and nutrition examination survey.

Background: There is only limited evidence for an association between calcium (Ca) and depression, and the relationship was inconsistent. Therefore, the aim of this study was to assess the relationship between dietary Ca and the risk of depressive symptoms in individuals over the age of 18 in the US. Methods: We extracted 14,971 participants from the US National Health and Nutrition Examination Survey (NHANES) 2007-2016 to probe their associations. Dietary Ca intake was measured through 24 h dietary recall method. Patients with the Patient Health Questionnaire-9 (PHQ-9) ≥ 10 scores were believed to have depressive symptoms. The association between dietary Ca and depressive symptoms was investigated using multivariate logistic regression, sensitivity analysis, and restricted cubic spline regression. Results: In this study, 7.6% (1,144/14,971) of them had depressive symptoms. After adjusting for sex, age, race, poverty to income ratio (PIR), marital status, education, body mass index (BMI), caffeine intake, carbohydrates intake, total energy intake, smoking status, alcohol consumption, physical activity, diabetes, hypertension, severe cardiovascular disease (CVD), cancer, serum vitamin D, serum Ca, and Ca supplement, the adjusted ORs value [95% confidence interval (CI)] of depression for the lowest category (Q1 ≤ 534 mg/day) vs. Q2-Q4 of Ca intake were 0.83 (0.69-0.99), 0.97 (0.65-0.95), and 0.80 (0.63-0.98) with the p for trend (p = 0.014). The relationship between dietary Ca intake and depressive symptoms was linear (non-linear p = 0.148). None of the interactions were significant except among races (p for interaction = 0.001). Conclusion: Association between dietary Ca and the prevalence of depressive symptoms in US adults. And Ca intake was negatively associated with the risk of depressive symptoms. As Ca intake increased, the prevalence of depressive symptoms decreased.

LncRNA BC promotes lung adenocarcinoma progression by modulating IMPAD1 alternative splicing.

BACKGROUND: The therapeutic value of targeted therapies in patients with lung cancer is reduced when tumours acquire secondary resistance after an initial period of successful treatment. However, the molecular events behind the resistance to targeted therapies in lung cancer remain largely unknown. AIMS: To discover the important role and mechanism of lncRNA BC in promoting tumor metastasis and influencing clinical prognosis of LUAD. MATERIALS & METHODS: Microarrays were used to screen a comprehensive set of lncRNAs with differential expression profiles in lung cancer cells. The functional role and mechanism of lncRNA were further investigated by gain- and loss-of-function assays. RNA pull-down, protein assays, and mass spectrometry were used to identify proteins that interacted with lncRNA. TaqMan PCR was used to measure lncRNA in lung adenocarcinoma and adjacent nontumor tissues from 428 patients. The clinical significance of lncRNA identified was statistically confirmed in this cohort of patients. RESULTS: In this study, we show that the long non-coding RNA BC009639 (BC) is involved in acquired resistance to EGFR-targeted therapies. Among the 235 long non-coding RNAs that were differentially expressed in lung cancer cell lines, with different metastatic potentials, BC promoted growth, invasion, metastasis, and resistance to EGFR-tyrosine kinase inhibitors (EGFR-TKIs), both in vitro and in vivo. BC was highly expressed in 428 patients with lung adenocarcinoma (LUAD) and high BC expression correlated with reduced efficacy of EGFR-TKI therapy. To uncover the molecular mechanism of BC-mediated EGFR-TKI resistance in lung cancer, we screened and identified nucleolin and hnRNPK that interact with BC. BC formed the splicing complex with nucleolin and hnRNPK to facilitate the production of a non-protein-coding inositol monophosphatase domain containing 1 (IMPAD1) splice variant, instead of the protein-coding variant. The BC-mediated alternative splicing (AS) of IMPAD1 resulted in the induction of the epithelial-mesenchymal transition and resistance to EGFR-TKI in lung cancer. High BC expression correlated with clinical progress and poor survival among 402 patients with LUAD. DISSCUSSION: Through alternative splicing, BC boosted the non-coding IMPAD1-203 transcript variant while suppressing the IMPAD1-201 variant. In order to control the processing of pre-mRNA, BC not only attracted RNA binding proteins (NCL, IGF2BP1) or splicing factors (hnRNPK), but also controlled the formation of the splicing-regulator complex by creating RNA-RNA-duplexes. CONCLUSION: Our results reveal an important role for BC in mediating resistance to EGFR-targeted therapy in LUAD through IMPAD1 AS and in implication for the targeted therapy resistance.

Pilose antler (Cervus elaphus Linnaeus) polysaccharide and polypeptide extract inhibits bone resorption in high turnover type osteoporosis by stimulating the MAKP and MMP-9 signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Pilose antler is a traditional Chinese medicine used to improve kidney function, strengthen tendons and bones, and prolong life, among other uses. It is widely employed in the treatment of osteoporosis. However, the molecular mechanisms underlying the treatment of high turnover osteoporosis are not fully understood. AIM OF THE STUDY: The present study aimed to investigate the molecular mechanism underlying pilose antler polysaccharide and polypeptide extracts in inhibiting bone resorption in high turnover osteoporosis, and compare the effects of the two components alone and in combination to explore whether they could produce synergistic enhancement effects. MATERIALS AND METHODS: The quantitative and qualitative characteristics of pilose antler polysaccharide and polypeptide extracts were detected by UV-visible spectrophotometry and high-performance liquid chromatography. A rat model of retinoic acid-induced osteoporosis was used to evaluate the inhibitory effect of the extracts on bone resorption. Enzyme-linked immunosorbent assay (ELISA) was used to detect the activity of factors related to high turnover type osteoporosis in rat serum. Western blotting was used to detect the expression of proteins related to the MAKP and MMP-9 signaling pathways in rat femurs. Fluorescence quantitative PCR was used to detect the transcription levels of genes related to the MAKP and MMP-9 signaling pathways in rat femur tissues. Hematoxylin and eosin staining were used to observe the osteoprotective effects of pilose antler polysaccharides and polypeptides. RESULTS: The yield of pilose antler polysaccharides was 8.3%, and was mainly composed of mannose, glucosamine hydrochloride, glucuronic acid, Galacturonic acid, Galactose hydrochloride, glucose, and galactose. The yield of the polypeptides was 26.2%, and eighty percent of the molecular weight of the antler polypeptides was 1.6 kDa-7kD, among which, the molecular weight of 7kD peptide accounted for 52% of the total. Both polysaccharides and peptides could reduce the activities of TRACP, OCN, ERK1, JNK, and MMP-9 in rat serum and reduce both the protein expression and gene transcription levels of ERK1, JNK, and MMP-9 in rat femur tissue with significant differences compared with the model group. Both extracts exerted significant protective effects on rat femur tissue. The effect of pilose antler polypeptides alone was better than that of polysaccharides either alone or in combination. CONCLUSIONS: Pilose antler polysaccharides, polypeptides, and their mixtures could inhibit the occurrence of bone resorption of high turnover osteoporosis by stimulating the MAKP and MMP-9 signaling pathways to reduce the expression of the ERK1, JNK, and MMP-9 genes and proteins, and could help alleviate bone loss caused by retinoic acid. Pilose antler polypeptides had a stronger effect on inhibiting bone resorption. The combination of the two components did not show synergistic enhancement effect, and the polysaccharide tended to moderate the inhibitory enhancement effect of the polypeptide.

Potential applications of JAK inhibitors, clinically approved drugs against autoimmune diseases, in cancer therapy.

Disturbances in immunoregulation may lead to both cancer and autoimmune diseases. Many therapeutic drugs for autoimmune diseases also display anti-tumor efficacy. The Janus kinase/signal transducer and activator of transcription signaling pathways are involved in the secretion of more than 50 distinct cytokines, which have critical roles in inducing autoimmune diseases and tumorigenesis. Thus, Janus kinases have become classical immunotherapeutic targets for immune disease. More than 70 Janus kinase inhibitors have been approved as immunomodulatory drugs for clinical use, of which 12 are used in the treatment of autoimmune diseases. This systematic review aims to elucidate the anti-tumor role of clinically approved Janus kinase inhibitors that were primarily designed for the treatment of autoimmune diseases and their potential for clinical translation as cancer treatments.

TIMM44 is a potential therapeutic target of human glioma.

TIMM44 (translocase of inner mitochondrial membrane 44) is essential for the maintenance of mitochondrial functions. Bioinformatics studies and results from the local high-grade glioma tissues showed that TIMM44 mRNA and protein levels are elevated in glioma, correlating with poor overall survival. Mitochondrial TIMM44 upregulation was also detected in patient-derived primary glioma cells and immortalized cell line. In primary and established glioma cells, TIMM44 depletion, using the lentiviral shRNA strategy or the CRISPR/Cas9 knockout (KO) method, robustly inhibited cell viability, proliferation and migration. Moreover, TIMM44 silencing/KO resulted in mitochondrial complex I inhibition, ATP depletion, mitochondrial membrane potential reduction, oxidative stress and DNA damage, and eventually provoked apoptosis. Conversely, ectopic overexpression of TIMM44 augmented glioma cell proliferation and migration. TIMM44 upregulation in glioma is possibly due to increased TIMM44 transcriptional machinery by the transcription factor GATA3 in a YME1L (YME1 Like 1 ATPase)-dependent manner. In vivo, the growth of subcutaneous glioma xenografts was suppressed after intratumoral injection of TIMM44 shRNA adeno-associated virus (AAV). TIMM44 depletion, ATP reduction, oxidative injury and apoptosis were detected in TIMM44 shRNA AAV-injected glioma xenografts. Moreover, the intracranial growth of TIMM44 KO glioma cells in the mouse brain was largely inhibited. Together, overexpressed TIMM44 could be a novel and promising therapeutic target of human glioma.

Potential biomarkers for clinical outcomes of IVF cycles in women with/without PCOS: Searching with metabolomics.

Background: Polycystic ovary syndrome (PCOS) is a heterogeneous endocrinological and metabolic disorder which is the common cause of female infertility. The dysmetabolism displayed in it has not been completely ascertained. Metabonomics may shed light on understanding many small molecule endogenous metabolites and their associated metabolic pathways. Objective: To analyze the different metabolites and related metabolic pathways in follicular fluid and embryo culture fluid of PCOS and non-PCOS groups. Finding markers predictable for clinical outcomes of in vitro fertilization-embryo transfer (IVF-ET) treatment. Population and sample: 60 women who underwent IVF-ET were selected, including 30 with PCOS and 30 with the fallopian tubal issues only. We collected the first tube follicular fluid (FF) of all patients at the time of oocyte pick up and the waste embryo culture medium (ECM) after D3 high-quality embryo transplant. Methods: All samples were performed nontargeted Ultra High Performance Liquid Chromatography-Mass Spectrometry (UHPLC-QE-MS) analysis. Related metabolic pathways were screened by KEGG annotation. To search potential indicators, the logistic regression was made combined with clinical data. Mean outcome measures: Predictive performance of markers of clinical outcomes (pregnancy rate, delivery rate, live birth rate, miscarriage rate) of assisted reproductive technology (ART). Results: Comparing the PCOS group against the non-PCOS group, we found 11 significantly different metabolites in the FF and 56 in the ECM. There are a total of 11 kinds of biomarkers associated with clinical outcomes. Androsterone sulfate, Glycerophosphocholine, and Elaidic carnitine seem robust to predict the abortion rate of the PCOS group, with an AUC of 0.941, 0.933, 0.933, respectively. The glycerol phospholipid metabolic pathway is enriched in both the follicular fluid and embryo culture fluid. Conclusions: The differential metabolites were mainly a variety of lipids. Some of them can predict clinical outcomes to a certain extent.

Spectrum-effect relationship between hplc fingerprint and anti-inflammatory activity of n-butanol parts of Tetrastigma planicaule (Hook) Gagnep.

The present study aimed to evaluate the spectrum-effect relationships between high-performance liquid chromatography fingerprints and anti-inflammatory effects of Tetrastigma planicaule(Hook.)Gagnep. Chemical fingerprints of ten batches of Tetrastigma planicaule from various sources were obtained by HPLC. The anti-inflammatory activity was investigated by a model of ear swelling in mice caused by xylene and a model of cotton pellet granuloma. Hierarchical cluster analysis (HCA) results showed that all the samples were clustered into four categories, which was basically consistent with the principal component analysis (PCA) results. The results of the joint grey relational analysis (GRA) and partial least squares regression analysis (PLSR) showed that peaks 1, 2 and 12 were positively correlated with the anti-acute inflammatory effect (ear swelling) in mice, and peaks 3, 5, 6 and 11 were positively correlated with the anti-chronic inflammatory effect (cotton pellet granuloma) in mice. The anti-inflammatory effect of Tetrastigma planicaule is the result of the synergistic effect of multiple components, which provides a basis for further exploring the anti-inflammatory substances and quality evaluation of the herb.

Bioinformatics analysis and experimental verification of the prognostic and biological significance mediated by fatty acid metabolism related genes for hepatocellular carcinoma.

Background: Liver cancer is among the leading causes of death related to cancer around the world. The most frequent type of human liver cancer is hepatocellular carcinoma (HCC). Fatty acid (FA) metabolism is an emerging hallmark that plays a promoting role in numerous malignancies. This study aimed to discover a FA metabolism-related risk signature and formulate a better model for HCC patients' prognosis prediction. Methods: We collected mRNA expression data and clinical parameters of patients with HCC using the TCGA databases, and the differential FA metabolism-related genes were explored. To create a risk prognostic model, we carried out the consensus clustering as well as univariate and multivariate Cox regression analyses. 16 genes were used to establish a prognostic model, which was then validated in the ICGC dataset. The accuracy of the model was performed using receiver operating characteristic (ROC) analyses, decision curve analysis (DCA) and nomogram. The immune cell infiltration level of risk genes was evaluated with single-sample GSEA (ssGSEA) algorithm. To reflect the response to immunotherapy, immunophenoscore (IPS) was obtained from TCGA-LIHC. Then, the expression of the candidate risk genes (p < 0.05) was validated by qRT-PCR, Western blotting and single-cell transcriptomics. Cellular function assays were performed to revealed the biological function of HAVCR1. Results: According to the TCGA-LIHC cohort analysis, the majority of the FA metabolism-related genes were expressed differentially in the HCC and normal tissues. The prognosis of patients with high-risk scores was observed to be worse. Multivariate COX regression analysis confirmed that the model can be employed as an independent prognosis factor for HCC patients. Furthermore, ssGSEA analysis revealed a link between the model and the levels of immune cell infiltration. Our model scoring mechanism also provides a high predictive value in HCC patients receiving anti-PDL1 immunotherapy. One of the FA metabolism-related genes, HAVCR1, displays a significant differential expression between normal and HCC cell lines. Hepatocellular carcinoma cells (Huh7, and HepG2) proliferation, motility, and invasion were all remarkably inhibited by HAVCR1 siRNA. Conclusion: Our study identified a novel FA metabolism-related prognostic model, revealing a better potential treatment and prevention strategy for HCC.

Timely vitrectomy without intraocular lens removal for acute endophthalmitis after cataract surgery.

AIM: To investigate the clinical features, causative organisms and effects of timely vitrectomy and silicone oil tamponade without intraocular lens (IOL) removal in the treatment of acute-onset endophthalmitis after cataract surgery (APCE). METHODS: We retrospectively analyzed the clinical features and microbiological factors in 10 eyes of 10 patients with APCE at Tianjin Medical University General Hospital from January 2010 to December 2018. Data on the clinical features, causative organisms, visual acuity, intraocular pressure (IOP) and complications were collected. The mean follow-up period was 25.5mo. RESULTS: The mean age of the patients was 71.4y. The mean time between cataract surgery and the onset of endophthalmitis was 2.0d. Preoperative visual acuity ranged from no light perception to hand motion. After vitrectomy, the visual acuity increased in nine eyes (90%), and was unchanged in one eye (10%). A significant difference was observed between the mean preoperative (36.3±7.1 mm Hg) and postoperative IOP (14.9±4.3 mm Hg, P<0.05). Staphylococcus epidermidis was isolated in 5 eyes, S. aureus in 2 eyes, and Enterococcus in 1 eye. Postoperative complications mainly included fibrin exudates in the anterior chamber at the early stages in all eyes and temporary IOP elevation in one eye. No retinal detachment or ocular atrophy was observed during the follow-up period. CONCLUSION: Under systemic antibiotic treatment and timely diagnosis, vitrectomy and silicone oil tamponade without IOL removal is a safe and effective method for APCE.

Copper peroxide coated upconversion nanoparticle modified with glucose oxidase for H2O2 self-supplying starvation-enhanced chemodynamic therapy in vitro.

Chemodynamic therapy (CDT) can convert endogenous hydrogen peroxide (H2O2) to highly reactive hydroxyl radical (˙OH) through Fenton or Fenton-like reaction to kill tumor cells, which is a promising anticancer strategy. However, the limited H2O2 and overexpressed glutathione (GSH) in tumor cells make CDT ineffective. Here, an efficient nanocomposite, UCN@CuO2-GOx (UCCuG), was synthesized, realizing both starvation therapy and H2O2 self-supplying CDT in vitro. In this case, the glucose oxidase (GOx) of the nanocomposite could consume glucose for starvation therapy after the UCCuG nanocomposite entered tumor cells. In addition, the acidic environment of the lysosome triggered the release of Cu2+ and H2O2 by the decomposition of UCCu; then, Cu2+ was reduced to Cu+ by GSH in tumor cells; and finally, Cu+ catalyzed the released H2O2 to generate ˙OH for CDT. The in vitro experiments demonstrated starvation-enhanced CDT with remarkable results. Meanwhile, under 980 nm laser irradiation, the upconversion luminescence signal of UCN in the UCCuG nanocomposite was reduced due to the CuO2-GOx coating, while it gradually recovered after the UCCuG nanocomposite reacted with glucose and GSH under the tumor microenvironment (TME). Such a luminescent intensity recovery process is expected to monitor the TME-activated therapeutic effect in real time. This strategy may solve the problem of insufficient CDT efficacy caused by limited endogenous H2O2 and overexpressed GSH in tumor cells. This multifunctional nanocomposite demonstrates the promising application of starvation-enhanced CDT in tumor treatment.

MiR-320b and miR-320d as Biomarkers to Predict and Participate in the Formation of Platinum Resistance in Ovarian Cancer Patients.

Patients with ovarian cancer who receive platinum-based chemotherapy typically develop platinum resistance, which leads to tumor recurrence and mortality. Therefore, finding the underlying mechanisms and biomarkers is critical. A total of 51 platinum-resistant and 70 platinum-sensitive ovarian cancer patients were enrolled in this study. We examined the GSE131978 dataset in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus database for differentially expressed long non-coding RNAs and messenger RNAs (mRNAs) between platinum-resistant and platinum-sensitive patients and completed a microRNA chip analysis. After filtering by Pearson correlation analysis, the competitive endogenous RNA (ceRNA) networks were subsequently constructed. Then, the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology enrichment analyses about mRNAs in ceRNA networks were accomplished. More crucially, we demonstrated the differentially expressed microRNAs using quantitative real-time PCR and fluorescence in situ hybridization. The feasibility of microRNAs as biomarkers to predict platinum resistance and tumor recurrence was assessed using the receiver operating characteristic curve and survival analysis. MiR-320b and miR-320d exhibited high area under the curve values of 0.757 and 0.702, respectively. In our study, ceRNA networks including miR-320b and miR-320d probably provided novel insights for platinum resistance in ovarian cancer patients.

A Novel Small Molecular Inhibitor of DNMT1 Enhances the Antitumor Effect of Radiofrequency Ablation in Lung Squamous Cell Carcinoma Cells.

Radiofrequency ablation (RFA) is a relatively new and effective therapeutic strategy for treating lung squamous cell carcinomas (LSCCs). However, RFA is rarely used in the clinic for LSCC which still suffers from a lack of effective comprehensive treatment strategies. In the present work, we investigate iDNMT, a novel small molecular inhibitor of DNMT1 with a unique structure. In clinical LSCC specimens, endogenous DNMT1 was positively associated with methylation rates of miR-27-3p's promoter. Moreover, endogenous DNMT1 was negatively correlated with miR-27-3p expression which targets PSEN-1, the catalytic subunit of γ-secretase, which mediates the cleavage and activation of the Notch pathway. We found that DNMT1 increased activation of the Notch pathway in clinical LSCC samples while downregulating miR-27-3p expression and hypermethylation of miR-27-3p's promoter. In addition of inhibiting activation of the Notch pathway by repressing methylation of the miR-27-3p promoter, treatment of LSCC cells with iDNMT1 also enhanced the sensitivity of LSCC tumor tissues to RFA treatment. These data suggest that iDNMT-induced inhibition of DNMT-1 enhances miR-27-3p expression in LSCC to inhibit activation of the Notch pathway. Furthermore, the combination of iDNMT and RFA may be a promising therapeutic strategy for LSCC.