Protein succinylation, hepatic metabolism, and liver diseases.

Succinylation is a highly conserved post-translational modification that is processed via enzymatic and non-enzymatic mechanisms. Succinylation exhibits strong effects on protein stability, enzyme activity, and transcriptional regulation. Protein succinylation is extensively present in the liver, and increasing evidence has demonstrated that succinylation is closely related to hepatic metabolism. For instance, histone acetyltransferase 1 promotes liver glycolysis, and the sirtuin 5-induced desuccinylation is involved in the regulation of the hepatic urea cycle and lipid metabolism. Therefore, the effects of succinylation on hepatic glucose, amino acid, and lipid metabolism under the action of various enzymes will be discussed in this work. In addition, how succinylases regulate the progression of different liver diseases will be reviewed, including the desuccinylation activity of sirtuin 7, which is closely associated with fatty liver disease and hepatitis, and the actions of lysine acetyltransferase 2A and histone acetyltransferase 1 that act as succinyltransferases to regulate the succinylation of target genes that influence the development of hepatocellular carcinoma. In view of the diversity and significance of protein succinylation, targeting the succinylation pathway may serve as an attractive direction for the treatment of liver diseases.

Purine salvage-associated metabolites as biomarkers for early diagnosis of esophageal squamous cell carcinoma: a diagnostic model-based study.

Esophageal squamous cell carcinoma (ESCC) remains an important health concern in developing countries. Patients with advanced ESCC have a poor prognosis and survival rate, and achieving early diagnosis remains a challenge. Metabolic biomarkers are gradually gaining attention as early diagnostic biomarkers. Hence, this multicenter study comprehensively evaluated metabolism dysregulation in ESCC through an integrated research strategy to identify key metabolite biomarkers of ESCC. First, the metabolic profiles were examined in tissue and serum samples from the discovery cohort (n = 162; ESCC patients, n = 81; healthy volunteers, n = 81), and ESCC tissue-induced metabolite alterations were observed in the serum. Afterward, RNA sequencing of tissue samples (n = 46) was performed, followed by an integrated analysis of metabolomics and transcriptomics. The potential biomarkers for ESCC were further identified by censoring gene-metabolite regulatory networks. The diagnostic value of the identified biomarkers was validated in a validation cohort (n = 220), and the biological function was verified. A total of 457 dysregulated metabolites were identified in the serum, of which 36 were induced by tumor tissues. The integrated analyses revealed significant alterations in the purine salvage pathway, wherein the abundance of hypoxanthine/xanthine exhibited a positive correlation with HPRT1 expression and tumor size. A diagnostic model was developed using two purine salvage-associated metabolites. This model could accurately discriminate patients with ESCC from normal individuals, with an area under the curve (AUC) (95% confidence interval (CI): 0.680-0.843) of 0.765 in the external cohort. Hypoxanthine and HPRT1 exerted a synergistic effect in terms of promoting ESCC progression. These findings are anticipated to provide valuable support in developing novel diagnostic approaches for early ESCC and enhance our comprehension of the metabolic mechanisms underlying this disease.

Single-cell transcriptomic analysis reveals the landscape of epithelial-mesenchymal transition molecular heterogeneity in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a prevalent and highly lethal malignant disease. The epithelial-mesenchymal transition (EMT) is crucial in promoting ESCC development. However, the molecular heterogeneity of ESCC and the potential inhibitory strategies targeting EMT remain poorly understood. In this study, we analyzed high-resolution single-cell transcriptome data encompassing 209,231 ESCC cells from 39 tumor samples and 16 adjacent samples obtained from 44 individuals. We identified distinct cell populations exhibiting heterogeneous EMT characteristics and identified 87 EMT-associated molecules. The expression profiles of these EMT-associated molecules showed heterogeneity across different stages of ESCC progression. Moreover, we observed that EMT primarily occurred in early-stage tumors, before lymph node metastasis, and significantly promoted the rapid deterioration of ESCC. Notably, we identified SERPINH1 as a potential novel marker for ESCC EMT. By classifying ESCC patients based on EMT gene sets, we found that those with high EMT exhibited poorer prognosis. Furthermore, we predicted and experimentally validated drugs targeting ESCC EMT, including dactolisib, docetaxel, and nutlin, which demonstrated efficacy in inhibiting EMT and metastasis in ESCC. Through the integration of scRNA-seq, RNA-seq, and TCGA data with experimental validation, our comprehensive analysis elucidated the landscape of EMT during the entire course of ESCC development and metastasis. These findings provide valuable insights and a reference for refining ESCC clinical treatment strategies.

Sex differences in alterations of brain functional network in tobacco use disorder.

INTRODUCTION: Many studies have found sex differences in alterations of brain function in cigarette smoking adults from the perspective of functional activity or connectivity. However, no studies have systematically found different alteration patterns in brain functional topology of cigarette smoking men and women from three perspectives: nodal and network efficiency, and modular connections. METHODS: Fifty-six tobacco use disorder (TUD) participants (25 women) and 66 non-TUD participants (28 women) underwent a resting-state functional magnetic resonance imaging scan. The whole-brain functional networks were constructed and a two-way analysis of covariance with false discovery rate correction (q < 0.05) were performed to investigate whether men and women TUD participants had different alterations in the topological features at global, modular and nodal levels. RESULTS: Compared to non-TUD participants, men but not women TUD participants showed significantly lower global efficiency (lower inter-modular connections between the visual and executive control, between the visual and subcortical modules did not pass the correction) and significantly lower nodal global efficiency in the right superior occipital gyrus, bilateral fusiform gyrus, the right pallidum, right putamen, the bilateral paracentral lobule, the postcentral gyrus, and lower nodal local efficiency in the left paracentral lobule. CONCLUSIONS: Men and women TUD participants have different topological properties of brain functional network, which may contribute to our understanding of neural mechanisms underlying sex differences in TUD. IMPLICATIONS: Compared to non-TUD participants, we found men but not women TUD participants with significantly lower network metrics at global, modular and nodal level, which could improve our understanding of neural mechanisms underlying sex differences in TUD and lay a solid foundation for future sex-based TUD prevention and treatment.

Interaction effects between smoking and internet gaming disorder on resting-state functional connectivity of the ventral tegmental area and hippocampus.

Background: Many reports have focused on cigarette smoking and internet gaming disorder (IGD), with widespread alterations of resting-state functional connectivity (rsFC) in the reward and memory circuits, respectively. Epidemiological studies have also shown high comorbidity of cigarette smoking and IGD. However, the underlying mechanisms are still unknown. Therefore, this study investigates the comorbidity and interaction effects between smoking and IGD from the rsFC perspective. Methods: Resting-state functional magnetic imaging data were collected from 60 healthy controls (HC), 46 smokers, 38 IGD individuals, and 34 IGD comorbid with smoking (IGDsm) participants. Voxel-wise rsFC maps were calculated for all subjects with the ventral tegmental area, rostral hippocampus, and caudal hippocampus as regions of interest, respectively. Results: Significant interaction effects between smoking and IGD were mainly involved in the reward and memory circuits; that is, the rsFC between the ventral tegmental area and right nucleus accumbens, between the rostral hippocampus and bilateral nucleus accumbens, sensorimotor areas, and left middle temporal gyrus. Specifically, in these circuits, smokers showed decreased rsFC compared to the HC group, while IGDsm showed increased rsFC compared to smokers and IGD individuals. The IGDsm and HC groups showed no significant difference. The altered rsFC also correlated with clinical measures. Conclusion: These findings indicate that lower rsFC in smokers or IGD individuals increases under the effect of another type of addiction, such as smoking and IGD, but only increases to the normal state, which might explain the comorbidity and interaction between smoking and IGD from the perspective of functional circuits.

Exploration of Interstitial Fibrosis in Chronic Kidney Disease by Diffusion-Relaxation Correlation Spectrum MR Imaging: A Preliminary Study.

BACKGROUND: Renal interstitial fibrosis is one of the most common pathways in the progression of chronic kidney disease (CKD). Noninvasive evaluation of interstitial fibrosis would help monitoring CKD progression and prognosis prediction. PURPOSE: To evaluate the severity of renal interstitial fibrosis by diffusion-relaxation correlation spectrum imaging (DR-CSI). STUDY TYPE: Prospective. SUBJECTS: Forty patients with CKD and 10 healthy controls (average age 49.2 ± 14.8 years, 18 females). FIELD STRENGTH/SEQUENCE: 3-T, DR-CSI with 36 axial spin-echo echo-planar diffusion-weighted images (6 b-values, 6 echo times). ASSESSMENT: Interstitial fibrosis level (IFL) was assessed from biopsy results (IFL = 1, fibrosis percentage <25%, defined as mild; IFL = 2, 25%-50%, moderate; IFL = 3, >50%, severe). Estimated glomerular filtration rate (eGFR) was calculated using serum creatinine. The regions of interest included cortex for both kidneys. The diffusivity-T2 spectrum was assessed considering three compartments (threshold: T2 30-40 msec, diffusivity 5-9 µm2 /msec, according to visible peaks): A (low diffusivity, short T2), B (low diffusivity, long T2), and C (high diffusivity). Volume fractions Vi (i = A, B, C) were calculated. STATISTICAL TESTS: Intra-class coefficient (ICC, >0.6 as good) to assess inter-reader agreement of DR-CSI Vi . Spearman's correlation to assess relationship of Vi to IFL and eGFR. Receiver operating characteristic analyses with the area under the curve (AUC) to discriminate patients with moderate-severe fibrosis from mild ones. Statistical significance criteria: P-value <0.05. RESULTS: ICCs were good for all Vi . Correlations were found between IFL and VB (r = 0.424, significant) and VC (r = -0.400, significant), and between eGFR and VB (r = -0.303, P = 0.058) and VC (r = 0.487, significant). Regarding VB and VC , the AUCs were 0.903 and 0.824. DATA CONCLUSION: DR-CSI help distinguish patients with moderate or severe renal interstitial fibrosis from mild ones. EVIDENCE LEVEL: 2 Technical Efficacy: Stage 2.

Reciprocal modulation between cigarette smoking and internet gaming disorder on participation coefficient within functional brain networks.

Many reports indicated that cigarette smoking was associated with internet gaming disorder (IGD). However, the underlying mechanism of comorbidity between smoking and IGD and whether they had interaction effects on topological organization of brain functional network are still unknown. Therefore, we investigated the interaction between smoking and IGD in resting-state brain functional networks for 60 healthy controls, 46 smokers, 38 IGD individuals and 34 IGD comorbid with smoking participants. The modular structures of functional networks were explored and participation coefficient (Pc) was used to characterize the importance of each brain region in the communication between modules. Significant main effect of IGD was found in the left superior frontal gyrus, bilateral medial part of superior frontal gyrus and bilateral posterior cingulate gyrus with lower Pc in IGD group than in non-IGD group. Significant interaction effects between smoking and IGD were found in the left posterior orbital gyrus, right lateral orbital gyrus, left supramarginal gyrus, left middle temporal gyrus and left inferior temporal gyrus. The interaction in these brain regions was characterized by no significant difference or significantly decreased Pc in smokers or IGD individuals while significantly increased Pc in IGD comorbid with smoking group under the influence of IGD or smoking. Our findings provide valuable information underlying the neurophysiological mechanisms of smoking and IGD, and also offer a potential target for future clinical treatment of smoking and IGD comorbidity.

Sex-Dependent Alterations of Regional Homogeneity in Cigarette Smokers.

Biological sex may play a large role in cigarette use and cessation outcomes and neuroimaging studies have demonstrated that cigarette smoking is associated with sex-related differences in brain structure and function. However, less is known about sex-specific alterations in spontaneous brain activity in cigarette smokers. In this study, we investigated the sex-related effects of cigarette smoking on local spontaneous brain activity using regional homogeneity (ReHo) based on resting-state fMRI. Fifty-six smokers (24 females) and sixty-three (25 females) healthy non-smoking controls were recruited. Whole-brain voxelwise 2-way analysis of covariance of ReHo was performed to detect brain regions with sex-dependent alterations on the spontaneous brain activity. Compared to non-smokers, smokers exhibited significant ReHo differences in several brain regions, including the right medial orbitofrontal cortex extended to the ventral striatum/amygdala/parahippocampus, left precuneus, and bilateral cerebellum crus. Smoking and sex interaction analysis revealed that male smokers showed significantly lower ReHo in the right ventral striatum, left cerebellum crus1, and left fusiform gyrus compared to male non-smokers, whereas there are no significant differences between female smokers and non-smokers. Furthermore, the ReHo within the left cerebellum crus1 was negatively correlated with craving scores in male smokers but not in female smokers. Such sex-dependent differences in spontaneous brain activity lays a foundation for further understanding the neural pathophysiology of sex-specific effects of nicotine addiction and promoting more effective health management of quitting smoking.

A nuclear receptor HR4 is essential for the formation of epidermal cuticle in the migratory locust, Locusta migratoria.

Nuclear receptors (NRs) function as key factors in diverse signaling and metabolic pathways. Previous studies have focused on the roles of a nuclear receptor, hormone receptor 4 (HR4), mainly in holometabolous insects, while current knowledge of its function in hemimetabolous insects is still limited. In this study, we identified a HR4 gene in the orthopteran species Locusta migratoria. The full-length open reading frame of LmHR4 comprises 2694-nucleotides encoding a polypeptide of 897 amino acids, which contained a DNA-binding and a ligand-binding domain. Analyzing LmHR4 expression by quantitative reverse-transcription PCR (RT-qPCR) revealed that LmHR4 was highly expressed in integument, hindgut and fat body. During development from 3rd and 5th nymphal instars, the expression of LmHR4 reached maximal levels before ecdysis. We further demonstrated that LmHR4 expression is induced by 20-hydroxyecdysone (20E) and suppressed by silencing LmEcR, suggesting that LmHR4 expression is controlled by 20E signaling. The dsLmHR4-injected nymphs failed to molt and remained in the nymphal stage until death. Hematoxylin and eosin staining of the integument indicated that apolysis in the dsLmHR4-injected insects was delayed compared to that in control insects. Chitin staining and ultra-structural analysis showed that both the synthesis of the new cuticle and the degradation of the old cuticle were blocked in dsLmHR4-injected insects. Silencing LmHR4 decreased 20E titer and down-regulated the transcript levels of genes involved in chitin synthesis and degradation. Taken together, these results suggest that LmHR4 is essential for the formation of epidermal cuticle by mediating the 20E signaling to regulate the expression of chitin synthesis and degradation genes.

MiR-195 inhibits the ubiquitination and degradation of YY1 by Smurf2, and induces EMT and cell permeability of retinal pigment epithelial cells.

The dysregulated microRNAs (miRNAs) are involved in diabetic retinopathy progression. Epithelial mesenchymal transition (EMT) and cell permeability are important events in diabetic retinopathy. However, the function and mechanism of miR-195 in EMT and cell permeability in diabetic retinopathy remain largely unclear. Diabetic retinopathy models were established using streptozotocin (STZ)-induced diabetic mice and high glucose (HG)-stimulated ARPE-19 cells. Retina injury was investigated by hematoxylin-eosin (HE) staining. EMT and cell permeability were analyzed by western blotting, immunofluorescence, wound healing, and FITC-dextran assays. MiR-195 expression was detected via qRT-PCR. YY1, VEGFA, Snail1, and Smurf2 levels were detected via western blotting. The interaction relationship was analyzed via ChIP, Co-IP, or dual-luciferase reporter assay. The retina injury, EMT, and cell permeability were induced in STZ-induced diabetic mice. HG induced EMT and cell permeability in ARPE-19 cells. MiR-195, YY1, VEGFA, and Snail1 levels were enhanced, but Smurf2 abundance was reduced in STZ-induced diabetic mice and HG-stimulated ARPE-19 cells. VEGFA knockdown decreased Snail1 expression and attenuated HG-induced EMT and cell permeability. YY1 silence reduced VEGFA and Snail1 expression, and mitigated HG-induced EMT and cell permeability. YY1 could bind with VEGFA and Snail1, and it was degraded via Smurf2-mediated ubiquitination. MiR-195 knockdown upregulated Smurf2 to decrease YY1 expression and inhibited HG-induced EMT and cell permeability. MiR-195 targeted Smurf2, increased expression of YY1, VEGFA, and Snail1, and promoted HG-induced EMT and cell permeability. MiR-195 promotes EMT and cell permeability of HG-stimulated ARPE-19 cells by increasing VEGFA/Snail1 via inhibiting the Smurf2-mediated ubiquitination of YY1.

Serum metabolomics analysis for the progression of esophageal squamous cell carcinoma.

BACKGROUND: Previous metabolomics studies have found differences in metabolic characteristics between the healthy and ESCC patients. However, few of these studies concerned the whole process of the progression of ESCC. This study aims to explore serum metabolites associated with the progression of ESCC. METHODS: Serum samples from 653 participants (305 normal, 77 esophagitis, 228 LGD, and 43 HGD/ESCC) were examined by ultra-high performance liquid chromatography quadruple time-of-flight mass spectrometry (UHPLC-QTOF/MS). Principal component analysis (PCA) was first applied to obtain an overview of the clustering trend for the multidimensional data. Fuzzy c-means (FCM) clustering was then used to screen metabolites with a changing tendency in the progression of ESCC. Univariate ordinal logistic regression analysis and multiple ordinal logistic regression analysis were applied to evaluate the association of metabolites with the risk of ESCC progression, and adjusted for age, gender, BMI, tobacco smoking, and alcohol drinking status. RESULTS: After FCM clustering analysis, a total of 38 metabolites exhibiting changing tendency among normal, esophagitis, LGD, and HGD/ESCC patients. Final results showed 15 metabolites associated with the progression of ESCC. Ten metabolites (dopamine, L-histidine, 5-hydroxyindoleacetate, L-tryptophan, 2'-O-methylcytidine, PC (14:0/0:0), PC (O-16:1/0:0), PE (18:0/0:0), PC (16:1/0:0), PC (18:2/0:0)) were associated with decreased risk of developing ESCC. Five metabolites (hypoxanthine, inosine, carnitine (14:1), glycochenodeoxycholate, PC (P-18:0/18:3)) were associated with increased risk of developing ESCC. CONCLUSIONS: These results demonstrated that serum metabolites are associated with the progression of ESCC. These metabolites are capable of potential biomarkers for the risk prediction and early detection of ESCC.

Suppressing long noncoding RNA OGRU ameliorates diabetic retinopathy by inhibition of oxidative stress and inflammation via miR-320/USP14 axis.

Long noncoding RNAs (lncRNAs) are important regulators in various diseases including diabetic retinopathy (DR). In this study, DR patients exhibited significantly increased expression of serum LncRNA-OGRU compared with normal individuals. Streptozotocin (STZ)-challenged rats with DR also had higher OGRU expression in retinas than that of the control group, which was confirmed in Müller cells upon high glucose (HG) stimulation. OGRU knockdown remarkably decreased vascular endothelial growth factor (VEGF) and transforming growth factor-ß1 (TGF-ß1) expression in HG-incubated Müller cells. HG-induced inflammatory response and oxidative stress in vitro were markedly mitigated by OGRU knockdown through restraining IκBɑ/nuclear factor kappa beta (NF-κB) and improving nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways, respectively. Further studies indicated that OGRU suppression greatly restored miR-320 expression, and a negative correlation between them was detected in DR patients. We also found that miR-320 over-expression considerably restrained TGF-ß1 signaling, and hindered inflammation and reactive oxygen species (ROS) production in HG-stimulated Müller cells. Additionally, OGRU knockdown or miR-320 over-expression could dramatically down-regulate ubiquitin-specific peptidase 14 (USP14) expression levels in HG-incubated Müller cells, and miR-320 could directly target USP14. Notably, OGRU/miR-320 axis-mediated TGF-ß1 signaling, inflammation and ROS were largely dependent on USP14. Intriguingly, our results showed that USP14 directly interacted with transforming growth factor-beta type 1 receptor (TßR1), and impeded TßR1 ubiquitination and degradation. Furthermore, USP14 could also facilitate IκBɑ deubiquitination and degradation, exacerbating IκBɑ phosphorylation and NF-κB activation. Finally, our in vivo studies confirmed that OGRU knockdown considerably ameliorated DR progression in STZ-challenged rats through mediating the mechanisms observed in vitro. Collectively, these findings implicated that LncRNA-OGRU mediated DR progression through competing for miR-320 to regulate USP14 expression, and thus LncRNA-OGRU/miR-320/USP14 axis may be considered as a therapeutic target for DR treatment.

Sex-specific effects of cigarette smoking on caudate and amygdala volume and resting-state functional connectivity.

Recent studies have demonstrated sex-specific differences in etiology, course and brain dysfunction that are associated with cigarette smoking. However, little is known about sex-specific differences in subcortical structure and function. In this study, structural and resting-state functional magnetic resonance imaging (fMRI) data were collected from 60 cigarette smokers (25 females) and 67 nonsmokers (28 females). The structural MRI was applied to identify deficits in sex-specific subcortical volume. Using resting-state fMRI, sex-related alterations in resting-state functional connectivity (rsFC) were investigated in subcortical nuclei with volume deficits as seed regions. Compared to nonsmokers, male but not female smokers demonstrated a significantly smaller volume in the left caudate, while female but not male smokers showed a smaller volume in the right amygdala. Resting-state FC analysis revealed that male but not female smokers had increased rsFC between the left caudate and the left prefrontal cortex but decreased rsFC within the bilateral caudate and between the right amygdala and right orbitofrontal cortex (OFC). Furthermore, the right amygdala volume was negatively correlated with the impulsivity score in female but not male smokers. The rsFC of the right amygdala-OFC circuit was negatively associated with the craving score in male but not female smokers. These findings indicate that cigarette smoking may have differential effects on the caudate and amygdala volumes as well as rsFC between men and women, contributing to our knowledge of sex-specific effects of nicotine addiction. Such sex-specific differences in subcortical structure and function may provide a methodological framework for the development of sex-specific relapse prevention therapies.

Interaction Between Smoking and Internet Gaming Disorder on Spontaneous Brain Activity.

Converging lines of evidence indicates that smoking and internet gaming disorder (IGD) affect spontaneous brain activity, respectively. However, little is known about whether these two factors work together on the human brain. In this study, we investigated the interaction between smoking and IGD on local spontaneous brain activity using amplitude of low-frequency fluctuation (ALFF) based on resting-state fMRI (rs-fMRI). Forty-six cigarette smokers, 38 IGD individuals, 34 participants with both IGD and cigarette smoking (IGD-Smoking), and 60 healthy individuals involved in the study. Voxel-wise analysis of covariance of ALFF revealed that there were significant interactions between IGD by smoking in the right medial pre-frontal cortex (MPFC)/ventral striatum, bilateral cerebellar, and visual-related regions as well as the left temporal gyrus. In the right MPFC/ventral striatum and left temporal gyrus, ALFF in smoking group was significantly higher than healthy group while there were no significant ALFF differences between IGD-Smoking group and IGD group. While in the bilateral cerebellar and visual-related regions, ALFF in the smoking group was significantly lower than healthy group while ALFF in IGD-Smoking group did not show significant difference with IGD group. In addition, in the smoking group, ALFF of the right MPFC/ventral striatum was associated positively with anxiety and depression scores while the ALFF value in the smoking group had a trend toward negative correlation with SDS scores in the bilateral cerebellar and visual-related regions. The ALFF value in the smoking group was associated positively with anxiety score in the left temporal gyrus. These findings indicate that smoking and IGD interacted with each other in the human brain. Our results, in terms of spontaneous brain activity, may imply the fact that IGD people are more tended to get smoking. Moreover, it is possible to predict that smokers may be more easily to get internet addiction than healthy people.

Clinicopathological characteristics and surgical outcomes of sarcomatoid hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the sixth most common type of cancer and the fourth leading cause of cancer-related death worldwide. Sarcomatoid HCC, which contains poorly differentiated carcinomatous and sarcomatous components, is a rare histological subtype of HCC that differs from conventional HCC. It is highly aggressive and has a poor prognosis. Its clinicopathological characteristics, surgical outcomes and underlying mechanisms of its highly aggressive nature have not been fully elucidated. AIM: To examine the clinicopathological characteristics and surgical outcomes of sarcomatoid HCC and explore the histogenesis of sarcomatoid HCC. METHODS: In total, 196 patients [41 sarcomatoid HCC and 155 high-grade (Edmondson-Steiner grade III or IV) HCC] who underwent surgical resection between 2007 and 2017 were retrospectively reviewed. The characteristics and surgical outcomes of sarcomatoid HCC were compared with those of patients with high-grade HCC. The histological composition of invasive and metastatic sarcomatoid HCCs was evaluated. RESULTS: Sarcomatoid HCC was more frequently diagnosed at an advanced stage with a larger tumor and higher rates of nonspecific symptom, adjacent organ invasion and lymph node metastasis than high-grade HCC (all P < 0.05). Compared with high-grade HCC patients, sarcomatoid HCC patients are less likely to have typical dynamic imaging features of HCC (44.4% vs 72.7%, P = 0.001) and elevated serum alpha-fetoprotein levels (> 20 ng/mL; 36.6% vs 78.7%, P < 0.001). The sarcomatoid group had a significantly shorter median recurrence-free survival (5.6 mo vs 16.4 mo, log-rank P < 0.0001) and overall survival (10.5 mo vs 48.1 mo, log-rank P < 0.0001) than the high-grade group. After controlling for confounding factors, the sarcomatoid subtype was identified as an independent predictor of poor prognosis. Pathological analyses indicated that invasive and metastatic lesions were mainly composed of carcinomatous components. CONCLUSION: Sarcomatoid HCC was associated with a more advanced stage, atypical dynamic imaging, lower serum alpha-fetoprotein levels and a worse prognosis. The highly aggressive nature of sarcomatoid HCC is perhaps mediated by carcinomatous components.

Risk factors for precancerous lesions of esophageal squamous cell carcinoma in high-risk areas of rural China: A population-based screening study.

Although many studies in China have found that environmental or lifestyle factors are major contributors to the etiology of esophageal cancer, most of the patients in the above studies are in the middle and late stages, the early-stage patients account for a small proportion. To clarify the risk/protective factors contributing to early lesions, we conducted the present cross-sectional study.A total of 2925 healthy controls and 402 patients with esophageal precancerous lesions were included in our study by endoscopic examination. Information on risk/protective factors was collected by personal interview, and unconditional logistic regression was used to determine adjusted odds ratios (AORs) by the maximum-likelihood method.Smoking >20 pack-years (AOR = 1.48), duration of drinking >30 years (AOR = 1.40), alcohol consumption >100 mL/d (AOR = 1.44), gastroesophageal reflux disease (AOR = 1.75), esophagitis (AOR = 1.25), a family history of esophageal cancer (AOR = 1.92), or stomach cancer (AOR = 1.92) were significant risk factors for esophageal precancerous lesions. There was a negative correlation between abdominal obesity and early esophageal cancer and precancerous lesions (AOR = 0.75). In addition, we found that there was a synergistic effect between a family history of esophageal cancer and drinking (AOR = 3.00) and smoking (AOR = 2.90).Lifestyle risk factors, genetic factors, and upper gastrointestinal diseases are associated with the development of esophageal precancerous lesions. These results highlight the need for primary prevention to reduce the future burden of cancer and other chronic diseases in high-risk areas of rural China.

Effect of endogenous metabolisms on survival and activities of denitrifying phosphorus removal sludge under various starvation conditions.

Denitrifying phosphorus removal sludge are usually faced with various famine environments in wastewater treatment plants (WWTPs). Endogenous metabolisms under aerobic, anoxic, and anaerobic starved conditions were characterized to investigate their impact on survival and activities of denitrifying polyphosphate accumulating organisms (DPAOs). DPAOs utilized intracellular polymers to survive and presented diverse consumed priorities of PHA types under various starvations. The biomass decay rate was approximately 2.7 and 1.7 times lower for aerobic condition than for anoxic and anaerobic conditions owing to the maximum maintenance energy requirement for aerobic condition (68.6 mmol/C-molVSS ATP). During short-term starvations, significant activity decay for anaerobic starved sludge was attributed to its distinctive endogenous metabolisms. For long-term starvations, the higher amounts and preponderant type of PHA (PHB) reserve favored to the greater DPAO activities for anoxic starved sludge. The results show that anoxic condition may be an implementable strategy for maintaining denitrifying phosphorus removal performance in WWTPs.

Apatinib combined with chemotherapy or concurrent chemo-brachytherapy in patients with recurrent or advanced cervical cancer: A phase 2, randomized controlled, prospective study.

OBJECTIVE: Apatinib mesylate is a novel vascular endothelial growth factor receptor 2 (VEGFR-2) inhibitor, which has exhibited good safety and efficacy in several types of solid tumors. The present study aimed to assess the clinical efficacy and safety of apatinib combined with chemotherapy and concurrent chemo-brachytherapy (CCBT) in patients with recurrent and advanced cervical cancer. METHODS: A total of 52 patients with first diagnosed recurrent or untreated International Federation of Gynecology and Obstetrics stage IVB cervical cancer admitted at Shandong Cancer Hospital and Institute between July 2016 and May 2018 were analyzed in the current randomized controlled trial. The patients were randomly divided into 2 groups: the apatinib-treated group and the control group. Patients with recurrent cervical cancer in the apatinib-treated group were administered apatinib and carboplatin-paclitaxel as first-line chemotherapy. Patients with advanced cervical cancer were administered apatinib in combination with CCBT. In control group, patients with recurrent cervical cancer were treated with chemotherapy alone while patients with advanced cervical cancer received CCBT. RESULTS: The progression-free survival was significantly prolonged in apatinib group compared with control group (10.1 months; 95% confidence interval (CI), 8.42-11.79 vs 6.4 months; 95% CI, 3.88-8.92; P < .01; hazard ratio (HR), 0.44; 95% CI, 0.25-0.78; P < .01). The objective response rate in apatinib group was obviously higher than that in control group (64.3% vs 33.3%, P < .05). Proteinuria, hand-foot syndrome, mucositis, and hypertension in all Grades were statistically more common in apatinib group than in control group. Apatinib did not obviously aggravate other radiotherapy or chemotherapy side effects. CONCLUSION: Apatinib exhibited promising clinical efficacy in cervical cancer patients, resulting in an improved response rate and prolonged progression-free survival compared with the control group, and had manageable side effects. Our study revealed that apatinib combination therapy, adenocarcinoma, and bone metastasis.

Single-Atom Iron as Lithiophilic Site To Minimize Lithium Nucleation Overpotential for Stable Lithium Metal Full Battery.

High lithium nucleation overpotential on a lithiophobic matrix results in uncontrollable growth of lithium dendrites and thus restricts the wide application of lithium-metal batteries. Herein, the single-atom iron in a N-doped carbon matrix (FeSA-N-C) is first reported as a lithiophilic site to minimize Li nucleation overpotential from 18.6 mV to a very low value of 0.8 mV. Molecular dynamics simulations quantitatively confirmed the excellent affinity between Li ions and FeSA-N-C in the atomic level. Induced by the homogeneously distributed FeSA-N in the carbon substrate, uniform and stable metallic Li plating/stripping behaviors are realized and lithium dendrite growth is greatly suppressed. The proposed strategy of using single-atom iron as a lithiophilic site to minimize lithium nucleation overpotential opens a promising avenue for solving intrinsic problems of Li-metal-based batteries.