Chlorogenic acid alleviates renal fibrosis by reducing lipid accumulation in diabetic kidney disease through suppressing the Notch1 and Stat3 signaling pathway.

AIMS: Abnormal renal lipid metabolism causes renal lipid deposition, which leads to the development of renal fibrosis in diabetic kidney disease (DKD). The aim of this study was to investigate the effect and mechanism of chlorogenic acid (CA) on reducing renal lipid accumulation and improving DKD renal fibrosis. METHODS: This study evaluated the effects of CA on renal fibrosis, lipid deposition and lipid metabolism by constructing in vitro and in vivo models of DKD, and detected the improvement of Notch1 and Stat3 signaling pathways. Molecular docking was used to predict the binding between CA and the extracellular domain NRR1 of Notch1 protein. RESULTS: In vitro studies have shown that CA decreased the expression of Fibronectin, α-smooth muscle actin (α-SMA), p-smad3/smad3, alleviated lipid deposition, promoted the expression of carnitine palmitoyl transferase 1 A (CPT1A), and inhibited the expression of cholesterol regulatory element binding protein 1c (SREBP1c). The expression of Notch1, Cleaved Notch1, Hes1, and p-stat3/stat3 were inhibited. These results suggested that CA might reduce intercellular lipid deposition in human kidney cells (HK2) by inhibiting Notch1 and stat3 signaling pathways, thereby improving fibrosis. Further, in vivo studies demonstrated that CA improved renal fibrosis and renal lipid deposition in DKD mice by inhibiting Notch1 and stat3 signaling pathways. Finally, molecular docking experiments showed that the binding energy of CA and NRR1 was -6.6 kcal/mol, which preliminarily predicted the possible action of CA on Notch1 extracellular domain NRR1. CONCLUSION: CA reduces renal lipid accumulation and improves DKD renal fibrosis by inhibiting Notch1 and stat3 signaling pathways.

IFIT1 modulates the proliferation, migration and invasion of pancreatic cancer cells via Wnt/ß-catenin signaling.

OBJECTIVES: Previously, Interferon-induced Protein with Tetratricopeptide Repeats 1 (IFIT1) has been shown to promote cancer development. Here, we aimed to explore the role of IFIT1 in the development and progression of pancreatic cancer, including the underlying mechanisms. METHODS: We explored IFIT1 expression in pancreatic cancer samples using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Cell Counting Kit-8 (CCK8), colony formation, scratch wound-healing and Transwell assays were performed to assess the proliferation, migration and invasion abilities of pancreatic cancer cells. Gene Set Enrichment Analysis (GSEA) and Western blotting were performed to assess the regulatory effect of IFIT1 on the Wnt/ß-catenin pathway. RESULTS: We found that upregulation of IFIT1 expression is common in pancreatic cancer and is negatively associated with overall patient survival. Knockdown of IFIT1 expression led to decreased proliferation, migration and invasion of pancreatic cancer cells. We also found that IFIT1 could regulate Wnt/ß-catenin signaling, and that a Wnt/ß-catenin agonist could reverse this effect. In addition, we found that IFIT1 can promote epithelial-mesenchymal transition (EMT) of pancreatic cancer cells. CONCLUSIONS: Our data indicate that IFIT1 increases pancreatic cancer cell proliferation, migration and invasion by activating the Wnt/ß-catenin pathway. In addition, we found that EMT could be regulated by IFIT1. IFIT1 may serve as a potential therapeutic target for pancreatic cancer.

Small extrachromosomal circular DNA harboring targeted tumor suppressor gene mutations supports intratumor heterogeneity in mouse liver cancer induced by multiplexed CRISPR/Cas9.

BACKGROUND: Primary liver cancer has significant intratumor genetic heterogeneity (IGH), which drives cancer evolution and prevents effective cancer treatment. CRISPR/Cas9-induced mouse liver cancer models can be used to elucidate how IGH is developed. However, as CRISPR/Cas9 could induce chromothripsis and extrachromosomal DNA in cells in addition to targeted mutations, we wondered whether this effect contributes to the development of IGH in CRISPR/Cas9-induced mouse liver cancer. METHODS: CRISPR/Cas9-based targeted somatic multiplex-mutagenesis was used to target 34 tumor suppressor genes (TSGs) for induction of primary liver tumors in mice. Target site mutations in tumor cells were analyzed and compared between single-cell clones and their subclones, between different time points of cell proliferation, and between parental clones and single-cell clones derived from mouse subcutaneous allografts. Genomic instability and generation of extrachromosomal circular DNA (eccDNA) was explored as a potential mechanism underlying the oscillation of target site mutations in these liver tumor cells. RESULTS: After efficiently inducing autochthonous liver tumors in mice within 30-60 days, analyses of CRISPR/Cas9-induced tumors and single-cell clones derived from tumor nodules revealed multiplexed and heterogeneous mutations at target sites. Many target sites frequently displayed more than two types of allelic variations with varying frequencies in single-cell clones, indicating increased copy number of these target sites. The types and frequencies of targeted TSG mutations continued to change at some target sites between single-cell clones and their subclones. Even the proliferation of a subclone in cell culture and in mouse subcutaneous graft altered the types and frequencies of targeted TSG mutations in the absence of continuing CRISPR/Cas9 genome editing, indicating a new source outside primary chromosomes for the development of IGH in these liver tumors. Karyotyping of tumor cells revealed genomic instability in these cells manifested by high levels of micronuclei and chromosomal aberrations including chromosomal fragments and chromosomal breaks. Sequencing analysis further demonstrated the generation of eccDNA harboring targeted TSG mutations in these tumor cells. CONCLUSIONS: Small eccDNAs carrying TSG mutations may serve as an important source supporting intratumor heterogeneity and tumor evolution in mouse liver cancer induced by multiplexed CRISPR/Cas9.

Prognostic value and immune infiltration of ARMC10 in pancreatic adenocarcinoma via integrated bioinformatics analyses.

Background: Armadillo repeat-containing 10 (ARMC10) is involved in the progression of multiple types of tumors. Pancreatic adenocarcinoma (PAAD) is a lethal disease with poor survival and prognosis. Methods: We acquired the data of ARMC10 in PAAD patients from the cancer genome atlas (TCGA) and gene expression omnibus (GEO) datasets and compared the expression level with normal pancreatic tissues. We evaluated the relevance between ARMC10 expression and clinicopathological factors, immune infiltration degree and prognosis in PAAD. Results: High expression of ARMC10 was relevant to T stage, M stage, pathologic stage, histologic grade, residual tumor, primary therapy outcome (P < 0.05) and related to lower Overall-Survival (OS), Disease-Specific Survival (DSS), and Progression-Free Interval (PFI). Gene set enrichment analysis showed that ARMC10 was related to methylation in neural precursor cells (NPC), G alpha (i) signaling events, APC targets, energy metabolism, potassium channels and IL10 synthesis. The expression level of ARMC10 was positively related to the abundance of T helper cells and negatively to that of plasmacytoid dendritic cells (pDCs). Knocking down of ARMC10 could lead to lower proliferation, invasion, migration ability and colony formation rate of PAAD cells in vitro. Conclusions: Our research firstly discovered ARMC10 as a novel prognostic biomarker for PAAD patients and played a crucial role in immune regulation in PAAD.

Risk stratification of clinically relevant delayed gastric emptying after pancreaticoduodenectomy.

BACKGROUND: Delayed gastric emptying (DGE) remains one of the major complications after pancreaticoduodenectomy (PD), with discrepant reports of its contributing factors. This study aimed to develop a nomogram to identify potential predictors and predict the probability of DGE after PD. METHODS: This retrospective study enrolled 422 consecutive patients who underwent PD from January 2019 to December 2021 at our institution. The LASSO algorithm and multivariate logistic regression were performed to identify independent risk and protective factors associated with clinically relevant delayed gastric emptying (CR-DGE). A nomogram was established based on the selected variables. Then, the calibration curve, ROC curve, decision curve analysis (DCA), and clinical impact curve (CIC) were applied to evaluate the predictive performance of our model. Finally, an independent cohort of 45 consecutive patients from January 2022 to March 2022 was enrolled to further validate the nomogram. RESULTS: Among 422 patients, CR-DGE occurred in 94 patients (22.2%). A previous history of chronic gastropathy, intraoperative plasma transfusion ≥ 400 ml, end-to-side gastrointestinal anastomosis, intra-abdominal infection, incisional infection, and clinically relevant postoperative pancreatic fistula (CR-POPF) were identified as risk predictors. Minimally invasive pancreaticoduodenectomy (MIPD) was demonstrated to be a protective predictor of CR-DGE. The areas under the curve (AUCs) were 0.768 (95% CI, 0.706-0.830) in the development cohort, 0.766 (95% CI, 0.671-0.861) in the validation cohort, and 0.787 (95% CI, 0.633-0.940) in the independent cohort. Then, we built a simplified scale based on our nomogram for risk stratification. CONCLUSIONS: Our study identified seven predictors and constructed a validated nomogram that effectively predicted CR-DGE for patients who underwent PD.

Influence of the casing layer on the specific volatile compounds and microorganisms by Agaricus bisporus.

One of the major variables affecting yield of the mushroom Agaricus bisporus is the casing layer, which directly affects the productivity and mass. Here, volatile organic compounds were extracted by headspace solid-phase microextraction and high-throughput sequencing was used to analyze the microbial community diversity. The relationship between mushroom yield at different cropping stages and the contents of volatile organic compounds and microorganisms in three different casing layers: peat, peat + soil and soil were systematically evaluated. The result shows that Benzaldehyde and (E)-2-octenal which stimulate yield, obviously increased as mushrooms grew, while 3-octanone, which inhibits yield, decreased over time in all three casing layers. However, there was not a strong correlation between the concentration of volatile compounds and yield. In addition, more than 3,000 bacterial operational taxonomic units (OTUs) by performing high throughput sequencing of the microbes were obtained in the three casing layers. Interestingly, the microbial community compositions were very similar between the three casing layers at a later cropping stage, but the community richness varied significantly in different casing layers and at different cropping stages. At the phylum level, the communities had similar structures but were quantitively very different, and this was even more obvious at the genus level. Principal component analysis revealed significant alterations in microbial community structure in different casing layers. Sphingomonas, Dongia and Achromobacter were the dominant genera at cropping stage 1, and the stage 3 were abundant in Saccharibacteria_norank, Pseudomonas, Flavobacterium and Brevundimonas, which was positively correlated with yield, while the abundance of Pseudomonas at stage 1 and Lactococcus and Bacillus at stage 3 was negatively correlated with yield. These results provide a guide for the development and agricultural application of microbial agents for yield improvement in the production of A. bisporus.

Enhancing the Activity of an Alcohol Dehydrogenase by Using "Aromatic Residue Scanning" at Potential Plasticity Sites.

An alcohol dehydrogenase LkADH was successfully engineered to exhibit improved activity and substrate tolerance for the production of (S)-2-chloro-1-(3,4-difluorophenyl)ethanol, an important precursor of ticagrelor. Five potential hotspots were identified for enzyme mutagenesis by using natural residue abundance as an indicator to evaluate their potential plasticity. A semi-rational strategy named "aromatic residue scanning" was applied to randomly mutate these five sites simultaneously by using tyrosine, tryptophan, and phenylalanine as "exploratory residues" to introduce steric hindrance or potential π-π interactions. The best variant Lk-S96Y/L199W identified with 17.2-fold improvement in catalytic efficiency could completely reduce up to 600 g/L (3.1 M) 2-chloro-1-(3,4-difluorophenyl)ethenone in 12 h with >99.5 % ee, giving the highest space-time yield ever reported. This study, therefore, offers a strategy for mutating alcohol dehydrogenase to reduce aromatic substrates and provides an efficient variant for the efficient synthesis of (S)-2-chloro-1-(3,4-difluorophenyl)ethanol.

Seasonal variations of low molecular alkyl amines in PM2.5 in a North China Plain industrial city: Importance of secondary formation and combustion emissions.

Atmospheric amines have unique acid-neutralizing capacity and play an important role in atmospheric chemical reactions. An integrated observation of PM2.5 samples (from Dec 2015 to Nov 15, 2016) was conducted in a typical industrial city (Xuzhou), China. Concentrations of total measured amines (∑amines, including methylamine (MA), ethylamine (EA), dimethylamine (DMA), propanamine (PA) and trimethylamine (TMA) + diethylamine (DEA)) were 172.0 ± 98.2 ng m-3, accounting 1.5 ± 0.6 ‰ of PM2.5 mass. ∑amines were higher in winter (249.0 ± 112.3 ng m-3) and spring (192.4 ± 75.9 ng m-3) than in summer (114.7 ± 33.3 ng m-3) and autumn (103.7 ± 34.3 ng m-3). Concentrations of MA and EA (the dominant amines) were highest in winter, while DMA, PA and TMA + DEA showed opposite seasonality. EA/MA ratios ranged from 0.04 to 8.7 with a median value of 0.3, and the averaged EA/MA ratio was 2.0 in winter, indicating large contribution of EA. Environmental factors including temperature (T), relative humidity (RH) and atmospheric oxidizing capacity (O3 and Ox represented) were found to influence concentrations of amines in PM2.5. The Positive Matrix Factorization (PMF) model identified secondary products (41.6 %), combustion emissions (39.8 %), soil and waste incineration emissions (13.2 %) and biological emissions and aging products (5.4 %) as the 4 sources of amines in PM2.5. MA was mainly secondary products (82.5 %) and had high contribution of local secondary formation, while EA was mainly derived from combustion emissions (83.7 %) and influenced by regional transportation. In winter, combustion emissions (including coal combustion, biomass burning and traffic emissions, contributed 57.7 %) surpassed secondary products (31.6 %) as the predominant sources of amines, especially under the influence of regional transportation (75.7 %).

DNA nicks induce mutational signatures associated with BRCA1 deficiency.

Analysis of human cancer genome sequences has revealed specific mutational signatures associated with BRCA1-deficient tumors, but the underlying mechanisms remain poorly understood. Here, we show that one-ended DNA double strand breaks (DSBs) converted from CRISPR/Cas9-induced nicks by DNA replication, not two-ended DSBs, cause more characteristic chromosomal aberrations and micronuclei in Brca1-deficient cells than in wild-type cells. BRCA1 is required for efficient homologous recombination of these nick-converted DSBs and suppresses bias towards long tract gene conversion and tandem duplication (TD) mediated by two-round strand invasion in a replication strand asymmetry. However, aberrant repair of these nick-converted one-ended DSBs, not that of two-ended DSBs in Brca1-deficient cells, generates mutational signatures such as small indels with microhomology (MH) at the junctions, translocations and small MH-mediated TDs, resembling those in BRCA1-deficient tumors. These results suggest a major contribution of DNA nicks to mutational signatures associated with BRCA1 deficiency in cancer and the underlying mechanisms.

Golgi phosphoprotein 3 promotes ovarian cancer progression and is associated with cisplatin resistance.

Background: Golgi phosphoprotein-3 (GOLPH 3) is involved in the development of several human cancers. However, the clinical significance and biological role of GOLPH 3 in ovarian cancer (OC) remains unknown. Methods: The expression of GOLPH 3 in OC cell lines was quantified using real-time quantitative polymerase chain reaction (RT-qPCR) and western blot assays. The role of GOLPH 3 in tumorigenicity, migration, and invasion of OC cell lines by small interference RNA, scratch wound-healing assays, and transwell assays was detected. In addition, western blotting was used to determine whether GOLPH 3 is associated with the PI3K/AKT/mTOR signaling pathway. Furthermore, RT-qPCR verified whether GOLPH 3 is associated with drug resistance. Results: GOLPH 3-positive expression rate was higher in OC. Downregulation of GOLPH 3 markedly inhibited the migration and invasion and may be related to the PI3K/AKT/mTOR signal pathway. Moreover, the result of the experiment proved that GOLPH 3 enhances the sensitivity of OC to cisplatin by regulating ATP7A/B. GOLPH 3 promoted the invasion and migration of OC, and the mechanism may be related to the PI3K/Akt/mTOR pathway. In addition, inhibition of GOLPH 3 increased the sensitivity of OC cells to cisplatin, which may be associated with ATP7A/B. Conclusion: This study found that GOLPH3 may promote the migration and invasion of OC cells through PI3K/Akt/mTOR pathway. At the same time, low expression of GOLPH3 increased the sensitivity of OC cells to cisplatin.

[Changes in Carbonaceous Aerosol in the Northern Suburbs of Nanjing from 2015 to 2019].

Carbonaceous aerosol is an important component of atmospheric fine particles that has an important impact on air quality, human health, and climate change. In order to explore the long-term changes in carbonaceous aerosol under the background of emission reduction, this study measured the mass concentrations of organic carbon (OC) and elemental carbon (EC) of PM2.5, which collected in the northern suburbs of Nanjing for five years (December 17, 2014 to January 5, 2020). The results showed that the five-year average ρ(OC) and ρ(EC) were (10.2±5.3) µg·m-3 and (1.6±1.1) µg·m-3, accounting for 31.1% and 5.2% of PM2.5, respectively. OC and EC concentrations were both high in winter and low in summer. According to the nonparametric Mann-Kendall test and Sen's slope, the mass concentrations of OC and PM2.5 decreased significantly[OC:P<0.0001, -0.79 µg·(m3·a)-1, -0.29%·a-1; PM2.5:P<0.0001, -4.59 µg·(m3·a)-1, -1.58%·a-1]. Although EC had an upward trend, the significance and range of change were not obvious[P=0.02, 0.05 µg·(m3·a)-1, 0.02%·a-1]. OC and EC decreased significantly during winter from 2014 to 2019[OC:P<0.0001, -2.05 µg·(m3·a)-1, -0.74%·a-1; EC:P=0.001, -0.15 µg·(m3·a)-1, -0.05%·a-1], and the decline was more obvious than the whole. The correlation between OC and EC showed that the sources in winter and summer were more complex than those in spring and autumn. According to the characteristic ratio of OC and EC, the contribution of coal combustion and biomass burning decreased from 2015 to 2019, whereas the impact of industrial sources and vehicle emissions became more significant. Corresponding to this was the obvious decline in OC and the slight recovery of EC. The OC/EC ratio was over 2.0, indicating that there was secondary pollution in the study area. Further calculation revealed that the variation in SOC was consistent with that in OC, showing a significant decrease[P<0.0001, -0.47 µg·(m3·a)-1, -0.17%·a-1]. The average mass concentration of SOC was (5.0±3.5) µg·m-3, accounting for 49.2% of OC. These changes indicate clear effects of the prevention and control of air pollution in Nanjing in recent years. Furthermore, future control can focus on the emissions of VOCs to reduce secondary pollution.

IFIT1 modulates the proliferation, migration and invasion of pancreatic cancer cells via Wnt/ß-catenin signaling.

OBJECTIVES: Previously, Interferon-induced Protein with Tetratricopeptide Repeats 1 (IFIT1) has been shown to promote cancer development. Here, we aimed to explore the role of IFIT1 in the development and progression of pancreatic cancer, including the underlying mechanisms. METHODS: We explored IFIT1 expression in pancreatic cancer samples using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Cell Counting Kit-8 (CCK8), colony formation, scratch wound-healing and Transwell assays were performed to assess the proliferation, migration and invasion abilities of pancreatic cancer cells. Gene Set Enrichment Analysis (GSEA) and Western blotting were performed to assess the regulatory effect of IFIT1 on the Wnt/ß-catenin pathway. RESULTS: We found that upregulation of IFIT1 expression is common in pancreatic cancer and is negatively associated with overall patient survival. Knockdown of IFIT1 expression led to decreased proliferation, migration and invasion of pancreatic cancer cells. We also found that IFIT1 could regulate Wnt/ß-catenin signaling, and that a Wnt/ß-catenin agonist could reverse this effect. In addition, we found that IFIT1 can promote epithelial-mesenchymal transition (EMT) of pancreatic cancer cells. CONCLUSIONS: Our data indicate that IFIT1 increases pancreatic cancer cell proliferation, migration and invasion by activating the Wnt/ß-catenin pathway. In addition, we found that EMT could be regulated by IFIT1. IFIT1 may serve as a potential therapeutic target for pancreatic cancer.

Identification METTL18 as a Potential Prognosis Biomarker and Associated With Immune Infiltrates in Hepatocellular Carcinoma.

Methyltransferase-like 18 (METTL18), a METTL family member, is abundant in hepatocellular carcinoma (HCC). Studies have indicated the METTL family could regulate the progress of diverse malignancies while the role of METTL18 in HCC remains unclear. Data of HCC patients were acquired from the cancer genome atlas (TCGA) and gene expression omnibus (GEO). The expression level of METTL18 in HCC patients was compared with normal liver tissues by Wilcoxon test. Then, the logistic analysis was used to estimate the correlation between METTL18 and clinicopathological factors. Besides, Gene Ontology (GO), Gene Set Enrichment Analysis (GSEA), and single-sample Gene Set Enrichment Analysis (ssGSEA) were used to explore relevant functions and quantify the degree of immune infiltration for METTL18. Univariate and Multivariate Cox analyses and Kaplan-Meier analysis were used to estimate the association between METTL18 and prognosis. Besides, by cox multivariate analysis, a nomogram was conducted to forecast the influence of METTL18 on survival rates. METTL18-high was associated with Histologic grade, T stage, Pathologic stage, BMI, Adjacent hepatic tissue inflammation, AFP, Vascular invasion, and TP53 status (P < 0.05). HCC patients with METTL18-high had a poor Overall-Survival [OS; hazard ratio (HR): 1.87, P < 0.001), Disease-Specific Survival (DSS, HR: 1.76, P = 0.015), and Progression-Free Interval (PFI, HR: 1.51, P = 0.006). Multivariate analysis demonstrated that METTL18 was an independent factor for OS (HR: 2.093, P < 0.001), DSS (HR: 2.404, P = 0.015), and PFI (HR: 1.133, P = 0.006). Based on multivariate analysis, the calibration plots and C-indexes of nomograms showed an efficacious predictive effect for HCC patients. GSEA demonstrated that METTL18-high could activate G2M checkpoint, E2F targets, KRAS signaling pathway, and Mitotic Spindle. There was a positive association between the METTL18 and abundance of innate immunocytes (T helper 2 cells) and a negative relation to the abundance of adaptive immunocytes (Dendritic cells, Cytotoxic cells etc.). Finally, we uncovered knockdown of METTL18 significantly suppressed the proliferation, invasion, and migration of HCC cells in vitro. This research indicates that METTL18 could be a novel biomarker to evaluate HCC patients' prognosis and an important regulator of immune responses in HCC.

Hindrances of peripherally inserted central catheter care of leukemia patients: a qualitative study.

OBJECTIVE: A peripherally inserted central catheter (PICC) needs regular care. However, clinical observations found that some discharged leukemia patients in mainland China had not complied with the requirement of regular care. Our study aims to explore the facilitators and hindrances of regular cares of PICC in leukemia patients with the Colaizzi phenomenon analysis. METHODS: This qualitative report used the descriptive phenomenological method to collect information and was conducted in accordance with the COREQ checklist. By purposive sampling, 11 leukemia patients with PICC were selected and interviewed in the Department of Hematology of a first-class hospital in Wuhan (central China). The interviews were conducted from March 2016 to May 2017. RESULTS: Two facilitators for PICC care were extracted through interviews, including fear of nosocomial infection and convenience for treatment. Eleven hindrances were summarized, including high costs, unavailability of local services, worries about affecting family members, a lack of health awareness, inconvenient transportations, fluke minds, physical discomfort, fears of leukemia and chemotherapy, short chemotherapy intervals, damage to appearance, and no insurance coverage of costs. CONCLUSION: Leukemia patients' compliance with PICC care was hindered by several factors. The improvement of PICC care may need joint efforts of patients, nursing professionals, hospitals' managerial staff, and governments.

EGCG targeting Notch to attenuate renal fibrosis via inhibition of TGFß/Smad3 signaling pathway activation in streptozotocin-induced diabetic mice.

Renal fibrosis is a characteristic of diabetic nephropathy, which is a serious complication of diabetes. It has been reported that (-)-epigallocatechin gallate (EGCG) attenuates renal fibrosis. However, the molecular mechanism of regulation by EGCG in this process remains unclear. Previous studies showed that abnormal activation of Notch signaling contributes to the development of renal fibrosis. Previous studies have demonstrated that EGCG attenuates Notch1 expression. In this study, we found that the levels of fibronectin and Notch1 expression were decreased in human embryonic kidney cells after treatment with EGCG. We also observed that the type II transforming growth factor beta receptor (TGFßRII) and Smad3 pathway were inhibited in kidney cells by treatment with EGCG. In the diabetic kidney, we found that the activation of Notch signaling was attenuated by administration of EGCG. Moreover, TGFßRII and Smad3 phosphorylation could be inhibited by treatment with EGCG in the kidney. These results indicated that EGCG may improve renal fibrosis by targeting Notch via inhibition of the TGFß/Smad3 pathway in diabetic mice. Our findings provide insight into the therapeutic strategy for diabetes-induced renal fibrosis, and suggest EGCG to be a novel potential medicine for the treatment of chronic kidney disease in patients with diabetes.

Microarray Analysis of lncRNA and mRNA Reveals Enhanced Lipolysis Along With Metabolic Remodeling in Mice Infected With Larval Echinococcus granulosus.

Parasitic infection improves metabolic homeostasis in "western diet"-induced obesity through the regulation of adipogenesis. However, the underlying mechanism is not yet fully understood. Using microarray analysis, this study investigated the long non-coding RNA (lncRNA) and messenger RNA (mRNA) profiles of subcutaneous adipose tissues from mice infected with Echinococcus granulosus protoscoleces. A total of 1052 mRNA (541 upregulated, 511 downregulated) and 220 lncRNA (126 upregulated, 94 downregulated) transcripts were differentially expressed (fold change ≥2, P < 0.05) in the infected subcutaneous adipose tissues. When compared with the control group, the infected mice showed a decrease in adipose tissue mass and a reduction in adipocyte size. Indirect calorimetry revealed the change in the energy metabolism after infection, characterized by a lower CO2 production and O2 consumption, a sharp decline in carbohydrate oxidation, and a slight increase in fat oxidation. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that the parasitic infection reprogrammed a complex metabolic network. Notably, "lipoxygenase" and "arginine and proline metabolism" pathways were significantly upregulated while "glycolysis," "tricarboxylic acid cycle," "de novo lipogenesis," and "lipid droplet" pathways were dramatically downregulated. In addition, several key lncRNAs were associated with insulin resistance and adipocyte differentiation. Overall, the present study suggested that E. granulosus infection could enhance lipolysis. Thus, our findings provide novel insights into parasite-mediated metabolic homeostasis, and into the mechanism of hypertrophic adipocytes in obesity.

[Characteristics and Sources of Inorganic Ions and Organic Acids in Precipitation in the Northern Suburb of Nanjing, China].

Rainwater samples were collected in Nanjing from December 2016 to November 2017. Water-soluble ion and organic acid content in rainwater samples was determined to analyze the chemical characteristics of precipitation and their seasonality. The positive matrix factorization (PMF) model was employed to identify the potential sources of precipitation. The results show that the volume-weighted mean of pH in precipitation was 5.6, which was higher than the results of previous studies conducted in Nanjing. The volume-weighted mean of total ions was 297.3 µmol·L-1, and the concentrations of each species were in the order of NH4+ > Ca2+ > K+ > Na+ > Mg2+ for cations and NO3- > SO42- > Cl- > F- for anions. The volume-weighted mean of organic acids was 2.86 µmol·L-1, with organic acids accounting for 2.2% of the total anions. CHO2-, C2H3O2-, and C2O42- were the main organic acids in precipitation with annual volume-weighted means of 1.35, 1.05, and 0.26 µmol·L-1, respectively. A significant seasonality was observed for the ions and organic acids. The volume-weighted mean of inorganic ions was higher in winter and spring compared to those in summer and autumn. On the other hand, the volume-weighted mean of total organic acids was the highest in summer, followed by spring, and the lowest in winter. High concentrations of organic acids in the summer can be attributed to the biogenic emissions from plants. The ratio of formic and acetic (F/A) showed that organic acids mainly originated from primary emissions (e.g., biogenic emissions, combustion of organics, and traffic emissions) rather than atmospheric oxidation processes. Using the PMF model, we found that marine sources and secondary inorganic products (40.0%) were the predominant sources of inorganic ions and organic acids in precipitation, followed by burning of biomass (22.2%), continental origin and waste incineration (22.0%), secondary organic products (14.5%), and biological emissions along with their secondary products (1.3%).

Relationship between caffeine intake and infertility: a systematic review of controlled clinical studies.

BACKGROUND: For a long time, the relationship between caffeine consumption and infertility in the general population is unclear, this study is aimed to systematically review the evidence from any type of controlled clinical studies to explore whether caffeine intake is a risk factor for human infertility. METHODS: Seven databases were searched from inception to May 2019. We included women/men without a history of infertility but were willing to have children in prospective studies and women/men who were diagnosed with infertility in retrospective studies. The observed exposure factor should be caffeine or caffeine containing beverage. Diagnosis of infertility or not for participants was the key outcome. The Newcastle-Ottawa scale (NOS) or Cochrane risk of bias tool were used to assess the methodological quality of included studies. Meta-analysis was conducted if there were acceptable clinical and statistical heterogeneity among studies. The GRADE method was used to assess the certainty of the evidence. RESULTS: Four studies (one cohort study and three case-control studies) involving 12,912 participants were included. According NOS, the average score of case-control studies was 6, and the cohort study achieved 9. Meta-analysis and subgroup analysis were conducted. The results showed that low (OR 0.95, 95%CI 0.78-1.16), medium (OR 1.14, 95%CI 0.69-1.86) and high doses (OR 1.86, 95%CI 0.28-12.22) of caffeine intake may not increase the risk of infertility. The quality of the current evidence bodies were all low. CONCLUSION: Our study provides low quality evidence that regardless of low, medium and high doses of caffeine intake do not appear increase the risk of infertility. But the conclusion should be treated with caution.

Near-future levels of ocean temperature weaken the byssus production and performance of the mussel Mytilus coruscus.

Marine mussels are key ecological engineers that form dense aggregations to maintain the vital habitat in benthic systems. It is essential to understand the consequences of mussel byssus attachment in elevated temperatures associated with ocean warming. We evaluated byssus production and the mechanical performance of threads in the mussel Mytilus coruscus at 21° (control), 27 °C (average temperature in the M. coruscus habitat during the summer season) and 31 °C (4 °C raised) for 72 h. We quantified byssus secretion and shedding number, measured byssal breaking force, byssal polyphenol oxidase (PPO) activity, byssal thread length and diameter. Expression of byssus foot protein genes was analyzed by quantitative real-time PCR in foot tissue. High seawater temperature decreased the number of newly secreted byssus and the diameter of byssal threads, leading to the reduction of byssal breaking force and the alteration of the weakest part of the thread. Increased breakpoints in the upper part of the thread (proximal region) were higher at 27 °C than at 21 °C. High-temperature stress significantly reduced the PPO activity in byssus at 31 °C in comparison to 21 °C. The expression of mussel foot protein genes was affected by elevated temperature. The increased gene expression of byssus collagen-like protein 2 (Mccol2) at 31 °C conflicted with the number of byssuses produced. Suggesting the reduction of mussel foot protein abundance is not the cause of decreased byssus production at 31 °C. These results show that byssus, as an extracellular structure of mussels, may be highly susceptible to the adverse effects of ocean warming.