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Background: Peptide transporter 1 (PepT1) transports bacterial oligopeptide products and induces inflammation of the bowel. Nutritional peptides compete for the binding of intestinal bacterial products to PepT1. We investigated the mechanism of short-peptide-based enteral nutrition (SPEN) on the damage to the gut caused by the bacterial oligopeptide product muramyl dipeptide (MDP), which is transported by PepT1. The gut-lung axis is a shared mucosal immune system, and immune responses and disorders can affect the gut-respiratory relationship. Methods and results: Sprague-Dawley rats were gavaged with solutions containing MDP, MDP + SPEN, MDP + intact-protein-based enteral nutrition (IPEN), glucose as a control, or glucose with GSK669 (a NOD2 antagonist). Inflammation, mitochondrial damage, autophagy, and apoptosis were explored to determine the role of the PepT1-nucleotide-binding oligomerization domain-containing protein 2 (NOD2)-beclin-1 signaling pathway in the small intestinal mucosa. MDP and proinflammatory factors of lung tissue were explored to determine that MDP can migrate to lung tissue and cause inflammation. Induction of proinflammatory cell accumulation and intestinal damage in MDP gavage rats was associated with increased NOD2 and Beclin-1 mRNA expression. IL-6 and TNF-α expression and apoptosis were increased, and mitochondrial damage was severe, as indicated by increased mtDNA in the MDP group compared with controls. MDP levels and expression of proinflammatory factors in lung tissue increased in the MDP group compared with the control group. SPEN, but not IPEN, eliminated these impacts. Conclusions: Gavage of MDP to rats resulted in damage to the gut-lung axis. SPEN reverses the adverse effects of MDP. The PepT1-NOD2-beclin-1 pathway plays a role in small intestinal inflammation, mitochondrial damage, autophagy, and apoptosis. [ABSTRACT FROM AUTHOR]

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/β-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/β-catenin signaling, and that a Wnt/β-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/β-catenin pathway. In addition, we found that EMT could be regulated by IFIT1. IFIT1 may serve as a potential therapeutic target for pancreatic cancer. [ABSTRACT FROM AUTHOR]

Purpose: To compare the objective visual quality of moderate-to-high myopia corrected by small incision lenticule extraction (SMILE) and transepithelial photorefractive keratectomy (TransPRK) at a 1,050-Hz ablation frequency, assisted by Smart-Pulse technology (SCHWIND eye-tech-solutions). Methods: This study involved 123 patients (123 eyes) with moderate-to-high myopia between July 2020 and January 2021. They were categorized into the SMILE group (67 patients, 67 eyes) and the TransPRK group (56 patients, 56 eyes). Follow-ups were conducted at 6 months postoperatively to record the logarithm of the minimum angle of resolution visual acuity, and the Strehl ratio and higher order aberrations were measured using the Sirius anterior segment analysis device (SCHWIND eye-tech-solutions) under a 6-mm pupil diameter at various postoperative intervals. Results: At 1 week and 1 month postoperatively, the uncorrected distance visual acuity (UDVA) in the SMILE group was superior to that in the TransPRK group (P <.05 for both). At 1 week and 1 month postoperatively, the Strehl ratio value in the SMILE group was higher than that in the TransPRK group (P <.05 for both). At 1, 3, and 6 months postoperatively, coma was greater in the SMILE group than in the TransPRK group (P <.05 for all). Spherical aberrations were lower in the SMILE group than in the TransPRK group at 3 and 6 months postoperatively (P <.05). At 6 months postoperatively, UDVA was −0.09 ± 0.08 and −0.11 ± 0.05 logMAR in the SMILE and TransPRK groups, respectively, which exceeded their preoperative corrected distance visual acuity of −0.05 ± 0.04 and −0.09 ± 0.08 logMAR (all P <.001). Compared with preoperative values, the Strehl ratio, total higher order, coma, and spherical aberration differences were significantly increased postoperatively in both groups (all P <.001). Conclusions: Both surgical methods improved UDVA and each had its advantages. The visual quality of SMILE was superior at 1 week and 1 month postoperatively (Strehl ratio values were higher than those of the TransPRK group), and its spherical aberration was lower than that of the TransPRK group at 3 and 6 months; TransPRK with SmartPulse technology with a 1,050-Hz ablation frequency showed that coma was significantly lower than that of the SMILE group at 1, 3, and 6 months postoperatively. [J Refract Surg. 2024;40(7):e490–e498.] [ABSTRACT FROM AUTHOR]

The influence of continental emissions on the origin and formation mechanisms of atmospheric particulate nitrate (ρ‐NO3−) aerosols in the marine boundary layer remains unclear. Here, synchronous observations of nitrogen isotope ratios (δ15N–NO3−) and oxygen isotope anomaly (Δ17O–NO3−) in ρ‐NO3− were conducted across the Yellow Sea and Bohai Sea in Eastern China. Nitrate concentrations, δ15N–NO3− and Δ17O–NO3− exhibited a pronounced north‐to‐south latitudinal gradient. Combined with backward air mass trajectory analysis, the high nitrate concentration and isotopic characteristics in the northern sea area were found to be affected by the continental outflow near China while the low values in the southern sea area were more related to the oceanic inflow. Stable isotope analysis in R (SIAR) indicated that near the northern sea area, the nitrate radicals (NO3) reacted with hydrocarbons (HC) or dimethyl sulfides (DMS) pathway (NO3 + HC/DMS) played a leading role in nitrate production, whereas the NO2 + OH pathway dominated near the southern sea area. Nitrate in the northern seas originated mainly from nitrogen oxides (NOx = NO + NO2, the gaseous precursor of nitrate) emitted from continental sources, especially coal combustion and biomass burning. While closer to the southern seas, the proportion of NOx generated in the marine environment (from ship and biogenic emissions) increased. Overall, the differential relative contributions of continental and marine atmospheric chemistry and NOx sources lead to the spatial distribution characteristics of atmospheric nitrate concentrations and isotopic values over the Yellow and Bohai Seas. Plain Language Summary: This study investigated the impact of emissions from land sources on the formation of nitrate particles in the air above the marine boundary layer. The researchers conducted observations of nitrogen and oxygen isotopes in nitrate particles across the Yellow Sea and Bohai Sea in Eastern China. They found that nitrate concentrations and isotopic ratios showed a clear gradient from north to south. By analyzing the trajectory of air masses, they determined that high nitrate concentrations in the northern sea area were influenced by emissions from the nearby continent, while lower values in the southern sea area were more related to the ocean. The analysis also revealed that different chemical pathways were responsible for nitrate production in these regions. In the northern seas, nitrate production was primarily driven by the reaction of nitrate radicals with hydrocarbons or dimethyl sulfides, while in the southern seas, the dominant pathway involved the reaction of nitrogen dioxide with hydroxyl radicals. The study further showed that nitrate in the northern seas mainly originated from nitrogen oxides emitted by continental sources such as coal combustion and biomass burning, whereas closer to the southern seas, a larger proportion of nitrogen oxides were generated within the marine environment. Key Points: Continental outflow significantly affects the sources and formation mechanisms of atmospheric nitrate in nearshore marine areasAs continental outflow diminishes, local chemistry and marine‐generated NOx become pivotal in producing atmospheric NO3− in the open ocean. In polluted marine boundary layers, NO3 radical‐related chemistry may play a significant role in the formation of nitrate [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Spirocyclic frameworks could enhance the drug‐like properties of planar bioactive molecules by increasing their three‐dimensionality, making the development of synthetic methodology and bioactivity assays for spiro compounds highly attractive. This work reported the silver‐catalyzed tandem cycloisomerization/Povarov reaction between β‐alkynyl ketones and hexahydro‐1,3,5‐triazines, access to spiro[isochromene‐1,4'‐quinoline]. This synthetic protocol was characterized by remarkable efficiency, low catalyst‐loading and high diastereoselectivity. Moreover, the spirocyclic quinolines exhibited good cytotoxicity in U937 cells by activating the Notch‐signaling pathway exclusively. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Lightweight metal‐polymer composited foam has drawn considerable attention in fields of wearable electronics, acoustic and electromagnetic shielding, automotive and aerospace manufacturing, owing to its unique advantages like electrical conductivity and mechanical properties. Herein, a facile strategy is studied for one‐step fabrication of multifunctional liquid metal (LM) permeated expancel microspheres foam (EMLM foam) with controllable shape and size. Specifically, the formation process and mechanism of bicontinuous structure with polymer and liquid metal are explored by real‐time monitoring and finite element simulation. Both experimental and simulating results confirmed a stable 3D metal interconnected network that can be constructed with lower limit of LM (3 vol.%). In addition, based on the unique features of reversible rigidity control, lightweight, electrical conductivity, and mechanical stability, the EMLM foam can exhibit intelligent performance in tunable acoustic, energy absorption, and thermal driving repair. Combined with EMLM foam's facile preparation process and versatility, it can provide the remarkable opportunity to develop the lightweight intelligent devices. [ABSTRACT FROM AUTHOR]

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. It remains unclear how BRCA1-associated mutational sigantures are generated in cancer. Here, the authors develop nCas9-based approaches to uncover that aberrant repair of one-ended DSBs converted from DNA nicks by replication, not that of two-ended DSBs, induces such mutational signatures. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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/β-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/β-catenin signaling, and that a Wnt/β-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/β-catenin pathway. In addition, we found that EMT could be regulated by IFIT1. IFIT1 may serve as a potential therapeutic target for pancreatic cancer. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Disordered glucose and lipid metabolism contributes to the progression of several liver diseases, while the upregulation of phosphatase and tensin homology deleted on chromosome ten (PTEN), a well-known tumour suppressor gene, can improve the condition through metabolic programming. This study first characterized the metabolic profiles and the involvement of PTEN in the hepatic fibrosis induced by Schistosoma japonicum (S. japonicum) to provide a novel clue for metabolism-targeted treatment. Compared with control mice, infected mice showed infiltrated immune cells in their livers, increased levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and decreased glucose levels in their sera. The expression of key enzymes in the glycolytic pathway was significantly increased, and the expression of gluconeogenic genes was distinctly decreased. Moreover, the infection upregulated the hepatic expression of enzymes involved in fatty acid oxidation, which was consistent with the decreased number of lipid droplets in livers and the lowered levels of triglyceride in sera. Consistently, PTEN and its downstream signalling were significantly inhibited. In vitro, soluble egg antigen (SEA) downregulated the expression of PTEN in both the macrophage RAW264.7 cell line and the murine hepatocellular carcinoma HEP1-6 cell line, and induced a metabolic phenotype similar to the in vivo results. Overall, this study showed that S. japonicum infection induced the reprogramming of glucose and lipid metabolism in mice during the period of liver fibrosis and that SEA could act as a modulator to trigger such a metabolic switch in macrophages and hepatocytes. PTEN might play an essential role in mediating these metabolic reprogramming events. [ABSTRACT FROM AUTHOR]

In order to explore a new and safe preservation technology for winter jujube storage, the effects of 1-methylcyclopropene (1-MCP) and chlorine dioxide (ClO2) in single and/or in combination (fumigation with 3 µL/L 1-MCP and 100 µL/L ClO2, storage at 4 °C) on postharvest physiology and storage characteristics of winter jujube were studied. The variations of color, decay, firmness, water content, total soluble solids (TSS), titratable acid (TA), vitamin C (VC), total phenolics, reducing power and DPPH free radical scavenging rate were evaluated. The results showed that treatment with 1 -MCP or ClO2 alone both effectively delayed color changing, reduced decay, maintained high levels of water content, firmness, TSS content, TA content, VC content, total phenolics content, reducing power and DPPH free radical scavenging rate, and enhanced postharvest storage quality of winter jujube. In comparision with the treatment with 1-MCP or ClO2 alone, the combination of 1-MCP and ClO2 treatment showed a better preservation effect and it could be used as a useful method in postharvest preservation of winter jujube. [ABSTRACT FROM AUTHOR]

This study aimed to investigate whether the classic hepatoprotective drug polyene phosphatidylcholine (PPC) regulates macrophage polarization and explores the potential role of TLR-2 in this process. In RAW264.7 macrophages and murine bone marrow-derived macrophages (BMDMs) stimulated by lipopolysaccharide (LPS), PPC significantly inhibited the production of IL-6, TNF-α, and the mRNA expression of M1-type macrophage markers. Consistently, PPC reduced the mRNA expression of several key enzymes in the pathways of glycolysis and lipid synthesis while increasing the expression of key enzymes associated with lipid oxidation. Moreover, blocking the glycolytic pathway using 2-deoxy-d-glucose (2-DG) significantly enhanced the anti-inflammatory effect of PPC. However, inhibition of lipid oxidation using GW9662 (an inhibitor of PPAR-γ) and GW6471 (an inhibitor of PPAR-α) abolished the anti-inflammatory effect of PPC. Interestingly, TLR-2 expression in macrophages was significantly downregulated after exposure to PPC. Moreover, pre-activation of TLR-2 hampered the anti-inflammatory effect of PPC. In addition, PPC did not inhibit the secretion of IL-6 and TNF-α in TLR-2−/− BMDMs that were activated by LPS. This was consistent with the increased expression of M1 markers and glycolytic and lipid synthesis enzymes but decreased lipid oxidation-related enzymes. These results showed that PPC inhibits the differentiation of M1-type macrophages, which was most likely related to TLR-2-mediated metabolic reprogramming. [ABSTRACT FROM AUTHOR]

The article titled "Retraction Note: IFIT1 modulates the proliferation, migration and invasion of pancreatic cancer cells via Wnt/β-catenin signaling" has been retracted by the Editors-in-Chief at the authors' request. The authors discovered image overlap with their other article and requested a correction. Further investigation by the Publisher revealed additional cases of image overlap and similarities between figures in this article and another. The authors have provided raw data for validation, but due to the high number of errors, they have decided to retract the article. The authors have been invited to submit a corrected version for peer review. [Extracted from the article]

Microglia-mediated neuroinflammation plays a critical role in the pathological development of Parkinson's disease ( PD). Orphan nuclear receptor Nur77 (Nur77) is abundant in neurons, while its role in microglia-mediated neuroinflammation remains unclear. The present data demonstrated that the expression of Nur77 in microglia was reduced accompanied by microglia activation in response to lipopolysaccharide ( LPS) in vitro and in experimental 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- PD mouse model. Nur77 over-expression or application of Nur77 agonist cytosporone B suppressed the expression of proinflammatory genes, such as inducible nitric oxide NOS, cyclooxygenase-2, IL-1β, and tumor necrosis factor-α in the activated microglia, while silenced Nur77 exaggerated the inflammatory responses in microglia. Moreover, activation of Nur77 suppressed the LPS-induced NF-κB activation which was partly dependent on p38 MAPK activity, since inhibition of p38 MAPK by SB203580 abolished the LPS-activated NF-κB in microglia. On the other hand, inhibition of p38 MAPK attenuated LPS-induced Nur77 reduction. Furthermore, in a microglia-conditioned cultured media system, Nur77 ameliorated the cytotoxicity to MN9D dopaminergic cells. Lastly, cytosporone B attenuated microglia activation and loss of dopaminergic neuron in the substantia nigra pars compacta ( SNpc) of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- PD mouse model. Taken together, these findings revealed the first evidence that Nur77 was an important modulator in microglia function that associated with microglia-mediated dopaminergic neurotoxicity, and thus modulation of Nur77 may represent a potential novel target for treatment for neurodegenerative disease. [ABSTRACT FROM AUTHOR]

Background/Aims: The aim of the present study is to investigate whether the single nucleotide polymorphism (SNP) in lipid metabolism related genes would affect the effectiveness of atorvastatin in both Han and Uighur populations. Methods: 200 ischemic stroke patients were treated with atorvastatin. The differences of blood lipid level and their ratios were measured. Six lipid related genes, HMGCR, APOA5, LPL, CETP, LDLR and PCSK9 were selected as candidate genes. And nine SNP loci in these six genes were genotyped by SNaPshot technique. Results: In all patients treated with atorvastatin, the SNP rs662799 significantly affected the ratio of ΔLDL and ΔLDL/LDL (p < 0.05); the SNP rs320 significantly affected the ratio of ΔLDL/LDL and Δ(LDL/HDL)/(LDL/HDL) (p < 0.01) and the SNP rs708272 significantly affected the ratio of ΔLDL (p < 0.05). In Han population treated with atorvastatin, the SNP rs662799 significantly affected the ratio of ΔTG (p < 0.05); the SNP rs320 significantly affected the ratio of ΔLDL/LDL and Δ(LDL/HDL)/(LDL/HDL) (p < 0.01). In Uighur population treated with atorvastatin, the SNP rs2266788 significantly affected the ratio of ΔHDL (p < 0.05); the SNP rs662799 significantly affected the ratio of ΔLDL/LDL (p < 0.05) and the SNP rs708272 significantly affected the ratio of ΔLDL (p < 0.05). Conclusion: Polymorphisms of rs662799 and rs2266788 in APOA5 gene, rs320 in LPL gene and rs708272 in CETP gene had significant association with the effect of the lipid-lowering therapy via atorvastatin calcium on ischemic stroke patients. [ABSTRACT FROM AUTHOR]

Objective: Haemostatic biomarkers associated with poor outcome in acute ischemic stroke (AIS). The objective of the study was to evaluate the predictive value of plasma D-dimer (D-D) on functional outcome at 90-day follow-up from stroke onset. Methods: We conducted a prospective, observational cohort study in the emergency department and enrolled 220 patients with AIS. Plasma D-D concentrations, determined by a particle-enhanced, immunoturbidimetric assay, were measured. Each patient’s medical record was reviewed, and demographic, clinical, laboratory and neuroimaging information was abstracted. Results: There was a positive correlation between levels of D-D and the NIHSS (r = 0.361, p<0.001), and the infarct volume (r = 0.449, p<0.001). In the 69 patients with an unfavorable functional outcome, D-D levels were higher compared with those in patients with a favorable outcome [3.24(IQR, 2.18–4.60)mg/L vs 0.88(IQR, 0.35–1.77) mg/L; p<0.001]. After adjusting for all other significant outcome predictors, D-D level remained an independent predictor for unfavorable functional outcome and mortality with an odds ratio of 2.18 (95% CI, 1.55–2.83), 3.22 (95% CI, 2.05–6.43); respectively. Conclusions: D-D levels are a useful tool to predict outcome and mortality 90-day after acute ischemic stroke and have a potential to assist clinicians. [ABSTRACT FROM AUTHOR]

Today, the trend of fast fashion as synonymous with the change and development for fashion has played a catalytic role. Under the impact of the fast fashion, knitted garment gradually break the original design thinking frameworks. This article introduces the fast fashion knit couture under current situation, highlight the advantages of fast fashion and trends guide. By studying stylish knit clothes, yarns, colors, patterns, styles, organizational development, it can enrich the knitted dress design ideas, enhance the design potential of knit dress. Thereby promoting the production and development of knitted dress quickly and efficiently. Let the knitting female attire change be diverserand reinforced knit ladies' overall design standards in the industry. [ABSTRACT FROM AUTHOR]

ABSTRACT Al-activated organic acid anion efflux from roots is an important Al resistance mechanism in plants. We have conducted homologous cloning and isolated Vigna umbellata multidrug and toxic compound extrusion ( VuMATE), a gene encoding a de novo citrate transporter from rice bean. Al treatment up-regulated VuMATE expression in the root apex, but neither in the mature root region nor in the leaf. The degree of up-regulation of VuMATE was both partially Al concentration and time dependent, consistent with the delay in the onset of the Al-induced citrate efflux in rice bean roots. While La3+ moderately induced VuMATE expression, Cd2+ and Cu2+ did not induce the expression. Electrophysiological analysis of Xenopus oocytes expressing VuMATE indicated this transporter can mediate significant anion efflux across the plasma membrane. [14C]citrate efflux experiments in oocytes demonstrated that VuMATE is a H+-dependent citrate transporter. In addition, expression of VuMATE in transgenic tomato resulted in increased Al resistance, which correlated with an enhanced citrate efflux. Taken together, these findings suggest that VuMATE is a functional homolog of the known citrate transporters in sorghum, barley, maize and Arabidopsis. The similarities and differences of all the known citrate transporters associated with Al stress in the MATE family are also discussed. [ABSTRACT FROM AUTHOR]

Background: We sought to study the blood pressure variability statuses among different subtypes of acute ischemic stroke. Methods: From July 2009 to July 2011, 226 acute ischemic stroke patients aged 66.2±11.9 years, including 128 men and 98 women, were enrolled from the Departments of Neurology and Emergency at Urumqi Friendship Hospital. Based on the criteria and classification of “trial of Org 10 172 in acute stroke treatment,” the patients were divided into 3 groups: arterial atherothrombolism (AT) group (n = 98), cardioaortic embolism (CE) group (n = 39), and small artery disease (SAD) group (n = 89). Two-hundred twenty-six healthy subjects aged 65.6±10.8 years, including 140 men and 86 women were selected as control subjects. Their blood pressure level and variability were examined by 24-hour ambulatory blood pressure monitoring. Results: Compared with the control group, patients in the AT, CE and SAD groups had significantly higher 24-hour mean systolic blood pressure (136.7±11.7, 131.2±12.5, and 138.1±15.3mm Hg, respectively, vs. 116.7±13.2mm Hg), 24-hour mean diastolic blood pressure (77.9±12.5, 70.2±11.4, and 77.2±12.7mm Hg, respectively vs. 64.4±11.5mm Hg), pulse pressure index (0.46±0.08, 0.42±0.07, and 0.45±0.05, respectively, vs. 0.37±0.07), and variability of 24-hour diastolic blood pressure (0.17±0.05, 0.14±0.02, and 0.17±0.01, respectively, vs. 0.11±0.04) (all P < 0.05). There were significant differences in the distribution of blood pressure circadian rhythms among patients in the 3 groups (P < 0.05). Conclusions: The blood pressure variability in acute ischemic stroke patients was significantly larger than that in the control group. Furthermore, there were also significant differences in blood pressure variability among different ischemic stroke subtypes. [ABSTRACT FROM PUBLISHER]

This study evaluates the reversal effects of graphene oxide (GO) used as a carrier for adriamycin (ADR) in cancer drug resistance, and provides a preliminary investigation into the reversal mechanism. ADR was loaded onto the GO surface (ADR–GO) by physical mixing and drug loading content was found to be high, up to 93.6%. In vitro releases of ADR from ADR–GO were studied using a dialysis method, and they exhibited a significant pH-sensitive property. Cell experiments showed that GO significantly enhanced the accumulation of ADR in MCF-7/ADR cells (an ADR resistant breast cancer cell line) and exhibited much higher cytotoxicity than free ADR, suggesting that ADR–GO could effectively reverse ADR resistance of MCF-7/ADR, with the reversal index reaching 8.35. Microscopy studies found that GO could effectively carry drug molecules into cells in both endocytosis-dependent and independent manners. In conclusion, use of GO as a carrier for chemotherapeutic agents is favorable for the treatment of drug resistant cancers. [ABSTRACT FROM AUTHOR]