Mechanisms and structure-activity relationships of polysaccharides in the intervention of Alzheimer's disease: A review.

Alzheimer's disease (AD) is a complex neurodegenerative disease. Despite several decades of research, the development of effective treatments and responses for Alzheimer's disease remains elusive. The utilization of polysaccharides for Alzheimer's disease became more popular due to their beneficial characteristics, notably their multi-target activity and low toxicity. This review mainly focuses on the researches of recent 5 years in the regulation of AD by naturally derived polysaccharides, systematically lists the possible intervention pathways of polysaccharides from different mechanisms, and explores the structure-activity relationship between polysaccharide structural activities, so as to provide references for the intervention and treatment of AD by polysaccharides.

Plastid phylogenomics of the tribe potentilleae (Rosaceae).

The tribe Potentilleae comprises approximately 1700 species in 13 genera, making it one of the largest of the 16 tribes in Rosaceae. Our understanding of the composition and relationships among members of Potentilleae has advanced dramatically with the application of molecular markers in the last two decades. Yet there is still much work remaining toward a robust phylogenetic framework for the entire Potentilleae and a comprehensive genus-level dating framework for the tribe. The goals of the present study were to establish a phylogenetic framework for Potentilleae, infer the origin and diversification of the tribe using a temporal framework, and explore the taxonomic implications in light of the updated phylogenetic framework. We used the plastome sequences from 158 accessions representing 139 taxa covering all 13 recognized genera of the tribe to reconstruct the Potentilleae phylogeny. High phylogenetic resolution was recovered along the Potentilleae backbone. Two major clades were recovered within Potentilleae, corresponding to the two subtribes Fragariinae and Potentillinae. Within Fragariinae, two subclades were recovered. In one subclade, Sibbaldia sensu stricto is sister to a clade containing Sibbaldianthe, Comarum, Farinopsis, and Alchemilla sensu lato. In the other subclade, Fragaria is sister to a clade comprising Chamaerhodos, Chamaecallis, Drymocallis, Dasiphora, and Potaninia. Within Potentillinae, Argentina is sister to Potentilla sensu stricto. Within Potentilla sensu stricto, clade Himalaya is sister to Alba, and the Himalaya-Alba clade together is sister to a clade comprising Reptans, Potentilla ancistrifolia Bunge, Fragarioides, Ivesioid, and Argentea. Divergence time estimates indicated that tribe Potentilleae originated during the middle Eocene, and subtribes Fragariinae and Potentillinae diverged around the Eocene-Oligocene transition, and divergence times dated for Potentilleae genera ranged from the early Miocene to the late Pleistocene.

The complete chloroplast genome of Geum longifolium (Maxim.) Smedmark 2006 (Rosaceae: Colurieae) and its phylogenomic implications.

Geum longifolium (Maxim.) Smedmark 2006 belongs to the family Rosaceae, subfamily Rosoideae, tribe Colurieae. Geum longifolium is endemic to China and its whole herb is used in Chinese medicine. Here, the first complete chloroplast (cp) genome of G. longifolium was assembled and annotated based on genome skimming, and its phylogenetic position was investigated using phylogenomic evidence. The cp genome size of G. longifolium was 155,884 bp with the total GC content of 36.7%. Its cp genome presented a typical tetrad structure, composed of a large single copy (LSC) region (85,338 bp), a small single copy (SSC) region (18,358 bp), and a pair of inverted repeat (IR) regions (26,094 bp). The cp genome encoded 129 genes, including 84 protein-coding genes, 37 tRNA genes, and eight rRNA genes. Phylogenetic analysis indicated that G. longifolium was sister to G. elatum Wall. ex G.Don 1832 in current taxa sampling. This study can enrich the chloroplast genomic resource of Geum and lay the foundation for future phylogenetic studies on Geum.

Three-dimensional visualization and evaluation of hilar cholangiocarcinoma resectability and proposal of a new classification.

BACKGROUND: As digital medicine has exerted profound influences upon diagnosis and treatment of hepatobiliary diseases, our study aims to investigate the accuracy of three-dimensional visualization and evaluation (3DVE) system in assessing the resectability of hilar cholangiocarcinoma (hCCA), and explores its potential clinical value. MATERIALS AND METHODS: The discovery cohort, containing 111 patients from April 2013 to December 2019, was retrospectively included to determine resectability according to revised criteria for unresectability of hCCA. 3D visualization models were reconstructed to evaluate resectability parameters including biliary infiltration, vascular involvement, hepatic atrophy and metastasis. Evaluation accuracy were compared between contrast-enhanced CT and 3DVE. Logistic analysis was performed to identify independent risk factors of R0 resection. A new comprehensive 3DVE classification of hCCA based on factors influencing resectability was proposed to investigate its role in predicting R0 resection and prognosis. The main outcomes were also analyzed in cohort validation, including 34 patients from January 2020 to August 2022. RESULTS: 3DVE showed an accuracy rate of 91% (95%CI 83.6-95.4%) in preoperatively evaluating hCCA resectability, significantly higher than 81% (95%CI 72.8-87.7%) of that of CT (p = 0.03). By multivariable analysis, hepatic artery involvement in 3DVE was identified an independent risk factor for R1 or R2 resection (OR = 3.5, 95%CI 1.4,8.8, P < 0.01). New 3DVE hCCA classification was valuable in predicting patients' R0 resection rate (p < 0.001) and prognosis (p < 0.0001). The main outcomes were internally validated. CONCLUSIONS: 3DVE exhibited a better efficacy in evaluating hCCA resectability, compared with contrast-enhanced CT. Preoperative 3DVE demonstrated hepatic artery involvement was an independent risk factor for the absence of R0 margin. 3DVE classification of hCCA was valuable in clinical practice.

Association between C-reactive protein-albumin-lymphocyte (CALLY) index and overall survival in patients with colorectal cancer: From the investigation on nutrition status and clinical outcome of common cancers study.

Background: Colorectal cancer (CRC) is among the most common malignant cancers worldwide, and its development is influenced by inflammation, nutrition, and the immune status. Therefore, we combined C-reactive protein (CRP), albumin, and lymphocyte, which could reflect above status, to be the CRP-albumin-lymphocyte (CALLY) index, and evaluated its association with overall survival (OS) in patients with CRC. Methods: The clinicopathological and laboratory characteristics of 1260 patients with CRC were collected from the Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) study. Cox regression analysis was performed to assess the association between the CALLY index and OS. A nomogram including sex, age, the CALLY index and TNM stage was constructed. The Concordance Index (C-index) was utilized to evaluate the prognostic value of the CALLY index and classical CRC prognostic factors, such as modified Glasgow prognostic score (mGPS), neutrocyte to lymphocyte ratio (NLR), systemic immune inflammation index (SII), and platelet to lymphocyte ratio (PLR), as well as to assess the prognostic value of the nomogram and TNM stage. Results: Multivariate Cox regression analyses demonstrated that the CALLY index was independently associated with OS in patients with CRC [Hazard ratio (HR) = 0.91, 95% confidence interval (CI) = 0.87-0.95, P<0.001]. The CALLY index showed the highest prognostic value (C-index = 0.666, 95% CI = 0.638-0.694, P<0.001), followed by mGPS, NLR, SII, and PLR. The nomogram demonstrated higher prognostic value (C-index = 0.784, 95% CI = 0.762-0.807, P<0.001) than the TNM stage. Conclusion: The CALLY index was independently associated with OS in patients with CRC and showed higher prognostic value than classical CRC prognostic factors. The nomogram could provide more accurate prognostic prediction than TNM stage.

Metabolomics reveals size-dependent persistence and reversibility of silver nanoparticles toxicity in freshwater algae.

Although the toxicity of silver nanoparticles (AgNPs) has been widely reported, the persistence and reversibility of AgNPs toxicity are poorly understood. In the present work, AgNPs with particle sizes of 5 nm, 20 nm, and 70 nm (AgNPs5, AgNPs20, and AgNPs70) were selected to investigate the nanotoxicity and recovery effects of Chlorella vulgaris in the exposure (72 h) and recovery (72 h) stages using non-targeted metabolomics techniques. The exposure of AgNPs exerted size-dependent effects on several aspects of C. vulgaris physiology, including growth inhibition, chlorophyll content, intracellular silver accumulation, and differential expression of metabolites, and most of these adverse effects were reversible. Metabolomics revealed that AgNPs with small sizes (AgNPs5 and AgNPs20) mainly inhibited glycerophospholipid and purine metabolism, and the effects were reversible. In contrast, AgNPs with large sizes (AgNPs70) reduced amino acid metabolism and protein synthesis by inhibiting aminoacyl-tRNA biosynthesis, and the effects were irreversible, demonstrating the persistence of nanotoxicity of AgNPs. The size-dependent persistence and reversibility of AgNPs toxicity provides new insights to further understand the mechanisms of toxicity of nanomaterials.

Systemic inflammation with sarcopenia predicts survival in patients with gastric cancer.

OBJECTIVE: The levels of platelet-related inflammation indicators and sarcopenia have been reported to affect the survival of patients with cancer. To evaluate the prognostic influence of platelet count (PLT), platelet lymphocyte ratio (PLR), and systemic immune inflammation index (SII), and SII combined with sarcopenia on the survival of patients with gastric cancer (GC). METHODS: A total of 1133 patients with GC (812 male and 321 female, average age: 59.43 years) were evaluated. Receiver-operating characteristic curves were used to determine the best cutoff values of PLT, PLR, and SII, and univariate and multivariate Cox risk regression models were used to evaluate whether SII is an independent predictor of overall survival (OS). The prognostic SS (SII-sarcopenia) was established based on SII and sarcopenia. Finally, a comprehensive analysis of the prognostic SS was performed. RESULTS: SII had the strongest prognostic effect. The SII and OS of patients with GC were in an inverted U-shape (adjusted HR = 1.07; 95% CI 0.97-1.19; adjusted P = 0.179). In patients with SII > 1800, SII was negatively correlated with OS (adjusted HR = 0.57; 95% CI 0.29-1.12; adjusted P = 0.102), however, there is no statistical difference. Interestingly, a high SS was associated with a poorer prognosis. The higher the SS score was, the worse the OS (P < 0.001). CONCLUSION: SII is an independent prognostic indicator of GC, and high SII is related to poor prognosis. A higher SS score had worse survival. Thus, the prognostic SS is a reliable predictor of OS in patients with GC.

Metabolomics reveals the mechanism of polyethylene microplastic toxicity to Daphnia magna.

Microplastic exposure leads to various toxic effects in Daphnia magna; however, the effects of microplastics on the metabolic processes in D. magna and the corresponding molecular toxicity mechanisms remain unclear. In the present study, the effects of acute exposure to polyethylene microplastics with different particle sizes (20 µm [MPs-20] and 30 µm [MPs-30]) on metabolites in D. magna and the mechanisms of toxicity were investigated by combining metabolomics and traditional toxicology techniques. Exposure to both MPs-20 and MPs-30 resulted in significant accumulation of microplastics in the gut of D. magna and significantly reduced D. magna survival and heart rate. Metabolomics analysis revealed that MPs-20 and MPs-30 induced significant changes in up to 88 and 91 differential metabolites, respectively, and collectively induced significant changes in 75 metabolites in D. magna. Among lipid metabolites, MPs-20 specifically downregulated phosphatidylcholine and upregulated phosphatidylethanolamine, which mainly affected phospholipid metabolism, whereas MPs-30 specifically downregulated amino acid metabolites l-glutamine, l-glutamate and malic acid, which mainly interfered with energy metabolism. The results of this study provide novel insights into the mechanism of effects of microplastics on metabolic processes in D. magna.

Associations of prenatal exposure to perfluoroalkyl substances with preterm birth: A family-based birth cohort study.

Studies have investigated associations between maternal exposure to PFAS and preterm birth, but the impact of paternal and overall family exposure to PFAS mixtures on preterm birth remains unknown. To address this knowledge gap, a total of 355 preterm births and 481 controls were selected for a family-based birth cohort study in a coastal area of China, between 2016 and 2018. Seven PFAS, including perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA), were quantified in maternal, paternal and neonatal sera. Preterm birth was defined as live delivery at <37 completed gestational weeks. Bayesian kernel machine regression (BKMR) model was used to inspect the combined effect of family PFAS mixtures. Latent class analysis was used to identify family-level PFAS exposure profiles. Multiple linear regression analysis showed higher odds of preterm birth in association with higher maternal PFBA (OR = 1.16, 95%CI:1.09, 1.25), PFOA (OR = 1.51, 95%CI:1.27, 1.80), PFOS (OR = 2.07, 95%CI:1.70, 2.52) and PFNA (OR = 1.36, 95%CI: 1.01, 1.83), and neonatal PFBA (OR = 1.16, 95%CI:1.05,1.29), PFHxA (OR = 1.46, 95%CI:1.32, 1.62), PFHxS (OR = 1.15, 95%CI:1.05, 1.26) and PFNA (OR = 1.30, 95%CI:1.09,1.56). The associations were reversed between individual paternal PFAS exposures and preterm birth. At the family level, higher PFAS mixture concentration was associated with higher odds of preterm birth. In particular, higher PFNA and PFDA exposure was associated with greater preterm birth risk (OR = 2.55, 95%CI:1.45, 4.50). The PFAS-preterm association was modified by family-level seafood consumption. Our results suggest that higher family-level PFNA and PFDA exposure was associated with greater preterm birth risk, although the results for individual paternal, maternal and neonatal PFAS exposures were contradictory. If replicated in other coastal areas, these findings highlight a need to focus on the family triad and to consider seafood consumption when assessing the reproductive toxicity of PFAS exposure.

Prognostic Roles of Glucose to Lymphocyte Ratio and Modified Glasgow Prognosis Score in Patients With Non-small Cell Lung Cancer.

Background: Non-small cell lung cancer (NSCLC) is among the most prevalent malignancies worldwide. Previous studies have shown that the status of inflammation, nutrition and immune are closely related to overall survival (OS) of patients with NSCLC, but little is known about their interactive and combined roles. Hence, we chose glucose to lymphocyte ratio (GLR) and modified Glasgow Prognosis Score (mGPS) as prognostic factors and assessed the prognostic values of them for patients with NSCLC. Methods: Baseline clinicopathologic and laboratory characteristics of 862 patients with NSCLC were obtained from a multicenter prospective cohort. The Cox proportional hazard regression models were used to determine prognostic values of the clinical factors. A nomogram was also constructed integrating the clinical factors with clinical significance or independent prognostic values. Concordance index (C-index) was utilized to evaluate the prediction accuracy of the TNM stage and the nomogram. Results: Multivariate analyses demonstrated that GLR [Hazard ratio (HR) = 1.029, 95% confidence interval (CI) = 1.004-1.056, P = 0.023] and mGPS (score of 1: HR = 1.404, 95% CI = 1.143-1.726, P = 0.001; score of 2: HR = 1.515, 95% CI = 1.159-1.980, P = 0.002) were independent prognostic factors for patients with NSCLC. The C-indexes of the TNM stage and the nomogram were 0.642 (95% CI = 0.620-0.663) and 0.694 (95% CI = 0.671-0.717), respectively. Conclusion: GLR and mGPS were independent prognostic factors for patients with NSCLC. Moreover, our constructed nomogram might be superior in predicting prognosis of patients with NSCLC compared with the TNM stage.

[Volatile Organic Compound Emission Characteristics and Influences Assessment of a Petrochemical Industrial Park in the Pearl River Delta Region].

The petrochemical industry is one of the major emission sources of volatile organic compounds (VOCs). However, the current studies have mostly focused on the identification of the chemical characteristics of non-methane hydrocarbon (NMHC) VOCs species from the petroleum refining sub-sector. Research on the characteristics of VOCs components in oxygenated VOCs (OVOCs) species and other important sub-sectors is still lacking. Therefore, eight enterprises at a petrochemical industrial park in the Pearl River Delta region were carefully selected to represent three major subsectors, namely petroleum refining, synthetic materials, and organic chemicals, for the petrochemical industry. The VOCs (including 22 OVOCs species) from stack emissions and fugitive emissions, as well as nearby sensitive sites, were sampled, and the source reactivity (SR), the thresholds of malodor, and the carcinogenic and non-carcinogenic risks were assessed. The main results were as follows:① the VOCs concentrations of the stack emissions from the petrochemical industrial park were between 0.2-46.3 mg·m-3. The VOCs species were greatly affected by the type of after-treatment technology. A major VOC species emitted from the combustion-based after treatments was formaldehyde, whereas the species emitted from the non-combustion-based equipment were acetone, 1,3-butadiene, acrylic, and isobutane. ② The fugitive VOCs emissions from the petroleum storage tank area were dominated by alkanes, whereas the other fugitive emission sites and the sensitive sites were dominated by OVOCs such as acetone, formaldehyde, and ethyl acetate. ③ The SRs were mainly contributed by OVOCs, aromatics, and olefins, with average proportions of 43.1%, 24.2%, and 21.1%, respectively, with the major species being formaldehyde, acetaldehyde, m/p-xylene, ethylene, and toluene. ④ The malodor appeared both in fugitive emission areas and the sensitive sites. The main odor components were OVOCs such as n-butyraldehyde, propionaldehyde, hexanal, and valeraldehyde. ⑤ The non-carcinogenic risks occurred in the fugitive emission areas and the sensitive sites of resin, alcohol, and aldehyde production, which were mainly caused by OVOCs such as free acetaldehyde, acrolein, and propionaldehyde. No carcinogenic risk was found in any of the sampled sites. This research can provide scientific support for the formulation of priority VOCs species-based precise control strategies in petrochemical industrial parks.

Association of Systemic Inflammation and Overall Survival in Elderly Patients with Cancer Cachexia - Results from a Multicenter Study.

BACKGROUND: Systemic inflammation and cachexia are associated with adverse clinical outcomes in elderly patients with cancer. The survival outcomes of elderly patients with cancer cachexia (EPCC) with high inflammation and a high risk of mortality are unknown. This study aimed to investigate the impact of high inflammation on the prognosis of EPCC patients with high mortality. PATIENTS AND METHODS: This multicenter cohort study included 746 EPCC (age >65 years) with a mean age of 72.00 ± 5.24 years, of whom 489 (65.5%) were male. The cut-off value for the inflammation index was obtained using the optimal survival curve. The different inflammatory indicators were assessed using the concordance index (C-index), decision curve analysis (DCA), and prognostic receiver operating characteristic (ROC). The high mortality risk group of EPCC was defined by the 2011 Fearon Cancer Diagnostic Consensus. EPCC were divided into the high-risk group, which satisfies three diagnostic criteria, and a low-risk group, which satisfies only one or two diagnostic criteria. RESULTS: The C-index, DCA, and prognostic ROC indicated the superiority of advanced lung cancer inflammation index (ALI) compared with other indicators, including neutrophil-lymphocyte ratio (NLR), prognostic nutritional index (PNI), systemic immune-inflammation index (SII), and platelet-lymphocyte ratio (PLR). Whether ALI was used as a continuous or a categorical variable, ALI had a better prognostic value in EPCC compared with other inflammatory indicators. In particular, patients with low ALI (<25.03) had a worse overall survival (OS) than patients with high ALI (≥25.03) (P < 0.001, HR [95% CI] = 2.092 [1.590-2.751]). The combination effect analysis showed that the risk of mortality of the patients in the low-ALI and high-risk groups was 3.095-fold higher than that of patients in the high-ALI and low-risk groups. CONCLUSION: The prognostic and discriminative value of the inflammatory indicator ALI was better than that of NLR, PNI, SII, and PLR in EPCC. The high-risk group of EPCC with a low ALI would increase the death risk of OS.

Geriatric Nutrition Risk Index: Prognostic factor related to inflammation in elderly patients with cancer cachexia.

BACKGROUND: Systemic inflammation and cachexia are associated with adverse clinical outcomes in elderly patients with cancer. The Geriatric Nutritional Risk Index (GNRI) is a simple and useful tool to assess these conditions, but its predictive ability for elderly patients with cancer cachexia (EPCC) is unknown. METHODS: This multicentre cohort study included 746 EPCC with an average age of 72.00 ± 5.24 years, of whom 489 (65.5%) were male. The patients were divided into two groups (high GNRI group ≥91.959 vs. low GNRI group <91.959) according to the optimal cut-off value of the ROC curve. The calibration curves were performed to analyse the prognostic, predictive ability of GNRI. Comprehensive survival analyses were utilized to explore the relationship between GNRI and the overall survival (OS) of EPCC. Interaction analysis was used to investigate the comprehensive effects of low GNRI and subgroup parameters on the OS of EPCC. RESULTS: In this study, a total of 2560 patients were diagnosed with cancer cachexia, including 746 cases of EPCC. During the 3.6 year median follow-up, we observed 403 deaths. The overall mortality rate for EPCC at 12 months was 34.3% (95% CI: 62.3% to 69.2%), and resulting in rate of 278 events per 1000 patient-years. The GNRI score of EPCC was significantly lower than those of young patients with cancer cachexia (P < 0.001). The 1, 3, and 5 year calibration curves showed that the GNRI score had good survival prediction in the OS of EPCC. The GNRI could predict the OS of EPCC, whether as a continuous variable or a categorical variable. Particularly, we also found that low GNRI score (<91.959) of EPCC had a worse prognosis than those with a high GNRI score (≥91.959, P = 0.001, HR = 1.728, 95% CI: 1.244-2.401). Consistent results were observed in the tumour subgroups of gastric cancer and colorectal cancer. Notably, similar results were observed in the sensitivity analysis. In the subgroup analysis, the low GNRI has a combined effect with age (<70 years) on poor OS of EPCC. The results of the prognostic risk model found that the lower the GNRI score, the greater the prognostic risk score, and the greater the risk of death in EPCC. CONCLUSIONS: For the first time, this study found that the GNRI score can serve as an independent prognostic factor for the OS of EPCC.

Relationship Between Prognostic Nutritional Index and Mortality in Overweight or Obese Patients with Cancer: A Multicenter Observational Study.

BACKGROUND: Overweight and obese patients with cancer present with chronic inflammation, dysfunctional antitumor immunity and malnutrition risk. Prognostic nutritional index (PNI) is a promising indicator for predicting inflammatory, immunological and nutritional states; however, its prognostic value in overweight and obese patients with cancer has not been explored. Therefore, the aim of the current study was to explore the prognostic value of PNI levels in overweight and obese patients with cancer. METHODS: The current large-scale retrospective cohort multicenter study included 3532 patients. Time-dependent receiver operating characteristic (ROC) curve analysis was used to determine the prediction accuracy of PNI levels for mortality of overweight and obese patients with cancer. Restricted cubic splines were used to model the association between PNI levels and mortality. Association between low PNI and overall survival rate was analyzed using the Kaplan-Meier method and Cox regression model. RESULTS: Area under the curve (AUC) of the PNI for all-cause mortality was higher compared with that of the neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) in overweight and obese patients with cancer. There was a significant inverse relationship between PNI levels and all-cause mortality (per SD increment-HR: 0.79; 95% CI: 0.74, 0.85; P<0.001). Subgroup analysis showed that the risk for mortality significantly decreased with increase in PNI levels in patients at risk of malnutrition (per SD increment-HR: 0.67; 95% CI: 0.57, 0.78; P<0.001) and elderly patients (per SD increment-HR: 0.74; 95% CI: 0.64, 0.84; P<0.001). In addition, PNI levels showed an inverse association with mortality in patients without malnutrition risk (per SD increment-HR: 0.81; 95% CI: 0.75, 0.88; P<0.001). Subgroup analysis based on tumor type showed that low PNI was an independent predictor of poor prognosis for patients with lung cancer, gastric cancer and hepatobiliary and pancreatic cancer. CONCLUSION: Low PNI levels are associated with an increased risk for all-cause mortality. PNI level is a potential effective inflammation-based prognostic tool for overweight and obese patients with cancer.

Metabolic profiling of nanosilver toxicity in the gills of common carp.

Studies have shown silver nanoparticles (AgNPs) exposure can result in a series of toxic effects in fish gills. However, it is still unclear how AgNPs affect metabolite expression and their related molecular metabolic pathways in fish gills. In this study, we employed untargeted metabolomics to study the effects of AgNPs and silver supernatant ions on fish gill metabolites. The results showed that AgNPs can induce significant changes in 96 differentially expressed metabolites, which mainly affect amino acid metabolism and energy metabolism in fish gills. Among these metabolites, AgNPs specifically induce significant changes in 72 differentially expressed metabolites, including L-histidine, L-isoleucine, L-phenylalanine, and citric acid. These metabolites were significantly enriched in the pathways of aminoacyl-tRNA biosynthesis, ABC transporters, and the citrate cycle. In contrast, Ag+ supernatant exposure can specifically induce significant changes in 14 differentially expressed metabolites that mainly interfere with sphingolipid metabolism in fish gills. These specifically regulated fish gill metabolites include sphinganine, sphingosine, and phytosphingosine, which were significantly enriched in the sphingolipid metabolism pathway. Our results clearly reveal the effects and potential toxicity mechanisms of AgNPs on fish gill metabolites. Furthermore, our study further determined the unique functions of released silver ions in AgNPs toxicity in fish gills.

[Application of Array-based Comparative Genomic Hybridization in Diagnostic Assessment of Abnormal Prenatal Serological Screening Results of Down's Syndrome].

OBJECTIVE: To explore the application of array-based comparative genomic hybridization (a-CGH) technology in the prenatal diagnostic assessment of abnormal serological prenatal screening results of Down's syndrome (DS). METHODS: A total of 3 578 amniotic fluid samples from pregnant women who underwent amniocentesis for prenatal diagnosis solely due to abnormal serological prenatal screening results were selected. The samples were categorized into 3 groups, 2 624 in the high-risk group, 662 in the borderline-risk group, and 292 in the abnormal multiple of median (MoM) group. a-CGH was performed on the Agilent CGX ™ (8×60K) platform and the data were analyzed by the Genoglyphix ® software. RESULTS: The overall detection rate of chromosomal abnormalities was 3.38% (121/3 578). Among the chromosomal abnormalities, 49.59% (60/121) was aneuploidies, 42.15% (51/121) was pathogenic copy number variants (pCNVs), and 8.26% (10/121) was likely pathogenic CNVs (lpCNVs). The detection rate of copy number variant of uncertain significance (VUS) was 1.03% (37/3 578). In the high-risk, the borderline-risk and the abnormal MoM groups, the detection rate of chromosomal abnormalities was 3.54% (93/2 624), 2.87% (19/662) and 3.08% (9/292), respectively; the detection rate of p/lp CNVs was 1.64% (43/2 624), 1.81% (12/662) and 2.05% (6/292), respectively; the detection rate of trisomy 21 and trisomy 18 was 1.37% (36/2 624), 0.76% (5/662) and 0.34% (1/292) in the three groups, respectively. There were no significant differences in all the detection rate among these groups ( P>0.05). One sample with X(51)/XYY(49) confirmed by fluorescence in situ hybridization (FISH) was misdiagnosed by a-CGH. CONCLUSION: Prenatal diagnosis with a-CGH is of great significance for reducing birth defects in pregnancies with abnormal serological prenatal screening results of DS. It can also be used to detect CNVs of microdeletion/microduplication syndromes.

The complete chloroplast genome of Geum macrophyllum (Rosaceae: Colurieae).

The complete chloroplast genome of Geum macrophyllum is reported and characterized in this study. The chloroplast genome of G. macrophyllum was a circular form with a size of 155,940 bp in length. The genome presented a typical quadripartite structure composed of a pair of inverted repeats (IRa and IRb) of 26,152 bp separated by a large single copy (LSC) region of 85,307 bp and a small single copy (SSC) region of 18,329 bp. The genome contained a set of 129 genes, including 84 protein-coding genes, 37 tRNA genes, and eight rRNA genes, in which 17 were duplicated and 112 were unique. Phylogenetic analysis placed G. macrophyllum as sister to G. triflorum based on current sampling.

[Application of Array-based Comparative Genomic Hybridization in the Prenatal Diagnosis of Fetal Chromosomal Aberration in Gravidas with Advanced Age].

OBJECTIVE: To evaluate the clinical application of array-based comparative genomic hybridization (a-CGH) in the prenatal diagnosis of fetal chromosomal aberrations in gravidas with advanced maternal age (AMA). METHODS: A total of 3 677 amniotic fluid samples from pregnant women who underwent amniocentesis for prenatal diagnosis solely due to AMA were selected. Array-CGH was performed on the Agilent CGX TM (8X60K) platform and the data were analyzed by the Genoglyphix software. RESULTS: The overall detection rate of chromosomal aberration was 2.04% (75/3677), with 53.33% (40/75) being aneuploidies, including 22 cases of trisomy-21, 5 cases of trisomy-18, 8 cases with XXY, 3 cases of XYY and 2 cases of mosaic monosomy X, 32.00% (24/75) being pathogenic copy number variations (pCNVs), including 19 cases of microdeletion and 5 cases of microduplication, with the fragment size ranging from 323 kb to 26 780 kb, and 14.67% (11/75) being likely pathogenic CNVs (lpCNVs), including 7 cases of microdeletion and 7 cases of microduplication, with the fragment size ranging from 358 kb to 16 873 kb. Besides, the detection rate of CNVs of unknown clinical significance (VUS) was 0.84% (31/3 677). The detection rate of aneuploidies increased significantly with increased maternal age ( P<0.05). However, there were no significant differences in the detection rate of p/lpCNVs among different maternal age groups ( P>0.05). CONCLUSION: Our findings suggest that, compared with traditional karyotype analysis, a-CGH not only detects aneuploidies, but also detect pathogenic CNVs, including microdeletion/microduplication syndromes. The detection rate of fetal aneuploidies was closely correlated to maternal age. However, no correlation was found between the detection rate of p/lpCNVs and maternal age.

Association Between Systemic Inflammation and Malnutrition With Survival in Patients With Cancer Sarcopenia-A Prospective Multicenter Study.

OBJECTIVE: Systemic inflammation and malnutrition are correlated with cancer sarcopenia and have deleterious effects on oncological outcomes. However, the combined effect of inflammation and malnutrition in patients with cancer sarcopenia remains unclear. METHODS: We prospectively collected information on 1,204 patients diagnosed with cancer sarcopenia. the mean (SD) age was 64.5 (11.4%) years, and 705 (58.60%) of the patients were male. The patients were categorized into the high advanced lung cancer inflammation index (ALI) group (≥18.39) and the low ALI group (<18.39) according to the optimal survival cut-off curve. We selected the optimal inflammation marker using the C-index, decision curve analysis (DCA), and a prognostic receiver operating characteristic curve. Univariate and multivariate survival analyses were performed to determine the prognostic value of the optimal inflammation indicator. We also analyzed the association between inflammation and malnutrition in patients with cancer. RESULTS: The C-index, DCA, and prognostic area under the curve of ALI in patients with cancer sarcopenia were higher or better than those of neutrophil-lymphocyte ratio (NLR), prognostic nutritional index (PNI), systemic immune-inflammation index (SII), and platelet-lymphocyte ratio (PLR). The prognosis for patients in the low ALI group was worse than that of patients in the high ALI group [HR (95%CI) = 1.584 (1.280-1.959), P < 0.001]. When the ALI was divided into quartiles, we observed that decreased ALI scores strongly correlated with decreased overall survival (OS). Patients with both a low ALI and severe malnutrition (vs. patients with high ALI and well-nourished) had a 2.262-fold death risk (P < 0.001). Subgroup analysis showed a significant interactive association between the ALI and death risk in terms of TNM stage (P for interaction = 0.030). CONCLUSIONS: The inflammation indicator of the ALI was better than those of the NLR, PNI, SII, and PLR in patients with cancer sarcopenia. Inflammation combined with severe malnutrition has a nearly 3-fold death risk in patients with cancer sarcopenia, suggesting that reducing systemic inflammation, strengthening nutritional intervention, and improving skeletal muscle mass are necessary.