Disruptions of Gut Microbiota are Associated with Cognitive Deficit of Preclinical Alzheimer's Disease: A Cross-Sectional Study.

BACKGROUND: Alzheimer's Disease (AD) is the most prevalent type of dementia. The early change of gut microbiota is a potential biomarker for preclinical AD patients. OBJECTIVE: The study aimed to explore changes in gut microbiota characteristics in preclinical AD patients, including those with Subjective Cognitive Decline (SCD) and Mild Cognitive Impairment (MCI), and detect the correlation between gut microbiota characteristics and cognitive performances. METHODS: This study included 117 participants [33 MCI, 54 SCD, and 30 Healthy Controls (HC)]. We collected fresh fecal samples and blood samples from all participants and evaluated their cognitive performance. We analyzed the diversity and structure of gut microbiota in all participants through qPCR, screened characteristic microbial species through machine learning models, and explored the correlations between these species and cognitive performances and serum indicators. RESULTS: Compared to the healthy controls, the structure of gut microbiota in MCI and SCD patients was significantly different. The three characteristic microorganisms, including Bacteroides ovatus, Bifidobacterium adolescentis, and Roseburia inulinivorans, were screened based on the best classification model (HC and MCI) having intergroup differences. Bifidobacterium adolescentis is associated with better performance in multiple cognitive scores and several serum indicators. Roseburia inulinivorans showed negative correlations with the scores of the Functional Activities Questionnaire (FAQ). CONCLUSION: The gut microbiota in patients with preclinical AD has significantly changed in terms of composition and richness. Correlations have been discovered between changes in characteristic species and cognitive performances. Gut microbiota alterations have shown promise in affecting AD pathology and cognitive deficit.

Integrative analysis of metabolism subtypes and identification of prognostic metabolism-related genes for glioblastoma.

Increasing evidence has demonstrated that cancer cell metabolism is a critical factor in tumor development and progression; however, its role in glioblastoma (GBM) remains limited. In the present study, we classified GBM into three metabolism subtypes (MC1, MC2, and MC3) through cluster analysis of 153 GBM samples from the RNA-sequencing data of The Cancer Genome Atlas (TCGA) based on 2752 metabolism-related genes (MRGs). We further explored the prognostic value, metabolic signatures, immune infiltration, and immunotherapy sensitivity of the three metabolism subtypes. Moreover, the metabolism scoring model was established to quantify the different metabolic characteristics of the patients. Results showed that MC3, which is associated with a favorable survival outcome, had higher proportions of isocitrate dehydrogenase (IDH) mutations and lower tumor purity and proliferation. The MC1 subtype, which is associated with the worst prognosis, shows a higher number of segments and homologous recombination defects and significantly lower mRNA expression-based stemness index (mRNAsi) and epigenetic-regulation-based mRNAsi. The MC2 subtype has the highest T-cell exclusion score, indicating a high likelihood of immune escape. The results were validated using an independent dataset. Five MRGs (ACSL1, NDUFA2, CYP1B1, SLC11A1, and COX6B1) correlated with survival outcomes were identified based on metabolism-related co-expression module analysis. Laboratory-based validation tests further showed the expression of these MRGs in GBM tissues and how their expression influences cell function. The results provide a reference for developing clinical management approaches and treatments for GBM.

Comprehensive effects of climate, land use/cover and management practices on runoff and nutrient variations in a rapidly urbanizing watershed.

As non-point source pollution has emerged as a significant global and regional concern, climate change (CC), land use/cover transformation (LUCT), and management practices (MP) play vital roles in addressing nutrient pollution. However, current studies lack comprehensive quantification and consistent conclusions on the response to these factors, especially for management practices. To quantify and elucidate the impact of representative environmental factors on rapidly urbanizing regions, this study focused on the Shenzhen River, which serves as the most typical urbanizing watershed. Using a process-based distributed hydrological model with a factor-controlled simulation method, we identified significant differences in nutrient concentrations and the impacts of climate variability, land use/cover changes, and anthropogenic interventions from 2003 to 2020. Moreover, effective measures greatly improved water quality in the Shenzhen River during study period, as evident from trend and cluster analysis. However, ecological water supplements implemented since 2016 have led to a slight reduction in simulated runoff performance, and CC may amplify the synergistic effects of precipitation and temperature on the river system. While the implemented practices have been effective in reducing total nitrogen (TN) and total phosphorus (TP) loads, strong TN pollution control is still needed in rapidly urbanizing areas due to the results of land use/cover type changes. Our findings emphasize the intricate interplay among CC, LUCT, and MP in shaping water quality and hydrological processes in rapidly urbanizing watersheds, and clarify the independent effects of these factors on nutrients. This study contributes to a better understanding of the complex interactions between multiple factors in watersheds and provides guidance for sustainable watershed management.

Assessing water quality in the Pearl River for the last decade based on clustering: Characteristic, evolution and policy implications.

The Pearl River (PR) is China's second-largest river, playing a crucial role in regulating and supplying water in the southeast. However, for the last decade, the PR has been experiencing water quality deterioration due to population growth, rapid economic development, and diverse human activities, particularly in its delta areas. This study analyzed the characteristics and evolution of eight water quality variables, including pH values (pH), water temperature (WT), dissolved oxygen (DO), five-day biochemical oxygen demand (BOD5), permanganate index (PI), total phosphorus (TP), ammonia nitrogen (NH3N), and fluoride (F-), which were monitored monthly at 16 water quality monitoring stations from January 2009 to August 2019. Overall, annual average BOD5 and F- concentrations met Class I water quality standards, while TP and NH3N conformed to lower standards. The cluster results showed noticeable differences for parameter grouping (DO-organic parameters-nutrient and solutes), seasonal variation (wet and dry), and water quality status (contaminated-remediating-fine). The Water Quality Index (WQI) ranged from 8.3 ("very poor") to 91.7 ("excellent") in the entire basin from 2009 to 2019, and NH3N-DO based WQImins were identified using the All-Subsets Linear Regression method. The fitting results of the Generalized Additive Models displayed that the deviance explained by natural factors ranged from 37.2% to 61.3%, while the socioeconomic explanation exceeded 70%. The WQImin component evolution (2003-2019) of Shenzhen River estuary, the most important part of the PR estuary, agreed with key parameter variations in heterogeneous clusters in the entire basin. Moreover, Shenzhen's water quality remediation applications indicated that reasonable-efficient-powerful efforts and support from governments could accelerate recovery. For the management departments, consistent measures should be strictly enforced, and elaborate regionalized management based on clusters could be attempted to maintain excellent water quality.

Profile of gut microbiota in patients with traumatic thoracic spinal cord injury and its clinical implications: a case-control study in a rehabilitation setting.

Gut microbiota are the candidate biomarkers for neurogenic bowel dysfunction (NBD) in patients with spinal cord injury (SCI). We aimed to identify the common features between patients with varying degree of thoracic SCI and healthy individuals and subpopulations of microbiota correlated with the serum biomarkers. Twenty-one patients with complete thoracic SCI (CTSCI), 24 with incomplete thoracic SCI (ITSCI), and 24 healthy individuals (HC) were enrolled in this study. Fresh stool samples and clinical data were collected from all participants, and their bowel functions with SCI were assessed. Microbial diversity and composition were analyzed by sequencing the 16S rRNA gene. The features of gut microbiota correlated with the serum biomarkers and their functions were investigated. The mean NBD score of patients with CTSCI was higher than that of patients with ITSCI. Diversity of the gut microbiota in SCI group was reduced, and with an increase in the degree of damage, alpha diversity had decreased gradually. The composition of gut microbiota in patients with SCI was distinct from that in healthy individuals, and CTSCI group exhibited further deviation than ITSCI group compared to healthy individuals. Four serum biomarkers were found to be correlated with most differential genera. Patients with thoracic SCI present gut dysbiosis, which is more pronounced in patients with CTSCI than in those with ITSCI. Therefore, the gut microbiota profile may serve as the signatures for bowel and motor functions in patients with thoracic SCI.

Antibacterial, anti-inflammatory, analgesic, and hemostatic activities of Acanthopanax trifoliatus (L.) merr.

Acanthopanax trifoliatus (L.) Merr (AT) is a medicinal and edible plant with high nutritional value. The biological activity of A. trifoliatus (L.) Merr and its basis for injury treatment are explored in this paper. AT was ethanol-extracted then refined separately with petroleum ether, chloroform, ethyl acetate, and n-butanol. Active ingredients were analyzed, and anti-bacterial, anti-inflammatory, analgesic, and hemostatic effects were explored. Petroleum ether layer (PEL) extract produced the strongest antibacterial effect. Ethyl acetate layer (EAL) extract had the highest active substance content, with strong hemostatic and analgesic activities. Chloroform layer (CL) extract had the strongest anti-inflammatory effect and significantly reduced IL-1ß protein expression. Active ingredients were analyzed using HPLC and UPLC-MS to determine saponin, polyphenol, flavonoid, and characteristic ingredient contents. EAL extract had the highest polyphenol and flavonoid levels, including rutin, chlorogenic acid, isochlorogenic acid A, and isochlorogenic acid C, which may contribute to its nutritional activities. The study provides a reliable theoretical and practical basis for the applications of AT nutraceutical products.

A Prognostic Microenvironment-Related Immune Signature via ESTIMATE (PROMISE Model) Predicts Overall Survival of Patients With Glioma.

OBJECTIVE: In the development of immunotherapies in gliomas, the tumor microenvironment (TME) needs to be investigated. We aimed to construct a prognostic microenvironment-related immune signature via ESTIMATE (PROMISE model) for glioma. METHODS: Stromal score (SS) and immune score (IS) were calculated via ESTIMATE for each glioma sample in the cancer genome atlas (TCGA), and differentially expressed genes (DEGs) were identified between high-score and low-score groups. Prognostic DEGs were selected via univariate Cox regression analysis. Using the lower-grcade glioma (LGG) data set in TCGA, we performed LASSO regression based on the prognostic DEGs and constructed a PROMISE model for glioma. The model was validated with survival analysis and the receiver operating characteristic (ROC) in TCGA glioma data sets (LGG, glioblastoma multiforme [GBM] and LGG+GBM) and Chinese glioma genome atlas (CGGA). A nomogram was developed to predict individual survival chances. Further, we explored the underlying mechanisms using gene set enrichment analysis (GSEA) and Cibersort analysis of tumor-infiltrating immune cells between risk groups as defined by the PROMISE model. RESULTS: We obtained 220 upregulated DEGs and 42 downregulated DEGs in both high-IS and high-SS groups. The Cox regression highlighted 155 prognostic DEGs, out of which we selected 4 genes (CD86, ANXA1, C5AR1, and CD5) to construct a PROMISE model. The model stratifies glioma patients in TCGA as well as in CGGA with distinct survival outcome (P<0.05, Hazard ratio [HR]>1) and acceptable predictive accuracy (AUCs>0.6). With the nomogram, an individualized survival chance could be predicted intuitively with specific age, tumor grade, Isocitrate dehydrogenase (IDH) status, and the PROMISE risk score. ROC showed significant discrimination with the area under curves (AUCs) of 0.917 and 0.817 in TCGA and CGGA, respectively. GSEA between risk groups in both data sets were significantly enriched in multiple immune-related pathways. The Cibersort analysis highlighted four immune cells, i.e., CD 8 T cells, neutrophils, follicular helper T (Tfh) cells, and Natural killer (NK) cells. CONCLUSIONS: The PROMISE model can further stratify both LGG and GBM patients with distinct survival outcomes.These findings may help further our understanding of TME in gliomas and shed light on immunotherapies.

Synergistic effects and mechanisms of impressic acid or acankoreanogein in combination with docetaxel on prostate cancer.

Prostate cancer (PCa) is a common cancer among males and a leading cause of cancer deaths. Docetaxel (DOC) was recommended in guidelines as the first first-line drug of PCa; however, treatment with high doses of DOC ultimately results in resistance. This study examined the proliferation, viability, and apoptosis of VCaP cells evaluated by the MTT assay, trypan blue exclusion assay, and morphological assessments to investigate the effects and mechanisms of action by impressic acid (E12-1) or acankoreanogein (E13-1), isolated from Acanthopanax trifoliatus (L.) Merr., in combination with DOC in VCaP PCa cells. The research, which also contained cell migration, was examined under a light microscope. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activity was assessed by the luciferase reporter assay. Finally, the expression of B-cell lymphoma 2 (Bcl-2), NF-κB, phosphorylated Akt (p-Akt), phosphorylated signal transducer and activator of transcription 3 (p-Stat 3), phosphorylated c-Jun N-terminal kinase (p-JNK), and extracellular signal-related protein kinases 1 and 2 in VCaP cells was evaluated by western blotting. The result is combination of DOC with E12-1 or E13-1 which synergistically inhibited growth, induced apoptosis, and reduced migration of VCaP cells compared with treatment with DOC, E12-1, or E13-1 alone. The potential molecular mechanisms were related to significant decreases in the expression of NF-κB, Bcl-2, p-Stat 3, p-JNK, and p-Akt in VCaP cells. DOC combined with E12-1 or E13-1 may be an effective approach for inhibiting the growth and apoptosis of PCa cells, thus making it possible to reduce the dose of DOC in patients with PCa who experience systemic toxicity.

Risk Factors for Necrotizing Enterocolitis in Neonates: A Retrospective Case-Control Study.

BACKGROUND: Necrotizing enterocolitis (NEC) in neonates is devastating, and risk-factor identification is crucial. This study aimed to evaluate risk factors for NEC in different gestational age (GA) groups. METHODS: Risk factors associated with NEC were investigated using a retrospective case-control design. Patients with Bell's Stage NEC≥II were divided into three groups based on GA: I, <34 weeks; II, ≥34 weeks but <37 weeks; III, ≥37 weeks. Each case was paired with two GA- and weight-matched controls. Data were collected from medical records, and univariate and conditional logistic regression analyses employed. RESULTS: A total of 238 cases and 476 controls were enrolled. Variation in the months when NEC was diagnosed was noted, with a peak in January and a trough in August. Intrahepatic cholestasis of pregnancy and transfusion with packed red blood cells were significantly associated with NEC in preterm infants. Meconium aspiration syndrome was an independent risk factor for a greater chance of NEC development in full-term infants. Postnatal asphyxia and sepsis were associated with an increased risk of NEC in all groups. Probiotic use was associated with a reduced risk of NEC. Patients aged >34 weeks with congenital heart disease were more likely than controls to have NEC. CONCLUSION: Intrahepatic cholestasis of pregnancy and meconium aspiration syndrome may be new risk factors for NEC.

Pathogen and antimicrobial resistance profiles of culture-proven neonatal sepsis in Southwest China, 1990-2014.

AIM: Neonatal sepsis (NS) sustains high mortality and morbidity in China, but data on the epidemiology and antimicrobial resistance patterns of NS pathogens are limited. METHODS: The clinical features, aetiology and antimicrobial resistance of culture-proven NS were analysed over a period of 25 years in the metropolitan city of Chongqing in Southwest China. RESULTS: The occurrence rates of neonatal early-onset sepsis (EOS) were found to gradually decrease while late-onset sepsis (LOS) was kept stable from 1990 to 2014. Although coagulase-negative staphylococcus (CoNS) sepsis accounted for most infections, the occurrence rates of CoNS sepsis gradually decreased, especially in EOS. Escherichia coli and Klebsiella were common Gram-negative bacteria. The occurrence rates of E. coli and Klebsiella remained stable in EOS; however, in LOS, those had increased mildly, especially from 2009 to 2014. Although a high-degree resistance to common first- and second-line antimicrobials was observed for the main causative pathogens of NS, the gentamicin-resistance rate declined gradually from the year 2003. Similarly, the ceftazidime-resistance rate of E. coli dropped gradually from the year 2007. CONCLUSIONS: The alarmingly high degree of antibiotic resistance calls for urgent evaluation and development of antibiotic policy and protocols for the treatment of NS. Clinicians should strictly control the antibiotics use, decrease invasive manipulations and shorten hospitalisation to prevent LOS.

Biosynthesis, Antibacterial Activity and Anticancer Effects Against Prostate Cancer (PC-3) Cells of Silver Nanoparticles Using Dimocarpus Longan Lour. Peel Extract.

Metal nanoparticles, particularly silver nanoparticles (AgNPs), are developing more important roles as diagnostic and therapeutic agents for cancers with the improvement of eco-friendly synthesis methods. This study demonstrates the biosynthesis, antibacterial activity, and anticancer effects of silver nanoparticles using Dimocarpus Longan Lour. peel aqueous extract. The AgNPs were characterized by UV-vis absorption spectroscopy, X-ray diffraction (XRD), high-resolution transmission electron microscopy (HRTEM), scanning electron microscopy (SEM), and Fourier transform infrared spectroscope (FTIR). The bactericidal properties of the synthesized AgNPs were observed via the agar dilution method and the growth inhibition test. The cytotoxicity effect was explored on human prostate cancer PC-3 cells in vitro by trypan blue assay. The expressions of phosphorylated stat 3, bcl-2, survivin, and caspase-3 were examined by Western blot analysis. The longan peel extract acted as a strong reducing and stabilizing agent during the synthesis. Water-soluble AgNPs of size 9-32 nm was gathered with a face-centered cubic structure. The AgNPs had potent bactericidal activities against gram-positive and gram-negative bacteria with a dose-related effect. AgNPs also showed dose-dependent cytotoxicity against PC-3 cells through a decrease of stat 3, bcl-2, and survivin, as well as an increase in caspase-3. These findings confirm the bactericidal properties and explored a potential anticancer application of AgNPs for prostate cancer therapy. Further research should be focused on the comprehensive study of molecular mechanism and in vivo effects on the prostate cancer.

Effects of green-synthesized silver nanoparticles on lung cancer cells in vitro and grown as xenograft tumors in vivo.

Silver nanoparticles (AgNPs) have now been recognized as promising therapeutic molecules and are extending their use in cancer diagnosis and therapy. This study demonstrates for the first time the antitumor activity of green-synthesized AgNPs against lung cancer in vitro and in vivo. Cytotoxicity effect was explored on human lung cancer H1299 cells in vitro by MTT and trypan blue assays. Apoptosis was measured by morphological assessment, and nuclear factor-κB (NF-κB) transcriptional activity was determined by a luciferase reporter gene assay. The expressions of phosphorylated stat3, bcl-2, survivin, and caspase-3 were examined by Western blot analysis. AgNPs showed dose-dependent cytotoxicity and stimulation of apoptosis in H1299 cells. The effects on H1299 cells correlated well with the inhibition of NF-κB activity, a decrease in bcl-2, and an increase in caspase-3 and survivin expression. AgNPs significantly suppressed the H1299 tumor growth in a xenograft severe combined immunodeficient (SCID) mouse model. The results demonstrate the anticancer activities of AgNPs, suggesting that they may act as potential beneficial molecules in lung cancer chemoprevention and chemotherapy, especially for early-stage intervention.

Interleukin-8 for diagnosis of neonatal sepsis: a meta-analysis.

BACKGROUND: Neonatal sepsis (NS) is a life-threatening disorder and an important cause of morbidity and mortality in neonates. Previous studies showed that interleukin 8 (IL-8) may effectively and rapidly diagnose NS. OBJECTIVE: We conducted the systematic review and meta-analysis to investigate the diagnostic value of the IL-8 in NS. METHODS: The literature was searched in PUBMED, EMBASE, Cochrane Library, CNKI, VIP and other Chinese Medical Databases during October 1998 to January 2014 using set search criteria. Each included study was evaluated by quality assessment of diagnostic accuracy studies tool. Two investigators independently extracted the data and study characteristics, and disagreements, if any, were resolved by consensus. Meta-disc software was used to calculate the pooled sensitivity, specificity and summary diagnostic odds ratio (SDOR), I² or Cochrane Q to test heterogeneity, and meta-regression to investigate the source of heterogeneity. Funnel plots were used to test the potential presence of publication bias. False-positive report probability (FPRP) was calculated to confirm the significance of the results. RESULTS: Eight studies (548 neonates) were included in this meta-analysis. The pooled sensitivity and specificity of IL-8 were 0.78 and 0.84, respectively, which had moderate accuracy in the diagnosis of NS. The pooled diagnostic odds ratio (DOR) and area under curve (AUC) was 21.64 and 0.8908 (Q*=0.8215), respectively. The diagnostic threshold analysis showed that there was no threshold effect. The meta-regression analysis showed the cut-off, QUADAS and onset time have no effect on the heterogeneity. The funnel plots showed the existence of publication bias. CONCLUSION: Meta-analysis showed IL-8 had a moderate accuracy (AUC=0.8908) for the diagnosis of NS. IL-8 is a helpful biomarker for early diagnosis of NS. However, we should combine the results with clinical symptoms and signs, laboratory and microbial results.

Serologic Intestinal-Fatty Acid Binding Protein in Necrotizing Enterocolitis Diagnosis: A Meta-Analysis.

BACKGROUND: Previous studies showed that intestinal-fatty acid binding protein (I-FABP) may be a valid and promising serologic biomarker for early diagnosis of necrotizing enterocolitis (NEC). OBJECTIVE: To investigate the early diagnostic value of serologic I-FABP in NEC for the premature neonates. METHODS: All major databases were searched from January 1, 1990, to May 1, 2015. We used Meta-Disc 1.4 and Revman5.0 software to calculate the diagnostic accuracy. RESULTS: Seven studies with 444 subjects were identified. The pooled sensitivity of I-FABP was 0.67 for NEC I, 0.74 for NEC II, and 0.83 for NEC III, and the pooled specificity was 0.84, respectively, which showed a moderate diagnostic accuracy. The area under curve (AUC) for each stage was 0.75 (Q (⁎) = 0.69), 0.82 (Q (⁎) = 0.76), and 0.91 (Q (⁎) = 0.84). The diagnostic threshold analysis showed no significant difference in threshold effect. The metaregression showed that the cut-off value has the largest effect on heterogeneity. The funnel plots indicated the existence of publication bias. CONCLUSION: I-FABP is a valid serologic biomarker for early diagnosis in NEC for the premature neonates with a moderate accuracy.