Prognostic Role of Lymphocyte-C-Reactive Protein Ratio in Colorectal Cancer: A Systematic Review and Meta Analysis.

Introduction: The lymphocyte-C-reactive protein ratio (LCR) is a new immunoinflammatory score and prognostic marker, but the relationship between this index and the prognosis of colorectal cancer patients remains controversial.Therefore, aim of the study was to assess the relationship between LCR and prognosis for colorectal cancer patients through a systematic evaluation and meta-analysis. Methods: We systematically searched PubMed, EMBASE, Web of Science, and Cochrane Library databases for randomized controlled studies and observational studies on the relationship between LCR and prognosis of colorectal cancer patients, all searched from the date of database creation to January 6, 2022.Our primary endpoints observed were overall survival (OS) and disease-free survival (DFS) of colorectal cancer patients, and secondary observables were basic characteristics of included studies, such as country, study duration, sample size, LCR threshold, and pathological characteristics of patients in each study, such as degree of differentiation, gender, tumor location, T stage, and lymphatic metastasis. Results: A total of 10 case-control studies including 7068 patients were included. Meta-analysis results showed that overall survival (OS) and disease-free survival (DFS) were worse in colorectal cancer patients with lower levels of LCR (HR=0.44, 95% CI=0.38-0.52, P<0.001; HR=0.56, 95% CI=0.41-0.76, P< 0.001).Subgroup analysis based on country, study length, sample size, and LCR threshold showed that lower levels of LCR were all associated with poorer OS (P < 0.05). Regarding pathological characteristics, patients in the low LCR group were generally poorly differentiated (OR=1.79, 95% CI=1.55-2.07, P<0.001), while there was no significant relationship with gender, tumor location, T stage, and lymphatic metastasis (P>0.05). Discussion/Conclusion: LCR can be used as a prognostic marker for colorectal cancer patients, and patients with lower levels of LCR may have a poor prognosis. Due to the limitation of the number and quality of the included studies, the above findings need to be validated by more high-quality studies. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022296563.

Comparative functional genomic analysis of Alzheimer's affected and naturally aging brains.

BACKGROUND: Alzheimer's disease (AD) is a prevalent progressive neurodegenerative human disease whose cause remains unclear. Numerous initially highly hopeful anti-AD drugs based on the amyloid-ß (Aß) hypothesis of AD have failed recent late-phase tests. Natural aging (AG) is a high-risk factor for AD. Here, we aim to gain insights in AD that may lead to its novel therapeutic treatment through conducting meta-analyses of gene expression microarray data from AG and AD-affected brain. METHODS: Five sets of gene expression microarray data from different regions of AD (hereafter, ALZ when referring to data)-affected brain, and one set from AG, were analyzed by means of the application of the methods of differentially expressed genes and differentially co-expressed gene pairs for the identification of putatively disrupted biological pathways and associated abnormal molecular contents. RESULTS: Brain-region specificity among ALZ cases and AG-ALZ differences in gene expression and in KEGG pathway disruption were identified. Strong heterogeneity in AD signatures among the five brain regions was observed: HC/PC/SFG showed clear and pronounced AD signatures, MTG moderately so, and EC showed essentially none. There were stark differences between ALZ and AG. OXPHOS and Proteasome were the most disrupted pathways in HC/PC/SFG, while AG showed no OXPHOS disruption and relatively weak Proteasome disruption in AG. Metabolic related pathways including TCA cycle and Pyruvate metabolism were disrupted in ALZ but not in AG. Three pathogenic infection related pathways were disrupted in ALZ. Many cancer and signaling related pathways were shown to be disrupted AG but far less so in ALZ, and not at all in HC. We identified 54 "ALZ-only" differentially expressed genes, all down-regulated and which, when used to augment the gene list of the KEGG AD pathway, made it significantly more AD-specific.

Driver's adaptive glance behavior to in-vehicle information systems.

The purpose of this study was to examine the adaptive behavior of drivers as they engage with in-vehicle devices over time and in varying driving situations. Behavioral adaptation has been shown to occur among drivers after prolonged use of in-vehicle devices, but few studies have examined drivers' risk levels across different driving demands. A multi-day simulator study was conducted with 28 young drivers (under 30 years old) as they engaged in different text entry and reading tasks while driving in two different traffic conditions. Cluster analysis was used to categorize drivers based on their risk levels and random coefficient models were used to assess changes in drivers' eye glance behavior. Glance duration significantly increased over time while drivers were performing text entry tasks but not for text reading tasks. High-risk drivers had longer maximum eyes-off-road when performing long text entry tasks compared to low-risk drivers, and this difference increased over time. The traffic condition also had a significant impact on drivers' glance behavior. This study suggests that drivers may exhibit negative behavioral adaptation as they become more comfortable with using in-vehicle technologies over time. Results of this paper may provide guidance for the design of in-vehicle devices that adapt based on the context of the situation. It also demonstrates that random coefficient models can be used to obtain better estimations of driver behavior when there are large individual differences.

Synthesis and biological evaluation of ring A and/or C expansion and opening echinocystic acid derivatives for anti-HCV entry inhibitors.

Echinocystic acid (EA), a naturally occurring oleanane-type triterpene isolated from Dipsacus asperoides, was found to have anti-HCV entry activity in our previous study. Expansion of triterpene structural diversity, including the ring A and/or C expansion and opening, was performed. To elucidate the pharmacophore of EA, seven lactones (8, 16, 17, 24, 26, 35 and 41), three 3,28-dioic acids (9, 36 and 42) and two pentols (10 and 27) were synthesized. The anti-HCV entry activities of those derivatives, along with their parental compound EA and analogs α,ß-unsaturated ketone (18), were evaluated. All the products showed no improvement but detrimental effect on potency of EA. The results demonstrated that ring A and C of EA are highly conserved, indicating the steric effects of the rigid skeleton have a profound effect on the potency.

Development of bivalent oleanane-type triterpenes as potent HCV entry inhibitors.

The development of entry inhibitors is an emerging approach to the prevention and reduction of HCV infection. Starting from echinocystic acid (EA), a µM HCV entry inhibitor, we have developed a series of bivalent oleanane-type triterpenes which, upon optimization of the length, rigidity and hydrophobicity of the linker, exert dramatically potent enhancement of inhibition with IC50 values extending into the nM level. This study establishes the importance of triterpene natural products as new leads in the development of potential HCV entry inhibitors.

Development of oleanane-type triterpenes as a new class of HCV entry inhibitors.

Development of hepatitis C virus (HCV) entry inhibitors represents an emerging approach that satisfies a tandem mechanism for use with other inhibitors in a multifaceted cocktail. By screening Chinese herbal extracts, oleanolic acid (OA) was found to display weak potency to inhibit HCV entry with an IC50 of 10 µM. Chemical exploration of this triterpene compound revealed its pharmacophore requirement for blocking HCV entry, rings A, B, and E, are conserved while ring D is tolerant of some modifications. Hydroxylation at C-16 significantly enhanced its potency for inhibiting HCV entry with IC50 at 1.4 µM. Further modification by conjugation of this new lead with a disaccharide at 28-COOH removed the undesired hemolytic effect and, more importantly, increased its potency by ~5-fold (54a, IC50 0.3 µM). Formation of a triterpene dimer via a linker bearing triazole (70) dramatically increased its potency with IC50 at ~10 nM. Mechanistically, such functional triterpenes interrupt the interaction between HCV envelope protein E2 and its receptor CD81 via binding to E2, thus blocking virus and host cell recognition. This study establishes the importance of triterpene natural products as new leads for the development of potential HCV entry inhibitors.

Driver's lane keeping ability with eyes off road: Insights from a naturalistic study.

Many studies have shown that driver inattention can influence lane-keeping ability. The majority of studies on lane keeping have been conducted in controlled on-road networks or in simulated environments. However, few studies have examined lane-keeping ability in naturalistic settings for the same purpose. In this current study, the relationship between driver inattention and lane keeping ability was examined using naturalistic data for 24 drivers. Driver inattention was placed into two categories based on whether drivers were looking forward toward the roadway (inattention with eyes-on-road) or not looking forward (inattention with eyes-off-road) while engaged in a secondary task. Repeated measures regression models were used to account for within-subject correlations. The results showed that, after accounting for driving speed and lane width, the eyes-off-road significantly increased the standard deviation of lane position (SDLP). The findings from this study are consistent with other studies that show that the amount of time drivers spend looking away from the road can impact drivers' ability to maintain their lane position. Additionally, this paper demonstrates how driver inattention can be examined with real world data while accounting for the roadway, environment, and driver behavior.

Conjugation of cyclodextrin with fullerene as a new class of HCV entry inhibitors.

An α-cyclodextrin-[60]fullerene conjugate with a flexible linker at the secondary face of α-cyclodextrin has been prepared, which displays significant water solubility and, more importantly, acts as a new class of HCV entry inhibitor with IC(50) at 0.17 µM level.