Should we perform sigmoidoscopy for colorectal cancer screening in people under 45 years?

BACKGROUND: The strategy for preventing colorectal cancer is screening by colonoscopy, which offers a direct way for detection and removal of adenomatous polyps (APs). American College of Gastroenterology guidelines recommend that people aged ≥ 45 years should undergo colonoscopy; however, how to deal with people aged ≤ 45 years is still unknown. AIM: To compare the prevalence of APs and high-grade neoplasia between the left and right colon in patients ≤ 45 years. METHODS: A retrospective observational study was conducted at a single tertiary III hospital in China. This study included patients aged 18-45 years with undergoing initial colonoscopy dissection and pathological diagnosis AP or high-grade neoplasia between February 2014 and January 2021. The number of APs in the entire colon while screening and post-polypectomy surveillance in following 1-3 years were evaluated. RESULTS: A total of 3053 cases were included. The prevalence of APs in the left and right colon was 55.0% and 41.6%, respectively (OR 1.7, 95%CI 1.6-2.4; P < 0.05). For APs with high-grade neoplasia, the prevalence was 2.7% and 0.9%, respectively (OR 3.0, 95%CI 2.0-4.6; P < 0.05). Therefore, the prevalence of APs and high-grade neoplasia in the left colon was significantly higher than in the right colon in patients aged ≤ 45 years. There were 327 patients who voluntarily participated in post-polypectomy surveillance in following 1-3 years, and APs were found in 216 cases (66.1%); 170 cases had 1-3 polyps (52.0%) and 46 cases had > 3 polyps (14.1%; OR 0.3, 95%CI 0.1-0.6; P < 0.05). CONCLUSION: This study suggests that flexible sigmoidoscopy would be an optimal approach for initial screening in people aged ≤ 45 years and would be a more cost-effective and safe strategy.

Autocleaving Bonds for Better Drugs.

While bond formation has historically been the mainstay of medicinal chemistry, the phenomenon of bond cleavage has received less focus. However, the success of numerous oral medications demonstrates the importance of controlled cleavage in prodrugs to achieve desired therapeutic outcomes. Nevertheless, effective strategies to control this cleavage remain limited. This concept article introduces a novel approach: employing peptides as conjugates to drugs to modulate the hydrolysis of these conjugates and enhance drug efficacy. The article begins by briefly outlining common prodrug strategies, followed by a few representative examples of how peptides can be leveraged to control the autohydrolysis of peptide-conjugated prodrugs for bacterial and cancer cell inhibition. Finally, it provides a brief outlook on the future potential of this promising new research direction in molecular medicine.

A copper-loaded self-assembled nanoparticle for disturbing the tumor redox balance and triple anti-tumor therapy.

Both chemodynamic therapy and photodynamic therapy, based on the production of reactive oxygen (ROS), have excellent potential in cancer therapy. However, the abnormal redox homeostasis in tumor cells, especially the overexpressed glutathione (GSH) could scavenge ROS and reduce the anti-tumor efficiency. Therefore, it is essential to develop a simple and effective tumor-specific drug delivery system for modulating the tumor microenvironment (TME) and achieving synergistic therapy at the tumor site. In this study, self-assembled nanoparticles (named CDZP NPs) were developed using copper ion (Cu2+), doxorubicin (Dox), zinc phthalocyanine (ZnPc) and a trace amount of poly(2-(di-methylamino)ethylmethacrylate)-poly[(R)-3-hydroxybutyrate]-poly(2-(dimethylamino)ethylmethacrylate) (PDMAEMA-PHB-PDMAEMA) through chelation, π-π stacking and hydrophobic interaction. These triple factor-responsive (pH, laser and GSH) nanoparticles demonstrated unique advantages through the synergistic effect. Highly controllable drug release ensured its effectiveness at the tumor site, Dox-induced chemotherapy and ZnPc-mediated fluorescence (FL) imaging exhibited the distribution of nanoparticles. Meanwhile, Cu2+-mediated GSH-consumption not only reduced the intracellular ROS elimination but also produced Cu+ to catalyze hydrogen peroxide (H2O2) and generated hydroxyl radicals (˙OH), thereby enhancing the chemodynamic and photodynamic therapy. Herein, this study provides a green and relatively simple method for preparing multifunctional nanoparticles that can effectively modulate the TME and improve synergetic cancer therapy.

Structural Modification of Noscapine via Photoredox/Nickel Dual Catalysis for the Discovery of S-Phase Arresting Agents.

Herein, we disclose a powerful strategy for the functionalization of the antitumor natural alkaloid noscapine by utilizing photoredox/nickel dual-catalytic coupling technology. A small collection of 37 new noscapinoids with diverse (hetero)alkyl and (hetero)cycloalkyl groups and enhanced sp3 character was thus synthesized. Further in vitro antiproliferative activity screening and SAR study enabled the identification of 6o as a novel, potent, and less-toxic anticancer agent. Furthermore, 6o exerts superior cellular activity via an unexpected S-phase arrest mechanism and could significantly induce cell apoptosis in a dose-dependent manner, thereby further highlighting its potential in drug discovery as a promising lead compound.

The CSF1-CSF1R pathway in the trigeminal ganglion mediates trigeminal neuralgia via inflammatory responses in mice.

BACKGROUND: Trigeminal neuralgia (TN) is the most severe type of neuropathic pain. The trigeminal ganglion (TG) is a crucial target for the pathogenesis and treatment of TN. The colony-stimulating factor 1 (CSF1) - colony-stimulating factor 1 receptor (CSF1R) pathway regulates lower limb pain development. However, the effect and mechanism of the CSF1-CSF1R pathway in TG on TN are unclear. METHODS: Partial transection of the infraorbital nerve (pT-ION) model was used to generate a mouse TN model. Mechanical and cold allodynia were used to measure pain behaviors. Pro-inflammatory factors (IL-6, TNF-a) were used to measure inflammatory responses in TG. PLX3397, an inhibitor of CSF1R, was applied to inhibit the CSF1-CSF1R pathway in TG. This pathway was activated in naïve mice by stereotactic injection of CSF1 into the TG. RESULTS: The TN model activated the CSF1-CSF1R pathway in the TG, leading to exacerbated mechanical and cold allodynia. TN activated inflammatory responses in the TG manifested as a significant increase in IL-6 and TNF-a levels. After using PLX3397 to inhibit CSF1R, CSF1R expression in the TG declined significantly. Inhibiting the CSF1-CSF1R pathway in the TG downregulated the expression of IL-6 and TNF-α to reduce allodynia-related behaviors. Finally, mechanical allodynia behaviors were exacerbated in naïve mice after activating the CSF1-CSF1R pathway in the TG. CONCLUSIONS: The CSF1-CSF1R pathway in the TG modulates TN by regulating neuroimmune responses. Our findings provide a theoretical basis for the development of treatments for TN in the TG.

Comparison of hydrophobic cellulose nanofibrils modified with different diisocyanates for circulating oil absorption.

A large number of polluting substances, including chlorinated organic substances that were highly stable and hazardous, has been emitted due to the rapidly developing chemical industry, which will affect the ecological environment. Nanocellulose aerogels are effective carriers for adsorption of oil substances and organic solvents, however, the extremely strong hydrophilicity and poor mechanical properties limited their widespread applications. In this study, TEMPO-oxidized cellulose nanofibrils was modified with 2, 4-toluene diisocyanate (TDI) and 4,4'-diphenylmethane diisocyanate (MDI) to prepare strong and hydrophobic aerogels for oil adsorption. The main purpose was to evaluate and compare the effects of two diisocyanates on various properties of modified aerogels. It was found that the modified aerogel had better hydrophobic properties, mechanical properties and adsorption properties. In particular, the modified aerogel with TDI as crosslinker showed a better performance, with a maximum chloroform adsorption capacity of 99.3 g/g, a maximum water contact angle of 131.3°, and a maximum compression stress of 36.3 kPa. This study provides further evidence of the potential of functional nanocellulose aerogel in addressing environmental pollution caused by industrial emissions.

UBE2C promotes malignancy of cutaneous squamous cell carcinoma.

BACKGROUND: Our study aimed to study the involvement of ubiquitin-conjugating enzyme E2C (UBE2C) in cutaneous squamous cell carcinoma (cSCC). As the second most common malignancy with a rising incidence, understanding the molecular mechanisms driving cSCC is crucial for improved diagnosis and treatment. METHODS: We combined multiple datasets of cSCC in Gene Expression Omnibus (GEO) repository to investigate its expression and diagnostic value. We collected patient specimens and performed immunohistochemistry to examine its expression in patients and its correlation with tumor histological grade. Moreover, we compared UBE2C expression between cSCC cells and primary human epidermal keratinocytes. Subsequently, we explored the effects of UBE2C inhibition on tumor cell proliferation, migration and apoptosis through CCK8, wound healing, Transwell, and flow cytometry assay. RESULTS: The integrated analysis revealed an upregulation of UBE2C level in cSCC. Immunohistochemistry demonstrated high UBE2C expression was associated with poorer tumor histological grade. Cell experiments further supported the crucial role of UBE2C in promoting the malignant behavior of cSCC cells. CONCLUSION: Our findings indicate UBE2C is up-regulated in cSCC and contributes to its malignant behavior. These results suggest UBE2C has the potential to serve as both a cSCC biomarker and a therapeutic target.

The causal relationship between pure hypercholesterolemia and psoriasis: A bidirectional, two-sample Mendelian randomization study.

BACKGROUND: Several studies have reported the association between pure hypercholesterolemia (PH) and psoriasis, but the causal effect remains unclear. METHODS: We explored the causal effect between PH and psoriasis using two-sample bidirectional Mendelian randomization (MR) analysis using data from genome-wide association studies. Single nucleotide polymorphisms related with exposures at the genome-wide significance level (p < 5×10-8 ) and less than the linkage disequilibrium level (r2  < 0.001) were chosen as instrumental variables. Subsequently, we used inverse variance weighting (IVW), MR-Egger and weighted median (WM) methods for causal inference. p < 0.05 was considered statistically significant. Heterogeneity was tested using Cochran's Q-test, and horizontal pleiotropy was examined using the MR-Egger intercept. Leave-one-out analyses were performed to assess the robustness and reliability of the results. RESULTS: MR results showed a positive causal effect of PH on psoriasis [IVW: odds ratios (OR): 1.139, p = 0.032; MR-Egger: OR: 1.434, p = 0.035; WM: OR: 1.170, p = 0.045] and psoriatic arthritis (PsA) (IVW: OR: 1.210, p = 0.049; MR-Egger regression: OR: 1.796, p = 0.033; WM: OR: 1.317, p = 0.028). However, there is no causal relationship between PH and psoriasis vulgaris as well as other unspecified psoriasis. Inverse MR results suggested a negative causal relationship between PsA and PH (IVW: OR: 0.950, p = 0.037). No heterogeneity and horizontal pleiotropy exist, and these results were confirmed to be robust. CONCLUSION: PH has a positive casual effect on psoriasis and PsA, and PsA may reduce the risk of having PH.

Enzyme-Instructed Intracellular Peptide Assemblies.

Higher-order or supramolecular protein assemblies, usually regulated by enzymatic reactions, are ubiquitous and essential for cellular functions. This evolutionary fact has provided a rigorous scientific foundation, as well as an inspiring blueprint, for exploring supramolecular assemblies of man-made molecules that are responsive to biological cues as a novel class of therapeutics for biomedicine. Among the emerging man-made supramolecular structures, peptide assemblies, formed by enzyme reactions or other stimuli, have received most of the research attention and advanced most rapidly.In this Account, we will review works that apply enzyme-instructed self-assembly (EISA) to generate intracellular peptide assemblies for developing a new kind of biomedicine, especially in the field of novel cancer nanomedicines and modulating cell morphogenesis. As a versatile and cell-compatible approach, EISA can generate nondiffusive peptide assemblies locally; thus, it provides a unique approach to target subcellular organelles with exceptional cell selectivity. We have arranged this Account in the following way: after introducing the concept, simplicity, and uniqueness of EISA, we discuss the EISA-formed intracellular peptide assemblies, including artificial filaments, in the cell cytosol. Then, we describe the representative examples targeting subcellular organelles, such as mitochondria, endoplasmic reticulum, Golgi apparatus, lysosomes, and the nucleus, by enzyme-instructed intracellular peptide assemblies for potential cancer therapeutics. After that, we highlight the recent exploration of the transcytosis of peptide assemblies for controlling cell morphogenesis. Finally, we provide a brief outlook of enzyme-instructed intracellular peptide assemblies. This Account aims to illustrate the promise of EISA-generated intracellular peptide assemblies in understanding diseases, controlling cell behaviors, and developing new therapeutics from a class of less explored molecular entities, which are substrates of enzymes and become building blocks of self-assembly after the enzymatic reactions.

Kallistatin Improves High-Fat-Induced Insulin Resistance via Epididymal Adipose Tissue-Derived Exosomes.

Objective: Studies have found that high expression of human Kallistatin (HKS) in adipose tissue can improve obesity and its associated comorbidities, but the underlying mechanism of specific regulation is unclear. Methods: An obesity model was built by injecting 8-week-old C57BL/6 mice (n = 6 mice per group) with Ad.Null and Ad.HKS adenovirus into epididymal adipose tissue and fed with a high-fat diet (HFD). Insulin resistance-related proteins, AKT and IRS1, were detected in the liver, subcutaneous fat, and skeletal muscle by western blotting after one month of HFD. Epididymal adipose tissue was isolated after 24 h for culture, and exosomes were extracted by differential centrifugation. Enzyme-linked immunosorbent assay detected the expression of HKS protein in serum and exosomes. To examine the role of exosomes in AML12 insulin resistance, we used epididymal adipose tissue-derived exosomes or transfected Ad.HKS into mature 3T3L1-derived exosomes to interfere with palmitic acid (PA)-induced mouse AML12 insulin resistance model. GW4869 was used to inhibit exosome biogenesis and release. Results: Our results showed that HFD-induced mice with high expression of HKS in epididymal adipose tissue had slower weight gain, lower serum triglycerides, reduced free fatty acids, and improved liver insulin resistance compared with the Ad.Null group. We also demonstrated that HKS was enriched in epididymal adipose tissue-derived exosomes and released through the exosome pathway. In PA-induced AML12 cells, insulin resistance was alleviated after incubation of the HKS-related exosome; this effect was reversed with GW4869. Conclusion: High expression of HKS in epididymal adipose tissue could lead to its exocrine secretion in the form of exosomes and improve liver insulin resistance by promoting the phosphorylation of AKT. Production of high HKS vesicles might be a possible way to alleviate insulin resistance associated with obesity.

Temporal Patterns of Diet and Physical Activity and of Diet Alone Have More Numerous Relationships With Health and Disease Status Indicators Compared to Temporal Patterns of Physical Activity Alone.

BACKGROUND: Daily temporal patterns of energy intake (temporal dietary patterns [TDPs]) and physical activity (temporal physical activity patterns [TPAPs]) have been independently and jointly (temporal dietary and physical activity patterns [TDPAPs]) associated with health and disease status indicators. OBJECTIVE: The aim of this study was to compare the number and strength of association between clusters of daily TDPs, TPAPs, and TDPAPs and multiple health and disease status indicators. DESIGN: This cross-sectional study used 1 reliable weekday dietary recall and 1 random weekday of accelerometer data to partition to create clusters of participants representing the 3 temporal patterns. Four clusters were created via kernel-k means clustering algorithm of the same constrained dynamic time warping distance computed over the time series for each temporal pattern. PARTICIPANTS/SETTING: From the National Health and Nutrition Examination Survey (2003-2006), 1,836 US adults aged 20 through 65 years who were not pregnant and had valid diet, physical activity, sociodemographic, anthropometric, questionnaire, and health and disease status indicator data were included. MAIN OUTCOME MEASURES: Health status indicators used as outcome measures were body mass index, waist circumference, fasting plasma glucose, hemoglobin A1c, triglycerides, high-density lipoprotein cholesterol, total cholesterol, and systolic and diastolic blood pressure; disease status indicators included obesity, type 2 diabetes mellitus, and metabolic syndrome. STATISTICAL ANALYSES PERFORMED: Multivariate regression models determined associations between the clusters representing each pattern and health and disease status indicators, controlling for confounders and adjusting for multiple comparisons. The number of significant differences among clusters and adjusted R2 and Akaike information criterion compared the strength of associations between clusters of patterns and continuous and categorical health and disease status indicators. RESULTS: TDPAPs showed 21 significant associations with health and disease status indicators, including body mass index, waist circumference, obesity, and type 2 diabetes; TDPs showed 19 significant associations; and TPAPs showed 8 significant associations. CONCLUSIONS: TDPAPs and TDPs had stronger and more numerous associations with health and disease status indicators compared with TPAPs. Patterns representing the integration of daily dietary habits hold promise for early detection of obesity.

Saikosaponin D reverses epinephrine- and norepinephrine-induced gemcitabine resistance in intrahepatic cholangiocarcinoma by downregulating ADRB2/glycolysis signaling.

Intrahepatic cholangiocarcinoma (iCCA) is a highly fatal malignancy with rapidly increasing incidence and mortality worldwide. Currently, gemcitabine-based systemic chemotherapy is the main clinical therapeutic regimen; however, its efficacy is poor, and its mechanism has not been elucidated. In this study, we use a Seahorse Extracellular Flux analyser to measure glycolysis capacity (extracellular acidification rate, ECAR) and oxygen consumption rate (OCR). The glucose uptake or lactic acid content is detected, and the effects of saikosaponin D, an active compound derived from Bupleuri Radix (a traditional Chinese medicine for soothing the liver and relieving depression), on gemcitabine cytotoxicity in norepinephrine-stimulated iCCA cells are analysed. We find that adrenergic signaling plays a fundamental role in chronic stress-induced therapeutic resistance in iCCA. Norepinephrine (NE) and epinephrine (E) enhance the proliferation of iCCA cells and interfere with the response to gemcitabine through activation of the ß2-adrenergic receptor (ADRB2). Furthermore, we find that NE upregulates the expressions of several drug efflux-related genes (such as ABCG2 and MDR1) and promotes glycolysis in iCCA cells. In addition, saikosaponin D reverses the poor response of iCCA cells to gemcitabine by downregulating ADRB2 level. Furthermore, saikosaponin D inhibits drug efflux and glycolysis in iCCA cells by regulating the expressions of MDR1, ABCG2, HK2, and GLUT1. Collectively, saikosaponin D enhances the antitumor effect of gemcitabine by controlling glucose metabolism and drug efflux by inhibiting the ADRB2 signaling. Therefore, the combination of saikosaponin D and gemcitabine may be a potential therapeutic strategy for the treatment of iCCA.

PDGF-BB/PDGFRß induces tumour angiogenesis via enhancing PKM2 mediated by the PI3K/AKT pathway in Wilms' tumour.

Platelet-derived growth factor receptor-ß (PDGFRß) is a critical type III receptor tyrosine kinase family member, which is involved in Wilms' tumour (WT) metastasis and aerobic glycolysis. The role of PDGFRß in tumour angiogenesis has not been fully elucidated. Here, we examined the effect of PDGFRß on angiogenesis in WT. First, the NCBI database integrated three datasets, GSE2712, GSE11151, and GSE73209, to screen differentially expressed genes. The R language was used to analyse the correlation between PDGFRB and vascular endothelial growth factor (VEGF). The results showed that PDGFRB, encoding PDGFRß, was upregulated in WT, and its level was correlated with VEGFA expression. Next, PDGFRß expression was inhibited by small interfering RNA (siRNA) or activated with the exogenous ligand PDGF-BB. The expression and secretion of the angiogenesis elated factor VEGFA in WT G401 cells were detected using Western blotting and ELISA, respectively. The effects of conditioned medium from G401 cells on endothelial cell viability, migration, invasion, the total length of the tube, and the number of fulcrums were investigated. To further explore the mechanism of PDGFRß in the angiogenesis of WT, the expression of VEGFA was detected after blocking the phosphatidylinositol-3-kinase (PI3K) pathway and inhibiting the expression of PKM2, a key enzyme of glycolysis. The results indicated that PDGFRß regulated the process of tumour angiogenesis through the PI3K/AKT/PKM2 pathway. Therefore, this study provides a novel therapeutic strategy to target PDGFRß and PKM2 to inhibit glycolysis and anti-angiogenesis, thus, developing a new anti-vascular therapy.

Continental drift shifts tropical rainfall by altering radiation and ocean heat transport.

Shifts in the position of the intertropical convergence zone (ITCZ) have great importance for weather, climate, and society. The ITCZ shifts have been extensively studied in current and future warmer climate; however, little is known for its migration in the past on geological time scales. Using an ensemble of climate simulations over the past 540 million years, we show that ITCZ migrations are controlled primarily by continental configuration through two competing pathways: hemispheric radiation asymmetry and cross-equatorial ocean heat transport. The hemispheric asymmetry of absorbed solar radiation is produced mainly by land-ocean albedo contrast, which can be predicted using only the landmass distribution. The cross-equatorial ocean heat transport is strongly associated with the hemispheric asymmetry of surface wind stress, which is, in turn, controlled by the hemispheric asymmetry of ocean surface area. These results allow the influence of continental evolution on global ocean-atmosphere circulations to be understood through simple mechanisms that depend primarily on the latitudinal distribution of land.

Visceral adipose tissue-directed human kallistatin gene therapy improves adipose tissue remodeling and metabolic health in obese mice.

OBJECTIVE: Adipose tissue remodeling is a dynamic process that is pathologically expedited in the obese state and is closely related to obesity-associated disease progression. This study aimed to explore the effects of human kallistatin (HKS) on adipose tissue remodeling and obesity-related metabolic disorders in mice fed with a high-fat diet (HFD). METHODS: Adenovirus-mediated HKS cDNA (Ad.HKS) and a blank adenovirus (Ad.Null) were constructed and injected into the epididymal white adipose tissue (eWAT) of 8-weeks-old male C57B/L mice. The mice were fed normal or HFD for 28 days. The body weight and circulating lipids levels were assessed. Intraperitoneal glucose tolerance test (IGTT) and insulin tolerance test (ITT) were also performed. Oil-red O staining was used to assess the extent of lipid deposition in the liver. Immunohistochemistry and HE staining were used to measure HKS expression, adipose tissue morphology, and macrophage infiltration. Western blot and qRT-PCR were used to evaluate the expression of adipose function-related factors. RESULTS: At the end of the experiment, the expression of HKS in the serum and eWAT of the Ad.HKS group was higher than in the Ad.Null group. Furthermore, Ad.HKS mice had lower body weight and decreased serum and liver lipid levels after four weeks of HFD feeding. IGTT and ITT showed that HKS treatment maintained balanced glucose homeostasis. Additionally, inguinal white adipose tissue (iWAT) and eWAT in Ad.HKS mice had a higher number of smaller-size adipocytes and had less macrophage infiltration than Ad.Null group. HKS significantly increased the mRNA levels of adiponectin, vaspin, and eNOS. In contrast, HKS decreased RBP4 and TNFα levels in the adipose tissues. Western blot results showed that local injection of HKS significantly upregulated the protein expressions of SIRT1, p-AMPK, IRS1, p-AKT, and GLUT4 in eWAT. CONCLUSIONS: HKS injection in eWAT improves HFD-induced adipose tissue remodeling and function, thus significantly improving weight gain and dysregulation of glucose and lipid homeostasis in mice.

Preparation of Cod Skin Collagen Peptides/Chitosan-Based Temperature-Sensitive Gel and Its Anti-Photoaging Effect in Skin.

Background: Photoaging decreases quality of life and increases the risk of skin cancer, underscoring the urgent need to explore natural, high-efficacy, anti-skin photoaging (SP) active substances. Methods: In this study, a gel (CS/CSCPs/ß-GP gel) was prepared using chitosan (CS) and sodium ß-glycerophosphate (ß-GP) through crosslinking with small molecular CSCPs as the carried drug. We evaluated its structural characteristics and properties. The effect of CS/CSCPs/ß-GP gel on the degree of ultraviolet (UV)-induced skin aging of mice was investigated through comparative analysis of skin damage, the integrity of collagen tissues and elastic fibers, levels of reactive oxygen species (ROS) and key inflammatory factors (tumor necrosis factor [TNF]-α and interleukin [IL]-1ß, IL-6, and IL-10), and tissue expression of matrix metalloproteinase-3 (MMP-3) after repeated UV irradiation in a nude mice SP model. Results: The results showed that CS/CSCPs/ß-GP gel was successfully prepared and had the desired characteristics. Compared with CSCPs alone, the CS/CSCPs/ß-GP gel more evidently improved typical photoaging characteristics on mouse dorsal skin. It also increased the moisture content, causing the skin to become glossy and elastic. Pathological skin analysis revealed that this peptide-carrying gel can effectively inhibit epidermal thickening, reduce tissue inflammatory infiltration, suppress collagen fiber degradation, increase the collagen content, alleviate structural elastic fiber damage, and significantly inhibit abnormal MMP-3 expression. In addition, biochemical analysis showed that the CS/CSCPs/ß-GP gel can effectively inhibit the elevated expressions of ROS and key proinflammatory factors (TNF-α, IL-1ß, IL-6) in photoaging skin tissues and promote expression of the anti-inflammatory factor IL-10. Conclusion: SP can cause many clinical skin diseases, such as solar freckle-like nevus, solar keratosis, cutaneous melanoma, and squamous cell carcinoma. CSCPs are a high-efficacy anti-SP natural active substance and CS/CSCPs/ß-GP gel can synergistically enhance the CSCPs' anti-SP effect. The mechanism is likely related to the inhibited activation of ROS/nuclear transcription factor-κB signaling and the expression of downstream inflammatory factors.

Cluster Analysis to Find Temporal Physical Activity Patterns Among US Adults.

Physical activity (PA) is known to be a risk factor for obesity and chronic diseases such as diabetes and metabolic syndrome. Few attempts have been made to pattern the time of physical activity while incorporating intensity and duration in order to determine the relationship of this multi-faceted behavior with health. In this paper, we explore a distance-based approach for clustering daily physical activity time series to estimate temporal physical activity patterns among U.S. adults (ages 20-65) from the National Health and Nutrition Examination Survey 2003-2006 (NHANES). A number of distance measures and distance-based clustering methods were investigated and compared using various metrics. These metrics include the Silhouette and the Dunn Index (internal criteria), and the associations of the clusters with health status indicators (external criteria). Our experiments indicate that using a distance-based cluster analysis approach to estimate temporal physical activity patterns through the day, has the potential to describe the complexity of behavior rather than characterizing physical activity patterns solely by sums or labels of maximum activity levels.

Joint Temporal Patterns By Integrating Diet and Physical Activity.

Both diet and physical activity are associated with obesity and chronic diseases such as diabetes and metabolic syndrome. Early efforts in connecting dietary and physical activity behaviors to generate patterns rarely considered the use of time. In this paper, we propose a distance-based cluster analysis approach to find joint temporal diet and physical activity patterns among U.S. adults ages 20-65. Dynamic Time Warping (DTW) generalized to multi-dimensions is combined with commonly used clustering methods to generate unbiased partitioning of the National Health and Nutrition Examination Survey 2003-2006 (NHANES) dataset. The clustering results are evaluated using visualization of the clusters, the Silhouette Index, and the associations between clusters and health status indicators based on multivariate regression models. Our experiments indicate that the integration of diet, physical activity, and time has the potential to discover joint temporal patterns with association to health.

Five-year follow-up on two revascularization methods used on patients with left main artery disease and/or multivessel coronary artery disease.

BACKGROUND: Coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI) are the main treatment methods for left main artery disease (LMAD) and triple-vessel coronary artery disease (TVCAD). OBJECTIVE: This study aimed to evaluate the five-year post-treatment effects of CABG and PCI in patients with severe coronary vasculopathy. METHODS: A total of 430 patients with LMAD and/or triple-vessel coronary artery disease from November 2014 to July 2015 were enrolled retrospectively in the affiliated cardiovascular hospital of Shanxi Medical University and divided into the CABG group and PCI group. The living conditions of the patients were obtained through medical records and telephonic follow-ups five years after the surgery date. The independent risk factors for major adverse cardiovascular and cerebrovascular events (MACCE) were analyzed using logistic regression analysis. The effects of the two treatment methods were followed up and evaluated to measure the predictive ability of the Global Risk Classification (GRC) scoring system for MACCE after five years. RESULTS: There were 212 cases in the CABG group and 218 cases in the PCI group. Smoking (P= 0.047), diabetes (P= 0.031), LVEF (P= 0.020), LMAD (P= 0.008), and anterior descending branch lesions (P= 0.038) were significantly correlated with MACCE. The prevalence of MACCE in the CABG group and PCI group had no significant difference (P= 0.549). The GRC scoring system received an AUC of 0.701 for predicting MACCE. CONCLUSION: For patients with severe coronary artery disease, there was no significant difference in the prevalence of MACCE between the CABG and the PCI groups. Several independent risk factors for MACCE were found. The GRC scoring system showed a strong predictive ability for MACCE after five years of revascularization.

Seasonal variations of airborne phthalates and novel non-phthalate plasticizers in a test residence in cold regions: Effects of temperature, humidity, total suspended particulate matter, and sources.

As a class of plasticizers widely used in consumer products, some phthalate esters (PAEs) have been restricted due to their adverse health effects and ubiquitous presence, leading to the introduction of alternative non-phthalates plasticizers (NPPs) to the market. However, few studies focus on the influence of environmental parameters on the presence of these plasticizers and the potential human health risks for people living in poorly ventilated indoor spaces in cold regions. We investigated the trends of PAEs and NPPs in air in a typical indoor residence in northern China for over one year. The air concentrations of PAEs were significantly higher than those of NPPs (p < 0.05), indicating that PAEs are still the dominant plasticizers currently being used in the studied residence. PAEs showed seasonal fluctuation patterns of the highest levels found in summer and autumn. The temperature and relative humidity dependence for most PAEs and NPPs decreased with decreasing vapor pressure. Concentrations of the high molecular weight NPPs and PAEs positively correlated with total suspended particles (TSP). It is worth noting that the peak concentrations of PAEs and NPPs were found when the haze occurred in autumn. Principal component analysis (PCA) suggested the diverse applications of PAEs and NPPs in the indoor environment. The hazard index (HI) values observed in this study were all below international guidelines (<1); however, the average carcinogenic risk (CR) values for some compounds exceeded acceptable levels (One in a million), which raised concerns about the possibility of carcinogenicity for people living indoors for long periods of time in cold regions.