Nutritional impairment, psychological health and quality of life among older adults with advanced cancer: A secondary analysis of a randomized clinical trial.

BACKGROUND: Nutritional impairment is associated with treatment toxicity and worse overall survival in patients with cancer. We aimed to (1) evaluate the association of nutritional impairment with psychological health and quality of life (QOL) and (2) examine which measures of nutrition had the strongest association with psychological health and QOL among older adults receiving cancer treatment with palliative intent. METHODS: This secondary analysis was performed on baseline data from a nationwide cluster randomized clinical trial (ClinicalTrials.gov identifier: NCT02107443; PI: Mohile). Adults age ≥70 with advanced cancer and ≥1 geriatric assessment (GA) impairment were enrolled from 2014 to 2017. In line with geriatric oncology standards, we defined nutritional impairment as Mini Nutritional Assessment Short Form (MNA-SF) ≤11, body mass index (BMI) <21 kg/m2, or >10% involuntary weight loss in the past 6 months. We conducted multivariable linear regressions to evaluate the association of nutritional impairment with each measure of psychological health and QOL: Geriatric Depression Scale (GDS-15, range 0-15), Generalized Anxiety Disorder-7 (GAD-7, range 0-21), NCCN Distress Thermometer (NCCN DT, range 0-10), and Functional Assessment of Cancer Therapy-General (FACT-G, range 0-108). Analyses were adjusted for patient demographics, clinical characteristics, and GA. RESULTS: Among 541 patients, the mean age was 77 (range 70-96) and 60% had nutritional impairment. Mean baseline scores: GDS-15 3.1 (SD 2.7), GAD-7 2.9 (SD 4.0), NCCN DT 2.9 (SD 2.7), and FACT-G 80 (SD 15). In the adjusted model, compared to those with no nutritional impairment, older adults with nutritional impairment had greater depression (ß = 0.79, 95% CI 0.36-1.23) and anxiety severity (ß = 0.86, 95% CI 0.19-1.53), and worse QOL (ß = -6.31, 95% CI -8.62 to -4.00). Of the measures of nutrition, MNA-SF ≤11 demonstrated the strongest associations with depression, anxiety, distress, and QOL. CONCLUSION: Nutritional impairment is associated with impaired psychological health and worse QOL. Clinicians should use the MNA-SF to screen older adults for nutritional impairment and offer tailored supportive interventions.

Directed Evolution and Immobilization of Lactobacillus brevis Alcohol Dehydrogenase for Chemo-Enzymatic Synthesis of Rivastigmine.

Rivastigmine is one of the several pharmaceuticals widely prescribed for the treatment of Alzheimer's disease. However, its practical synthesis still faces many issues, such as the involvement of toxic metals and harsh reaction conditions. Herein, we report a chemo-enzymatic synthesis of Rivastigmine. The key chiral intermediate was synthesized by an engineered alcohol dehydrogenase from Lactobacillus brevis (LbADH). A semi-rational approach was employed to improve its catalytic activity and thermal stability. Several LbADH variants were obtained with a remarkable increase in activity and melting temperature. Exploration of the substrate scope of these variants demonstrated improved activities toward various ketones, especially acetophenone analogs. To further recycle and reuse the biocatalyst, one LbADH variant and glucose dehydrogenase were co-immobilized on nanoparticles. By integrating enzymatic and chemical steps, Rivastigmine was successfully synthesized with an overall yield of 66 %. This study offers an efficient chemo-enzymatic route for Rivastigmine and provides several efficient LbADH variants with a broad range of potential applications.

Production of Biobased Ethylbenzene by Cascade Biocatalysis with an Engineered Photodecarboxylase.

Production of commodity chemicals, such as benzene, toluene, ethylbenzene, and xylenes (BTEX), from renewable resources is key for a sustainable society. Biocatalysis enables one-pot multistep transformation of bioresources under mild conditions, yet it is often limited to biochemicals. Herein, we developed a non-natural three-enzyme cascade for one-pot conversion of biobased l-phenylalanine into ethylbenzene. The key rate-limiting photodecarboxylase was subjected to structure-guided semirational engineering, and a triple mutant CvFAP(Y466T/P460A/G462I) was obtained with a 6.3-fold higher productivity. With this improved photodecarboxylase, an optimized two-cell sequential process was developed to convert l-phenylalanine into ethylbenzene with 82 % conversion. The cascade reaction was integrated with fermentation to achieve the one-pot bioproduction of ethylbenzene from biobased glycerol, demonstrating the potential of cascade biocatalysis plus enzyme engineering for the production of biobased commodity chemicals.

Insights on the binding mechanism between specified aldehydes and flaxseed protein using multispectral image and molecular docking.

The binding and release behavior of flaxseed proteins to aldehydes is significant for the sensory properties of flaxseed foods. The key aldehydes of flaxseed were selected by headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) and odor activity value (OAV) method, and the interaction between flaxseed protein and flaxseed protein was investigated by multispectral, molecular docking, molecular dynamics simulation, and particle size techniques. The results showed that 2,4-decadienal presented a higher binding capability and a higher Stern-Volmer constant with flaxseed protein than pentanal, benzaldehyde, and decanal. Thermodynamic analysis revealed that hydrogen bonding and hydrophobic interactions were the main forces. Aldehydes contributed to a certain reduction in radius of gyration (Rg) value and α-helix content of flaxseed protein. In addition, the results of particle size showed that aldehydes caused the proteins to aggregate toward larger particles. This study could provide new insights into the interactions between flaxseed food and flavor.

Phenotyping of Methicillin-Resistant Staphylococcus aureus Using a Ratiometric Sensor Array.

Chemical tools capable of classifying multidrug-resistant bacteria (superbugs) can facilitate early-stage disease diagnosis and help guide precision therapy. Here, we report a sensor array that permits the facile phenotyping of methicillin-resistant Staphylococcus aureus (MRSA), a clinically common superbug. The array consists of a panel of eight separate ratiometric fluorescent probes that provide characteristic vibration-induced emission (VIE) profiles. These probes bear a pair of quaternary ammonium salts in different substitution positions around a known VIEgen core. The differences in the substituents result in varying interactions with the negatively charged cell walls of bacteria. This, in turn, dictates the molecular conformation of the probes and affects their blue-to-red fluorescence intensity ratios (ratiometric changes). Within the sensor array, the differences in the ratiometric changes for the probes result in "fingerprints" for MRSA of different genotypes. This allows them to be identified using principal component analysis (PCA) without the need for cell lysis and nucleic acid isolation. The results obtained with the present sensor array agree well with those obtained using polymerase chain reaction (PCR) analysis.

LncRNA LINC00473 promoted colorectal cancer cell proliferation and invasion by targeting miR-195 expression.

Long noncoding RNAs (lncRNAs) have been shown to play crucial roles in cancer development. However, the role of LINC00473 in colorectal cancer has not been explored. In our study, we showed that LINC00473 expression was upregulated in colorectal cancer samples compared to nontumor samples. The expression of LINC00473 in colorectal cancer tissues from patients with distant metastasis was higher than that from cases without distant metastasis. The higher expression level of LINC00473 was positively correlated with advanced clinical stage. The elevated expression of LINC00473 accelerated colorectal cancer cell proliferation, cell cycle progression and invasion. Moreover, overexpression of LINC00473 induced epithelial to mesenchymal (EMT) progression in HT29 and SW480 cells. Ectopic expression of LINC00473 suppressed miR-195 expression in colorectal cancer cells. miR-195 expression was downregulated in colorectal cancer samples compared with nontumor samples. The expression of miR-195 in colorectal cancer tissues from patients with distant metastasis was lower than that from cases without distant metastasis. The lower expression level of miR-195 was positively correlated with advanced clinical stage. In addition, we showed that the expression of miR-195 was negatively correlated with the LINC00473 expression level in colorectal cancer tissues. LINC00473 accelerated colorectal cancer cell proliferation and cell cycle progression and regulated EMT progression by regulating miR-195 expression. These data suggested that LINC00473 induced cell proliferation, cell cycle progression and EMT progression by acting as a ceRNA for miR-195 in colorectal cancer.

Self-assembled sialyllactosyl probes with aggregation-enhanced properties for ratiometric detection and blocking of influenza viruses.

Infection and dissemination of influenza viruses (IVs) causes serious health concerns worldwide. However, effective tools for the accurate detection and blocking of IVs remain elusive. Here, we develop a new sialyllactosyl probe with self-assembled core-shell structure for the ratiometric detection and blocking of IVs. N,N'-diaryl-dihydrodibenzo[a,c]phenazines were used to form the core structure by hydrophobic assembly in an aqueous solution with an aggregation-enhanced blue fluorescence mission. Subsequently, dicyanomethylene-4H-pyran-based sialyllactosides were used for self-assembly with the core structure, producing the sialyllactosyl probe that emits a red fluorescence due to Förster resonance energy transfer. The probe developed has been proven to be available for (1) the fluorescence ratiometric detection of IVs through selective interaction with the sialyllactosyl-binding proteins on the virus surface, and (2) effectively blocking the invasion of human-infecting IVs towards host cells as accentuated by the sialyllactosides on the surface of the probes.

Apoptotic Cell Death Induced by Resveratrol Is Partially Mediated by the Autophagy Pathway in Human Ovarian Cancer Cells.

Resveratrol (trans-3,4,5'-trihydroxystilbene) is an active compound in food, such as red grapes, peanuts, and berries. Resveratrol exhibits an anticancer effect on various human cancer cells. However, the mechanism of resveratrol-induced anti-cancer effect at the molecular level remains to be elucidated. In this study, the mechanism underlying the anti-cancer effect of resveratrol in human ovarian cancer cells (OVCAR-3 and Caov-3) was investigated using various molecular biology techniques, such as flow cytometry, western blotting, and RNA interference, with a major focus on the potential role of autophagy in resveratrol-induced apoptotic cell death. We demonstrated that resveratrol induced reactive oxygen species (ROS) generation, which triggers autophagy and subsequent apoptotic cell death. Resveratrol induced ATG5 expression and promoted LC3 cleavage. The apoptotic cell death induced by resveratrol was attenuated by both pharmacological and genetic inhibition of autophagy. The autophagy inhibitor chloroquine, which functions at the late stage of autophagy, significantly reduced resveratrol-induced cell death and caspase 3 activity in human ovarian cancer cells. We also demonstrated that targeting ATG5 by siRNA also suppressed resveratrol-induced apoptotic cell death. Thus, we concluded that a common pathway between autophagy and apoptosis exists in resveratrol-induced cell death in OVCAR-3 human ovarian cancer cells.

[Studies on hyperspectral characteristics of Microcystis aeruginosa under the cultivation conditions with different phosphorus concentrations].

Microcystis aeruginosa is one of the most common species in the algae-bloom events of domestic lakes. Illumination incubator was used to cultivate M. aeruginosa under conditions of different phosphorus concentrations in the laboratory. Spectroscopic data of culture solutions were collected by GER1500 spectrometer under the sunlight. The study focused on the growth rhythm of M. aeruginosa and the characteristics of spectral variation in the culture solutions. The results showed that low phosphorus concentration (< or =10 microg x L(-1)) is a restricting factor for the growth and reproduction of M. aeruginosa. Moreover, the reflections of spectrum from culture solutions of M. aeruginosa showed significant changes along with cultivation period, such as at the wavelengths of 550, 610, 660, 700-710 and 760 nm.