We observed unexpected thiazole 1B formation when 2,6‐dichlorobenzothioamide 1 and ethyl bromopyruvate were reacted under basic conditions at elevated temperatures in ethanol. Thiazole 1B, ...regio‐isomeric to that expected under conventional Hantzsch conditions, was extensively characterized and later confirmed by single crystal X‐ray structure. We carried out this transformation with several substituted benzothioamides and found that the formation of the unexpected thiazole regio‐isomer was highly dependent on the steric as well as the electronic characteristics of the ortho‐substituents on the phenyl ring. A mechanism to account for this novel transformation was proposed.
Heterocycles containing 2 or 3 chlorine atoms have been converted to libraries of N-alkylaminoheterocycles by parallel solution phase nucleophilic aromatic substitution. The first chloride ...displacement was achieved with stoichiometric nucleophilic alcohols, or amines. In the final substitution, excess amine was used to ensure that all active electrophiles were consumed. The excess amine and salts were removed by automated solid
s
upported
l
iquid
e
xtraction (SLE). SLE is partition chromatography using buffered water immobilized on a solid support and elution by a water immiscible solvent. This is a high throughput method for liquid-liquid extraction which is easily automated using simple liquid handling robotics.
Chloroheterocycles were converted to spatially separated libraries by parallel solution phase nucleophilic aromatic substitution. Excess reagent amines and water soluble impurities were removed from the products by automated solid supported liquid extraction (SLE).
Kinesins are microtubule-based motors involved in various intracellular transports. Neurons, flagellated cells, and pigment cells have been traditionally used as model systems to study the cellular ...functions of kinesins. Here, we report silkworm posterior silkgland （PSG）, specialized cells with an extensive endomembrane system for intracellular transport and efficient secretion of fibroin, as a novel model for kinesin study. To investigate kinesindriven intracellular transport in PSG cells, we cloned five silkworm kinesin-like proteins （KLPs）, BmKinesin-1, BmKinesin-6, BmKinesin-7, BmKinesin-13, and BmKinesin-14A. We determined their expression patterns by relative real-time PCR and western blotting. Immunofluorescence microscopy verified their colocalization with microtubules. By combining pull-down assays, LC-MS/MS, and western blotting analysis, we identified many potential cargoes of BmKinesin-1 in PSG, including fibroin-containing granules and exuperantia-associated ribonucleoprotein （RNP） complexes. Moreover, BmKinesin-13 overexpression disrupted the microtubule network in BmN cells, which is consistent with a role of Kinesin-13 in regulating microtubule dynamics in other organisms. On the basis of these results, we concluded that PSG might have advantages in elucidating mechanisms of intracellular transport in secretory tissues and could serve as a potential model for kinesin studies.
Phosphonoacetamide esters bound to solid supported peptides or peptide synthesis supports are active as Horner-Wadsworth-Emmons (HWE) reagents with a variety of aldehydes. HWE reagents can be ...attached to the solid support via the amide or phosphono ester. Mild basic conditions, triethylamine and Li salts, with excess aldehyde give high conversions to alkenes.
Chronic heart failure (CHF) is the final outcome of many cardiovascular diseases, and is a severe health issue faced by the elderly population. Mixed lineage kinase 3 (MLK3), a member of MAP3K ...family, is associated with aging, inflammation, oxidative stress, and related diseases, such as CHF. MLK3 has also been reported to play an important role in protecting against cardiomyocyte injury; however, its function in myocardial fibrosis is unknown. To investigate the role of MLK3 in myocardial fibrosis, we inhibited the expression of MLK3, and examined cardiac function and remodeling in TAC mice. In addition, we assessed the expression of MLK3 protein in ventricular cells and its downstream associated protein. We found that MLK3 mainly regulates NF-κB/NLRP3 signaling pathway-mediated inflammation and that pyroptosis causes myocardial fibrosis in the early stages of CHF. Similarly, MLK3 mainly regulates the JNK/p53 signaling pathway-mediated oxidative stress and that ferroptosis causes myocardial fibrosis in the advanced stages of CHF. We also found that promoting the expression of miR-351 can inhibit the expression of MLK3, and significantly improve cardiac function in mice subjected to TAC. These results suggest the pyroptosis and ferroptosis induced by MLK3 signaling in cardiomyocytes are essential for adverse myocardial fibrosis, in response to pressure overload. Furthermore, miR-351, which has a protective effect on ventricular remodeling in heart failure caused by pressure overload, may be a key target for the regulation of MLK3.
Objective
Frailty and poor oral health are both common age-related conditions. However, the association between oral health and frailty has not been explored thoroughly among older Chinese adults. We ...aimed to investigate the associations between number of teeth, denture use, and frailty among older adults in western China.
Design
Cross-sectional study.
Setting
Community-based.
Participants
Participants were 4037 community-dwelling individuals aged 60 and older from the West China Health and Aging Trend (WCHAT) study.
Measurements
Frailty was assessed using the physical frailty phenotype (PFP) and categorized as non-frail, prefrail and frail. In addition, number of teeth and denture use were examined by calibrated dentists. Multinomial logistic regression models were performed to examine the association between number of teeth, denture use, and frailty.
Results
The overall prevalence of frailty was 6.7% among 4037 participants aged 60 and older in western China. Participants with no more than 20 teeth were associated with higher odds of being prefrail or frail whether wearing dentures or not. Denture using could not help lower the odds of being prefrail or frail for older adults with fewer teeth.
Conclusions
This study suggested that frailty was associated with having fewer teeth (≤20 teeth) among older Chinese adults. Future research involving targeted interventions addressing number of teeth may help provide information to establish effective strategies for frailty prevention in older adults.
It has been noticed in recent years that the unfavorable effects of the gut microbiota could exhaust host vigor and life, yet knowledge and theory are just beginning to be established. Increasing ...documentation suggests that the microbiota-gut-brain axis not only impacts brain cognition and psychiatric symptoms but also precipitates neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). How the blood-brain barrier (BBB), a machinery protecting the central nervous system (CNS) from the systemic circulation, allows the risky factors derived from the gut to be translocated into the brain seems paradoxical. For the unique anatomical, histological, and immunological properties underpinning its permeable dynamics, the BBB has been regarded as a biomarker associated with neural pathogenesis. The BBB permeability of mice and rats caused by GM dysbiosis raises the question of how the GM and its metabolites change BBB permeability and causes the brain pathophysiology of neuroinflammation and neurodegeneration (NF&ND) and brain aging, a pivotal multidisciplinary field tightly associated with immune and chronic systemic inflammation. If not all, gut microbiota-induced systemic chronic inflammation (GM-SCI) mainly refers to excessive gut inflammation caused by gut mucosal immunity dysregulation, which is often influenced by dietary components and age, is produced at the interface of the intestinal barrier (IB) or exacerbated after IB disruption, initiates various common chronic diseases along its dispersal routes, and eventually impairs BBB integrity to cause NF&ND and brain aging. To illustrate the immune roles of the BBB in pathophysiology affected by inflammatory or "leaky" IB resulting from GM and their metabolites, we reviewed the selected publications, including the role of the BBB as the immune barrier, systemic chronic inflammation and inflammation influences on BBB permeability, NF&ND, and brain aging. To add depth to the bridging role of systemic chronic inflammation, a plausible mechanism indispensable for BBB corruption was highlighted; namely, BBB maintenance cues are affected by inflammatory cytokines, which may help to understand how GM and its metabolites play a major role in NF&ND and aging.
The intrinsic relationship between mechanics and luminescent signals in mechanoluminescence materials presents unique advantages for visualized mechanics sensing. However, the quantitative or ...semi-quantitative sensing of mechanics in previous mechanoluminescence-based devices are always established based on brightness/intensity variations, which are hard to apply in practice. In this work, we designed an efficient mechanoluminescent system, Sr2P2O7:Eu,Y, in which two types of luminescent centers are introduced with blue and red emissions, respectively. The luminescent centers exhibited a strikingly distinct stress/strain responsiveness, and therefore a stress/strain-induced color manipulation is realized. Based on this intriguing performance, a visualized semi-quantitative sensing technique for mechanics was developed, by which the detailed stress/strain level could be acquired from the mechanoluminescent color. Because the luminescent color possessed a relatively high reliability with no need for complicated monitoring equipment, this visualized semi-quantitative sensing for mechanics presents high application values in various fields.
A closed three-dimensional structure of Sr2P2O7:Eu,Y containing two types of luminescent centers with distinct emitting color was designed, which exhibited a stress/strain-induced mechanoluminescent color manipulation and could be utilized for visualized mechanics sensing. Display omitted
•A mechanoluminescent color manipulation strategy for visualized mechanics sensing was proposed.•Sr2P2O7:Eu,Y was designed to have efficient and persistent mechanoluminescence.•Sr2P2O7:Eu,Y exhibited a mechanoluminescent color evolution in response to stress.•Stress/strain level could be visually sensed from the mechanoluminescent color.
A new term, malnutrition-sarcopenia syndrome (MSS), was recently coined to describe the clinical presentation of both malnutrition and sarcopenia. The aim of this study was to investigate the ...association between MSS and long-term mortality in older inpatients. We conducted a prospective study in acute geriatric wards of two local hospitals in China. Muscle mass and malnutrition were estimated by anthropometric measures and the Mini Nutritional Assessment (MNA). Of the 453 participants, 14 (3.1%) had sarcopenia with normal nutrition, 139 (30.7%) had malnutrition risk without sarcopenia, 48 (10.6%) had malnutrition risk with sarcopenia, 25 (5.5%) had malnutrition without sarcopenia, and 22 (4.9%) had MSS at baseline. Compared with non-sarcopenic subjects with normal nutrition, subjects with MSS and subjects with malnutrition risk and sarcopenia were more than four times more likely to die (hazard ratio HR, 4.78; 95% confidence interval CI, 2.09-10.97; and HR, 4.25; 95% CI, 2.22-8.12, respectively); non-sarcopenic subjects with malnutrition risk were more than two times more likely to die (HR, 2.41; 95% CI, 1.32-4.39). In conclusion, MSS may serve as a prognostic factor in the management of hospitalized older patients.
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