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  • Winstead posted an update 9 months ago

    Frailty is a state of decreased physiological reserve and increased vulnerability to adverse outcomes in aging, and is characterized by dysregulation across various biological pathways. Frailty may manifest biologically as alteration in protein expression, possibly regulated at genetic, transcriptional and epigenetic levels. In this study, we examined the proteomic profile associated with frailty defined by an established cumulative frailty index (FI). Using the SomaScan® assay, 4265 proteins were measured in plasma, of which 55 were positively associated and 88 were negatively associated with the FI. The proteins most strongly associated with frailty were fatty acid-binding proteins, including fatty acid-binding protein (FABP) (p = 1.96 × 10-19 ) and FABPA (p = 8.10 × 10-16 ), leptin (p = 1.43 × 10-14 ), and ANTR2 (p = 7.95 × 10-20 ). Pathway analysis with the top 143 frailty-associated proteins revealed enrichment for proteins in pathways related to lipid metabolism, musculoskeletal development and function, cell-to-cell signaling and interaction, cellular assembly, and organization. JAK2 inhibitors clinical trials Frailty prediction model constructed with elastic net regression utilizing 110 proteins demonstrated a correlation between predicted frailty and observed frailty (r = 0.57, p less then 2.2 × 10-16 ). Predicted frailty was also more strongly correlated with chronological age (r = 0.54, p less then 2.2 × 10-16 ) than observed frailty (r = 0.37, p = 1.2 × 10-15 ). This study identified novel proteins and pathways related to frailty that may offer improved frailty phenotyping and prediction.Rechargeable potassium-ion batteries (KIBs) have demonstrated great potential as alternative technologies to the currently used lithium-ion batteries on account of the competitive price and low redox potential of potassium which is advantageous to applications in the smart grid. As the critical component determining the energy density, appropriate cathode materials are of vital need for the realization of KIBs. Layered oxide cathodes are promising candidates for KIBs due to high reversible capacity, appropriate operating potential, and most importantly, facile and easily scalable synthesis. In light of this trend, the recent advancements and progress in layered oxides research for KIBs cathodes, covering material design, structural evolution, and electrochemical performance are comprehensively reviewed. The structure-performance correlation and some effective optimization strategies are also discussed. Furthermore, challenges and prospects of these layered cathodes are included, with the purpose of providing fresh impetus for future development of these materials for advanced energy storage systems.Controversial biodegradability and nonspecific pre-drug leakage are major limitations for inorganic nanoparticles in cancer treatment. To solve these problems, we developed organic-inorganic hybridized hollow mesoporous silica nanoparticles with polydopamine modifications on the surface to simultaneously achieve enhanced biodegradability and controllable drug release. The morphology and chemical structure of the nanoparticles were characterized by TEM, N2 adsorption-desorption isotherms, TEM-mapping and XPS. Moreover, the release behavior of nanoparticles under various pH conditions and the degradation behavior in the presence of GSH were evaluated. With effective controlled release, HMONs-PTX@PDA were shown to significantly inhibit cancer cell proliferation and achieve antitumor effects in vivo through dual-response release in the tumor microenvironment. Overall, this nanoplatform has significant potential to achieve tumor microenvironment-responsive degradation and release to enhance tumor accumulation, which is very promising for cancer treatment.African swine fever (ASF) continues to spread across Asia, devastating pig populations. The disease is nearly 100% fatal in pigs, and currently, there is no effective vaccine available. Therefore, early detection of ASF is critical for effective disease control. The testing process usually requires samples to be shipped to a central laboratory, which may take many hours of travel or shipping time, delaying the results needed for a rapid response. The ability to confirm ASFV-infected animals on-site or in a regional laboratory that has limited technical capacity and/or infrastructure should eliminate these issues. This study describes the successful transfer of a highly sensitive and specific laboratory-validated real-time PCR assay to a portable pen-side thermocycler, which can be operated in the field for rapid detection of ASFV following a quick manual nucleic acid extraction from a wide array of clinical samples including aggregate samples such as oral fluids. The performance of the portable assay was comparable to the laboratory-based assay. The true portability of the assay was evaluated in seven ASF-suspected farms in Vietnam by testing eighty-nine freshly collected whole blood samples on-site. The results obtained on-site were in agreement with the laboratory data obtained the following day. Availability of this field-deployable molecular assay would eliminate the need to ship samples to a central laboratory, when rapid laboratory results are required, ultimately improving the response time.Human carbonic anhydrase I and II isoenzymes (hCA I and II) are important metabolic enzymes. In this study, a new series of thiazol-(2(3H)-ylideneamino)benzenesulfonamide derivatives were synthesized and also some inhibition parameters including IC50 (hydratese) and inhibition constant values (Ki , esterase) were determined. All studied compounds exhibited potent inhibition against these enzymes. They inhibited carbonic anhydrases (CAs) with the IC50 values of 113 to 395.8 nM (Ki  = 77.38-319.59 nM) for hCA I and 91.9 to 516 nM (Ki  = 62.79-425.89 nM) for hCA II. Among the compounds, 5c was found to be the most active one (Ki 77.38 nM) for hCA I and 5g was found for hCA II with the value of 62.79 nM.Magnetic resonance-guided focused ultrasound (MRgFUS) ablation of the ventral intermediate (Vim) thalamic nucleus is an incisionless treatment for essential tremor (ET). The standard initial targeting method uses an approximate, atlas-based stereotactic approach. We developed a new patient-specific targeting method to identify an individual’s Vim and the optimal MRgFUS target region therein for suppression of tremor. In this retrospective study of 14 ET patients treated with MRgFUS, we investigated the ability of WMnMPRAGE, a highly sensitive and robust sequence for imaging gray matter-white matter contrast, to identify the Vim, FUS ablation, and a clinically efficacious region within the Vim in individual patients. We found that WMnMPRAGE can directly visualize the Vim in ET patients, segmenting this nucleus using manual or automated segmentation capabilities developed by our group. WMnMPRAGE also delineated the ablation’s core and penumbra, and showed that all patients’ ablation cores lay primarily within their Vim segmentations.

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