Encapsulation of 2-amino-2-methyl-1-propanol with tetraethyl orthosilicate for CO2 capture

Carbon capture is widely recognised as an essential strategy to meet global goals for climate protection. Although various CO2 capture technologies including absorption, adsorption and membrane exist, they are not yet mature for post-combustion power plants mainly due to high energy penalty. Hence researchers are concentrating on developing non-aqueous solvents like ionic liquids, CO2-binding organic liquids, nanoparticle hybrid materials and microencapsulated sorbents to minimize the energy consumption for carbon capture. This research aims to develop a novel and efficient approach by encapsulating sorbents to capture CO2 in a cold environment. The conventional emulsion technique was selected for the microcapsule formulation by using 2-amino-2-methyl-1-propanol (AMP) as the core sorbent and silicon dioxide (SiO2) as the shell. This paper reports the findings on the formulated microcapsules including key formulation parameters, microstructure, size distribution and thermal cycling stability. Furthermore, the effects of microcapsule quality and absorption temperature on the CO2 loading capacity of the microcapsules were investigated using a self-developed pressure decay method. The preliminary results have shown that the AMP microcapsules are promising to replace conventional sorbents.Engineering and Physical Sciences Research Council (EPSRC

PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer

Abstract The PI3K/AKT/mTOR (PAM) signaling pathway is a highly conserved signal transduction network in eukaryotic cells that promotes cell survival, cell growth, and cell cycle progression. Growth factor signalling to transcription factors in the PAM axis is highly regulated by multiple cross-interactions with several other signaling pathways, and dysregulation of signal transduction can predispose to cancer development. The PAM axis is the most frequently activated signaling pathway in human cancer and is often implicated in resistance to anticancer therapies. Dysfunction of components of this pathway such as hyperactivity of PI3K, loss of function of PTEN, and gain-of-function of AKT, are notorious drivers of treatment resistance and disease progression in cancer. In this review we highlight the major dysregulations in the PAM signaling pathway in cancer, and discuss the results of PI3K, AKT and mTOR inhibitors as monotherapy and in co-administation with other antineoplastic agents in clinical trials as a strategy for overcoming treatment resistance. Finally, the major mechanisms of resistance to PAM signaling targeted therapies, including PAM signaling in immunology and immunotherapies are also discussed.

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Novel lysosome targeted molecular transporter built on a guanidinium-poly-(propylene imine) hybrid dendron for efficient delivery of doxorubicin into cancer cells

An efficient synthetic approach has been adopted to construct a new dendron-based octa-guanidine appended molecular transporter with a lysosomal targeted peptide–doxorubicin conjugate. The transporter alone (G8-PPI-FL) is found to be non-toxic, showed higher cellular uptake compared to Arg-8-mer and exhibited excellent selectivity towards lysosomes in cathepsin B expressing HeLa cells, while the Dox-conjugate showed significant cytotoxicity to cancer cells without affecting the non-cancerous cells

Plasmonically Enhanced Galactoxyloglucan Endowed Gold Nanoparticles Exposed Tumor Targeting Biodistribution Envisaged in a Surface-Enhanced Raman Scattering Platform

Biopolymer-capped gold nanoparticles (AuNPs) were perceived for tracing biodistribution in a solid tumor mice through surface-enhanced Raman scattering (SERS) fingerprinting. In this strategy, a robust and ecofriendly green chemistry approach was adopted to construct galactoxyloglucan (PST001) endowed AuNPs (PST-GNPs) with cancer-cell-selective toxic nature and excellent biocompatibility. Plasmonically enhanced light-scattering properties facilitated PST-GNPs to be a superior SERS substrate with high Raman signal enhancement. In this context, PST-GNPs were scrutinized for the noninvasive label-free SERS live-cell spectral imaging to evaluate the fingerprint molecular details of cellular processes. Consequently, the inherent SERS feature of PST-GNPs enabled us to investigate the dynamic and complex nature with NP biodistrubution in tumor-bearing mice on a SERS platform that illustrated the tumor targeting nature. Henceforth, the present findings emphasized a futuristic clinically relevant scenario for tracing the in vivo NP dissemination in a label-free fashion for providing vital biochemical details on a molecular level

New Insight of Tetraphenylethylene-based Raman Signatures for Targeted SERS Nanoprobe Construction Toward Prostate Cancer Cell Detection

We have designed and synthesized novel tetraphenylethylene (TPE) appended organic fluorogens and unfold their unique Raman fingerprinting reflected by surface-enhanced Raman scattering (SERS) upon adsorption on nanoroughened gold surface as a new insight in addition to their prevalent aggregation-induced emission (AIE) and aggregation-caused quenching (ACQ) phenomena. A series of five TPE analogues has been synthesized consisting of different electron donors such as (1) indoline with propyl (TPE-In), (2) indoline with lipoic acid (TPE-In-L), (3) indoline with Boc-protected propyl amine (TPE-In-Boc), (4) benzothaizole (TPE-B), and (5) quinaldine (TPE-Q). Interestingly, all five TPE analogues produced multiplexing Raman signal pattern, out of which TPE-In-Boc showed a significant increase in signal intensity in the fingerprint region. An efficient SERS nanoprobe has been constructed using gold nanoparticles as SERS substrate, and the TPE-In as the Raman reporter, which conjugated with a specific peptide substrate, Cys-Ser-Lys-Leu-Gln-OH, well-known for the recognition of prostate-specific antigen (PSA). The designated nanoprobe TPE-In-PSA@Au acted as SERS “ON/OFF” probe in peace with the vicinity of PSA protease, which distinctly recognizes PSA expression with a limit of detection of 0.5 ng in SERS platform. Furthermore, TPE-In-PSA@Au nanoprobe was efficiently recognized the overexpressed PSA in human LNCaP cells, which can be visualized through SERS spectral analysis and SERS mapping

TEMPO-Oxidized Nanocellulose Fiber-Directed Stable Aqueous Suspension of Plasmonic Flower-like Silver Nanoconstructs for Ultra-Trace Detection of Analytes

The synthesis of shape-tuned silver (Ag) nanostructures with high plasmon characteristics has become of significant importance in in vitro diagnostic applications. Herein, we report a simple aqueous synthetic route using 2,2,6,6-tetramethylpiperidine-1-oxyl-oxidized nanocellulose fibers (T-NCFs) and trisodium citrate (TSC) that results in anisotropically grown flower-like Ag nanoconstructs (AgNFs). A detailed investigation of the concentration and sequence of the addition of reactants in the formation of these anisotropic Ag structures is presented. Our experimental results show that the mechanism underlying the formation of AgNFs is facilitated by the synergistic action of T-NCFs and TSC on the directional growth of Ag nuclei during the primary stage, which later develop into a flower-like structure by the ripening of larger particles consuming smaller Ag particles. As a result the final structure comprises flower-like morphology over which several smaller Ag particles (of size <10 nm) are adhered. The aqueous AgNF colloid exhibits high stability (ζ = −69.4 mV) and long shelf-life at neutral pH (>4 months) by the efficient capping action of T-NCFs. Further, an as-synthesized nanoconstructs shows excellent surface-enhanced Raman scattering activity, which enables ultrasensitive detection of <i>p</i>-aminothiophenol with a concentration down to 10 aM (10^–17 M) in a reproducible way. This biosupported synthesis of stable aqueous colloids of AgNF may find potential applications as a biomedical sensing platform for the trace level detection of analyte molecules

Exploration of Biogenic Nano-chemobiotics Fabricated by Silver Nanoparticle and Galactoxyloglucan with an Efficient Biodistribution in Solid Tumor Investigated by SERS Fingerprinting

An incredible exploration ensued of a dual modality nanocomposite wherein chemotherapy in fusion with antibacterial efficacy is obtained in a biogenic fabrication, which transformed as a novel nano-chemobiotics (NCB) prevailing fundamental molecular level investigation by surface-enhanced Raman scattering (SERS) platform. The nanocomposite is a facile, robust, and ecofriendly constitution between silver nanoparticles (SNPs) and a naturally occurring galactoxyloglucan (PST001) denoted as SNP@PST, which displayed biocompatibility with an upgraded selective cytotoxicity toward cancer cells. The relatively nontoxic nature of the SNP@PST on normal cells and red blood cells was further proved by detailed toxicological profiling on BALB/c mice. As a unique outcome, we observed excellent antibacterial activity, which is complementary to the greater cytotoxicity by the NCB. In diagnostic aspect, SNP@PST was revealed to be a superior SERS substrate with multiscale Raman signal enhancement contributed by homogeneous hot-spot distribution. Finally, the inherent SERS feature enabled us to investigate the biodistribution of the NCB in tumor-challenged mice using Raman fingerprinting and mapping analysis. Hence, the unrevealed SNP@PST orchestrated with the surfactant-free green method resembled a potential theransonstic NCB construct with synergistic anticancer and antibacterial potential in a single platform