Novel erythrocyte-shaped electrosprayed nanoparticles for co-delivery of paclitaxel and osimertinib: Preparation, characterization, and evaluation.

In this work, novel erythrocyte-shaped electrosprayed nanoparticles (EENPs) were designed and constructed by tri-axial electrospraying technique with PEG as the outer layer, PLGA as the middle drugs (paclitaxel [PTX] and osimertinib [OSI]) carrier layer and air as the inner layer. The prepared EENP were characterized and evaluated based on their spectral and morphological attributes. After the PTX/OSI ratio and process optimization, the EENP has inspiring features, including nanoscale size, erythrocyte morphology with a concave disk shape, and satisfactory drug loading (DL) and encapsulation efficiency (EE). In vitro drug release showed that PTX and OSI in the formulation were released in the same ratio, and the cumulative release percentage at 24 h was close to 80 %. Furthermore, the TGIR in the EENP formulation group exceeded 90 %, approximately 3.8-fold higher than that in the free drug group. In summary, we developed an erythrocyte three-core-shell nanoparticle for the co-delivery of PTX and OSI, providing a potential chemotherapeutic delivery system for the treatment of breast cancer.

Joint daily functional trajectory and risk of new-onset Alzheimer's disease and related dementias in older adults with normal and abnormal weight.

BACKGROUND: Associations between daily functional trajectories and new-onset all-cause dementia and Alzheimer's disease (AD) and the role of body weight are underexplored. METHODS: Data were from the Health and Retirement Study (HRS) 1994-2020. Daily function was assessed using (instrumental) activities of daily living ([I]ADLs). All-cause dementia and AD were defined by self- or proxy-reported physician diagnoses. Body weight was assessed using body mass index (BMI) and categorized as normal (18.5 kg/m2 ≤ BMI < 30 kg/m2) and abnormal (BMI < 18.5 kg/m2 or ≥30 kg/m2). The group-based trajectory modeling and Cox proportional hazards regression were utilized. RESULTS: Of 18,763 adults included, 1236 developed new-onset dementia during a 10-year follow-up. The associations of ADL and IADL limitations at baseline with all-cause dementia and AD were much more pronounced in those with abnormal weight (P for interaction < 0.005). Five joint trajectories of ADL and IADL limitations were identified: No (72.7 %), Recovery (4.0 %), Recent emerging (16.4 %), Early emerging (4.8 %), and Severe (2.1 %). Furthermore, the 'Severe' joint trajectory (vs. 'No') was associated with 3.57- and 3.59-times higher risks of new-onset all-cause dementia and AD in participants with abnormal weight (P for interaction = 0.002 and 0.005). Notably, the Recovery joint trajectory (vs. No) was not associated with increased risks of all-cause dementia or AD. LIMITATIONS: Self-/proxy-reported all-cause dementia and AD may introduce misclassification bias. Lifestyle factors were not quantified. BMI at baseline, but not its trajectory, was utilized. Potential reverse causation deserved attention. CONCLUSIONS: Body weight control can help reduce the risk of progression from functional limitations to all-cause dementia and AD.

Intertwined depressive and cognitive trajectories and the risk of dementia and death in older adults: a competing risk analysis.

Background: Depressive symptoms and cognitive impairment often interact, rendering their associations controversial. To date, their joint trajectories and associations with dementia and death remain underexplored. Aims: To explore the interactions between depressive symptoms and cognitive function, their developmental trajectories and the associations with all-cause dementia, Alzheimer's disease (AD) and all-cause death in older adults. Methods: Data were from the Health and Retirement Study. Depressive symptoms and cognitive function were measured using the 8-item Centre for Epidemiologic Studies Depression Scale and the Telephone Interview of Cognitive Status, respectively. All-cause dementia and AD were defined by self-reported or proxy-reported physician diagnoses. All-cause death was determined by interviews. The restricted cubic spline, group-based trajectory modelling and subdistribution hazard regression were used. Results: Significant interactions between depressive symptoms and cognitive function in 2010 in their association with new-onset all-cause dementia and AD from 2010 to 2020 were found, especially in women (p for interaction <0.05). Independent trajectory analysis showed that emerging or high (vs no) depressive trajectories and poor or rapidly decreased cognitive trajectories (vs very good) from 1996 to 2010 were at significantly higher risk of subsequent all-cause dementia, AD and all-cause death. 15 joint trajectories of depressive symptoms and cognitive function from 1996 to 2010 were determined, where rapidly decreased cognitive function was more common in those with no depressive symptoms. Compared with older adults with the trajectory of no depressive symptoms and very good cognitive function, those with the trajectory of no depressive symptoms but rapidly decreased cognitive function were much more likely to develop new-onset all-cause dementia and death, with subdistribution hazard ratios (95% confidence intervals) of 4.47 (2.99 to 6.67) and 1.84 (1.43 to 2.36), especially in women. Conclusions: To effectively mitigate the risk of dementia and death, it is crucial to acknowledge the importance of preventing cognitive decline in older adults without depressive symptoms, particularly in women.

Engineering nanosystems for transdermal delivery of antihypertensive drugs.

To control hypertension, long-term continuous antihypertensive therapeutics are required and five classes of antihypertensive drugs are frequently involved, including diuretics, ß-blockers, calcium channel blockers, angiotensin II receptor blockers, and angiotensin-converting enzyme inhibitors. Although with demonstrated clinical utility, there is still room for the improvement of many antihypertensive drugs in oral tablet or capsule dosage form, in terms of reducing systemic side effects and first-pass hepatic drug uptake. Meanwhile, nanocarrier-mediated transdermal drug delivery systems have emerged as a powerful tool for various disease treatments. With benefits such as promoting patient compliance for long-time administration, enhancing skin permeability, and reducing systemic side effects, these systems are reasonably investigated and developed for the transdermal delivery of multiple antihypertensive drugs. This review aims to summarize the literature relating to nanosystem-based transdermal antihypertensive drug delivery and update recent advances in this field, as well as briefly discuss the challenges and prospects of engineering transdermal delivery nanosystems for hypertension treatment.

A Link between Prenatal Stage of Life during the Great Chinese Famine and Subsequent Depressive Symptoms among Middle-Aged and Older Adults.

Prenatal malnutrition may increase the risk of depressive symptoms in adulthood. This study investigated the association between prenatal exposure to malnutrition with risk of depressive symptoms in middle-aged and older adults using the Chinese Great Famine of 1959-1961 as a natural experiment. Data were obtained from the China Health and Retirement Longitudinal Study baseline survey (2011). A total of 5391 individuals born from 1956 to 1965 were included in the study. Depressive symptoms were ascertained via the Center for Epidemiological Studies Depression Scale short form. Famine severity was measured using the cohort size shrinkage index. Difference-in-differences models were used to explore the association between prenatal famine exposure and later-life depressive symptoms. Compared with the post-famine cohort (1963-1965), famine cohorts (1959-1962) were 4.74 times (95% CI = 1.28-8.20) as likely to develop depressive symptoms. The stratified analysis found that prenatal exposure to famine was associated with depressive symptoms in rural residents but not those living in urban areas. In rural females, prenatal malnutrition was associated with a higher risk of depressive symptoms. However, there was no significant association between prenatal malnutrition and depressive symptoms in rural males. Our results indicated that prenatal malnutrition may contribute to a higher risk for depressive symptoms in later life among female rural residents.

Comparison Between High School Youth and College Freshmen Toward Their Psychological Disorders Under the Influence of Sleep Hygiene During COVID-19 Pandemic.

OBJECTIVE: Adolescents experience the critical period for physical and psychological growth. Few studies focus on the influence of sleep hygiene on the psychological health of adolescence aging from high school to freshmen year. Also, the influence from the COVID-19 pandemic has a public health significance. METHODS: A total of 698 students from high schools and colleges were included in the manuscript, and a cross-sectional procedure was conducted, objective to make an epidemiological comparison of the social phobia/depression prevalence, and discuss the effects of potential determinants. RESULTS: Psychological problems including social phobia and depression were prevalent especially among the high school students, with the female gender showing higher possibilities. Current results also indicated that the association between sleep status and the occurrence of social phobia is most obvious among high school students, while relatively higher MMR risks was found both for high school students showing symptoms of social phobia and college freshmen with depressive symptoms. Moreover, the interaction between social phobia and depression was obvious for both populations. CONCLUSIONS: Psychological problems including social phobia symptoms and depression are more prevalent among the high school females when compared with their male and freshemen peers. Sgnificant influencial factors for the risk of psychological problems among 2 populations are different, but media multitasking status should be paid attention to for both.

Phase Behavior of Ionic Liquid-Based Aqueous Two-Phase Systems.

As an environmentally friendly separation medium, the ionic liquid (IL)-based aqueous two-phase system (ATPS) is attracting long-term attention from a growing number of scientists and engineers. Phase equilibrium data of IL-based ATPSs are an important basis for the design and optimization of chemical reactions and separation processes involving ILs. This article provides the recent significant progress that has been made in the field and highlights the possible directions of future developments. The effects of each component (such as salting-out agents and ILs) on the phase behavior of IL-based ATPSs are summarized and discussed in detail. We mainly focus on the phase behavior of ATPSs by using ILs, expecting to provide meaningful and valuable information that may promote further research and application.

The signature based on seven genomic instability-related genes could predict the prognosis of acute myeloid leukemia patients.

BACKGROUND: Acute myeloid leukemia (AML) is the most common acute blood malignancy in adults. The complicated and dynamic genomic instability (GI) is the most prominent feature of AML. Our study aimed to explore the prognostic value of GI-related genes in AML patients. METHODS: The mRNA data and mutation data were downloaded from the TCGA and GEO databases. Differential expression analyses were completed in limma package. GO and KEGG functional enrichment was conducted using clusterProfiler function of R. Univariate Cox and LASSO Cox regression analyses were performed to screen key genes for Risk score model construction. Nomogram was built with rms package. RESULTS: We identified 114 DEGs between high TMB patients and low TMB AML patients, which were significantly enriched in 429 GO terms and 13 KEGG pathways. Based on the univariate Cox and LASSO Cox regression analyses, seven optimal genes were finally applied for Risk score model construction, including SELE, LGALS1, ITGAX, TMEM200A, SLC25A21, S100A4 and CRIP1. The Risk score could reliably predict the prognosis of AML patients. Age and Risk score were both independent prognostic indicators for AML, and the Nomogram based on them could also reliably predict the OS of AML patients. CONCLUSIONS: A prognostic signature based on seven GI-related genes and a predictive Nomogram for AML patients are finally successfully constructed.

Lymphocytes screening on admission is essential for predicting in-hospital clinical outcome in COVID-19 patients: A retrospective cohort study.

INTRODUCTION: We aimed to identify the associations between the lymphocytes (LYM) absolute count on admission and clinical outcomes in COVID-19 patients. METHODS: In this retrospective study, 224 COVID-19 patients who were admitted to General Hospital of Central Theater Command of the PLA from January 22 to April 4, 2020, were consecutively included. These patients were divided into the lymphopenia group and the nonlymphopenia group according to whether the LYM count on admission was below the normal range. RESULTS: During hospitalization, patients in the lymphopenia group have a much higher all-cause mortality (14.5% vs 0.0%; P < .001) and an evidently longer length of hospital stay (24.0 vs 17.5 days; P < .001) than patients in the nonlymphopenia group. The correlation analysis results indicated that the LYM count was negatively correlated with the values of NEU (R = -.2886, P < .001), PT (R = -.2312, P < .001), FIB (R = -.2954, P < .001), D-D (R = -.3554, P < .001), CRP (R = -.4899, P < .001), IL-6 (R = -.5459, P < .001), AST (R = -.2044, P < .01), Cr (R = -.1350, P < .05), CPK (R = -.2119, P < .01), CK-Mb (R = -.1760, P < .01), and LDH (R = -.4330, P < .001), and was positively correlated with the count of PLT (R = .2679, P < .001). In addition, LYM as a continuous variable was associated with 97% decreased risk of in-hospital mortality in the fully adjusted models (OR = 0.03, 95%CI, 0.00-0.37, P < .001). DISCUSSION: LYM screening on admission is a critical predictor for assessment of disease severity and clinical outcomes in patients with COVID-19, and lymphopenia substantially correlates with poor clinical outcomes.

Rethinking the Applications of Ionic Liquids and Deep Eutectic Solvents in Innovative Nano-Sorbents.

With the development of green chemistry and nano materials, new alternatives to traditional volatile solvents are one of many important hotspots in the field of nano materials. Ionic liquids (ILs) and deep eutectic solvents (DESs) as excellent alternative solvents are being applied in the innovation of nano-sorbents, including nanoparticles, nanogels, and nanofluid. ILs and DESs are often used as carriers/modifiers/dispersers of nano-sorbents to enhance the adsorption capacity and selectivity in the extraction procedure. Various extraction technologies, such as solid-phase extraction, solid-phase microextraction, micro-solid phase extraction, hollow fiber liquid phase microextraction, and magnetic solid-phase extraction, have also been promoted by them to achieve rapid development. This paper focused on the latest development of nano-sorbents based on ILs and DESs. The problems and bottlenecks encountered were analyzed in order to provide meaningful and valuable references for the related research and thus promote further development and application of alternative solvents-assisted nano-sorbents.

Recent advances in the enantioseparation promoted by ionic liquids and their resolution mechanisms.

More and more various chemical media are being applied in enantioseparation; among them, ionic liquids (ILs) have attracted the long-term attention in this decade as green designable solvents. This paper provides comprehensive overview for the applications of ILs in chiral extraction, gas chromatography, liquid chromatography, capillary electrophoresis and other techniques for enantioseparation. Additionally, the important resolution mechanisms based on ILs have also been summarized and discussed. This review focuses on the latest development of enantioseparation methods by using ILs in various modes, leading to meaningful and valuable information to related fields and thus promotes further research and application of reported methods.

Extraction in cholinium-based magnetic ionic liquid aqueous two-phase system for the determination of berberine hydrochloride in Rhizoma coptidis.

A magnetic ionic liquids (MILs)-based aqueous two-phase system (MIL-ATPs) obtained by mixing with a series of inorganic salts, which involves five cholinium MILs with the piperidinyloxy radical anion is reported for the first time. Phase diagrams for the new ATPs were experimentally determined at different temperatures (298.15-318.15 K) and the liquid-liquid equilibrium data for two-phase systems were correlated according to the empirical nonlinear expression. The effects of the types of MILs, temperature and inorganic salts on the binodal curve are discussed in detail. The MIL-ATPs coupled with HPLC-UV analysis was developed in the quantitation of berberine hydrochloride in Rhizoma coptidis. Under optimal conditions, the partition coefficient of berberine hydrochloride was 127.68 with the precision values (RSD%) of 1.40% and 2.83% for intra-day (n = 6) and inter-day (n = 3), respectively. The limit of detection (LOD) and limit of quantification (LOQ) for berberine hydrochloride were 0.023 mg L-1 and 0.077 mg L-1, respectively. The recoveries were obtained in the acceptable range of 97.4-101.2%. Moreover, the content of berberine hydrochloride in the raw material of Rhizoma coptidis was measured as 123.95 mg g-1 with this method. Finally, 99.8% MIL was recovered for cycle application after the removal of berberine hydrochloride by using D101 resin. This study provides a meaningful reference for the application of MIL-ATPs with great prospects.

Recent Research Progress in Natural Bioactive Constituents against Lipid Metabolic Diseases.

Lipid metabolic disorder refers to the dyslipidemia in the plasma. Abnormal working or lipid metabolism process leads to supernormal increase of one or multi kinds of lipids in plasma. It is a significant risk factor for many diseases and has become a serious danger to the mankind health. The clinical drugs adjusting lipid levels have a great variety in the market, side effects and adverse reactions. Meanwhile, many Chinese herbal medicines and natural medicines have the unnegligible role of regulating lipid metabolism, which become the research focus of medical workers in past decades. With advantages of fewer side effects, abundant resources and multi-target functions, terrestrial and marine bioactive constituents are proved as one of the important sources of the lead compounds in drug discovery and have been widely applied in the treatment and prevention of lipid metabolic diseases. In this paper, the recent advancements and current status of natural medicinal ingredients mainly based on lipid-lowering activities were reviewed in detail. Moreover, their bioactivity screening and important mechanisms in hyperlipemia progression were summarized and compared. It was also selectively introduced about related structural modification and new drug development on the basis of promising lead compounds. Finally, the current problems and possible prospects of natural constituents against lipid metabolism disorder in the future were discussed.

Online NIR Analysis and Prediction Model for Synthesis Process of Ethyl 2-Chloropropionate.

Online near-infrared spectroscopy was used as a process analysis technique in the synthesis of 2-chloropropionate for the first time. Then, the partial least squares regression (PLSR) quantitative model of the product solution concentration was established and optimized. Correlation coefficient (R (2)) of partial least squares regression (PLSR) calibration model was 0.9944, and the root mean square error of correction (RMSEC) was 0.018105 mol/L. These values of PLSR and RMSEC could prove that the quantitative calibration model had good performance. Moreover, the root mean square error of prediction (RMSEP) of validation set was 0.036429 mol/L. The results were very similar to those of offline gas chromatographic analysis, which could prove the method was valid.