Preparation of Chitosan Nanoparticles through a Readily Solvent-Exchange Process for Efficient and Enhanced Gene Delivery.

In view of the excellent prospects of gene therapy and the potential safety and immunogenicity issues challenged by viral vectors, it is of great significance to develop a nonviral vector with low toxicity and low cost. In this work, we report a chitosan nanoparticle (CSNP) to be used as a gene vector prepared through a facile solvent-exchange strategy. Chitosan is first dissolved in ionic liquid 1-ethyl-3-methylimidazolium acetate (EMIM Ac), and then, the solvent is exchanged with water/phosphate-buffered saline (PBS) to remove ionic liquid, forming a final CSNP dispersion after ultrasonication. The prepared CSNP shows a positive surface charge and can condense green fluorescent protein-encoding plasmid (pGFP) at weight ratios (CSNP/pGFP) of 5/1 or higher. Dynamic light scattering size and ζ-potential characterization and gel retardation results confirm the formation of CSNP/pGFP complexes. Compared with plain pGFP, efficient cellular internalization and significantly enhanced green fluorescent protein (GFP) expression are observed by using CSNP as a plasmid vector. Benefitting from the intrinsic biocompatibility, low cost, low immunogenicity, and abundant sources of chitosan, as well as the facile preparation and the efficient gene transfection capacity of CSNP, it is believed that this CSNP could be used as a nonviral gene vector with great clinical translational potentials.

Localized Sustained Release of Copper Enhances Antitumor Effects of Disulfiram in Head and Neck Cancer.

Drug repurposing uses approved drugs as candidate anticancer therapeutics, harnesses previous research and development efforts, and benefits from available clinically suitable formulations and evidence of patient tolerability. In this work, the drug used clinically to treat chronic alcoholism, disulfiram (DSF), was studied for its antitumor efficacy in a copper-dependent manner. The combination of DSF and copper could achieve a tumor cell growth inhibition effect comparable to those of 5-fluorouracil and taxol on head and neck cancer cells. Both bulk dendrimer hydrogel and microsized dendrimer hydrogel particles were utilized for the localized sustained release of copper in the tumor site. The localized sustained release of copper facilitated the tumor inhibition effect following intratumoral injection in a mouse's head and neck cancer model.

Dendritic Oligoethylenimine Decorated Liposome with Augmented Corneal Retention and Permeation for Efficient Topical Delivery of Antiglaucoma Drugs.

The topically administered glaucoma medications usually encounter serious precorneal drug loss and low corneal penetration, leading to a low bioavailability. In addition, due to the complexity of glaucoma etiology, a single medication is often insufficient. In this work, we report a novel dendritic oligoethylenimine decorated liposome for codelivery of two antiglaucoma drugs, latanoprost and timolol. The liposome showed a uniform nanoscopic particle size, positive surface charge, and excellent dual-drug loading capacity. A prolonged precorneal retention is observed by using this liposomal delivery system. This liposomal delivery system presents increased cellular uptake and tight junctions opening capacity, contributing respectively to the transcellular and paracellular permeation, thereby enhancing the trans-corneal transportation. Following topical administration of one eye drop in brown Norway rats, the dual-drug-loaded liposome formulation resulted in a sustained and effective intraocular pressure reduction as long as 5 days, without inducing ocular inflammation, discomfort, and tissue damage.

MCC950 Ameliorates Diabetic Muscle Atrophy in Mice by Inhibition of Pyroptosis and Its Synergistic Effect with Aerobic Exercise.

Diabetic muscle atrophy is an inflammation-related complication of type-2 diabetes mellitus (T2DM). Even though regular exercise prevents further deterioration of atrophic status, there is no effective mediator available for treatment and the underlying cellular mechanisms are less explored. In this study, we investigated the therapeutic potential of MCC950, a specific, small-molecule inhibitor of NLRP3, to treat pyroptosis and diabetic muscle atrophy in mice. Furthermore, we used MCC950 to intervene in the protective effects of aerobic exercise against muscle atrophy in diabetic mice. Blood and gastrocnemius muscle (GAS) samples were collected after 12 weeks of intervention and the atrophic state was assessed. We initially corroborated a diabetic muscle atrophy phenotype in db/db mice (D) by comparison with control m/m mice (W) by examining parameters such as fasting blood glucose (D vs. W: 24.47 ± 0.45 mmol L-1 vs. 4.26 ± 0.6 mmol L-1, p < 0.05), grip strength (D vs. W: 166.87 ± 15.19 g vs. 191.76 ± 14.13 g, p < 0.05), exercise time (D vs. W: 1082.38 ± 104.67 s vs. 1716 ± 168.55 s, p < 0.05) and exercise speed to exhaustion (D vs. W: 24.25 ± 2.12 m min-1 vs. 34.75 ± 2.66 m min-1, p < 0.05), GAS wet weight (D vs. W: 0.07 ± 0.01 g vs. 0.13 ± 0.01 g, p < 0.05), the ratio of GAS wet weight to body weight (D vs. W: 0.18 ± 0.01% vs. 0.54 ± 0.02%, p < 0.05), and muscle fiber cross-sectional area (FCSA) (D vs. W: 1875 ± 368.19 µm2 vs. 2747.83 ± 406.44 µm2, p < 0.05). We found that both MCC950 (10 mg kg-1) treatment and exercise improved the atrophic parameters that had deteriorated in the db/db mice, inhibited serum inflammatory markers and significantly attenuated pyroptosis in atrophic GAS. In addition, a combined MCC950 treatment with exercise (DEI) exhibited a further improvement in glucose uptake capacity and muscle performance. This combined treatment also improved the FCSA of GAS muscle indicated by Laminin immunofluorescence compared to the group with the inhibitor treatment alone (DI) (DEI vs. DI: 2597 ± 310.97 vs. 1974.67 ± 326.15 µm2, p < 0.05) or exercise only (DE) (DEI vs. DE: 2597 ± 310.97 vs. 2006.33 ± 263.468 µm2, p < 0.05). Intriguingly, the combination of MCC950 treatment and exercise significantly reduced NLRP3-mediated inflammatory factors such as cleaved-Caspase-1, GSDMD-N and prevented apoptosis and pyroptosis in atrophic GAS. These findings for the first time demonstrate that targeting NLRP3-mediated pyroptosis with MCC950 improves diabetic muscle homeostasis and muscle function. We also report that inhibiting pyroptosis by MCC950 can enhance the beneficial effects of aerobic exercise on diabetic muscle atrophy. Since T2DM and muscle atrophy are age-related diseases, the young mice used in the current study do not seem to fully reflect the characteristics of diabetic muscle atrophy. Considering the fragile nature of db/db mice and for the complete implementation of the exercise intervention, we used relatively young db/db mice and the atrophic state in the mice was thoroughly confirmed. Taken together, the current study comprehensively investigated the therapeutic effect of NLRP3-mediated pyroptosis inhibited by MCC950 on diabetic muscle mass, strength and exercise performance, as well as the synergistic effects of MCC950 and exercise intervention, therefore providing a novel strategy for the treatment of the disease.

Framework Nucleic Acids Enabled Pulmonary Artery Endothelial Cell Growth Inhibition by Targeting microRNA-152.

Pulmonary artery vascular endothelial dysfunction plays a pivotal role in the occurrence and progression of pulmonary vascular remodeling (PVR). To address this, aberrantly expressed non-coding microRNAs (miRNAs) are excellent therapeutic targets in human pulmonary artery endothelial cells (HPAECs). Here, we discovered and validated the overexpression of miRNA-152 in HPAECs under hypoxia and its role in endothelial cell dysfunction. We constructed a framework nucleic acid nanostructure that harbors six protruding single-stranded DNA segments that can fully hybridize with miRNA-152 (DNT-152). DNT-152 was efficiently taken up by HPAECs with increasing time and concentration; it markedly induced apoptosis, and inhibited HPAEC growth under hypoxic conditions. Mechanistically, DNT-152 silenced miRNA-152 expression and upregulated its target gene Meox2, which subsequently inhibited the AKT/mTOR signaling pathway. These results indicate that miRNA-152 in HPAECs may be an excellent therapeutic target against PVR, and that framework nucleic acids with carefully designed sequences are promising nanomedicines for noncancerous cells and diseases.

Revealing the Neuroimaging Mechanism of Acupuncture for Poststroke Aphasia: A Systematic Review.

Background: Aphasia is a common symptom in stroke patients, presenting with the impairment of spontaneous speech, repetition, naming, auditory comprehension, reading, and writing function. Multiple rehabilitation methods have been suggested for the recovery of poststroke aphasia, including medication treatment, behavioral therapy, and stimulation approach. Acupuncture has been proven to have a beneficial effect on improving speech functions in repetition, oral speech, reading, comprehension, and writing ability. Neuroimaging technology provides a visualized way to explore cerebral neural activity, which helps reveal the therapeutic effect of acupuncture therapy. In this systematic review, we aim to reveal and summarize the neuroimaging mechanism of acupuncture therapy on poststroke aphasia to provide the foundation for further study. Methods: Seven electronic databases were searched including PubMed, Web of Science, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, the Wanfang databases, and the Chinese Scientific Journal Database. After screening the studies according to the inclusion and exclusion criteria, we summarized the neuroimaging mechanism of acupuncture on poststroke aphasia, as well as the utilization of acupuncture therapy and the methodological characteristics. Result: After searching, 885 articles were retrieved. After removing the literature studies, animal studies, and case reports, 16 studies were included in the final analysis. For the acupuncture type, 10 studies used manual acupuncture and 5 studies used electroacupuncture, while body acupuncture (10 studies), scalp acupuncture (7 studies), and tongue acupuncture (8 studies) were applied for poststroke aphasia patients. Based on blood oxygen level-dependent (BOLD) and diffusion tensor imaging (DTI) technologies, 4 neuroimaging analysis methods were used including amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), seed-based analysis, and independent component analysis (ICA). Two studies reported the instant acupuncture effect, and 14 studies reported the constant acupuncture's effect on poststroke aphasia patients. 5 studies analyzed the correlation between the neuroimaging outcomes and the clinical language scales. Conclusion: In this systematic review, we found that the mechanism of acupuncture's effect might be associated with the activation and functional connectivity of language-related brain areas, such as brain areas around Broca's area and Wernicke's area in the left inferior temporal gyrus, supramarginal gyrus, middle frontal gyrus, and inferior frontal gyrus. However, these studies were still in the preliminary stage. Multicenter randomized controlled trials (RCT) with large sample sizes were needed to verify current evidence, as well as to explore deeply the neuroimaging mechanisms of acupuncture's effects.

Nano-in-Nano Dendrimer Gel Particles for Efficient Topical Delivery of Antiglaucoma Drugs into the Eye.

Low bioavailability of topically applied drugs remains a significant challenge for long-term glaucoma therapy. To enhance drug delivery efficiency, we developed dendrimer gel particles that collectively exhibit structural benefits of dendrimer, hydrogel, and particles, using the inverse emulsion method coupled with the highly efficient aza-Michael addition reaction (IEaMA). This hierarchical approach would maximize the utility of the structural features of existing ocular drug delivery systems. We have tested the delivery efficiency and efficacy of two first-line antiglaucoma drugs, brimonidine tartrate (BT) and timolol maleate (TM), which were loaded into dendrimer gel particles of various sizes, i.e., nDHP (nano-in-nano dendrimer hydrogel particles, ~200 nm), µDHP3 (3 µm), and µDHP10 (9 µm). We found that nDHP was superior to µDHP3 and µDHP10 in terms of cytocompatibility, degradability, drug release kinetics, and corneal permeability. The nDHPs increased drug corneal permeability by 17-fold compared to plain drug solution and enabled zero-order prolonged drug release kinetics. The nDHP-based formulation demonstrated pronounced IOP-lowering effects in both single-dose test and 7-day chronic daily dosing test in both Brown Norway rats and glaucoma mice. Taken together, we have developed nano-in-nano dendrimer gel particles for precise dosing and enabling sustained and synergistic efficacy of antiglaucoma drugs, which could be clinically impactful for improving glaucoma treatment.

Identifying novel biomarkers in hepatocellular carcinoma by weighted gene co-expression network analysis.

Hepatocellular carcinoma (HCC) is a highly malignant tumor found in the bile duct epithelial cells, and the second most common tumor of the liver. However, the pivotal roles of most molecules of tumorigenesis in HCC are still unclear. Hence, it is essential to detect the tumorigenic mechanism and develop novel prognostic biomarkers for clinical application. The data of HCC mRNA-seq and clinical information from The Cancer Genome Atlas (TCGA) database were analyzed by weighted gene co-expression network analysis (WGCNA). Co-expression modules and clinical traits were constructed by the Pearson correlation analysis, interesting modules were selected and gene ontology and pathway enrichment analysis were performed. Intramodule analysis and protein-protein interaction construction of selected modules were conducted to screen hub genes. In addition, upstream transcription factors and microRNAs of hub genes were predicted by miRecords and NetworkAnalyst database. Afterward, a high connectivity degree of hub genes from two networks was picked out to perform the differential expression validation in the Gene Expression Profiling Interactive Analysis database and Human Protein Atlas database and survival analysis in Kaplan-Meier plotter online tool. By utilizing WGCNA, several hub genes that regulate the mechanism of tumorigenesis in HCC were identified, which was associated with clinical traits including the pathological stage, histological grade, and liver function. Surprisingly, ZWINT, CENPA, RACGAP1, PLK1, NCAPG, OIP5, CDCA8, PRC1, and CDK1 were identified statistically as hub genes in the blue module, which were closely implicated in pathological T stage and histologic grade of HCC. Moreover, these genes also were strongly associated with the HCC cell growth and division. Network and survival analyses found that nine hub genes may be considered theoretically as indicators to predict the prognosis of patients with HCC or clinical treatment target, it will be necessary for basic experiments and large-scale cohort studies to validate further.

Weighted gene coexpression network analysis reveals hub genes involved in cholangiocarcinoma progression and prognosis.

AIM: Cholangiocarcinoma (CCA) is a highly malignant tumor found in the bile duct epithelial cells, and the second most common primary tumor of the liver. However, the pivotal roles of molecular biomarkers in oncogenesis of CCA are unclear. Therefore, we aim to explore the underlying mechanisms of progression and screen for novel prognostic biomarkers and treatment targets. METHOD: The data of mRNA sequencing and clinical information of CCA patients in The Cancer Genome Atlas was analyzed by weighted gene coexpression network analysis (WGCNA). Modules and clinical traits were constructed according to Pearson's correlation analysis, and Gene Ontology and pathway enrichment analysis were applied. Hub genes of these modules were screened by intramodule analysis; Cytoscape with Search Tool for the Retrieval of Interacting Genes was utilized to visualize protein-protein interaction of these modules; hub genes of these modules were validated afterwards. Furthermore, the significance of these genes was confirmed by survival analysis. RESULTS: Genes MRPS18A, CST1, and SCP2 were identified as candidate genes in the module, which was associated with clinical traits including pathological stage, histological grade, and liver function and which also affected overall survival of CCA patients. Nineteen hub genes were analyzed together and were associated with progression and prognosis of CCA. Survival analyses found that several of the multiple genes could serve as biomarkers to stratify CCA patients into low- and high-risk groups. CONCLUSION: These candidate genes could be involved in progression of CCA, which could serve as novel prognostic markers and treatment targets. Moreover, most of them were first reported in CCA and deserve further research.

Probing Laser-Induced Heterogeneous Microenvironment Changes in Room-Temperature Ionic Liquids.

Modulating the heterogeneous microenvironment in room-temperature ionic liquids (RTILs) by external stimuli is an important approach for understanding and designing external field-induced chemical reactions in natural and applied systems. Here, we report for the first time the redistribution of oxygen molecules related to microstructure changes in RTILs induced by an external laser field, which is probed simultaneously by the triplet-state dynamics of porphyrin. A remarkably long-lived triplet state of porphyrin is observed with changes of microstructures after irradiation, suggesting that charge-shifted O2 molecules are induced by the external field and/or rearranged intrinsic ions move from nonpolar domains into the polar domains of RTILs through electrostatic interactions. The results suggest that heterogeneous systems like ionic liquids in the presence of external stimuli can be designed for reaction systems associated with not only O2 but also for CO2 , CS2 , etc. and many other similar solvent molecules for many promising applications.

Morphological Evolution of Self-Assembled Structures Induced by the Molecular Architecture of Supra-Amphiphiles.

A series of telechelic supramolecular amphiphiles [POSS-Azo8@(ß-CD-PDMAEMA)1→8] was accomplished by orthogonally coupling the multiarm host polymer ß-cyclodextrin-poly(dimethylaminoethyl methacrylate) (ß-CD-PDMAEMA) with an octatelechelic guest molecule azobenzene modified-polyhedral oligomeric silsesquioxanes (POSS-Azo8) under different host-guest ratios. These telechelic supramolecular amphiphiles possess a rigid core and flexible corona. Increasing the multiarm host polymer coupled onto the rigid POSS core made the molecular architecture tend to be symmetrical and spherical. POSS-Azo8@[ß-CD-PDMAEMA]1→8 could self-assemble into diverse morphologies evolving from spherical micelles, wormlike micelles, and branched aggregates to bowl-shaped vesicles. Distinct from the traditional linear amphiphilic polymers, we discovered that the self-assembly of POSS-Azo8@[ß-CD-PDMAEMA]1→8 was dominantly regulated by their molecular architectures instead of hydrophilicity, which has also been verified using computer simulation results.

Solubilization of chitosan in biologically relevant solvents by a low-temperature solvent-exchange method for developing biocompatible chitosan materials.

Chitosan has great potential for biomedical applications. However, the intractable solubility of chitosan is a major bottleneck hampering its utilization. In this work, we report a low-temperature solvent-exchange method to solubilize chitosan in biologically relevant solvents (bio-solvents) including water, salines, and cell culture media. Chitosan was firstly dissolved in ionic liquid (IL) 1-ethyl-3-methylimidazolium acetate (EMIM Ac). The chitosan/IL solution was then dialyzed against bio-solvents at 4 °C, during which a solvent exchange process took place. At the end of 24 h dialysis, aqueous chitosan pseudosolutions formed. Low temperature is found to be crucial for efficient solubilization of chitosan during the solvent exchange process. Increasing temperature to 50 °C leads to the formation of solid chitosan hydrogel. Chitosan in the water-based pseudosolution presents as positively charged particles. The pseudosolution shows a high positive zeta potential of about +52.6 mV and good colloidal stability. The water-based pseudosolutions with different amounts of chitosan contents exhibit the rheological features of weak liquid gels. By using these pseudosolutions, the fabrication of various chitosan materials is realized readily. Both chitosan pseudosolution and its downstream products are highly biocompatible. In this strategy, using IL as a solvent-medium and processing a low-temperature solvent exchange are the two key parameters to solubilize chitosan.

The mechanistic effects of acupuncture in rodent neurodegenerative disease models: a literature review.

Neurodegenerative diseases refer to a battery of medical conditions that affect the survival and function of neurons in the brain, which are mainly presented with progressive loss of cognitive and/or motor function. Acupuncture showed benign effects in improving neurological deficits, especially on movement and cognitive function impairment. Here, we reviewed the therapeutic mechanisms of acupuncture at the neural circuit level in movement and cognition disorders, summarizing the influence of acupuncture in the dopaminergic system, glutamatergic system, γ-amino butyric acid-ergic (GABAergic) system, serotonergic system, cholinergic system, and glial cells at the circuit and synaptic levels. These findings can provide targets for clinical treatment and perspectives for further studies.

Manipulating hyperbolic transient plasmons in a layered semiconductor.

Anisotropic materials with oppositely signed dielectric tensors support hyperbolic polaritons, displaying enhanced electromagnetic localization and directional energy flow. However, the most reported hyperbolic phonon polaritons are difficult to apply for active electro-optical modulations and optoelectronic devices. Here, we report a dynamic topological plasmonic dispersion transition in black phosphorus via photo-induced carrier injection, i.e., transforming the iso-frequency contour from a pristine ellipsoid to a non-equilibrium hyperboloid. Our work also demonstrates the peculiar transient plasmonic properties of the studied layered semiconductor, such as the ultrafast transition, low propagation losses, efficient optical emission from the black phosphorus's edges, and the characterization of different transient plasmon modes. Our results may be relevant for the development of future optoelectronic applications.

Effect of Acupuncture vs Sham Acupuncture on Patients With Poststroke Motor Aphasia: A Randomized Clinical Trial.

Importance: Motor aphasia is common among patients with stroke. Acupuncture is recommended as an alternative therapy for poststroke aphasia, but its efficacy remains uncertain. Objective: To investigate the effects of acupuncture on language function, neurological function, and quality of life in patients with poststroke motor aphasia. Design, Setting, and Participants: This multicenter, sham-controlled, randomized clinical trial was conducted in 3 tertiary hospitals in China from October 21, 2019, to November 13, 2021. Adult patients with poststroke motor aphasia were enrolled. Data analysis was performed from February to April 2023. Interventions: Eligible participants were randomly allocated (1:1) to manual acupuncture (MA) or sham acupuncture (SA) groups. Both groups underwent language training and conventional treatments. Main Outcomes and Measures: The primary outcomes were the aphasia quotient (AQ) of the Western Aphasia Battery (WAB) and scores on the Chinese Functional Communication Profile (CFCP) at 6 weeks. Secondary outcomes included WAB subitems, Boston Diagnostic Aphasia Examination, National Institutes of Health Stroke Scale, Stroke-Specific Quality of Life Scale, Stroke and Aphasia Quality of Life Scale-39, and Health Scale of Traditional Chinese Medicine scores at 6 weeks and 6 months after onset. All statistical analyses were performed according to the intention-to-treat principle. Results: Among 252 randomized patients (198 men [78.6%]; mean [SD] age, 60.7 [7.5] years), 231 were included in the modified intention-to-treat analysis (115 in the MA group and 116 in the SA group). Compared with the SA group, the MA group had significant increases in AQ (difference, 7.99 points; 95% CI, 3.42-12.55 points; P = .001) and CFCP (difference, 23.51 points; 95% CI, 11.10-35.93 points; P < .001) scores at week 6 and showed significant improvements in AQ (difference, 10.34; 95% CI, 5.75-14.93; P < .001) and CFCP (difference, 27.43; 95% CI, 14.75-40.10; P < .001) scores at the end of follow-up. Conclusions and Relevance: In this randomized clinical trial, patients with poststroke motor aphasia who received 6 weeks of MA compared with those who received SA demonstrated statistically significant improvements in language function, quality of life, and neurological impairment from week 6 of treatment to the end of follow-up at 6 months after onset. Trial Registration: Chinese Clinical Trial Registry: ChiCTR1900026740.

Acupuncture for insomnia symptoms in hypertensive patients: a systematic review and meta-analysis.

Purpose: In the realm of pain management, traditional Chinese medicine, specifically acupuncture, has garnered increasing attention. This meta-analysis pioneers the evaluation of acupuncture's effectiveness in treating insomnia among hypertensive patients. Methods: We conducted a comprehensive search across several databases-PubMed, Web of Science, Cochrane Library, WANFANG, China National Knowledge Infrastructure (CNKI), Sinomed, and the Chinese Journal of Science and Technology (VIP). Additionally, forward and backward articles of studies published from the inception of these databases until 10 September 2023, were reviewed. This systematic review and meta-analysis included all randomized controlled trials (RCTs) focusing on acupuncture for insomnia in hypertensive patients, without imposing language or date restrictions. We rigorously assessed all outcome measures reported in these trials. The evidence was synthesized by calculating the difference between mean differences (MD) in symptom change. The quality of the evidence was determined using the Cochrane Risk of Bias tool. This study is registered with PROSPERO under number CRD42023461760. Results: Our analysis included 16 RCTs, comprising 1,309 patients. The findings revealed that acupuncture was significantly more effective than the control group in reducing insomnia symptoms, as indicated by a greater decrease in the PSQI score (MD = -3.1, 95% CI [-3.77 to -2.62], p < 0.00001). Additionally, improvements in both systolic and diastolic blood pressure were more pronounced in the acupuncture group compared to the control group (SBP: MD = -10.31, 95% CI [-16.98 to -3.64], p = 0.002; DBP: MD = -5.71, 95% CI [-8.19 to -3.23], p < 0.00001). These results suggest that acupuncture not only improves sleep quality but also lowers blood pressure in patients suffering from hypertension and insomnia. Further research is warranted to elucidate optimal acupuncture points and the duration of treatment for maximized therapeutic effect.Systematic review registration:https://www.crd.york.ac.uk/prospero, CRD42023461760.

Unraveling heterogeneous microviscosities of the 1-alkyl-3-methylimidazolium hexafluorophosphate ionic liquids with different chain lengths.

The rotational dynamics of coumarin 153 (C153) have been investigated in a series of 1-alkyl-3-methylimidazolium hexafluorophosphate ionic liquids with different alkyl chain lengths (alkyl = butyl, pentyl, hexyl, heptyl, octyl) ([Cnmim][PF6], n = 4-8) to examine the alkyl chain length dependent local viscosity of the microenvironment surrounding the probe molecules. The excimer-to-monomer fluorescence emission intensity ratio (IE/IM) of a well-known microviscosity probe, 1,3-bis(1-pyrenyl)propane (BPP), is also employed to study the microviscosity of [Cnmim][PF6] as a complementary measurement. The rotational dynamics of C153 show that at a certain length of the alkyl chain there are incompact and compact domains within [Cnmim][PF6], resulting in fast and slow components of C153 rotational dynamics. The microviscosities in different structural domains of [Cnmim][PF6] with different alkyl chain lengths are investigated by studying the fluorescence anisotropy decay of probe molecules. The obtained average rotation time constants show that with an increase in the length of the alkyl chain, the microviscosity of [Cnmim][PF6] is obviously increased first and then slightly decreased. The steady state fluorescence measurements with the microviscosity probe of BPP further prove that the microviscosity is not increased as much as expected when ionic liquids [Cnmim][PF6] have a relatively long alkyl chain. The different heterogeneous structures of [Cnmim][PF6] with different lengths of the alkyl chain are proposed to interpret the unusual microviscosity behaviors.

Excited state dynamics of ß-carotene studied by means of transient absorption spectroscopy and multivariate curve resolution alternating least-squares analysis.

Determination of the excited-state dynamics of carotenoids has attracted considerable interest, engendering a number of controversial hypotheses because of the strongly overlapping spectral peaks and complicated dynamics of transient species. In the present work, aiming for better understanding the complexity of excited-state processes in carotenoids, excited-state dynamics of all-trans-ß-carotene in ethanol was investigated by femtosecond pump-probe spectroscopy. Following the excitation of the strongly allowed S2 state of the ß-carotene, transient absorption spectra were recorded in the visible spectral range. For comparison, the time-resolved transient absorption spectra are analyzed in a conventional way, fitting kinetic traces with a multi-exponential function at chosen wavelengths from obtained spectra, and then again by means of the soft-modeling multivariate curve resolution alternating least-squares analysis (MCR-ALS) method for modeling pure profiles and the generalized two-dimensional (2D) correlation spectroscopy data analysis for providing additional information on the dynamics of spectral features. MCR-ALS analysis shows that both the dynamics of the S* state, identified using the 2D correlation spectra, and the S1 state develop on a different timescale than the relaxation of the vibrationally hot S1v' state. Hot S1v' and S* states are shown to have different species associated difference spectra. Results of our analysis indicate that the S* state observed in this work is not the hot S1v' state but instead a separate singlet state.

Dendrimer and dendrimer gel-derived drug delivery systems: Breaking bottlenecks of topical administration of glaucoma medications.

Due to high structural flexibility, multidrug carrying capability, and tunable size, dendrimers have been used as suitable carriers for ophthalmic drug delivery. Drug molecules can be either encapsulated or chemically coupled to dendrimers. The nanoscopic size, spheroidal shape, and cationic surface of polyamidoamine (PAMAM) dendrimers promote their interaction with the cornea and result in prolonged precorneal retention. Dendrimers could be further cross-linked to produce three-dimensional hydrogel networks or dendrimer hydrogels (DH). The properties of the DH can be readily adjusted to maintain both fluidity and adhesiveness, making them suitable for developing topical ocular drug formulations. Micro-/nano-sized DHs, that is, dendrimer micro-/nano-gels, have unique properties such as ease of administration, large specific surface area for adhesion, and drug targeting functionalities, making them attractive for ophthalmic drug delivery. This perspective reports advances in PAMAM dendrimer based drug delivery systems including drug conjugates and micro- and nano-gels to enhance and sustain the delivery of multiple anti-glaucoma drugs, Dendrimer and dendrimer gel-derived drug delivery systems hold great potential as multifunctional topical drug delivery systems for the eye.

Prospective observational studies on nutrition intake and the incidence of cognitive impairment in middle-aged and older adults: A protocol for systematic review and meta-analysis.

INTRODUCTION: According to several studies, a specific dietary pattern can reduce the risk of dementia and cognitive impairment. However, the robustness of these results has not been tested. The study intends to investigate the association between nutrition intake and cognitive impairment in middle-aged and older adults (≥45-years) and provide reliable, evidence-based references for healthcare decision-makers, researchers, and policymakers. REVIEW QUESTION: Are the dietary characteristics of community-dwelling adults (≥45-years) associated with the occurrence of cognitive impairment? OBJECTIVES: The primary objective of this protocol is to synthesize the longitudinal observational evidence on the relationship between nutrition intake patterns and the incidence of cognitive impairment in middle-aged and older adults (≥45-years), and to provide detailed dietary recommendations for the prevention of cognitive impairment in this population. METHODS AND ANALYSIS: Cohort studies conducted among adults (≥45-years) will be included. The following electronic databases will be searched for relevant records published by July 2023, with a restriction on language to English: Pubmed, Medline, Embase, Web of science, Cochrane Library. The studies will be selected, the data will be extracted, and the bias risk will be assessed by two independent investigators. The Meta-analysis of Observational Studies in Epidemiology guidelines will be followed to summarize observational studies, and the protocol will adhere to the recommendations from the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 statement. Endnote X9 will be used to manage data screening. We will use Review Manager 5.4 and Stata 16.0 to conduct data analysis, and a random-effects model will be applied to pool clinically homogenous studies. The results will be presented based on the form of nutrition intake. For assessing publication bias, Egger's test and visual inspection of funnel plots will be utilized. ETHICS AND DISSEMINATION: As this study does not involve primary data, ethical approval is not required. The final report will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: A registration number of DOI 10.17605/OSF.IO/NAKC3 was assigned to it on October 15, 2022 on Prospero.