Nanocarriers for gene delivery to the cardiovascular system.

Cardiovascular diseases have posed a great threat to human health. Fortunately, gene therapy holds great promise in the fight against cardiovascular disease (CVD). In gene therapy, it is necessary to select the appropriate carriers to deliver the genes to the target cells of the target organs. There are usually two types of carriers, viral carriers and non-viral carriers. However, problems such as high immunogenicity, inflammatory response, and limited loading capacity have arisen with the use of viral carriers. Therefore, scholars turned their attention to non-viral carriers. Among them, nanocarriers are highly valued because of their easy modification, targeting, and low toxicity. Despite the many successes of gene therapy in the treatment of human diseases, it is worth noting that there are still many problems to be solved in the field of gene therapy for the treatment of cardiovascular diseases. In this review, we give a brief introduction to the common nanocarriers and several common cardiovascular diseases (arteriosclerosis, myocardial infarction, myocardial hypertrophy). On this basis, the application of gene delivery nanocarriers in the treatment of these diseases is introduced in detail.

Host-derived peptide signals regulate Pseudomonas aeruginosa virulence stress via the ParRS and CprRS two-component systems.

Pseudomonas aeruginosa, a versatile bacterium, has dual significance because of its beneficial roles in environmental soil processes and its detrimental effects as a nosocomial pathogen that causes clinical infections. Understanding adaptability to environmental stress is essential. This investigation delves into the complex interplay of two-component system (TCS), specifically ParRS and CprRS, as P. aeruginosa interprets host signals and navigates stress challenges. In this study, through phenotypic and proteomic analyses, the nuanced contributions of ParRS and CprRS to the pathogenesis and resilience mechanisms were elucidated. Furthermore, the indispensable roles of the ParS and CprS extracellular sensor domains in orchestrating signal perception remain unknown. Structural revelations imply a remarkable convergence of TCS sensors in interacting with host peptides, suggesting evolutionary strategies for bacterial adaptation. This pioneering work not only established links between cationic antimicrobial peptide (CAMP) resistance-associated TCSs and virulence modulation in nosocomial bacteria, but also transcended conventional boundaries. These implications extend beyond clinical resistance, permeating into the realm of soil revitalization and environmental guardianship. As it unveils P. aeruginosa intricacies, this study assumes a mantle of guiding strategies to mitigate clinical hazards, harness environmental advantages, and propel sustainable solutions forward.

High-sensitivity silicon carbide divacancy-based temperature sensing.

Color centers in silicon carbide have become potentially versatile quantum sensors. Particularly, wide temperature-range temperature sensing has been realized in recent years. However, the sensitivity is limited due to the short dephasing time of the color centers. In this work, we developed a high-sensitivity silicon carbide divacancy-based thermometer using the thermal Carr-Purcell-Meiboom-Gill (TCPMG) method. First, the zero-field splitting D of the PL6 divacancy as a function of temperature was measured with a linear slope of -99.7 kHz K-1. The coherence times of TCPMG pulses linearly increased with the pulse number and the longest coherence time was about 21 µs, which was ten times higher than . The corresponding temperature-sensing sensitivity was 13.4 mK Hz-1/2, which was about 15 times higher than previous results. Finally, we monitored the laboratory temperature variations for 24 hours using the TCMPG pulse. The experiments pave the way for the application of silicon carbide-based high-sensitivity thermometers in the semiconductor industry, biology, and materials sciences.

Functional characterization of MdERF113 in apple.

The AP2/ERF family is an important class of transcription factors involved in plant growth and various biological processes. One of the AP2/ERF transcription factors, RAP2.6L, participates in various stresses responses. However, the function of RAP2.6L is largely unknown in apples (Malus domestica). In this study, an apple gene homologous to Arabidopsis AtRAP2.6L, MdERF113, was analyzed by bioinformatic characterization, gene expression analysis and subcellular localization assessment. MdERF113 was highly expressed in the sarcocarp and was responsive to hormonal signals and abiotic stresses. MdERF113-overexpression apple calli were less sensitive to low temperature, drought, salinity, and abscisic acid than wild-type. Subcellular localization revealed that MdERF113 was a nuclear-localized transcription factor, and yeast experiments confirmed that MdERF113 has no autonomous activation activity. Overall, this study indicated that MdERF113 plays a role in regulating plant growth under abiotic conditions.

Multicolor Circularly Polarized Photoluminescence and Electroluminescence with 1,2-Diaminecyclohexane Enantiomers.

Development of simple chiral materials with tunable circularly polarized photoluminescence (CPPL) and circularly polarized electroluminescence (CPEL) for efficient circularly polarized organic light-emitting diodes (CP-OLEDs) is the key toward future 3D displays. In this study, four pairs of chiral 1,2-diaminocyclohexane-based fluorescence enantiomers were efficiently prepared with high yields (up to 92%) and enantiomeric excesses (ee >99%). By the introduction of N-methyl, carbazole, and diphenylamine-donating groups, these materials showed multicolor CPPL and CPEL from blue (420 nm) to red (610 nm) with good thermal and conformational stability. The multilayer CP-OLEDs based on these enantiomers show high external quantum efficiency of up to 5.5% with low-efficiency roll-off and microimage circularly polarized electroluminescence with a dissymmetry factor (gEL) of up to -1.4 × 10-3/+1.3 × 10-3. These results push forward the development of future multicolor circularly polarized electroluminescent materials.

Application of Naphthylindole-Derived Phosphines as Organocatalysts in [4 + 1] Cyclizations of o-Quinone Methides with Morita-Baylis-Hillman Carbonates.

An organocatalytic [4 + 1] cyclization of o-QMs with MBH carbonates has been established using naphthylindole-derived phosphine (NIP) as an organocatalyst. By using this approach, a series of 2,3-dihydrobenzofuran derivatives have been synthesized in high yields and excellent diastereoselectivities (up to 99% yield, >95:5 dr). This reaction not only has established the first [4 + 1] cyclization of o-QMs with MBH carbonates but also represents the first application of naphthylindole-derived phosphines as organocatalysts in catalytic reactions. In addition, this reaction has also provided a useful method for constructing 2,3-dihydrobenzofuran scaffolds.

Bone Cement-Augmented Short-Segment Pedicle Screw Fixation for Kümmell Disease with Spinal Canal Stenosis.

BACKGROUND This study aimed to explore the feasibility and efficacy of bone cement-augmented short-segmental pedicle screw fixation in treating Kümmell disease. MATERIAL AND METHODS From June 2012 to June 2015, 18 patients with Kümmell disease with spinal canal stenosis were enrolled in this study. Each patient was treated with bone cement-augmented short-segment fixation and posterolateral bone grafting, and posterior decompression was performed when needed. All patients were followed up for 12-36 months. We retrospectively reviewed outcomes, including the Oswestry disability index (ODI), visual analog scale (VAS) score, anterior and posterior heights of fractured vertebrae, kyphotic Cobb angle, and neurological function by Frankel classification. RESULTS The VAS grades, ODI scores, anterior heights of affected vertebrae, and kyphotic Cobb angles showed statistically significant differences between pre- and postoperative and between preoperative and final follow-up values (P<0.05), whereas the differences between postoperative and final follow-up values were not statistically significant (P>0.05). The differences between posterior vertebral heights at each time point were not statistically significant (P>0.05). Improved neurological function was observed in 12 cases at final follow-up. Three cases had complications, including asymptomatic cement leakage in 2 patients and delayed wound infection in 1 patient. CONCLUSIONS Bone cement-augmented short-segment pedicle screw fixation is safe and effective for treating Kümmell disease, and can achieve satisfactory correction of kyphosis and vertebral height, with pain relief and improvement in neurological function, with few complications.

Catalytic Asymmetric Dearomative [3 + 2] Cycloaddition of Electron-Deficient Indoles with All-Carbon 1,3-Dipoles.

The first catalytic asymmetric dearomative [3 + 2] cycloaddition of 3-nitroindoles with vinylcyclopropanes has been established, which constructed chiral cyclopenta[b]indoline scaffolds in generally high enantioselectivities (up to 97% ee). This reaction also represents the first application of all-carbon 1,3-dipoles in catalytic asymmetric dearomative [3 + 2] cycloadditions of 3-nitroindoles. This approach will not only advance the catalytic asymmetric dearomatization reactions of electron-deficient indoles but also provide an efficient method for constructing chiral cyclopenta[b]indoline scaffolds.

Enantioselective Direct α-Arylation of Pyrazol-5-ones with 2-Indolylmethanols via Organo-Metal Cooperative Catalysis.

The first catalytic asymmetric α-arylation of pyrazol-5-ones has been established by using 2-indolylmethanols as direct electrophilic arylation reagents under the cooperative catalysis of Pd(0) and a chiral phosphoric acid, which afforded the α-arylation products of pyrazol-5-ones in generally high yields and good enantioselectivities (up to 99% yield, >99% ee).

Brønsted acid-catalyzed stereoselective [4+3] cycloadditions of ortho-hydroxybenzyl alcohols with N,N'-cyclic azomethine imines.

The first [4+3] cycloaddition of ortho-hydroxybenzyl alcohols has been established by making use of N,N'-cyclic azomethine imines as suitable 1,3-dipoles under Brønsted acid catalysis. By using this strategy, biologically important seven-membered heterocyclic scaffolds have been constructed in good yields and excellent diastereoselectivities (up to 92% yield, most >95 : 5 dr).

Organocatalytic chemo-, (E/Z)- and enantioselective formal alkenylation of indole-derived hydroxylactams using o-hydroxystyrenes as a source of alkenyl group.

The first organocatalytic asymmetric formal alkenylation of multicyclic alcohols using non-metal-based alkenes instead of alkenyl metals as a source of an alkenyl group has been established via chiral phosphoric acid catalyzed tandem reactions. This transformation directly assembles isoindolo-ß-carboline-derived hydroxylactams with o-hydroxystyrenes via an asymmetric cascade vinylogous addition/hydrogen elimination reaction sequence, offering an easy access to functionalized chiral isoindolo-ß-carbolines with one quaternary stereogenic center in high chemo-, (E/Z)-, and enantioselectivities (up to >95:5 cr, >95:5 E/Z, 97:3 er). This approach also represents the first catalytic asymmetric formal alkenylation of isoindolo-ß-carboline-derived hydroxylactams, which provides a useful strategy for functionalization of isoindolo-ß-carbolines and synthesis of chiral isoindolo-ß-carboline derivatives. In addition, the investigation on the activating mode revealed that the hydroxyl group in o-hydroxystyrene was essentially important for generating a hydrogen-bond interaction with the catalyst. The dual activation mode of hydrogen bond and ion pair between the catalyst and the substrates cooperatively facilitated the desired formal alkenylation reaction in a chemo- and stereoselective way.