Bioinspired Wearable Hydrogel Composite with Sustained Drug-Release for Wound Healing and Naked-Eye Visual Early Warning of Wound Dehiscence.

Wound healing is critical to the structural and functional restoration of damaged tissue. However, effective wound closure and healing are always great challenges in regenerative engineering. This study provided bioinspired wearable hydrogel composites with drug-releasing hydrogel and nonclose-packed photonic crystals (NPCs) for wound therapy and naked-eye visual early warning of wound dehiscence. Molecular dynamics models and drug-releasing results illustrated the sustained drug release of ibuprofen, and the mechanical properties of the drug-releasing hydrogel were optimized with 1410% tensile strain by introducing fish collagen; their biocompatibility and adhesion were also improved. The structural color of the NPCs blue-shifted from 630 to 500 nm with 15.0% strain, and the original color was customized with poly(methyl methacrylate) (PMMA) concentration and acrylamide content. Compared with the gauze and the traditional hydrogels, the composite provided a moist environment and an effectively closed wound; the debridement and released drug avoided inflammation, and the rat wound was healed 40.5% on the third day and essentially 100% on the 14th day. The work provided a novel strategy for wound healing and naked-eye visual early warning when a wound deforms, which is expected to promote the synergistic development of clinical treatment and visualized early warning.

Comparison of mistakes on multiple-choice question and fill-in-the-blank examinations: A retrospective analysis.

OBJECTIVE: The objective was to compare the average number of mistakes made on multiple-choice (MCQ) and fill-in-the-blank (FIB) questions in anatomy lab exams. METHODS: The study was conducted retrospectively; every exam had both MCQs and FIBs. The study cohorts were divided into 3 tiers based on the number and percentage of mistakes in answering sheets: low (21-32, >40%), middle (11-20, 40%-20%), and high (1-9, <20%) tiers. The study used an independent 2-sample t test to compare the number of mistakes between MCQs and FIBs overall and per tier and a 1-way analysis of variance to compare the number of mistakes in both formats across the 3 tiers. RESULTS: The results show that there was a significant difference in the number of mistakes between the 2 formats overall with more mistakes found on FIBs (p < .001). The number of mistakes made in the high and middle tiers had a statistical difference, being higher on MCQs (p < .001). There was no significant difference in the number of mistakes made in the low tier between formats (p > .05). Furthermore, the study found significant differences in the number of mistakes made on MCQs and FIBs across the 3 tiers, being highest in the low-tier group (p < .001). CONCLUSION: There were fewer mistakes on the MCQ than the FIB format in exams. It also suggests that, in the low tier answering sheets, both formats could be used to identify students at academic risk who need more attention.

Effect of unproctored versus proctored examinations on student performance and long-term retention of knowledge.

OBJECTIVE: To compare unproctored and proctored online exams among chiropractic students. METHODS: Pre-existing data of 234 students across 4 consecutive endocrinology classes were analyzed for this study. The course was comprised of 3 lectures (50 minutes per lecture) each week. Student performance was evaluated by midterm exam and summative exam (S1). The students from 3 classes were asked to take a voluntary second summative exam (S2) approximately 7 months after the S1. Since this study was partially conducted during the COVID pandemic, some classes took the midterm and the S1 proctored in the classroom while others took them unproctored from a remote location. RESULTS: The mean midterm exam (p < .001) and S1 scores (p = .01) for the unproctored group (93.6 ± 7.0 and 88.8 ± 8.2) were significantly higher than the proctored group (88.1 ± 8.2 and 83.9 ± 11.2). The mean time taken by students was much greater for the unproctored exams than for the proctored exams (midterm: 40.7 ± 10.2 versus 16.7 ± 7.0, p < .001; S1: 47.0 ± 8.7 versus 21.5 ± 9.0, p < .001). By contrast, the mean unproctored S2 scores were lower than the proctored group (60.2 ± 14.7 versus 88.1 ± 8.2, p < .001). A linear regression test showed that the final exam was a statistically significant predictor of the recall exam (p < .01, R2 = 28.3%). CONCLUSION: The findings suggest that student performance is significantly altered by test format.

Bio-Inspired Photoelectric Dual-Mode Sensor Based on Photonic Crystals for Human Motion Sensing and Monitoring.

Photoelectric dual-mode sensors, which respond to strain signal through photoelectric dual-signals, hold great promise as wearable sensors in human motion monitoring. In this work, a photoelectric dual-mode sensor based on photonic crystals hydrogel was developed for human joint motion detection. The optical signal of the sensor originated from the structural color of photonic crystals, which was achieved by tuning the polymethyl methacrylate (PMMA) microspheres diameter. The reflective peak of the sensor, based on 250 nm PMMA PCs, shifted from 623 nm to 492 nm with 100% strain. Graphene was employed to enhance the electrical signal of the sensor, resulting in a conductivity increase from 9.33 × 10-4 S/m to 2 × 10-3 S/m with an increase in graphene from 0 to 8 mg·mL-1. Concurrently, the resistance of the hydrogel with 8 mg·mL-1 graphene increased from 160 kΩ to 485 kΩ with a gauge factor (GF) = 0.02 under 100% strain, while maintaining a good cyclic stability. The results of the sensing and monitoring of finger joint bending revealed a significant shift in the reflective peak of the photoelectric dual-mode sensor from 624 nm to 526 nm. Additionally, its resistance change rate was measured at 1.72 with a 90° bending angle. These findings suggest that the photoelectric dual-mode sensor had the capability to detect the strain signal with photoelectric dual-mode signals, and indicates its great potential for the sensing and monitoring of joint motion.

A PDMS-encapsulated cylindrical non-closed-packed photonic crystals composite with Bragg-enhanced Fresnel reflectance for optical gain and spectral selection.

According to the Fresnel theory, the reflectivity intensity of spherical and cylindrical convex surfaces decreases from their edge to center, and it is noteworthy and interesting for optical gain to study the enhancement of center reflectance. In this paper, a polydimethylsiloxane (PDMS) - encapsulated cylindrical non-closed-packed photonic crystals (NPCs) composite with Bragg-enhanced Fresnel reflectance was designed for spectral selectivity and optical gain. Theoretically and experimentally, the periodically ordered structure of NPCs achieved high-reflection of light in photonic bandgap and high-transmission in other bands, which enhanced Fresnel reflectivity of the convex center to specific bands. Furtherly, the cylindrical NPCs hydrogel with stretchability was applied for the dynamic tuning of optical signals. The reflection peak of the PDMS-encapsulated cylindrical NPCs composite blue-shifted from 608 nm to 413 nm with 50 % tensile strain and achieved a rapid transition of structural color from orange to blue-violet in 60 cycles. The new kind of photonic crystals composite for optical gain and spectral selection broke through the limitations of traditional Fresnel curved mirrors with the lowest central reflectivity and inability to perform spectral selectivity, and have great significance and application prospects in fields of signal transmission, optical measurement, and instrument design.

Polycationic Open-Shell Cyclophanes: Synthesis of Electron-Rich Chiral Macrocycles, and Redox-Dependent Electronic States.

π-Conjugated chiral nanorings with intriguing electronic structures and chiroptical properties have attracted considerable interests in synthetic chemistry and materials science. We present the design principles to access new chiral macrocycles (1 and 2) that are essentially built on the key components of main-group electron-donating carbazolyl moieties or the π-expanded aza[7]helicenes. Both macrocycles show the unique molecular conformations with a (quasi) figure-of-eight topology as a result of the conjugation patterns of 2,2',7,7'-spirobifluorenyl in 1 and triarylamine-coupled aza[7]helicene-based building blocks in 2. This electronic nature of redox-active, carbazole-rich backbones enabled these macrocycles to be readily oxidized chemically and electrochemically, leading to the sequential production of a series of positively charged polycationic open-shell cyclophanes. Their redox-dependent electronic states of the resulting multispin polyradicals have been characterized by VT-ESR, UV/Vis-NIR absorption and spectroelectrochemical measurements. The singlet (ΔES-T=-1.29 kcal mol-1) and a nearly degenerate singlet-triplet ground state (ΔES-T(calcd)=-0.15 kcal mol-1 and ΔES-T(exp)=0.01 kcal mol-1) were proved for diradical dications 12+2⋅ and 22+2⋅, respectively. Our work provides an experimental proof for the construction of electron-donating new chiral nanorings, and more importantly for highly charged polyradicals with potential applications in chirospintronics and organic conductors.

Naked-Eye Visual Thermometer Based on Glycerol─Nonclose-Packed Photonic Crystals for Real-Time Temperature Sensing and Monitoring.

Real-time sensing and monitoring of temperature are of great significance for assessing human health. The sensitivity and stability are inevitable issues for thermometers. In this study, a thermometer with the cylindrical thermochromic hydrogel was prepared for real-time visual monitoring of temperature, which had excellent temperature sensitivity, angle-independence axially, and environmental stability. The customization of their initial optical properties depended on the PMMA concentrations and the content of the hydrogel monomer. The glycerol introduced with solvent displacement formed hydrogen bonds with the hydrogel network, which stabilized their mechanical properties, and the reflection peak blue-shifted from 653 to 499 nm when tensile strain was 57.85%. At the same time, the environmental stability originated from the moisturizing properties of the glycerol, which enabled the hydrogel to reliably transmit the information on temperature into the air without losing moisture. The reflection peak of the cylindrical thermochromic hydrogel shifted from 657 to 455 nm when the temperature increased from 22 to 45 °C, which realized temperature visual monitoring in the full-color range. The temperature sensitivity of the glycerol─nonclose-packed photonic crystals remained stable for 1 month, which provided an optimal option for continuous visual temperature monitoring.

Synthesis of π-Conjugated Chiral Aza/Boracyclophanes with a meta and para Substitution.

We herein describe the synthesis of a new class of axially chiral aza/boracyclophanes (BDN1, BXN1, BDB1 and BXB1) using binaphthyls as chiral building blocks and the main-group (B/N) chemistry with tunable electronic effects. All macrocycles substituted with triarylamine donors or triarylborane acceptors are strongly luminescent. These macrocycles showed two distinct meta and para π-conjugation pathways, leading to the formation of quasi figure-of-eight and square-shaped conformations. Interestingly, comparison of such structural models revealed that the former type of macrocycles BXN1 and BXB1 gave higher racemization barriers relative to the other ones. The results reported here may provide a new approach to engineer the optical stability of π-conjugated chiral macrocycles by controlling π-substitution patterns. The ring constraints induced by macrocyclization were also demonstrated to contribute to the configurational persistence as compared with the open-chain analogues p-BTT and m-BTT.

Chiral Luminescent Aza[7]helicenes Functionalized with a Triarylborane Acceptor and Near-Infrared-Emissive Doublet-State Radicals.

This paper presents new chiral luminescent molecules (N7-BMes2 and N7-TTM) using configurationally stable aza[7]helicene (1) as a universal heteroatom-doped chiral scaffold. The respective reactions of electron-donating 1 with a triarylborane acceptor via palladium-catalyzed Buchwald-Hartwig C-N coupling and with the open-shell doublet-state TTM radical via nucleophilic aromatic substitution (SN2Ar) resulted not only in tunable emissions from blue to the NIR domain but also in significantly enhanced emission quantum efficiency up to Φ = 50%.

Synthesis of π-Conjugated Chiral Organoborane Macrocycles with Blue to Near-Infrared Emissions and the Diradical Character of Cations.

Highly emissive π-conjugated macrocycles with tunable circularly polarized luminescence (CPL) have sparked theoretical and synthetic interests in recent years. Herein, we report a synthetic approach to obtain new chiral organoborane macrocycles (CMC1, CMC2, and CMC3) that are built on the structurally chiral [5]helicenes and highly luminescent triarylborane/amine moieties embedded into the cyclic systems. These rarely accessible B/N-doped main-group chiral macrocycles show a unique topology dependence of the optoelectronic and chiroptical properties. CMC1 and CMC2 show a higher luminescence dissymmetry factor (glum) together with an enhanced CPL brightness (BCPL) as compared with CMC3. Electronic effects were also tuned and resulted in bathochromic shifts of their emission and CPL responses from blue for CMC1 to the near-infrared (NIR) region for CMC3. Furthermore, chemical oxidations of the N donor sites in CMC1 gave rise to a highly stable radical cation (CMC1·+SbF6-) and diradical dication species (CMC12·2+2SbF6-) that serve as a rare example of a positively charged open-shell chiral macrocycle.

Identification of a Cryptic Binding Site in CRISPR-Cas9 for Targeted Inhibition.

The need for precision control of CRISPR-Cas9 genome editing has created a demand for anti-CRISPR molecules. Recently, the first class of small-molecule Cas9 inhibitors has been identified, verifying the feasibility of regulating CRISPR-Cas9 activity using direct-acting small molecules. However, it remains enigmatic as to the location of the ligand binding site(s) on CRISPR-Cas9 and how the ligand binding leads to Cas9 functional inhibition. Here, we established an integrative computational protocol, including massive binding site mapping, molecular docking, molecular dynamics simulations, and free energy calculations. Ultimately, a Cas9 ligand binding site was discovered from the dynamics trajectories that is hidden within its carboxyl-terminal domain (CTD), a domain recognizing the protospacer adjacent motif (PAM). Using the top inhibitor BRD0539 as a probe, we demonstrated that the ligand binding induces significant CTD structural rearrangements toward an incompetent conformation for PAM DNA engagement. The revealed molecular mechanism of BRD0539 inhibiting Cas9 is in well agreement with the experimental data. This study provides a structural and mechanistic basis for the potency improvement of existing ligands and the rational discovery of novel small-molecule brakes for developing safer CRISPR-Cas9 technologies.

Long noncoding RNA SNHG15: A promising target in human cancers.

As oncogenes or tumor suppressor genes, lncRNAs played an important role in tumorigenesis and the progression of human cancers. The lncRNA SNHG15 has recently been revealed to be dysregulated in malignant tumors, suggesting the aberrant expression of which contributes to clinical features and regulates various oncogenic processes. We have selected extensive literature focused on SNHG15 from electronic databases, including studies relevant to its clinical significance and the critical events in cancer-related processes such as cell proliferation, apoptosis, autophagy, metastasis, and drug resistance. This review summarized the current understanding of SNHG15 in cancer, mainly focusing on the pathological features, known biological functions, and underlying molecular mechanisms. Furthermore, SNHG15 has been well-documented to be an effective diagnostic and prognostic marker for tumors, offering novel therapeutic interventions in specific subsets of cancer cells.

Red Emissive Double Aza[7]helicenes with Antiaromaticity / Aromaticity Switching via the Redox-Induced Radical Cation and Dication Species.

We herein present the synthetic approach to a new antiaromatic double aza[7]helicene C that features NN-embedded polycyclic aromatic hydrocarbons (PAHs). This heteroatom-doped helicene showed a rarely obtained long-wavelength emission and far-red circularly polarized luminescence (CPL) in the solid state. These optical and chiroptical properties could be ascribed to both the NN-PAH core structure and the further extension through angular ring fusions. Such a unique electronic structure also culminated in facile chemical oxidations of neutral C to the positively charged chiral radical (C⋅+ ) and dication species (C2+ ). Interestingly, DFT computations revealed that the pyridazine central core showed an antiaromaticity-to-aromaticity switching, in contrast to the inversed transition for the helical periphery in cationic states. The reported approaches are anticipated to lead to the development of further redox-active chiral systems for potential applications in chiroptoelectronics, spintronics as well as fluorescent bioimaging.

The impact of phyto- and endo-cannabinoids on central nervous system diseases：A review.

Background and aim: Cannabis sativa L. is a medicinal plant with a long history. Phyto-cannabinoids are a class of compounds from C. sativa L. with varieties of structures. Endocannabinoids exist in the human body. This article provides an overview of natural cannabinoids (phyto-cannabinoids and endocannabinoids) with an emphasis on their pharmacology activities. Experimental procedure: The keywords "Cannabis sativa L″, "cannabinoids", and "central nervous system (CNS) diseases" were used for searching and collecting pieces of literature from PubMed, ScienceDirect, Web of Science, and Google Scholar. The data were extracted and analyzed to explore the effects of cannabinoids on CNS diseases. Result and conclusion: In this paper, schematic diagrams are used to intuitively show the phyto-cannabinoids skeletons' mutual conversion and pharmacological activities, with special emphasis on their relevant pharmacological activities on central nervous system (CNS) diseases. It was found that the endocannabinoid system and microglia play a crucial role in the treatment of CNS diseases. In the past few years, pharmacological studies focused on Δ9-THC, CBD, and the endocannabinoids system. It is expected to encourage new studies on a more deep exploration of other types of cannabinoids and the mechanism of their pharmacological activities in the future.

Anlotinib combined with osimertinib reverses acquired osimertinib resistance in NSCLC by targeting the c-MET/MYC/AXL axis.

Favorable clinical evidence suggests that the next trend in new treatments for advanced non-small cell lung cancer (NSCLC) will be combination therapies. However, inevitable epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance greatly limits the clinical efficacy of patients carrying EGFR-activating mutants. In this study, we found a patient with clinical osimertinib resistance who regained a positive response after osimertinib plus anlotinib treatment. Two osimertinib-resistant cell lines were constructed, and AXL conferred resistance to osimertinib in NSCLC cell lines. The combined effects of anlotinib and osimertinib restored sensitivity to osimertinib in two osimertinib-resistant NSCLC cell lines and in xenografts. Moreover, anlotinib inhibits the phosphorylation of AXL in both resistant cell lines. Mechanistically, we confirmed that MYC binds to the promoter of AXL to promote its transcription in NSCLC cells, and we demonstrated that anlotinib combined with osimertinib treatment enhances the anti-tumor effect by inactivating the c-MET/MYC/AXL axis to reverse osimertinib resistance in NSCLC. In conclusion, our results provide strong support that this combination therapy may be effective in enhancing the efficacy of treatments in patients with advanced NSCLC.

The pseudogene DUXAP10 contributes to gefitinib resistance in NSCLC by repressing OAS2 expression.

Gefitinib, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI),is the currently recommended first-line therapy for advanced EGFR-mutant lung cancer, and understanding the mechanism of resistance is the key to formulating therapeutic strategies for EGFR-TKIs. In this study, we evaluate the expression patterns and potential biological functions of the pseudogene DUXAP10 in gefitinib resistance. We find that pseudogene DUXAP10 expression is significantly upregulated in NSCLC gefitinib-resistant cells and tissues. Gain and loss of function assays reveal that knockdown of DUXAP10 by siRNA reverses gefitinib resistance both in vitro and in vivo. Furthermore, DUXAP10 interacts with the histone methyltransferase enhancer of zeste homolog 2 (EZH2) to repress the expression of 2',5'-oligoadenylate synthetase (OAS2). Overall, our study highlights the pivotal role of DUXAP10 in gefitinib resistance, and the DUXAP10/EZH2/OAS2 axis might be a promising therapeutic target to overcome acquired gefitinib resistance in NSCLC.

Expanding new chemistry of aza-boracyclophanes with unique dipolar structures, AIE and redox-active open-shell characteristics.

π-Conjugated macrocycles involving electron-deficient boron species have received increasing attention due to their intriguing tunable optoelectronic properties. However, most of the reported B(sp2)-doped macrocycles are difficult to modify due to the synthetic challenge, which limits their further applications. Motivated by the research of non-strained hexameric bora- and aza-cyclophanes, we describe a new class of analogues MC-BN5 and MC-ABN5 that contain charge-reversed triarylborane (Ar3B) units and oligomeric triarylamines (Ar3N) in the cyclics. As predicted by DFT computations, the unique orientation of the donor-acceptor systems leads to an increased dipole moment compared with highly symmetric macrocycles (M1, M2 and M3), which was experimentally represented by a significant solvatochromic effect with large Stokes shifts up to 12 318 cm-1. Such a ring-structured design also allows the easy peripheral modification of aza-boracyclophanes with tetraphenylethenyl (TPE) groups, giving rise to a change in the luminescence mechanism from aggregation-caused quenching (ACQ) in MC-BN5 to aggregation-induced emission (AIE) in MC-ABN5. The open-shell characteristics have been chemically enabled and were characterized by UV-Vis-NIR spectroscopy and electron paramagnetic resonance (EPR) for MC-BN5. The present study not only showed new electronic properties, but also could expand the research of B/N doped macrocycles into the future scope of supramolecular chemistry, as demonstrated in the accessible functionalization of ring systems.

Pillar[5]arene-based Neutral Radicals with Doublet Red Emissions and Stable Chiroptical Properties.

Stable organic radicals with unique luminescence show great importance in photoelectromagnetic materials. We herein report two unusual radical-based systems (P5N-TTM and P5B-TTM) using the concerted effects of planar chiral pillar[5]arenes and tris(2,4,6-trichlorophenyl)methyl (TTM) radicals. The steric effect and electronic doublet-spin character of these radicals allowed the optical resolution and the first red emissions (∼650 nm) for pillar[5]arene derivatives. Notably, cross-coupling with macrocyclic pillar[5]arene, in turn, considerably enhanced the configurational stability of TTM radicals.

Long noncoding RNA SNHG17: a novel molecule in human cancers.

Many studies in recent years have found that dysregulation of long non-coding RNAs (lncRNAs) can contribute to disease. Small nucleolar RNA host gene 17 (SNHG17) is a novel cancer-related lncRNA of the SNHG family which is highly expressed in various tumors and may exert oncogenic functions. Several studies have demonstrated that SNHG17 is closely related to the proliferation, migration, invasion, apoptosis, and chemical drug resistance of tumor cells, and clinical studies have found an association between high SNHG17 expression and poor prognosis. In this review, we summarize relevant studies investigating SNHG17, focusing on its biological function as well as its potential value for clinical applications.