Preparation and Investigation of Cellulose Acetate/Gelatin Janus Nanofiber Wound Dressings Loaded with Zinc Oxide or Curcumin for Enhanced Antimicrobial Activity.

The skin, as the largest organ, serves as a protective barrier against external stimuli. However, when the skin is injured, wound healing becomes a complex process influenced by physiological conditions, bacterial infections, and inflammation. To improve the process of wound healing, a variety of wound dressings with antibacterial qualities have been created. Electrospun nanofibers have gained significant attention in wound dressing research due to their large specific surface area and unique structure. One interesting method for creating Janus-structured nanofibers is side-by-side electrospinning. This work used side-by-side electrospinning to make cellulose acetate/gelatin Janus nanofibers. Curcumin and zinc oxide nanoparticles were added to these nanofibers. We studied Janus nanofibers' physicochemical characteristics and abilities to regulate small-molecule medication release. Janus nanofibers coated with zinc oxide nanoparticles and curcumin were also tested for antibacterial activity. The Janus nanofibers with specified physicochemical characteristics were successfully fabricated. Nanofibers released small-molecule medicines in a controlled manner. Additionally, the Janus nanofibers loaded with curcumin exhibited excellent antibacterial capabilities. This research contributes to the development of advanced wound dressings for promoting wound healing and combating bacterial infections.

Metabolic profiles of Fufang Xiling Jiedu capsule in rats by ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry.

Fufang Xiling Jiedu capsule (FXJC), a traditional Chinese medicine that evolved from "Yinqiao Powder", is widely used for the treatment of cold and influenza. However, due to a lack of in vivo metabolism research, the chemical components responsible for the therapeutic effects still remain unclear. Hence, this study aimed to describe the metabolic profiles of the FXJC in rat plasma, urine, and feces. A combined data mining strategy based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry was employed and 201 xenobiotics, including 117 prototype components and 84 metabolites were detected. Phenolic acids, flavonoids, triterpenes, and lignans were prominent ingredients absorbed in vivo, and the major metabolic pathways of the detected metabolites were glucuronidation, sulfation, methylation, and oxidation. This is the first systematic study on the metabolism of the FXJC in vivo, providing valuable information for future studies on the efficacy, toxicity, and mechanism of the FXJC.

CRISPR-Cas9 Activities with Truncated 16-Nucleotide RNA Guides Are Tuned by Target Duplex Stability Beyond the RNA/DNA Hybrid.

CRISPR-Cas9 has been adapted as a readily programmable genome manipulation agent, and continuing technological advances rely on an in-depth mechanistic understanding of Cas9 target discrimination. Cas9 interrogates a target by unwinding the DNA duplex to form an R-loop, where the RNA guide hybridizes with one of the DNA strands. It has been shown that RNA guides shorter than the normal length of 20-nucleotide (-nt) support Cas9 cleavage activity by enabling partial unwinding beyond the RNA/DNA hybrid. To investigate whether DNA segment beyond the RNA/DNA hybrid can impact Cas9 target discrimination with truncated guides, Cas9 double-stranded DNA cleavage rates (kcat) were measured with 16-nt guides on targets with varying sequences at +17 to +20 positions distal to the protospacer-adjacent-motif (PAM). The data reveal a log-linear inverse correlation between kcat and the PAM+(17-20) DNA duplex dissociation free energy (ΔGNN(17-20)0), with sequences having smaller ΔGNN(17-20)0 showing faster cleavage and a higher degree of unwinding. The results indicate that, with a 16-nt guide, "peripheral" DNA sequences beyond the RNA/DNA hybrid contribute to target discrimination by tuning the cleavage reaction transition state through the modulation of PAM-distal unwinding. The finding provides mechanistic insights for the further development of strategies that use RNA guide truncation to enhance Cas9 specificity.

Piezoelectric Enhancement of Piezoceramic Nanoparticle-Doped PVDF/PCL Core-Sheath Fibers.

Electrospinning is considered to be an efficient method to prepare piezoelectric thin films because of its ability to transform the phase of the polymers. A core-sheath structure can endow fibers with more functions and properties. In this study, fibers with a core-sheath structure were prepared using polyvinylidene fluoride (PVDF) included with nanoparticles (NPs) as the shell layer and polycaprolactone (PCL) as the core layer. Their mechanical and piezoelectric properties were studied in detail. During the course of the electrospinning process, PVDF was demonstrated to increase the amount of its polar phase, with the help of nanoparticles acting as a nucleating agent to facilitate the change. PCL was chosen as a core material because of its good mechanical properties and its compatibility with PVDF. Transmission electron microscope (TEM) assessments revealed that the fibers have a core-sheath structure, and shell layers were loaded with nanoparticles. Mechanical testing showed that the core layer can significantly improve mechanical properties. The XRD patterns of the core-sheath structure fibers indicated the ß phase domain the main component. Piezoelectric testing showed that the doped nanoparticles were able to enhance piezoelectric performances. The increases of mechanical and piezoelectric properties of core-sheath structure fibers provide a feasible application for wearable electronics, which require flexibility and good mechanical properties.

Preparation of Tough, Binder-Free, and Self-Supporting LiFePO4 Cathode by Using Mono-Dispersed Ultra-Long Single-Walled Carbon Nanotubes for High-Rate Performance Li-Ion Battery.

Low-contents/absence of non-electrochemical activity binders, conductive additives, and current collectors are a concern for improving lithium-ion batteries' fast charging/discharging performance and developing free-standing electrodes in the aspects of flexible/wearable electronic devices. Herein, a simple yet powerful fabricating method for the massive production of mono-dispersed ultra-long single-walled carbon nanotubes (SWCNTs) in N-methyl-2-pyrrolidone solution, benefiting from the electrostatic dipole interaction and steric hindrance of dispersant molecules, is reported. These SWCNTs form a highly efficient conductive network to firmly fix LiFePO4  (LFP) particles in the electrode at low contents of 0.5 wt% as conductive additives. The binder-free LFP/SWCNT cathode delivers a superior rate capacity of 161.5 mAh g-1 at 0.5 C and 130.2 mAh g-1 at 5 C, with a high-rate capacity retention of 87.4% after 200 cycles at 2 C. The self-supporting LFP/SWCNT cathode shows excellent mechanical properties, which can withstand at least 7.2 MPa stress and 5% strain, allowing the fabrication of high mass loading electrodes with thicknesses up to 39.1 mg cm-2 . Such self-supporting electrodes display conductivities up to 1197 S m-1 and low charge-transfer resistance of 40.53 Ω, allowing fast charge delivery and enabling near-theoretical specific capacities.

Advances in the Preparation of Nanofiber Dressings by Electrospinning for Promoting Diabetic Wound Healing.

Chronic diabetic wounds are one of the main complications of diabetes, manifested by persistent inflammation, decreased epithelialization motility, and impaired wound healing. This will not only lead to the repeated hospitalization of patients, but also bear expensive hospitalization costs. In severe cases, it can lead to amputation, sepsis or death. Electrospun nanofibers membranes have the characteristics of high porosity, high specific surface area, and easy functionalization of structure, so they can be used as a safe and effective platform in the treatment of diabetic wounds and have great application potential. This article briefly reviewed the pathogenesis of chronic diabetic wounds and the types of dressings commonly used, and then reviewed the development of electrospinning technology in recent years and the advantages of electrospun nanofibers in the treatment of diabetic wounds. Finally, the reports of different types of nanofiber dressings on diabetic wounds are summarized, and the method of using multi-drug combination therapy in diabetic wounds is emphasized, which provides new ideas for the effective treatment of diabetic wounds.

Electrospun Nanofibers for Periodontal Treatment: A Recent Progress.

Periodontitis is a major threat to oral health, prompting scientists to continuously study new treatment techniques. The nanofibrous membrane prepared via electrospinning has a large specific surface area and high porosity. On the one hand, electrospun nanofibers can improve the absorption capacity of proteins and promote the expression of specific genes. On the other hand, they can improve cell adhesion properties and prevent fibroblasts from passing through the barrier membrane. Therefore, electrospinning has unique advantages in periodontal treatment. At present, many oral nanofibrous membranes with antibacterial, anti-inflammatory, and tissue regeneration properties have been prepared for periodontal treatment. First, this paper introduces the electrospinning process. Then, the commonly used polymers of electrospun nanofibrous membranes for treating periodontitis are summarized. Finally, different types of nanofibrous membranes prepared via electrospinning for periodontal treatment are presented, and the future evolution of electrospinning to treat periodontitis is described.

Site-Specific Labeling Reveals Cas9 Induces Partial Unwinding Without RNA/DNA Pairing in Sequences Distal to the PAM.

CRISPR-Cas9 is an RNA-guided nuclease that has been widely adapted for genome engineering. A key determinant in Cas9 target selection is DNA duplex unwinding to form an R-loop, in which the single-stranded RNA guide hybridizes with one of the DNA strands. To advance understanding on DNA unwinding by Cas9, we combined two types of spectroscopic label, 2-aminopurine and nitroxide spin-label, to investigate unwinding at a specific DNA base pair induced by Streptococcus pyogenes Cas9. Data obtained with RNA guide lengths varying from 13 to 20 nucleotide revealed that the DNA segment distal to the protospacer adjacent motif can adopt a "partial unwinding" state, in which a mixture of DNA-paired and DNA-unwound populations exist in equilibrium. Significant unwinding can occur at positions not supported by RNA/DNA pairing, and the degree of unwinding depends on RNA guide length and modulates DNA cleavage activity. The results shed light on Cas9 target selection and may inform developments of genome-engineering strategies.

Exosomal Delivery of FTO Confers Gefitinib Resistance to Recipient Cells through ABCC10 Regulation in an m6A-dependent Manner.

Gefitinib is suitable for the treatment of locally advanced or metastatic non-small cell lung cancer. However, the development of acquired resistance limits its long-term efficacy in regardless of significant clinical benefit to patients. Therefore, to elucidate the mechanism of gefitinib resistance in addition to target gene mutation may greatly increase its clinical efficacy. It was found first that N 6-methyladenosine RNA demethylase FTO was significantly enriched in serum exosomes of gefitinib-resistant (GR) patients compared with that of gefitinib-sensitive (GS) patients through exosomal RNA sequencing. Meanwhile, the average m6A proportion in GR patients was significantly lower when compared with that in GS patients. Besides, GR cell-derived exosome internalization attenuated the total m6A abundance and gefitinib sensitivity of PC9 cells. Not only FTO knockdown enhanced the gefitinib sensitivity of GR cells but also FTO reduction in donor exosomes alleviated the acquired resistance of recipient PC9 cells. GR cell-derived exosomal-FTO promoted ABCC10 of recipient cells in a m6A-dependent manner. FTO/YTHDF2/ABCC10 axis played a role in intercellular transmission of GR cell-derived exosome-mediated gefitinib resistance both in vitro and in vivo. In general, this research showed that m6A modification was involved in the decrease of gefitinib sensitivity. GR cell-derived exosomes could decrease gefitinib sensitivity of recipient cells in exosomal delivery of FTO-dependent manner. FTO/YTHDF2/ABCC10 axis played a role in intercellular transmission of GR cell-derived exosome-mediated gefitinib resistance. IMPLICATIONS: Our results elucidated another potential molecular mechanism of gefitinib resistance in non-small cell lung cancer besides secondary EGFR mutations.

Pulmonary Lymphoepithelioma-Like Carcinoma: A Mini-Review.

Pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare and distinct subtype of non-small-cell lung carcinoma associated with Epstein-Barr virus (EBV) infection. We systematically reviewed the recent research that expands our knowledge about PLELC, with main focus on its genetic profile, tumor-infiltrating environment, PD-L1 expression, circulating EBV-DNA, clinical utility of 18F-FDG PET/CT, and treatment strategy. A low frequency of typical driver mutations and widespread existence of copy number variations was detected in PLELC. Persistent EBV infection may trigger intense infiltration of lymphocytes, representing enhanced tumor immunity and possibly resulting in a better prognosis. Circulating EBV-DNA in the plasma of patients with PLELC may predict disease progression and response to therapy. PLELC is 18F-FDG avid, and 18F-FDG PET may help refine palliation strategies and subsequently improve the prognosis. Most of the reported patients present at early and resectable stage, and surgical resection with curative intent is the preferred approach. There is currently no consensus on the regimen of chemotherapy for patients with advanced stages. EGFR-targeted therapies seem to have no therapeutic effect, and the clinical impact of PD-1/PD-L1 therapy is uncertain but worthy of further research.

Coating Cutting Blades with Thin-Film Metallic Glass to Enhance Sharpness.

In this study, we sought to enhance the cutting properties of the various blades by coating them with Zr- and Fe-based thin film metallic glasses (TFMGs) to a thickness of 234-255 nm via sputter deposition. In oil-repellency/sliding tests on kitchen blades, the sliding angle and friction forces were as follows: bare blades (31.6°) and (35 µN), Ti-coated blades (20.3°) and (23.7 µN), and Z-TFMG coated blades (16.2°) and (19.2 µN). Comparisons were conducted with bare blades and those with a Teflon coating (a low-friction material commonly used for the coating of microtome blades). We also found that the Teflon coating reduced the cutting forces of an uncoated microtome blade by ~80%, whereas the proposed Z-TFMG achieved a ~51% reduction. The Z-TFMG presented no indications of delamination after being used 30 times for cutting; however, the Teflon coating proved highly susceptible to peeling and the bare blade was affected by surface staining. These results demonstrate the efficacy of the TFMG coating in terms of low friction, non-stick performance, and substrate adhesion. The performance of Z-TFMG and F-TFMG was also evaluated in split-thickness skin graft surgery using dermatome blades aimed at elucidating the influence of TFMG coatings on the healing of surgical incisions. When tested repeatedly on hairless skin, the surface roughness of uncoated blades increased by approximately 70%, whereas the surface roughness of TFMG-coated blades increases by only 8.6%. In the presence of hair, the surface roughness of uncoated blades increased by approximately ~108%, whereas the surface roughness of TFMG-coated blades increases by only ~23%. By Day 7, the wounds produced using TFMG-coated blades were noticeably smaller than those produced using uncoated blades, and these effects were particularly evident in hairy samples. This is a clear demonstration of the efficacy of TFMG surface coatings in preserving the cutting quality of surgical instruments.

Tracking mitochondrial pH fluctuation during cell apoptosis with two-photon phosphorescent iridium(iii) complexes.

Two iridium(iii) complexes with ligands containing morpholine groups were used to track mitochondrial pH fluctuation during cell apoptosis as their emissive intensities linearly increased with increase in pH values.

Two-photon photodynamic ablation of tumor cells by mitochondria-targeted iridium(iii) complexes in aggregate states.

By integrating targeting, imaging and treatment, organelle-targeted photodynamic therapy (PDT) has been reported to be an effective strategy for cancer therapy. However, targeting leads to the accumulation of photosensitizers (PSs) in the targeted organelles, which leads to a reduction in 1O2 generation and fluorescence quenching, especially for the lipophilic mitochondria-targeted PSs. Moreover, because PSs always need exposure to light for a specific period, photobleaching is difficult to avoid. To address these issues, two iridium(iii) complexes with aggregation-induced two-photon emission (AITPE) characteristics were developed. With lipophilicity, the complexes aggregated in water and targeted mitochondria. Owing to their impressive 1O2 production quantum yields and excellent two-photon properties in the aggregate states, the complexes were successfully used for mitochondria-targeted two-photon PDT in monolayer cells and multicellular spheroids. Our results highlighted that the use of a PS with aggregation enhanced 1O2 generation and fluorescence is an effective solution for aggregation in organelle-targeted PDT.

Biscylometalated iridium(iii) complexes target mitochondria or lysosomes by regulating the lipophilicity of the main ligands.

An efficient method was developed that controls biscylometalated iridium(iii) complexes to target mitochondria or lysosomes by regulating the lipophilicity of the main ligands.

Long-Term Lysosomes Tracking with a Water-Soluble Two-Photon Phosphorescent Iridium(III) Complex.

Lysosomes are the stomachs of the cells that degrade endocytosis and intracellular biomacromolecules and participate in various other cellular processes, such as apoptosis and cell migration. The ability of long-term tracking of lysosomes is very important to understand the details of lysosomal functions and to evaluate drug and gene delivery systems. For studying lysosomes, we designed and synthesized a water-soluble triscyclometalated iridium(III) complex (Ir-lyso) attaching morpholine moieties. The phosphorescent intensity of Ir-lyso is responsive to pH and decreases with an increase in the pH but not quenching in high pH. With excellent two-photon properties, Ir-lyso was used to light up the lysosomes in living cells and 3D tumor spheroids. Moreover, Ir-lyso could label lysosomes more than 4 days, so we developed this complex to act as a long-term probe for tracking lysosomes during cell migration and apoptosis. To the best of our knowledge, this is the first paradigm of metal complexes as the two-photon phosphorescent probe for long-term lysosomes tracking.

Mitochondria-specific imaging and tracking in living cells with two-photon phosphorescent iridium(iii) complexes.

Two-photon phosphorescent probes have emerged as promising molecular tools for imaging subcellular organelles. Here, the facile synthesis of four new iridium(iii)-based mitochondrial probes with two-photon phosphorescence, Ir1-Ir4, is presented. Ir1-Ir4 possess high specificity for mitochondrial localization, which is advantageous in comparison with commercially available mitochondrial trackers of changes in the mitochondrial membrane potential in live cells. In addition to low cytotoxicity and high resistance to photobleaching, Ir1-Ir4 are applicable for imaging and tracking of mitochondrial morphological changes during the early stages of apoptosis. While naturally possessing intensive two-photon properties, Ir1-Ir4 were further developed for imaging of the mitochondria in 3D multicellular spheroids.

Broadband pattern synthesis for circular sensor arrays.

The solutions of pattern synthesis are derived for circular sensor arrays based on the criterion of minimizing the mean square error between the desired and synthesized beampatterns. Specifically, the optimal weighting vector, the output beam, and the minimum mean square error are all expressed in closed-form exactly when the desired beampattern is properly formulated. These results provide a more effective and convenient scheme for designing practical frequency-invariant beamformers. Simulations and experimental results demonstrate the performance of the proposed approach.