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Combinations of different therapeutic strategies, including chemotherapy (CT), chemodynamic therapy (CDT), and photothermal therapy (PTT), are needed to effectively address evolving drug resistance and the adverse effects of traditional cancer treatment. Herein, a camouflage composite nanoformulation (TCBG@PR), an antitumor agent (tubercidin, Tub) loaded into Cu-doped bioactive glasses (CBGs) and subsequently camouflaged by polydopamine (PDA), and red blood cell membranes (RBCm), was successfully constructed for targeted and synergetic antitumor therapies by combining CT of Tub, CDT of doped copper ions, and PTT of PDA. In addition, the TCBG@PRs composite nanoformulation was camouflaged with a red blood cell membrane (RBCm) to improve biocompatibility, longer blood retention times, and excellent cellular uptake properties. It integrated with long circulation and multimodal synergistic treatment (CT, CDT, and PTT) with the benefit of RBCms to avoid immune clearance for efficient targeted delivery to tumor locations, producing an “all-in-one” nanoplatform. In vivo results showed that the TCBG@PRs composite nanoformulation prolonged blood circulation and improved tumor accumulation. The combination of CT, CDT, and PTT therapies enhanced the antitumor therapeutic activity, and light-triggered drug release reduced systematic toxicity and increased synergistic antitumor effects.

Meloidogyne hispanicainfects many economically important crops worldwide and has been listed as a quarantine pest in many countries and as an invasive alien species in China. Accurate identification of this pathogen is essential for the establishment of efficient and sustainable integrated pest management programs. During the field investigations in Hainan, China, we discovered galled roots caused by nematode infestation in the pepper field. Further identification of the nematode isolated from the root galls, including morphological and molecular techniques, confirmed that the isolated population infesting the pepper roots belonged to the species M. hispanica. Upon artificial inoculation under greenhouse conditions, the isolated nematodes induced symptoms that closely resembled those observed in the field. To the best of our knowledge, this is the first documented case of M. hispanicaparasitizing pepper crops in China, which will provide valuable basis to formulate targeted control strategies.

Bioinks are employed in the fabrication of 3D scaffolds containing cells and macromolecules that can be applied in regenerative medicine. The use of such bioinks facilitates the controlled introduction and localization of macromolecules, bioactives and cells for the biofabrication of living tissues. To enable the successful preparation of the bioinks, strategies involving the use of so-called cross linkers, which may be ionic, chemical, photo-etc.based, are employed. Some of these strategies such as the use of glutaraldehyde as a crosslinker or harsh crosslinking conditions may however compromise the cytocompatibility of the bioink. To circumvent this challenge, the employment of click chemistry technology has been proposed. This is because, click chemistry can enable the preparation of well-tuned bioinks in the absence of problematic cross-linkers, while ensuring that favorable gelation rate, degradation rate, and cell viability properties of the bioinks are not compromised. Indeed, the bio-orthogonal nature of click chemistry has been suggested to enhance the maintenance of high cell viability in scaffolds. In this regard, the current study explored the potential of using different click chemistries in specific bioprinting techniques. Major bioinks produced using click chemistry were also identified, with existing challenges and future trends discussed. It is anticipated that this review will be invaluable to the tissue engineering field by providing an important resource for bioengineers and a basis of future decisions regarding the selection of the preferred click chemistry for specific bioink functionalities.

Allopurinol (AP) is widely used to treat hyperuricemia which may cause severe side effects upon oral administration. Alternative means for the treatment of hyperuricemia are demanded to simultaneously facilitate drug absorption, patient compliance, and fewer side effects. In this study, a new polymer microneedle (MN) system was developed for the transdermal delivery of AP to acute hyperuricemic mice. This study aims to achieve the controllable regulation of serum uric acid (SUA) levels with fewer side effects compared with oral administration. The matrix of polymer MNs consisted of polyvinylpyrrolidone (PVP) and polycaprolactone (PCL), in which the rapid dissolution of PVP offers a rapid dissolution of AP into the blood and the biodegradability of PCL resulting in a sustainable drug release behavior. An in vivostudy demonstrated that the AP-loaded MN system can effectively reduce the SUA levels as oral administration with lower side effects, which will be conducive to reducing the adverse reactions and improving the bioavailability of AP. This MN-mediated strategy can facilitate transcutaneous hyperuricemia treatment and provide a new alternative for the exploration of clinical treatment of hyperuricemia and improvement of patient compliance.

ABSTRACTFraxetin, a natural product isolated from herb Cortex Fraxini, has been demonstrated to exhibit anti-cancer effects on various cancers. The aim of this work is to investigate the anti-tumor effect of Fraxetin in prostate cancer and the potential mechanisms. In this study, the prostatic epithelial cell RWPE-1 and prostate cancer cell DU145 were exposed to Fraxetin (10, 20, 40, and 80 μM) to detect the changes in cell viability using cell counting kit-8 (CCK-8) assay. Fraxetin (10, 20, and 40 μM) was utilized to treat DU145 cell, then the changes in cell proliferation, apoptosis, migration, and invasion were assessed. Western blot assay was employed to detect the expression of proteins that participate in the above cellular processes as well as Polo-like kinase 4 (PLK4), phosphatidylinositol 3-kinase (PI3K). In addition to 40 μM Fraxetin treatment, DU145 cells were overexpressed with PLK4, and then the above experiments were repeated. Results revealed that Fraxetin markedly decreased DU145 cell viability, but didn’t affect the cell viability of RWPE-1. Fraxetin suppressed cell proliferation, migration, invasion, and induced apoptosis of DU145 cells in a concentration-dependent manner. Furthermore, the expression of PLK4 and phosphorylated PI3K and protein kinase B (Akt) were reduced upon Fraxetin treatment. Finally, PLK4 overexpression significantly reversed all the effects of Fraxetin on DU145 cells. Collectively, Fraxetin acted as a cancer suppressor in prostate cancer through inhibiting PLK4 expression thereby inactivating PI3K/Akt signaling.

Skin ulcers are one of the complications of diabetes. At present, the treatment of diabetic skin wounds is still not satisfactory, and the efficiency of drug delivery is limited by the depth of penetration. Herein, a synergistically flexible microneedle dressing is presented for effectively promoting diabetic wound healing. Metformin, as an anti-diabetic drug, can be loaded into microneedles, which can effectively pierce into the skin of diabetic rats to trigger a response for regulating blood glucose levels. A novel multifunctional nanosystem CaO2@polydopamine (CaO2@PDA) was introduced into polycaprolactone and gelatin (PCL/Gel) electrospun nanofiber films as microneedle back patches to inhibit inflammation, provide oxygen, and absorb the excess exudate. Besides, the CaO2@PDA in back patches also provided effective antibacterial properties against both S. aureusand E. coli. Additionally, the as-fabricated flexible microneedle dressings loaded with metformin and CaO2@PDA nanoparticles demonstrated a high level of CD31 and low level of TNF-α, leading to accelerated diabetic skin-wound closure. These distinctive features demonstrate that our microneedle system can be a facile candidate for efficient wound healing in patients with diabetes and may be applied in various biomedical fields.

The development of multifunctional nanoformulations (NFs) include several features in a single nanosystem for these devices to overcome the disadvantages of inefficiency and undesirable toxicity of traditional therapies and provide new opportunities in the management of tumors. Herein, multifunctional CaO2@Mn-PDA NFs with a core–shell structure, integrating the photothermal conversion properties of Mn-PDA, the chemodynamic properties of doped Mn ions, and relieving hypoxia in the tumor microenvironment (TME) were developed. The as-fabricated CaO2@Mn-PDA NFs were embedded in microneedles (MNs) for transdermal delivery into tumor sites, leading to the generation of a new minimally invasive and synergistic therapeutic strategy against skin melanoma. Under near-infrared (NIR) light irradiation, the CaO2@Mn-PDA NFs exhibited a synergistic therapeutic effect, including photothermal therapy (PTT), chemodynamic therapy (CDT), and modulating hypoxia due to their high photothermal conversion efficiency, boosted intracellular production of reactive oxygen species, excellent chemodynamic reactions, etc. Therefore, the developed MN platform, which can build implanted multifunctional characteristics for on-demand NIR-induced synergistic therapy, have a bright future in tumor suppression.

Abstract: Injection therapy for diabetes has poor patient compliance, and the pain occurring at the site of subcutaneous injections causes significant inconvenience to diabetic patients. In this work, to demonstrate the benefits of an alternative drug delivery technique that overcomes these issues, methacrylated gelatin hydrogel-forming microneedles integrated with metformin were developed to adjust blood glucose levels in diabetic rats. Gelatin methacryloyl microneedles (GelMA-MNs) with different degrees of substitution were successfully prepared by a micro-molding method. The resultant GelMA-MNs exhibited excellent mechanical properties and moisture resistance. Metformin, an anti-diabetic drug, was further encapsulated into the GelMA-MNs, and its release rate could be controlled by the three-dimensional cross-linked network of microneedles, thereby exhibiting sustained drug release behaviors in vitro and implying a better therapeutic effect compared with that of subcutaneous injection in diabetic rats. The drug release period could be significantly prolonged by improving the cross-link density of GelMA-MNs. The results of hypoglycemic effect evaluation show that the application of GelMA-MNs for transdermal delivery in diabetic rats has promising benefits for diabetes treatment. Graphic abstract:

Engineering heterojunction with the interfacial synergism is an effective anode design strategy to innovate the surface pseudocapacitive reaction and facilitate the charge transfer dynamics, thus resulting in improved properties for sodium-ion batteries. Herein, the heterogeneous structure of Sb2S3-CoS2nanoboxes coated with nitrogen-doped carbon shell (Sb2S3-CoS2@NC) is fabricated through the replacement of Co2+with Sb3+, and the subsequent sulfurization reaction. The advantages of exquisite hollow structure and carbon coating not only effectively buffer the vast volumetric variation to prevent the collapse of electrode but also accelerate the charge transfer to optimize rate property. Moreover, the interfacial synergism between Sb2S3-CoS2heterojunction improves surface pseudocapacitive Na+uptake and boosts the Na+transport. Consequently, the developed Sb2S3-CoS2@NC nanoboxes exhibit advanced anode performances of high specific capacity, stable cyclic durability, and good rate capability. This approach can be utilized to develop other hollow structured heterogeneous materials for high performance energy storage and conversion application.

In this study, reduced graphene oxide/MXene-based composite electrodes combined with Fe2O3and NiCo-P as the negative and positive electrodes are prepared by a facile in-situ solvothermal route. Both rGO/MXene@Fe2O3and rGO/MXene@NiCo-P have an interconnected nanostructure with the specific surface areas at 17.1 and 131.9 m2·g−1. The specific capacitance of the as-prepared rGO/MXene@Fe2O3and rGO/MXene@NiCo-P composite electrodes are 248.13 and 214.66 mAh·g−1under current density at 1 A·g−1. An asymmetric supercapacitor (ASC) is further assembled using rGO/MXene@Fe2O3and rGO/MXene@NiCo-P as the negative and positive electrodes, respectively. The maximum energy density of the assembled ASC is 29.46 Wh·kg−1at a power density of 700.34 W·kg−1. After 10,000 cycles, 70.87 % of the capacity can be retained. These results demonstrate the potential application of composite electrode materials for supercapacitors.

AbstractIn this study, tri-sodium citrate (CA), a chelating agent of low-cost and non-toxicity, was used together with epichlorohydrin (ECH) to cross-link chitosan (CTS) for enhancing the adsorption of Pb (II) and Cu (II) ions onto CTS. The chemical structure changes of the cross-linked CTS and metal ions-loaded absorbent were confirmed by thermogravimetric analysis, FTIR spectroscopy and X-ray diffraction. The effects of these factors, such as pH, temperature, contact time, and initial concentration of metal ions on the adsorption of Pb (II) and Cu (II) ions onto CTS–CA–ECH beads were investigated. The adsorption kinetics was evaluated utilizing pseudo-first-order and pseudo-second-order (PSO) models, the results indicated that the adsorption process fit well with the PSO kinetic model. Meanwhile, adsorption equilibrium isotherms were examined by Langmuir and Freundlich models, the results showed that the experimental data agreed well with Langmuir models and the maximum adsorption capacities were 121.95 and 151.52 mg g−1for Pb (II) and Cu (II) ions, respectively. Furthermore, desorption and regeneration tests indicated that ethylenediamine tetra-acetic acid could effectively regenerate the metal ions loaded CTS–CA–ECH beads, suggesting that the currently prepared adsorbent possessed an excellent reusability for the adsorption of Pb (II) and Cu (II) ions.

In this study, tri-sodium citrate (CA), a chelating agent of low-cost and non-toxicity, was used together with epichlorohydrin (ECH) to cross-link chitosan (CTS) for enhancing the adsorption of Pb (II) and Cu (II) ions onto CTS. The chemical structure changes of the cross-linked CTS and metal ions-loaded absorbent were confirmed by thermogravimetric analysis, FTIR spectroscopy and X-ray diffraction. The effects of these factors, such as pH, temperature, contact time, and initial concentration of metal ions on the adsorption of Pb (II) and Cu (II) ions onto CTS–CA–ECH beads were investigated. The adsorption kinetics was evaluated utilizing pseudo-first-order and pseudo-second-order (PSO) models, the results indicated that the adsorption process fit well with the PSO kinetic model. Meanwhile, adsorption equilibrium isotherms were examined by Langmuir and Freundlich models, the results showed that the experimental data agreed well with Langmuir models and the maximum adsorption capacities were 121.95 and 151.52 mg g−1for Pb (II) and Cu (II) ions, respectively. Furthermore, desorption and regeneration tests indicated that ethylenediamine tetra-acetic acid could effectively regenerate the metal ions loaded CTS–CA–ECH beads, suggesting that the currently prepared adsorbent possessed an excellent reusability for the adsorption of Pb (II) and Cu (II) ions.

Exploring highly active catalysts with low-price materials is urgently needed for water-splitting electrolysis. Herein, selenium-doped CoP nanoneedles construct the grass-like structure, and the nanoneedles are vertically anchored on carbon cloth (Se–CoP/CC). Scanning electron microscopy and transmission electron microscopy reveal the nanoneedle array architecture of S–CoP, which is convenient for the adsorption of molecules on active centers. The small diameter of nanoneedles is beneficial for rapid charge transfer. X-ray photoelectron spectroscopy shows the electronic structure regulation of Se incorporation, which is beneficial for the optimized catalysis activity. Electrochemical tests show that Se dopants result in more catalysis sites and faster kinetics. Endowed with these advantages, good catalytic performance of the prepared sample for hydrogen evolution is disclosed, with low overpotentials of 47 mV at 10 mA cm–2and 145 mV at 100 mA cm–2in alkaline solution. This work highlights a promising way to improve the performance of transition-metal-based catalysts with non-metal-doping engineering toward water electrolysis application.

A 980?nm bottom-emitting vertical-cavity surface-emitting laser (VCSEL) with a p-contact diameter is reported to achieve high power and good beam quality. A numerical simulation is conducted on the current spreading in a VCSEL with oxidation between the active region and the p-type distributed Bragg reflector. It is found that, for a particular oxide aperture diameter, somewhat homogeneous current distribution can be achieved for a VCSEL with an optimized p-contact diameter. The far-field divergence angle from a 600?μm diameter VCSEL is suppressed from 30° to 15°, and no strong sidelobe is observed in the far-field pattern by using the optimized p-contact diameter. There is a slight rise in threshold and optical output power that is due to the p-contact optimization. By improving the device packaging method, the maximum optical output power of the device is 2.01?W.

A 980 nm bottom-emitting vertical-cavity surface-emitting laser array with a nonuniform linear arrangement is reported to realize emission with a Gaussian far-field distribution. This array is composed of five symmetrically arranged elements of 200 μm, 150 μm, and 100 μm diameter, with center spacing of 300 μm and 250 μm, respectively. An output power of 880 mW with a high power density of 1 kW/cm^2 is obtained. The divergence angle is below 20° in the range of operating current from 0 A to 6 A. The theoretical simulation of the near-field and the far-field distribution is in good agreement with the experimental result. The comparison between this nonuniform linear array, the single device, and the conventional two-dimensional array is carried out to demonstrate the good performance of the linear array.

Background: Berberine (Ber) is a herbal alkaloid with pharmacological activity in general and a high anticancer potency in particular. However, due to its low bioavailability, the difficulty in reaching a target and choosing the right dose, there is a need to improve approaches of Ber use in anticancer therapy. In this study, Ber, noncovalently bound to a carbon nanostructure C60fullerene (C60) at various molar ratios of the components, was explored against Lewis lung carcinoma (LLC). Methods: C60–Ber noncovalent nanocomplexes were synthesized in 1:2, 1:1 and 2:1 molar ratios. Ber release from the nanocomplexes was studied after prolonged incubation at different pH with the liquid chromatography–mass spectrometry analysis of free Ber content. Biological effects of the free and C60-complaxated Ber were studied in vitro towards LLC cells with phase-contrast and fluorescence microscopy, flow cytometry, MTT reduction, caspase activity and wound closure assays. The treatment with C60–Ber nanocomplex was evaluated in vivo with the LLC-tumored C57Bl mice. The mice body weight, tumor size, tumor weight and tumor weight index were assessed for four groups, treated with saline, 15 mg C60/kg, 7.5 mg Ber/kg or 2:1 C60-Ber nanocomplex (15 mg C60/kg, 7.5 mg Ber/kg). Results: Ber release from C60–Ber nanocomplexes was promoted with medium acidification. LLC cells treatment with C60–Ber nanocomplexes was followed by enhanced Ber intracellular uptake as compared to free Ber. The cytotoxicity of the studied agents followed the order: free Ber < 1:2 < 1:1 < 2:1 C60–Ber nanocomplex. The potency of cytotoxic effect of 2:1 C60–Ber nanocomplex was confirmed by 21.3-fold decrease of IC50value (0.8 ± 0.3 µM) compared to IC50for free Ber (17 ± 2 µM). C60–Ber nanocomplexes induced caspase 3/7 activation and suppressed the migration activity of LLC cells. The therapeutic potency of 2:1 C60–Ber nanocomplex was confirmed in a mouse model of LLC. The tumor growth in the group treated with 2:1 C60–Ber nanocomplex is suppressed by approximately 50% at the end of experiment, while in the tumor-bearing group treated with free Ber no therapeutic effect was detected. Conclusions: This study indicates that complexation of natural alkaloid Ber with C60may be a novel therapeutic strategy against lung carcinoma. Graphical abstract:

The technique of pulsed anodic oxidation is adopted in the fabrication of 980-nm bottom-emitting vertical-cavity surface-emitting lasers. A high-quality native oxide current blocking layer is formed with this method. A significant reduction of threshold current and a distinguished device performance are achieved. The threshold current of large aperture devices with active diameter up to 400 microns is as low as 0.45 A at room temperature, which is substantially lower than the lasers fabricated by SiO2 sputtering. The maximum continuous-wave output power is 0.83 W. The lasing peak wavelength is 990.2 nm, and the full width at half-maximum is 0.9 nm. Low lateral divergence angle of 15.3 deg. and vertical divergence angle of 13.8 deg. are obtained.

High power bottom-emitting In0.2Ga0.8As/GaAs 4*4 two-dimensional vertical-cavity surface-emitting laser (VCSEL) arrays, with high output power in the 980-nm wavelength regime are reported. At room temperature, the 16-element array with 200-micron aperture size of individual elements shows a continuous wave output power of 1.21 W with a lasing wavelength of 981.9 nm. Temperature dependent characteristics of VCSEL arrays with 90-micron aperture size of individual elements are investigated. The lasing wavelength, optical output power and threshold current are measured at various heatsink temperatures. With the increase of heatsink temperature, the maximum output power and slope efficiency are greatly decreased. A red shift of lasing wavelength and a widening of the lasing spectrum are also observed.

Helichrysum thianschanicumRegel was collected from Khorugh town of Kuhistoni Badakhshon Autonomous Province of Tajikistan. The essential oil was obtained by hydrodistillation and analyzed by gas chromatography – mass spectrometry. A total of 67 compounds were identified representing 88.4% of the total essential oil composition. The major components of H. thianschanicumessential oil were (E)-1-(6,10-dimethylundec-5-en-2-yl)-4-methylbenzene (pentylcurcumene) (21.6%), β-selinene (6.4%), δ-selinene (3.8%), (2E, 6E)-farnesol (3.3%), nerol (4.1%) and neryl decanoate (4.2%). To our best knowledge, no previous studies have been reported on the chemical composition of the essential oil of H. thianschanicum.