Oxygen and pH responsive theragnostic liposomes for early-stage diagnosis and photothermal therapy of solid tumours.

The development of cancer treatment is of great importance, especially in the early stage. In this work, we synthesized a pH-sensitive amphiphilic ruthenium complex containing two alkyl chains and two PEG chains, which was utilized as an oxygen sensitive fluorescent probe for co-assembly with lipids to harvest a liposomal delivery system (RuPC) for the encapsulation of a photothermal agent indocyanine green (ICG). The resultant ICG encapsulated liposome (RuPC@ICG) enabled the delivery of ICG into cells via a membrane fusion pathway, by which the ruthenium complex was localized in the cell membrane for better detection of the extracellular oxygen concentration. Such characteristics allowed ratiometric imaging to distinguish the tumour location from normal tissues just 3 days after cancer cells were implanted, by monitoring the hypoxia condition and tracing the metabolism. Moreover, the pH sensitivity of the liposomes favoured cell uptake, and improved the anti-tumour efficiency of the formulation in vivo under NIR irradiation. Assuming liposomal systems have fewer safety issues, our work not only provides a facile method for the construction of a theragnostic system by combining phototherapy with photoluminescence imaging, but hopefully paves the way for clinical translation from bench to bedside.

Constructing multifunctional Cu Single-Atom nanozyme for synergistic nanocatalytic Therapy-Mediated Multidrug-Resistant bacteria infected wound healing.

Developing an effective strategy to combat multi-drug-resistant (MDR) bacteria and promote wound healing without overuse of antibiotics remains an important and challenging goal. Herein, we established a synergistic reactive oxygen species (ROS) and reactive nitrogen species (RNS)-mediated nanocatalytic therapy, which was consisted of a multifunctional Cu single-atom nanozyme loaded with the l-arginine (l-Arg@Cu-SAzymes) and a low level of hydrogen peroxide (H2O2) as a trigger. l-Arg@Cu-SAzymes can possess excellent dual enzyme-like activities: catalase (CAT)-like activity that decompose H2O2 into O2, and subsequent oxidase (OXD)-like activity that convert O2 to cytotoxic superoxide anion radical (•O2-). Meanwhile, l-Arg@Cu-SAzymes can also be triggered by H2O2 to release nitric oxide (NO), which can continue to react with •O2- to generate more lethal peroxynitrite (ONOO-). Collectively, the synergistic ROS and RNS mediated by l-Arg@Cu-SAzymes endow the treatment system with an outstanding antibacterial ability against MDR bacteria and reduce the inflammation at the wound site. Furthermore, l-Arg@Cu-SAzymes-mediated NO and O2 release promote the cell proliferation, collagen synthesis, and the angiogenesis, as well as facilitate macrophage polarization to reparative M2 phenotype, thereby accelerating wound closure and tissue remodeling. Therefore, l-Arg@Cu-SAzymes-based synergistic nanocatalytic therapy can be regarded as a promising strategy for MDR bacterial infected wounds treatment, owing to their potent antibacterial efficacy and enhanced tissue remodeling effects.

Estradiol cypionate inhibits proliferation and promotes apoptosis of gastric cancer by regulating AKT ubiquitination.

Gastric cancer is a common gastrointestinal malignancy worldwide, with a high mortality rate and poor prognosis. Multidrug resistance remains a major obstacle to successful treatment for patients. Hence, it is of great significance to develop novel therapies to potentiate the anti-tumor effect. In this study, we have investigated the effect of estradiol cypionate (ECP) on gastric cancer in vitro and vivo. Our data show that ECP inhibited the proliferation, promoted apoptosis, and caused G1/S phase arrest of gastric cancer cells. The mechanism by which ECP promoted apoptosis of gastric cancer cells was related to the downregulation of AKT protein expression caused by the increased ubiquitination modification levels of AKT, which finally inhibited the over-activation of the PI3K-AKT-mTOR signaling pathway. In vivo tumorigenesis experiments showed that ECP significantly inhibited the growth of gastric cancer cells, showing promise for clinical application. The above findings indicate that ECP inhibited the growth of gastric cancer and induced apoptosis through the PI3K /Akt/mTOR pathway. In summary, the efficacy showed in our data suggests that ECP is a promising anti-tumor compound for gastric cancer.

Zinc oxide nanoparticles have biphasic roles on Mycobacterium-induced inflammation by activating autophagy and ferroptosis mechanisms in infected macrophages.

The ability of zinc oxide nanoparticles (ZnONPs) to induce bacteriostasis in Mycobacterium tuberculosis (M. tb) and their roles in regulating the pathogenic activities of immune cells have been reported previously, but the specific mechanisms underlying these regulatory functions remain unclear. This work aimed to determine how ZnONPs play the antibacterial role against M. tb. In vitro activity assays were employed to determine the minimum inhibitory concentrations (MICs) of the ZnONPs against various strains of M. tb (BCG, H37Rv, and clinical susceptible MDR and XDR strains). The ZnONPs had MICs of 0.5-2 mg/L against all tested isolates. In addition, changes in the expression levels of autophagy and ferroptosis-related markers in BCG-infected macrophages exposed to ZnONPs were measured. BCG-infected mice that were administered ZnONPs were used to determine the ZnONPs functions in vivo. ZnONPs decreased the number of bacteria engulfed by the macrophages in a dose-dependent manner, while different doses of ZnONPs also affected inflammation in different directions. Although ZnONPs enhanced the BCG-induced autophagy of macrophages in a dose-dependent manner, only low doses of ZnONPs activated autophagy mechanisms by increasing the levels of pro-inflammatory factors. The ZnONPs also enhanced BCG-induced ferroptosis of macrophages at high doses. Co-administration of a ferroptosis inhibitor with the ZnONPs improved the anti-Mycobacterium activity of ZnONPs in an in vivo mouse model and alleviated acute lung injury caused by ZnONPs. Based on the above findings, we conclude that ZnONPs may act as potential antibacterial agents in future animal and clinical studies.

Enhancement of single upconversion nanoparticle imaging by topologically segregated core-shell structure with inward energy migration.

Manipulating topological arrangement is a powerful tool for tuning energy migration in natural photosynthetic proteins and artificial polymers. Here, we report an inorganic optical nanosystem composed of NaErF4 and NaYbF4, in which topological arrangement enhanced upconversion luminescence. Three architectures are designed for considerations pertaining to energy migration and energy transfer within nanoparticles: outside-in, inside-out, and local energy transfer. The outside-in architecture produces the maximum upconversion luminescence, around 6-times brighter than that of the inside-out at the single-particle level. Monte Carlo simulation suggests a topology-dependent energy migration favoring the upconversion luminescence of outside-in structure. The optimized outside-in structure shows more than an order of magnitude enhancement of upconversion brightness compared to the conventional core-shell structure at the single-particle level and is used for long-term single-particle tracking in living cells. Our findings enable rational nanoprobe engineering for single-molecule imaging and also reveal counter-intuitive relationships between upconversion nanoparticle structure and optical properties.

Identification and characterization of transposable element AhMITE1 in the genomes of cultivated and two wild peanuts.

BACKGROUND: The cultivated peanut (Arachis hypogaea L., AABB) is an allotetraploid hybrid between two diploid peanuts, A. duranensis (AA genome) and A. ipaensis (BB genome). Miniature inverted-repeat transposable elements (MITEs), some of which are known as active nonautonomous DNA transposons with high copy numbers, play important roles in genome evolution and diversification. AhMITE1, a member of the MITE family of transposons, but information on the peanut genomes is still limited. Here, we analyzed AhMITE1, AuMITE1 and ApMITE1 in the cultivated (A. hypogaea) and two wild peanut (A. duranensis and A. ipaensis) genomes. RESULTS: The cultivated and the two wild peanut genomes harbored 142, 14 and 21 AhMITE1, AuMITE1 and ApMITE1 family members, respectively. These three family members exhibited highly conserved TIR sequences, and insertions preferentially occurred within 2 kb upstream and downstream of gene-coding and AT-rich regions. Phylogenetic and pairwise nucleotide diversity analysis showed that AhMITE1 and ApMITE1 family members have undergone one round of amplification bursts during the evolution of the peanut genome. PCR analyses were performed in 23 peanut varieties and demonstrated that AhMITE1 is an active transposon and that hybridization or chemical mutagenesis can promote the mobilization of AhMITE1. CONCLUSIONS: AhMITE1, AuMITE1 and ApMITE1 family members were identified based on local BLAST search with MAK between the cultivated and the two wild peanut genomes. The phylogenetic, nucleotide diversity and variation copy numbers of AhMITE1, AuMITE1 and ApMITE1 members provides opportunities for investigating their roles during peanut evolution. These findings will contribute to knowledge on diversity of AhMITE1, provide information about the potential impact on the gene expression and promote the development of DNA markers in peanut.

Identification of AhFatB genes through genome-wide analysis and knockout of AhFatB reduces the content of saturated fatty acids in peanut (Arichis hypogaea L.).

Peanut (Arachis hypogaea L.) is an allotetraploid oilseed crop worldwide due to its abundant high-quality oil production. Peanut oil stability and quality are determined by the relative proportions of saturated fatty acids (SFAs) and unsaturated fatty acids (UFAs). The principle approach to minimize the content of SFAs in peanut is to reduce the content of palmitic acid, which is linked to cardiovascular disease. Acyl-acyl carrier protein thioesterases (FATs) determine the types and levels of fatty acids that are exported them from the plastids. Two different classes of FAT have been classified into two families in plants, FatA and FatB. Among them, AhFatB has become the primary objective to genetically reduce the content of palmitic acid in peanut. Here, we identified 18 AhFatB genes in A. hypogaea genome and grouped into four major subfamilies through gene structures and phylogenetic relationships. Expression profiling of AhFatB genes was assessed using the publicly available RNA-seq data and qRT-PCR in 22 tissues. Using the CRISPR/Cas9 system, we designed two sgRNAs to edit the homologs AhFatB genes Arahy.4E7QKU and Arahy.L4EP3N, and identified different types of mutations. Additionally, we discovered mutations at Arahy.4E7QKU exhibited low palmitic acid and high oleic acid phenotypes. The obtained peanut mutants with altered SFAs content have great potential for improving peanut oil quality for human health.

Breeding of a new variety of peanut with high-oleic-acid content and high-yield by marker-assisted backcrossing.

Peanut (Arachis hypogaea L.) is an important crop used for oil production, and oleic acid is a major factor in determining oil quality. Alterations in the oleic acid content can improve the nutritional quality and oxidative stability and prolong the shelf life of peanut products. The objective of this study was to develop a peanut variety with a high-oleic-acid content and high yield. One elite variety, "huayu22," was hybridized with the high-oleic-acid "KN176" donor and backcrossed for four generations as the recurrent parent using fad2 marker-assisted backcross selection. Based on the Kompetitive allele-specific PCR (KASP) screening of fad2 markers, the oleic acid content of advanced generations derived by selfing was assessed by near-infrared reflectance spectroscopy and gas chromatography. The genetic background recovery rate of four BC4F4 lines showed an average of 92.34% and was confirmed by genotyping using the Axiom_Arachis 58 K SNP array. Across these superior lines in BC4F6 generations, one line with a high-oleic-acid content and high yield was detected and named "YH61." In particular, yield comparison experiments showed that YH61 exhibited high and stable yield at three different locations and was moderately resistant to leaf spot disease. The distinctness, uniformity and stability (DUS) testing for two consecutive years suggested that YH61 reached the standard for variety rights application. The use of the peanut variety YH61 contributed to the expansion of the cultivation area due to its high value in the oleic acid market and the proven economic benefits in China. This study demonstrated that the marker-assisted backcross strategy based on a cost-effective KASP assay and SNP array for the detection of mutations in fad2 and genetic background evaluation can be used to create efficient peanut breeding programs and contribute to oil quality and high-yield stability. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-022-01313-9.

Light-Responsive Luminescent Materials for Information Encryption Against Burst Force Attack.

Optical encryption with easy operation, multichannel and high security has been one of the most significant technologies for information security. Stimuli-responsive luminescent materials have emerged as an ideal candidate for optical encryption, owing to its smart responsive property and high security. Herein, a type of light-responsive multicolor luminescent materials for high-security information encryption, which are fabricated by combining sensitizer, consumption unit, and emitter is developed. Different types of sensitizers to achieve different stimulus light responses, and multicolor light-responsive luminescent can be obtained by varying the composition of perovskite nanocrystals emitter can be selected. Both stimulus light and emission color can be used as distinguishable encoding dimensions, which enable multiplexed encoding with high capacity and complexity. Importantly, the controllable consumption can be manipulated by varying the concentration of consumption unit, so the programmed information encoded in different channels can be selectively read and erased simultaneously by varying stimulus light. The method makes the encryption information highly resistive to brute force trial-and-error attacks, which achieves high security level of information protection.

STIM1 Regulates Endothelial Calcium Overload and Cytokine Upregulation During Sepsis.

BACKGROUND: Stromal interaction molecule 1 (STIM1)-mediated store-operated Ca2+ entry (SOCE) is now recognized as the main mechanism of the majority of nonexcitable cell calcium influx. Calcium overload is a primary mechanism of endothelial cell injury during systemic inflammatory response and sepsis. Whether STIM1-mediated SOCE plays a role in calcium overload in vascular endothelial cell injury remains unclear. MATERIALS AND METHODS: To explore the role of STIM1-gated SOCE in vascular endothelial cell calcium overload and inflammation, we established a human septic serum or lipopolysaccharide (LPS)-induced human umbilical vein endothelial cell (HUVEC) experimental system and derived ribonucleic acid interference (RNAi)-mediated STIM1, ORAI1 (orai gene [HGNC: 25896 Entrez Gene: 84876] coding protein, ORAI Calcium Release-Activated Calcium Modulator 1), and transient receptor potential channel 1 (TRPC1) (core components of store-operated Ca2+[SOC]) downregulated HUVECs, as well as STIM1 overinduced HUVECs. RESULTS: Our results show that sepsis serum or LPS stimulation increased STIM1 in HUVECs and increased all cytokines except for VEGF and the inflammatory mediators tumor necrosis factor, intercellular cell adhesion molecule-1, and endothelin-1 in a time-dependent manner. RNAi-mediated knockdown of STIM1 significantly inhibited serum or LPS-induced inflammatory cytokine expression, and STIM1 overexpression in HUVECs promoted LPS-mediated induction of these cytokines. Meanwhile, similar to the blocking effect of the specific SOC inhibitors Gd3+ and La3+ on LPS-induced calcium influx, RNAi-mediated depletion of STIM1 or the SOC proteins TRPC1 and ORAI1 could significantly inhibit serum or LPS-induced extracellular calcium influx, as well as the expression of the inflammatory cytokines tumor necrosis factor, intercellular cell adhesion molecule-1, and endothelin-1. Simultaneous downregulation of the SOCE core units TRPC1 and ORAI1 inhibited LPS-induced calcium influx and cytokine expression, which could not be restored by inducing STIM1. Forced expression of nuclear factor-κB (NF-κB) in HUVECs significantly induced STIM1 expression, whereas RNAi-mediated depletion of NF-κB significantly inhibited STIM1 mRNA levels and significantly reduced the thapsigargin-mediated SOCE calcium influx, which was similar to results with the NF-κB inhibitor wogonin. CONCLUSIONS: Septic serum stimulates the expression of STIM1, cytokines, and inflammatory mediators in HUVECs. STIM1-mediated SOCE is required for Ca2+ influx induced by LPS or septic serum and contributes cytokines and inflammatory mediators in septic serum-stimulated HUVECs. In addition, STIM1-mediated SOCE on Ca2+ influx by septic serum or LPS involves NF-κB signaling.

LPS-induced vein endothelial cell injury and acute lung injury have Btk and Orai 1 to regulate SOC-mediated calcium influx.

Patients with sepsis and sepsis-related complications have a high mortality. Endothelial cell dysfunction plays a central role in sepsis pathophysiological process. In sepsis patients, endothelial cell apoptosis is associated with intracellular calcium overload. Multiple functions in the apoptotic process have been found to be regulated by calcium signaling. Our previous work had proved that LPS-induced cell injury was associated with store-operated calcium (SOC) entry mediated by stromal interaction molecule-1 (STIM 1) in Human umbilical vein endothelial cells (HUVEC), but the underlying molecular mechanism has not been adequately defined. Here we report that the LPS-induced cell injury is related to the calcium overload in HUVEC. SOC entry mediated by calcium release-activated calcium modulator (Orai) 1 and transient receptor potential canonical (TRPC) 1 was associated with LPS-induced calcium overload and cell apoptosis. Bruton's tyrosine kinase (Btk)/Phospholipase C(PLC) γ/inositol 1,4,5-triphosphate receptor (IP3R) played a major role in regulating calcium overload in LPS-induced HUVEC. Knockdown of Btk markedly inhibited the expressions of Orai 1 and its downstream molecule IP3R but not that of TRPC1 in LPS-induced HUVEC. In mice, knockdown of Btk and Orai 1 inhibited LPS-induced calcium overload, pulmonary vascular endothelial cell (VEC) injury and acute lung injury. These findings demonstrated that Btk acts as a regulator of calcium-dependent signaling, especially in the Orai 1-mediated SOC entry of the LPS-induced VEC.

Measurement of Temperature Distribution at the Nanoscale with Luminescent Probes Based on Lanthanide Nanoparticles and Quantum Dots.

It is very challenging to probe the temperature in a nanoscale because of the lack of detection technique. Temperature-sensitive luminescent probes at a nanoscale provide the possibility to solve this problem. Herein, we fabricated a model, which combined two kinds of temperature sensitive nanoprobes and gold nanoparticle heater within mesoporous silica nanoparticles. Upconverting nanoparticles and quantum dots located at different positions inside 110 nm nanoparticles reported different temperatures when the gold nanoparticles generated heat by 532 nm laser irradiation. The temperature difference between two probes with an average distance of 55 nm can reach about 30 °C. Our results prove that the temperature distribution at a nanoscale can be measured, and it will be noteworthy if a nano-heater is applied.

Quantitative Mapping of Liver Hypoxia in Living Mice Using Time-Resolved Wide-Field Phosphorescence Lifetime Imaging.

Hypoxia has been identified to contribute the pathogenesis of a wide range of liver diseases, and therefore, quantitative mapping of liver hypoxia is important for providing critical information in the diagnosis and treatment of hepatic diseases. However, the existing imaging methods are unsuitable to quantitatively assess liver hypoxia due to the need of liver-specific contrast agents and be easily affected by other imaging factors. Here, a time-resolved lifetime-based imaging method is established for quantitative mapping of the distribution of hypoxia in the livers of mice by combining a wide-field luminescence lifetime imaging system with an oxygen-sensitive nanoprobe. It is shown that the method is suitable for real-time quantification of the change of oxygen pressure in the process of hepatic ischemia-reperfusion of the mouse. Moreover, the developed lifetime imaging methodology is used to quantitatively map liver hypoxia regions in the mouse model of orthotopic liver tumor, where the average oxygen pressure in tumorous liver is far below the normal liver.

Hydrogen attenuates radiation-induced intestinal damage by reducing oxidative stress and inflammatory response.

The small intestine is known to be particularly sensitive to radiation, and the major limiting factor of radiotherapy is the gastrointestinal syndrome that subsequently develops after its administration. The detrimental effects of radiation are mostly mediated via the overproduction of reactive oxygen species (ROS), especially the hydroxyl radical (·OH). Because hydrogen is a selective ·OH scavenger, we hypothesized that hydrogen might exert a protective effect against radiation-induced intestinal damage. Herein, radiation models were built both in mice and in an intestinal crypt epithelial cell (IEC-6) line. In the animal experiment, we demonstrated that hydrogen-rich saline significantly reduced radiation-induced intestinal mucosal damage, improved intestinal function, and increased the survival rate. In addition, radiation-induced oxidative stress damage and systemic inflammatory response were also mitigated by hydrogen treatment. Moreover, hydrogen treatment decreased cell apoptosis and maintained intestinal epithelial cell proliferation in mice. In vitro experiments using the IEC-6 cell line showed that hydrogen-rich medium significantly inhibited ROS formation, maintained cell viability, and inhibited cell apoptosis. Importantly, hydrogen treatment prevented mitochondrial depolarization, cytochrome c release, and activity of caspase-3, caspase-9, and PARP. Moreover, the decreased expression of Bcl-xl and Bcl-2 and the increased expression of Bax protein were also blocked by hydrogen treatment. In conclusion, our study concurrently demonstrated that hydrogen provides an obviously protective effect on radiation-induced intestinal and cell injuries. Our work demonstrated that this protective effect might be due to the blockage of the mitochondrial apoptotic pathway.

EDTA-Modified 17ß-Estradiol-Laden Upconversion Nanocomposite for Bone-Targeted Hormone Replacement Therapy for Osteoporosis.

Hormone therapy (HT) is one of the most effective treatments for osteoporosis. However, the nonselective accumulation of hormone in organs such as breast, heart and uterus other than bones causes serious side effects, which impedes the application of HT. Hence, it is critically important to develop a HT strategy with reduced non-specific enrichment of hormone drugs in non-target tissues and enhanced bone-targeting ability. Methods: Herein, a 17ß-estradiol (E2)-laden mesoporous silica-coated upconversion nanoparticle with a surface modification of ethylenediaminetetraacetic acid (EDTA) (NaLuF4:Yb,Tm@NaLuF4@mSiO2-EDTA-E2, E2-csUCNP@MSN-EDTA) is developed for bone-targeted osteoporosis hormone therapy. EDTA was attached onto the surface of E2 upconversion nanocomposite to enhance its affinity and efficiency targeting bone tissue and cells to optimize hormone replacement therapy for osteoporosis. We characterized the size, cytotoxicity, loading and release efficiency, in situ and ex vivo imaging. Further, in vitro and in vivo osteogenic ability was tested using preosteoblast and ovariectomy mouse model of osteoporosis. Results: The upconversion core of E2-csUCNP@MSN-EDTA nanoparticle serves as an excellent imaging agent for tracking the loaded hormone drug in vivo. The mesoporous silica layer has a high loading efficiency for E2 and provides a relatively long-lasting drug release within 50 h. EDTA anchored on the silica layer endows the nanocomposite with a bone targeting property. The nanocomposite effectively reverses estrogen deficiency-induced osteoporosis and reduces the damage of hormone to the uterus. The bone mineral density in the nanocomposite treatment group is nearly twice that of the ovariectomized (OVX) group. Compared with the E2 group, the uterine weight and luminal epithelial height were significantly lower in the nanocomposite treatment group. Conclusion: This work demonstrated that E2-csUCNP@MSN-EDTA alleviates the side effect of hormone therapy while maintaining its therapeutic efficacy, which has great potential for developing the next generation of methods for osteoporosis treatment.

Ratiometric upconversion nanothermometry with dual emission at the same wavelength decoded via a time-resolved technique.

The in vivo temperature monitoring of a microenvironment is significant in biology and nanomedicine research. Luminescent nanothermometry provides a noninvasive method of detecting the temperature in vivo with high sensitivity and high response speed. However, absorption and scattering in complex tissues limit the signal penetration depth and cause errors due to variation at different locations in vivo. In order to minimize these errors and monitor temperature in vivo, in the present work, we provided a strategy to fabricate a same-wavelength dual emission ratiometric upconversion luminescence nanothermometer based on a hybrid structure composed of upconversion emissive PbS quantum dots and Tm-doped upconversion nanoparticles. The ratiometric signal composed of two upconversion emissions working at the same wavelength, but different luminescent lifetimes, were decoded via a time-resolved technique. This nanothermometer improved the temperature monitoring ability and a thermal resolution and sensitivity of ~0.5 K and ~5.6% K-1 were obtained in vivo, respectively.

Monocular Visual-Inertial Odometry with an Unbiased Linear System Model and Robust Feature Tracking Front-End.

The research field of visual-inertial odometry has entered a mature stage in recent years. However, unneglectable problems still exist. Tradeoffs have to be made between high accuracy and low computation for users. In addition, notation confusion exists in quaternion descriptions of rotation; although not fatal, this may results in unnecessary difficulties in understanding for researchers. In this paper, we develop a visual-inertial odometry which gives consideration to both precision and computation. The proposed algorithm is a filter-based solution that utilizes the framework of the noted multi-state constraint Kalman filter. To dispel notation confusion, we deduced the error state transition equation from scratch, using the more cognitive Hamilton notation of quaternion. We further come up with a fully linear closed-form formulation that is readily implemented. As the filter-based back-end is vulnerable to feature matching outliers, a descriptor-assisted optical flow tracking front-end was developed to cope with the issue. This modification only requires negligible additional computation. In addition, an initialization procedure is implemented, which automatically selects static data to initialize the filter state. Evaluations of proposed methods were done on a public, real-world dataset, and comparisons were made with state-of-the-art solutions. The experimental results show that the proposed solution is comparable in precision and demonstrates higher computation efficiency compared to the state-of-the-art.

Near-Infrared Upconversion Luminescence and Bioimaging In Vivo Based on Quantum Dots.

Recently, upconversion luminescence (UCL) has been widely applied in bioimaging due to its low autofluorescence and high contrast. However, a relatively high power density is still needed in conventional UCL bioimaging. In the present study, an ultralow power density light, as low as 0.06 mW cm-2, is applied as an excitation source for UCL bioimaging with PbS/CdS/ZnS quantum dots (UCL-QDs) as probes. The speculated UCL mechanism is a phonon-assisted single-photon process, and the relative quantum yield is up to 4.6%. As determined by continuous irradiation with a 980 nm laser, the UCL-QDs show excellent photostability. Furthermore, UCL-QDs-based probe is applied in tumor, blood vessel, and lymph node bioimaging excited with an eye-safe low-power light-emitting diode light in a nude mouse with few heat effects.

Upconversion nanocomposite for programming combination cancer therapy by precise control of microscopic temperature.

Combinational administration of chemotherapy (CT) and photothermal therapy (PTT) has been widely used to treat cancer. However, the scheduling of CT and PTT and how it will affect the therapeutic efficacy has not been thoroughly investigated. The challenge is to realize the sequence control of these two therapeutic modes. Herein, we design a temperature sensitive upconversion nanocomposite for CT-PTT combination therapy. By monitoring the microscopic temperature of the nanocomposite with upconversion luminescence, photothermal effect can be adjusted to achieve thermally triggered combination therapy with a sequence of CT, followed by PTT. We find that CT administered before PTT results in better therapeutic effect than other administration sequences when the dosages of chemodrug and heat are kept at the same level. This work proposes a programmed method to arrange the process of combination cancer therapy, which takes full advantage of each therapeutic mode and contributes to the development of new cancer therapy strategies.

miR-27a protects against acute lung injury in LPS-treated mice by inhibiting NF-κB-mediated inflammatory response.

Acute lung injury (ALI), which is an excessive uncontrolled inflammatory response in the lung, is mediated by several pro-inflammatory mediators. Recent evidence has implicated microRNAs (miRNAs) in regulation of inflammation in different diseases. However, the roles and underlying molecular mechanism of miRNAs in ALI have not been adequately elucidated. Thus, the aim of the present study was to investigate the possible regulatory mechanism of miRNAs in ALI. In this study, microRNA microarray analysis showed that 48 miRNAs were differentially expressed in lung tissues of an ALI model induced by LPS. Downregulation of miR-27a, played a key role in the regulation of the inflammatory response and protection from traumatic injury. Functional analyses indicated that overexpression of miR-27a using miR-27a agomir (agomiR-27a) protected the animals from LPS-induced ALI through decreased pulmonary inflammation, decreased wet-to-dry weight ratio, and ameliorated lung histopathological changes. In addition, agomiR-27a also decreased production of inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) in bronchoalveolar lavage fluid (BALF). Moreover, transforming growth factor ß-activated kinase 1 binding protein 3 (TAB3), as an activator of NF-κB, was confirmed as a direct target of miR-27a. Further study showed that the anti-inflammatory mechanism of miR-27a is exerted via suppression NF-κB signaling by inhibiting expression of TAB3 in LPS-induced ALI mice. Taken together, these data define the protective mechanism of miR-27a via inhibition of the inflammatory response through blocking NF-κB pathway. Therefore, miR-27a/TAB3/NF-κB axis may be therapeutically targeted to repress inflammation following ALI in the future.