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.

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.

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.

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.

Fast-Clearable Nanocarriers Conducting Chemo/Photothermal Combination Therapy to Inhibit Recurrence of Malignant Tumors.

Inhomogeneous heating by photothermal therapy (PTT) during cancer treatment often results in the recurrence of tumors. Thus, integrating PTT with chemotherapy (CHT) may provide a complementary treatment for enhanced therapeutic efficiency. Herein, this study develops a hollow structured polymer-silica nanohybrid (HPSN) as a nanocarrier to simultaneously deliver the anticancer drug paclitaxel and photothermal agent palladium phthalocyanine to tumors through enhanced permeation and the retention effect. A combinational CHT/PTT therapy on mice bearing aggressive tumor grafts is conducted. The highly malignant tumor model, which recurs after sole treatment of PTT, can be eradicated by the combined CHT/PTT treatment. In addition, most of the off-targeted HPSN nanocarriers can be excreted through a hepatobiliary pathway in about 10 d. Serology results show that the fast-clearable HPSN can significantly reduce the side effect of the loaded paclitaxel drug. The present work provides an alternative approach for combinational cancer treatment with high therapeutic efficiency.

The effects of porcine pulmonary surfactant on smoke inhalation injury.

BACKGROUND: Our previous study, consistent with others, demonstrated that administering an exogenous surfactant was a potential therapy for acute lung injury and acute respiratory distress syndrome. However, the underlying mechanisms remain largely unknown. In the present study, we investigated the effect of instilled porcine pulmonary surfactant (PPS) on rat inhalation injury model induced by smoke and the possible mechanism. MATERIALS AND METHODS: Fifteen Sprague-Dawley rats were equally randomized to three groups as follows (n = 5 in each group): sham control group (C group), inhalation injury group (II group), and inhalation injury + PPS treatment group (PPS group). Lung tissues were assayed for wet/dry ratio, histologic, terminal dUTP nick-end labeling staining, and Western blotting examinations. The myeloperoxidase activity was tested in lung tissues as well. Bronchoalveolar lavage fluid was collected to determine the total protein concentrations, inflammatory cytokines, surfactant protein A (SP-A), and SP-D. RESULTS: Our present work exhibited that PPS had therapeutic effects on smoke inhalation injury reflected by significant increase of PaO2 values, improved edema status, decreased vascular permeability, amelioration of lung histopathology, and reduction of inflammatory response. In addition, PPS treatment could increase endogenous SP-A levels both in lung tissue and bronchoalveolar lavage fluid. Further correlation analysis showed that SP-A was negatively correlated with both myeloperoxidase activity and interleukin 8 levels. CONCLUSIONS: These results indicate that PPS can attenuate smoke-induced inhalation injury at least partly through stimulating production of endogenous SP-A and inhibiting the release of proinflammatory cytokines such as interleukin 8. The increasing production of endogenous SP-A may be due to the antioxidant effect of PPS, which contains no SP-A.

Using negative pressure wound therapy on microskin autograft wounds.

BACKGROUND: Microskin autografts with conventional wrap and compression are used extensively in the treatment of skin and tissue defects. This comparative study aimed at investigation of the clinical application of negative pressure wound therapy (NPWT) in combination with microskin autografts for repair of acute and chronic wounds. METHODS: A prospective case-control study was performed from December 1, 2010-December 31, 2013 in Changhai Hospital, Shanghai. We compared a study group of patients received microskin autografting covered by NPWT with that of a control group of patients received microskin autografting covered by a conventional gauze. RESULTS: A total of 81 patients were in this study, 27 patients were allocated to the study group and 54 patients to the control group. The study group exhibited significant low infection rate and pain score during removal of inner layer at first dressing change after skin grafting compared with those of the control group (P < 0.05). The time interval between skin grafting and first postoperative change was longer in the study group than that in the control group (P < 0.01), the study group showed a significant shorter 95% wound healing time (P < 0.05), and survival rate of microskin autografts in the study group was higher than that in the control group (P < 0.05). CONCLUSIONS: NPWT is beneficial for wound closure after microskin autografts, which prolongs the interval between skin transplantation and first postoperative dressing change, reduces pain during removal of inner layer dressing, increases skin graft survival rate, and shortens wound healing time. Therefore, NPWT can be recommended for repair of acute and chronic wounds with microskin autografts.

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.

Spatial transcriptomic sequencing reveals immune microenvironment features of Mycobacterium tuberculosis granulomas in lung and omentum.

Granulomas are a key pathological feature of tuberculosis (TB), characterized by cell heterogeneity, spatial composition, and cellular interactions, which play crucial roles in granuloma progression and host prognosis. This study aims to analyze the transcriptome profiles of cell populations based on their spatial location and to understand the core transcriptome characteristics of granuloma formation and development. Methods In this study, we collected four clinical biopsy samples including Mycobacterium tuberculosis (Mtb) infected lung (MTB-L) and omentum tissues (MTB-O), as well as two lung and omentum biopsies from non-TB patients. The tissues were analyzed by spatial transcriptomics to create a spatial atlas. Utilizing cell enrichment scores and intercellular communication analysis, we investigated the transcriptome signatures of cell populations in various spatial regions and identified genes that may play a decisive role in the formation of pulmonary and omental tuberculosis granulomas. To validate our major findings, an in vitro TB model based on organoid-macrophage co-culture was established. Results Spatial transcriptomics mapped the cell composition and spatial distribution characteristics of tuberculosis granulomas in lung and omental tissues infected with Mtb. The characteristics and evolutionary relationships of major cell populations in granulomas reveal a shift in the immune microenvironment: from a predominance of B cells and fibroblasts in pulmonary granulomas to a predominance of myeloid cells and fibroblasts in omental granulomas. Furthermore, our data identified key differentially expressed genes across cell clusters and regions, showing that upregulation of collagen genes is a common feature of granulomas. Using an organoid-macrophage co-culture model, we demonstrated the notable efficacy of Thrombospondin-1 (THBS1) in reducing protein expression levels related to extracellular matrix remodeling. Conclusion These results provide insights into the pathogenesis and development of tuberculosis, enhancing our understanding of the composition and interactions of tuberculosis granuloma cells from a spatial perspective, and pave the way for novel adjuvant treatments for tuberculosis.

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.

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.

A rat model of smoke inhalation injury.

CONTEXT: Smoke inhalation injury is the leading cause of acute respiratory failure in critical burn victims. Advances in the treatment of smoke inhalation injury have been limited in the past years. To further explore the pathogenesis, stable and practical animal models are necessary. OBJECTIVE: To develop a rat model of smoke inhalation injury. MATERIALS AND METHODS: The smoke composition including the particulate matters, irritant gases, chemical carcinogens was measured. The blood gas values, pro-inflammatory and protein concentration in bronchoalveolar lavage fluid and lung wet to dry weight ratio were assayed. Pathological evaluations of pulmonary were performed at 24 h, 96 h, 7 days and 28 days post-injury. Masson-Goldner trichrome staining was performed on day 7 and 28 post-injury, along with the measurement of hydroxyproline and collagen I and III. RESULTS: In our present animal model, smoke inhalation caused a significant hypoxemia and CO poisoning. A surge of pro-inflammatory response and microvascular hyperpermeability with neutrophils accumulations were also found in our animal model. At 24 h post-smoke inhalation, the hematoxylin and eosin results exhibited that there were inflammatory exudates and diffuse hemorrhage in the lung tissue with significant edema. With the time going, the lung injuries appeared at alveolar collapse and alveolar septum thickening, which indicated that smoke inhalation further induced damage to lung parenchyma. Specially, the markedly collagen deposition appeared at 28 days post-injury indicated that pulmonary fibrosis happened. DISCUSSION AND CONCLUSION: In conclusion, this rat smoke inhalation injury model induced by our novel self-made smoke generator could be used for acute and chronic lung injury experiments.

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 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.

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.

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.

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.

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.