Programming peptide-oligonucleotide nano-assembly for engineering of neoantigen vaccine with potent immunogenicity.

Background: Neoantigen nanovaccine has been recognized as a promising treatment modality for personalized cancer immunotherapy. However, most current nanovaccines are carrier-dependent and the manufacturing process is complicated, resulting in potential safety concerns and suboptimal codelivery of neoantigens and adjuvants to antigen-presenting cells (APCs). Methods: Here we report a facile and general methodology for nanoassembly of peptide and oligonucleotide by programming neoantigen peptide with a short cationic module at N-terminus to prepare nanovaccine. The programmed peptide can co-assemble with CpG oligonucleotide (TLR9 agonist) into monodispersed nanostructures without the introduction of artificial carrier. Results: We demonstrate that the engineered nanovaccine promoted the codelivery of neoantigen peptides and adjuvants to lymph node-residing APCs and instigated potent neoantigen-specific T-cell responses, eliciting neoantigen-specific antitumor immune responses with negligible systemic toxicity. Furthermore, the antitumor T-cell immunity is profoundly potentiated when combined with anti-PD-1 therapy, leading to significant inhibition or even complete regression of established melanoma and MC-38 colon tumors. Conclusions: Collectively, this work demonstrates the feasibility and effectiveness of personalized cancer nanovaccine preparation with high immunogenicity and good biosafety by programming neoantigen peptide for nanoassembly with oligonucleotides without the aid of artificial carrier.

EPAC inhibitor suppresses angiogenesis and tumor growth of triple-negative breast cancer.

AIMS: Exchange protein directly activated by cAMP 1 (EPAC1), a major isoform of guanine nucleotide exchange factors, is highly expressed in vascular endothelia cells and regulates angiogenesis in the retina. High intratumor microvascular densities (MVD) resulting from angiogenesis is responsible for breast cancer development. Downregulation of EPAC1 in tumor cell reduces triple-negative breast cancer (TNBC)-induced angiogenesis. However, whether Epac1 expressed in vascular endothelial cells contributes to angiogenesis and tumor development of TNBC remains elusive. MAIN METHODS: We employed NY0123, a previously identified potent EPAC inhibitor, to explore the anti-angiogenic biological role of EPAC1 in vitro and in vivo through vascular endothelial cells, rat aortic ring, Matrigel plug, and chick embryo chorioallantoic membrane (CAM) and yolk sac membrane (YSM) assays, as well as the in vivo xenograft tumor models of TNBC in both chick embryo and mice. KEY FINDINGS: Inhibiting EPAC1 in vascular endothelial cells by NY0123 significantly suppresses angiogenesis and tumor growth of TNBC. In addition, NY0123 possesses a better inhibitory efficacy than ESI-09, a reported specific EPAC inhibitor tool compound. Importantly, inhibiting EPAC1 in vascular endothelia cells regulates the typical angiogenic signaling network, which is associated with not only vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor-2 (VEGFR2) signaling, but also PI3K/AKT, MEK/ERK and Notch pathway. CONCLUSIONS: Our findings support that EPAC1 may serve as an effective anti-angiogenic therapeutic target of TNBC, and EPAC inhibitor NY0123 has the therapeutic potential to be developed for the treatment of TNBC.

Bioactive mesoporous silica nanoparticle-functionalized titanium implants with controllable antimicrobial peptide release potentiate the regulation of inflammation and osseointegration.

Bacterial infection and delayed osseointegration are two major challenges for titanium-based orthopedic implants. In the present study, we developed a functionalized titanium implant Ti-M@A by immobilizing antimicrobial peptide (AMP) HHC36-loaded diselenide-bridged mesoporous silica nanoparticles (MSNs) on the surface, which showed good long-term and mechanical stability. The functionalized implants can realize the sustained release of AMP over 30 days and exhibit over 95.71 % antimicrobial activity against four types of clinical bacteria (S. aureus, E. coli, P. aeruginosa and MRSA), which arose from the capability to destroy the bacterial membranes. Moreover, Ti-M@A can efficiently inhibit the biofilm formation of the bacteria. The functionalized implants can also significantly promote the osteogenic differentiation of mouse bone marrow-derived mesenchymal stem cells (mBMSCs) because of the Se in MSNs. Notably, it can trigger macrophages toward M2 polarization in vitro by scavenging ROS in LPS-activated macrophages. Consequently, in vivo assays with infection and non-infection bone defect models demonstrated that such bioactive implants can not only kill over 98.82 % of S. aureus, but also promote osseointegration. Hence, this study provides a combined strategy to resolve bacterial infection and delayed osseointegration for titanium implants.

Surface Energy Engineering of Buried Interface for Highly Stable Perovskite Solar Cells with Efficiency Over 25.

The abundant oxygen-related defects (e.g., O vacancies, O-H) in the TiO2 electron transport layer results in high surface energy, which is detrimental to effective carrier extraction and seriously impairs the photovoltaic performance and stability of perovskite solar cells. Here, novel surface energy engineering (SEE) is developed by applying a surfactant of heptadecafluorooctanesulfonate tetraethylammonium (HFSTA) on the surface of the TiO2 . Theoretical calculations show that the HFSTA-TiO2 is less prone to form O vacancies, leading to lower surface energy, thus improving the carrier-extraction efficiency. The experimental results show that superior perovskite film is obtained due to the reduced heterogeneous nucleation sites and improved crystallization process on the modified TiO2 . Furthermore, the flexible long alkyl chains in HFSTA considerably relieve the compressive stresses at the buried interface. By combining the passivation of TiO2 , crystallization process modulation, and stress relief, a champion PCE up to 25.03% is achieved. The device without encapsulation sustains 92.2% of its initial PCE after more than 2500 h storage under air ambient with relative humidity of 25-30%. The SEE of a buried interface paves a new way toward high-efficiency, stable perovskite solar cells.

In Situ Formation of 2D Perovskite Seeding for Record-Efficiency Indoor Perovskite Photovoltaic Devices.

With 40% efficiency under room light intensity, perovskite solar cells (PSCs) will be promising power supplies for low-light applications, particularly for Internet of Things (IoT) devices and indoor electronics, shall they become commercialized. Herein, ß-alaninamide hydrochloride (AHC) is utilized to spontaneously form a layer of 2D perovskite nucleation seeds for improved film uniformity, crystallization quality, and solar cell performance. It is found that the AHC addition indeed improves film quality as demonstrated by better uniformity, lower trap density, smaller lattice stress, and, as a result, a 10-fold increase in charge carrier lifetime. Consequently, not only does the small-area (0.09 cm2 ) PSCs achieve a power conversion efficiency of 42.12%, the large-area cells (1.00 cm2 , and 2.56 cm2 ) attain efficiency as high as 40.93%, and 40.07% respectively. All of these are the highest efficiency values for indoor photovoltaic cells with similar sizes, and more importantly, they represent the smallest efficiency loss due to area scale-up. This work provides a new method to fabricate high-performance indoor PSCs (i-PSCs) for IoT devices with great potential in large-area printing technology.

Iridium nanozyme-mediated photoacoustic imaging-guided NIR-II photothermal therapy and tumor microenvironment regulation for targeted eradication of cancer stem cells.

Cancer stem cells (CSCs) are found in many solid tumors, which play decisive roles in the occurrence, recurrence and metastasis of tumors. However, drugs are difficult to kill CSCs due to their limited number and location in oxygen-deprived tissue far from the blood vessels. Meanwhile, the survival and stemness maintenance of CSCs strongly depend on the tumor microenvironment (TME). Herein, we developed a CD44 antibody modified iridium nanosheet with enzyme-like activity (defined as Ir Nts-Ab) that effectively eradicates CSCs for cancer therapy. We observe that Ir Nts-Ab can enrich tumor tissues to remove excessive reactive oxygen species and produce oxygen, thus alleviating hypoxia and the inflammatory TME to reduce the proportion of CSCs and inhibit metastasis. In addition, Ir Nts-Ab targets CSCs and normal cancer cells with near infrared II-region photothermal therapy (NIR-II PTT), and is easily taken up by CSCs due to recognition of the CD44 proteins. Moreover, photoacoustic imaging helps monitor drug accumulation and hypoxic TME improvement in tumor tissue. Importantly, Ir Nts-Ab has good biological safety, making it suitable for biomedical applications. This iridium nanozyme based on TME regulation as well as NIR-II PTT will be a promising strategy for the treatment of cancer. STATEMENT OF SIGNIFICANCE: Cancer stem cells (CSCs) are key factors that make tumors difficult to eradicate, and strongly depend on the hypoxic tumor microenvironment (TME), which plays a crucial role in the occurrence and metastasis of tumors. Herein, an antibody modified iridium nanosheet (definition as Ir Nts-Ab) was developed for targeted eradication of CSCs by photoacoustic imaging guided photothermal therapy (PTT) and TME regulation. Ir Nts-Ab with catalase-like activity could inhibit HIF-1α by producing oxygen, thus effectively reducing the proportion of CSCs and inhibiting tumor metastasis. Additionally, Ir Nts-Ab achieved the eradication of CSCs by PTT, and eliminated reactive oxygen species to decrease the inflammatory response, resulting in reduced tumor metastasis, which was promising for the cure of solid tumors in the clinics.

A spatially-controlled DNA triangular prism nanomachine for AND-gated intracellular imaging of ATP in acidic microenvironment.

A DNA triangular prism nanomachine (TPN)-based logic device for intracellular AND-gated imaging of adenosine triphosphate (ATP) has been constructed. By using i-motif sequences and ATP-binding aptamers as logic control units, the TPN logic device is qualified to respond to the acidic environment and ATP in cancer cell lysosomes. Once internalized into the lysosome, the specific acidic microenvironment in lysosome causes the i-motif sequence to fold into a tetramer, resulting in compression of DNA tri-prism. Subsequently, the split ATP aptamer located at the tip of the collapsed triangular prism binds stably to ATP, which results in the fluorescent dyes (Cy3 and Cy5) modified at the ends of the split aptamer being in close proximity to each other, allowing Förster Resonance Energy Transfer (FRET) to occur. The FRET signals are excited at a wavelength of 543 nm and can be collected within the emission range of 646-730 nm. This enables the precise imaging of ATP within a cell. We also dynamically operate AND logic gates in living cells by modulating intracellular pH and ATP levels with the help of external drugs. Owing to the AND logic unit on TPN it can simultaneously recognize two targets and give corresponding intelligent logic judgment via imaging signal output. The accuracy of molecular diagnosis of cancer can be improved thus eliminating the false positive signal of single target-based detection. Hence, this space-controlled TPN-based logical sensing platform greatly avoids sensitivity to extracellular targets during the cell entry process, providing a useful tool for high-precision imaging of the cancer cell's endogenous target ATP.

Combination of specific proteins as markers for accurate detection of extracellular vesicles using proximity ligation-mediated bHCR amplification.

As the molecular characteristics of extracellular vesicles (EVs) are closely related to the occurrence and progression of cancer, the detection of tumor-derived EVs provides a promising non-invasive tool for the early diagnosis and treatment of cancer. However, it would be difficult for most of the existing methods to avoid false positives because the obtained result declares the amounts of proteins, but cannot accurately reflect the protein sources, including EV proteins and interfering proteins, in the actual samples. In this manuscript, a robust, accurate, and sensitive fluorescent strategy for profiling EV proteins is developed by using the combination of specific proteins as markers (Co-marker). Our strategy relies on the Co-marker recognition-activated cascade bHCR amplification, which forms numerous G-quadruplex structures that are integrated with fluorescent dyes for signal transduction. Notably, the detection accuracy can be improved owing to the effective avoidance of false positives from interfering proteins or single protein markers. Moreover, by using the double-positive protein recognition mode, unpurified detection can be achieved that avoids time-consuming EVs purification procedures. With its capacities of accuracy, portability, sensitivity, high throughput, and non-purification, the developed strategy might provide a practical tool for EV identification and the related early diagnosis and treatment of cancer.

Development of a QM/MM(ABEEM) method combined with a polarizable force field to investigate the excision reaction mechanism of damaged thymine.

This paper focuses on the development of a quantum mechanics/molecular mechanics method using the ABEEM polarizable force field (QM/MM(ABEEM) method) to investigate the excision reaction mechanism of damaged thymine. This method does not simply combine the QM method with the polarizable force field. A valence electronegativity piecewise function with the distance between atoms as a variable is introduced to describe the atomic partial charges, and changes greatly during the reaction process. At the same time, the charge transfer effect is treated using the condition of local charge conservation. Compared with the traditional QM/MM method, the QM/MM(ABEEM) method can more accurately simulate the polarization effect and charge transfer effect in the reaction process. Focusing on the controversial problems of the excision of damaged bases, six reaction pathways were designed for monofunctional and difunctional deglycosylation of neutral bases and protonated bases. The results show that the QM/MM(ABEEM) method accurately simulates the polarization effect, charge transfer effect, activation energy and other properties of the reaction process. The process in which the active residue Asp activates the nucleophile H2O to attack the protonated base is the preferred path. The average activation energy and free activation energy of the protonated base are 7.00-14.00 kcal mol-1 lower than that of the neutral base. The study in this paper is helpful to understand the mechanism of repair enzymes in repairing bases.

An autonomous synthetic DNA machine for ultrasensitive detection of Salmonella typhimurium based on bidirectional primers exchange reaction cascades.

Statistics show that food poisoning caused by Salmonella typhimurium (S. Typhimurium) often tops the list of bacterial food poisoning types in countries around the world. However, detecting traces of S. Typhimurium in real samples remains challenging. In recent years, primer exchange reaction (PER), a new isothermal amplification strategy, has rapidly attracted the attention of researchers in the field of biosensing. In this work, We developed a nanostructure called DNA arch bridge (DAB) and combined the DAB with cascade PER technology to construct a novel bidirectional PER (B-PER) for ultra-sensitive detection of pathogenic bacteria as a novel fluorescent biosensor. This strategy relies on the B-PER reaction mediated by binding of the target and adaptor, which occurs with the assistance of Klenow Fragment (KF) (3'-5'exo) polymerase and produces a good deal of G-quadruplex sequences that generate a fluorescent signal by embedding fluorescent dyes. Under the best conditions, the biosensor achieves ultrasensitive detection of S. Typhimurium, and the detection limit of the strategy is 9.3 cfu mL-1 over the linear detection scope of 101-105 cfu mL-1. The method has the merits of facile operation, rapid response, and high sensitivity. Furthermore, the biosensor is expected to achieve ultrasensitive detection of various small molecules through recognizing different target and primer sequences. Therefore, our proposed strategy provides an efficient, stable, universal, and practical sensing platform for pathogen and other small molecules detection.

Targeting the activity of T cells by membrane surface redox regulation for cancer theranostics.

T cells play a determining role in the immunomodulation and prognostic evaluation of cancer treatments relying on immune activation. While specific biomarkers determine the population and distribution of T cells in tumours, the in situ activity of T cells is less studied. Here we designed T-cell-targeting fusogenic liposomes to regulate and quantify the activity of T cells by exploiting their surface redox status as a chemical target. The T-cell-targeting fusogenic liposomes equipped with 2,2,6,6-tetramethylpiperidine (TEMP) groups neutralize reactive oxygen species protecting T cells from oxidation-induced loss of activity. Meanwhile, the production of paramagnetic 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) radicals allows magnetic resonance imaging quantification of the T cell activity. In multiple mouse models, the T-cell-targeting fusogenic liposomes led to efficient tumour inhibition and to early prediction of radiotherapy outcomes. This study uses a chemical targeting strategy to measure the in situ activity of T cells for cancer theranostics and may provide further understanding on engineering T cells for cancer treatment.

Genome-Wide Association Study on the Hematological Phenotypic Characteristics of the Han Population from Northwest China.

Background: Hematological characteristics have positive reference value as clinical indicators in the evaluation of various diseases. The purpose of this study was to determine the gene loci associated with 20 hematological phenotypes in the Han population from northwest China. Methods: A genome-wide association study (GWAS) was conducted on hematological indicators of 1005 Han people from northwest China. Genotyping was performed with a GeneTitan multichannel instrument and Axiom Analysis Suite 6.0. Using the 1000 Genomes Project (phase 3) as a reference, haplotype imputation was performed with IMPUTE2. SNVs (single nucleotide variants) significantly associated with hematological phenotypes were identified. The top SNV (p < 5E-7) was then selected for replication detection. Results: Ninety genetic variations identified in the GWAS were significantly associated with hematological indicators. Among them, only rs35289401 (CCDC157) was significantly associated (genome-wide) with red blood cell distribution width (RDW) (p = 4.21E-08). The fourteen top SNVs were selected for replication verification and were significantly associated with hematological phenotypes. However, only HBS1 L-MYB rs1331309 was significantly associated with the mean hemoglobin content (p = 6.42E-07). We also found that the mean corpuscular hemoglobin (MCH) level in the rs1331309 GG/GT genotype was significantly higher than that in the TT genotype (p = 0.023). Conclusion: The GWAS identified a total of 90 genetic variants significantly associated with hematological phenotypic indicators. In particular, rs1331309 (HBS1 L-MYB) is expected to be a biomarker for monitoring the dynamics of MCH levels. This study provides a reference for related studies on the genetic structure of hematological characteristics. It provides a valuable reference for the clinical diagnosis or prediction of a variety of diseases.

Andrographolide Suppresses the Growth and Metastasis of Luminal-Like Breast Cancer by Inhibiting the NF-κB/miR-21-5p/PDCD4 Signaling Pathway.

Tumor growth and metastasis are responsible for breast cancer-related mortality. Andrographolide (Andro) is a traditional anti-inflammatory drug used in the clinic that inhibits NF-κB activation. Recently, Andro has been found in the treatment of various cancers. Andro inhibits breast cell proliferation and invasion and induces apoptosis via activating various signaling pathways. Therefore, the underlying mechanisms with regard to the antitumor effects of Andro still need to be further confirmed. Herein, a MMTV-PyMT spontaneous luminal-like breast cancer lung metastatic transgenic tumor model was employed to estimate the antitumor effects of Andro on breast cancer in vivo. Andro significantly inhibited tumor growth and metastasis in MMTV-PyMT mice and suppressed the cell proliferation, migration, and invasion of MCF-7 breast cancer cells in vitro. Meanwhile, Andro significantly inhibited the expression of NF-κB, and the downregulated NF-κB reduced miR-21-5p expression. In addition, miR-21-5p dramatically inhibited the target gene expression of programmed cell death protein 4 (PDCD4). In the current study, we demonstrated the potential anticancer effects of Andro on luminal-like breast cancer and indicated that Andro inhibits the expression of miR-21-5p and further promotes PDCD4 via NF-κB suppression. Therefore, Andro could be an antitumor agent for the treatment of luminal-like breast cancer in the clinic.

Water-Mediated Oxidation of Guanine by a Repair Enzyme: Simulation Using the ABEEM Polarizable Force Field.

The recognition mechanism of oxidative damage in organisms has long been a research hotspot. Water is an important medium in the recognition process, but its specific role remains unknown. There is a need to develop a suitable force field that can adequately describe the electrostatic, hydrogen bond, and other interactions among the molecules in the complex system of the repair enzyme and oxidized base. The developing ABEEM polarizable force field (PFF) has been used to simulate the repaired enzyme hOGG1 and oxidized DNA (PDB ID: 1EBM) in a biological environment, and the corresponding results are better than those of the fixed-charge force fields OPLS/AA and AMBER OL15. 8-Oxo-G is recognized by Gln315 of hOGG1 mainly through hydrogen bonds mediated by continuous exchange of 2 water molecules. Phe319 and Cys253 are stacked on both sides of the π planes of bases to form sandwich structures. The charge polarization effect gives an important signal to drive the exchange of water molecules and maintains the recognition of oxidation bases by enzymes. The mediated main water molecule A and mediated auxiliary water molecule B together pull Gln315 to recognize 8-oxo-G by hydrogen bond interactions. Then, the charge polarization signal of solvent water molecule C with a large absolute charge causes the absolute charge of O atoms in water molecule A or B to increase by approximately 0.2 e, and water molecule A or B leaves Gln315 and 8-oxo-G. The other water molecule and water molecule C synergistically recognize 8-oxo-G with Gln315. Even though the water molecules between Gln315 and 8-oxo-G are removed, the MD simulation results show that water molecules appear between Gln315 and 8-oxo-G in a very short time (<2 ps). The dwell time of each water molecule is approximately 60 ps. The radial distribution function and dwell time support the correctness of the above mechanism. These polarization effects and hydrogen bonding interactions cannot be simulated by a fixed-charge force field.

A Bromodomain-Containing Protein 4 (BRD4) Inhibitor Suppresses Angiogenesis by Regulating AP-1 Expression.

Angiogenesis dysregulation contributes to inflammation, infections, immune disorders, and carcinogenesis. Bromodomain-containing protein 4 (BRD4) is an epigenetic reader that recognizes histone proteins and acts as a transcriptional regulator to trigger tumor growth and the inflammatory response. The pan-bromodomain and extra-terminal domain (BET) inhibitor, (+)-JQ1 (1), was reported to inhibit angiogenesis. However, owing to the non-selectivity action of (+)-JQ1 towards all BET family members, the role of BRD4 and that of its bromodomains (BD1 and BD2) in angiogenesis remains elusive. Herein, we identified a potent BRD4 inhibitor, ZL0513 (7), which exhibited significant anti-angiogenic effects in chick embryo chorioallantoic membrane (CAM) and yolk sac membrane (YSM) models. This inhibitor also directly suppressed the viability and tube formation of human umbilical vascular endothelial cells (HUVECs). Moreover, ZL0513 (7) was found to inhibit the phosphorylation of c-jun and c-fos, important members of activating protein-1 (AP-1) transcription factor complexes that enhance angiogenesis. The findings on this novel BRD4 inhibitor indicate that, in addition to being a powerful pharmacological tool for further elucidating the roles and functions of BRD4 and its BD domains in angiogenesis, it may serve as a potential therapeutic strategy for targeting the vasculature in various angiogenesis-dysregulated human diseases.

Correction: Yao, Y., et al. Activation of Slit2/Robo1 Signaling Promotes Tumor Metastasis in Colorectal Carcinoma through Activation of the TGF-ß/Smads Pathway. Cells 2019, 8, 635.

The author wishes to make the following correction to this paper [...].

Ozone Therapy Attenuates NF-κB-Mediated Local Inflammatory Response and Activation of Th17 Cells in Treatment for Psoriasis.

Ozone therapy has been widely used to treat many skin diseases, including infections, allergic dermatosis, and skin ulcers. However, its efficacy as a treatment for psoriasis is unclear. In this study, we explored the clinical efficacy and the underlying molecular mechanisms of ozone therapy on psoriasis. We found that topical ozone treatment significantly decreased patients' psoriasis area and severity index (PASI) scores and the expression of psoriasis-associated cytokines in their peripheral blood CD4+ T cells. In the IMQ-induced psoriasis mouse model, topical ozone treatment significantly inhibited the formation of IMQ-induced psoriasis-like lesions and the expression of psoriasis-associated inflammatory factors. High-throughput sequencing confirmed that IMQ-induced activation of toll-like receptor 2 (TLR2)/ nuclear factor-κB (NF-κB) signaling pathway was significantly suppressed in psoriasis-like lesions after topical ozone treatment. Furthermore, the activation of spleen T helper (Th) 17 cells was blocked in the mouse model; this was associated with the downregulation of cytokines and NF-κB pathways upon topical ozone treatment. Ozone therapy can attenuate local inflammatory reactions and the activation of Th17 cells in psoriasis by inhibiting the NF-κB pathway. Our results show that ozone therapy is effective in treating psoriasis. We recommend further evaluations for its clinical applications.

Promoted off-on recognition of H2O2 based on the fluorescence of silicon quantum dots assembled two-dimensional PEG-MnO2 nanosheets hybrid nanoprobe.

An "off-on" assay system for H2O2 determination was developed based on assembling ultra-bright fluorescent silicon quantum dots (SiQDs) and PEG-MnO2 nanosheets. Among them, SiQDs acted as fluorometric reporter, which can effectively eliminate the interference of plant pigments under excitation of 365 nm. PEG-MnO2 nanosheets played dual function of nanoquencher and H2O2 recognizer. Unlike previous reports, the quenching mechanism of SiQDs by PEG-MnO2 nanosheets is attributed to both the associative effect of inner filter effect and the static quenching effect. Thus, the fluorescence intensity of SiQDs at 445 nm decreased with increasing concentration of PEG-MnO2 nanosheets. After addition of H2O2, PEG-MnO2 nanosheets were reduced to Mn2+, consequently resulting in the recovery of the SiQDs fluorescence. Combined with these properties, an off-on fluorescent method was built for determination of H2O2 in plant leaves with high sensitivity and selectivity. The present method has two linear ranges: from 0.05 to 1 µM with a detection limit of 0.09 µM and from 1 to 80 µM with a detection limit of 4.04 µM. Graphical abstract Schematic representation of the mechanism of SiQD/PEG-MnO2 nanoprobe for determination of H2O2.

New land surface temperature retrieval algorithm for heavy aerosol loading during nighttime from Gaofen-5 satellite data.

Land surface temperature (LST) is a key variable used for studies of the water cycles and energy budgets of land-atmosphere interfaces. The Chinese Gaofen-5 (GF5) satellite, with an onboard visual and infrared multispectral imager (VIMS), is the only satellite that can capture the earth's thermal infrared information for use in the national high-resolution earth observation project of China; it can observe the earth surface at a high spatial resolution of 40 m in four thermal infrared channels and two mid-infrared channels. This article selects the optimum spectral channel combination for reducing the aerosol effect on LST retrieval with the aid of simulated data, and a new four-channel LST retrieval method from GF5 infrared data under heavy dust aerosol during nighttime is proposed. The results show that the channel combination of channels 7, 8, 9, and 10 (denoted as CC1) performed better than the combination of channels 7, 8, 11, and 12 (denoted as CC2). The root mean square errors (RMSEs) between the actual and estimated LST were 0.28 K for the CC1 group with an aerosol optical thickness (AOD) of 0.1 and 1.94 K for the CC1 group with an AOD of 1.0. The RMSEs for CC2 were 0.28 K for the group with an AOD of 0.1 and 2.54 K for the other group with an AOD of 1.0. Moreover, an error analysis for the proposed method was performed in terms of the noise equivalent temperature difference (NEΔT), the uncertainties of land surface emissivity (LSE), water vapor content (WVC) and AOD. The results show that the LST errors caused by an LSE uncertainty of 0.01, a NEΔT of 0.2 K, a WVC uncertainty of 20%, an AOD uncertainty of 0.1 were 0.31 ∼ 1.01 K, 0.4 ∼ 2.0 K, within 0.6 K, and within 0.3 K for CC1 and 0.32 ∼ 3.08 K, 0.4 ∼ 1.7 K, within 0.7 K, and within 0.3 K for CC2, respectively.

The deubiquitylase OTUD3 stabilizes GRP78 and promotes lung tumorigenesis.

The deubiquitylase OTUD3 plays a suppressive role in breast tumorigenesis through stabilizing PTEN protein, but its role in lung cancer remains unclear. Here, we demonstrate that in vivo deletion of OTUD3 indeed promotes breast cancer development in mice, but by contrast, it slows down KrasG12D-driven lung adenocarcinoma (ADC) initiation and progression and markedly increases survival in mice. Moreover, OTUD3 is highly expressed in human lung cancer tissues and its higher expression correlates with poorer survival of patients. Further mechanistic studies reveal that OTUD3 interacts with, deubiquitylates and stabilizes the glucose-regulated protein GRP78. Knockdown of OTUD3 results in a decrease in the level of GRP78 protein, suppression of cell growth and migration, and tumorigenesis in lung cancer. Collectively, our results reveal a previously unappreciated pro-oncogenic role of OTUD3 in lung cancer and indicate that deubiquitylases could elicit tumor-suppressing or tumor-promoting activities in a cell- and tissue-dependent context.