Enantioselective α-Trifluoromethylthiolation of Carbonyl Compounds with AgSCF3 and Trichloroisocyanuric Acid.

We successfully developed an enantioselective trifluoromethylthiolation of structurally diverse carbonyl compounds. Trichloroisocyanuric acid and AgSCF3 were employed to generate active electrophilic trifluoromethylthio species in situ for asymmetric C-SCF3 bond formation. A broad variety of chiral SCF3-carbon nucleophiles (pyrazolones, ß-keto esters, and ß-keto amides) were obtained in excellent yields with high enantioselectivities (up to 92% ee) by Cinchona alkaloid derived squaramide catalysts. The reaction exhibits high efficiency, good enantioselectivity, and high functional group tolerance, which provided a novel and efficient way for asymmetric synthesis of trifluoromethylthiolated carbonyl compounds.

A method for extraction of exosomes from breast tumour cells and characterisation by transmission electron microscopy.

Exosomes can not only be used as markers of tumour metastasis but also be used for noninvasive diagnosis of clinical diseases, which holds significant medical research value. Observing the morphology and distribution of exosomes using transmission electron microscopy (TEM) is highly significant. In this study, we use breast tumour cell (MDA-MB-231) exosomes as a representative sample and focus on the extraction and purification of exosomes, as well as the investigation of optimal conditions for the observation of exosomes using TEM. Through comparative tests, we obtained the optimal dilution concentration and staining method for TEM of exosomes, the best dilution concentration is 100 times, the best negative staining time is 1.5 min. Western blotting and scanning electron microscopy (SEM) confirmed the presence of exosome. The particle size experiment shows that the size of exosomes is mainly distributed between 60 nm and 150 nm. This method provides a reference for TEM sample preparation of subcellular structures and small molecular biomaterials other than exosomes.

Clinical Report of a Rare Mucinous Staphylococcus Aureus Infection.

BACKGROUND: Staphylococcus aureus is the most common pathogen in suppurative infection, which can cause local suppurative infection, pneumonia, etc. A case of double renal calculi complicated with chronic renal insufficiency and mucinous Staphylococcus aureus infection was analyzed and discussed. METHODS: Bacterial culture, identification, and next-generation sequencing. RESULTS: The mucous colony was identified as Staphylococcus aureus, and the condition improved after symptomatic treatment. CONCLUSIONS: Mucinous Staphylococcus is a rare clinical microorganism, which needs to be verified by experiments to avoid false negative results. Genetic sequencing is used to identify strains if necessary.

Ratiometric fluorescence sensing of formaldehyde in food samples based on bifunctional MOF.

A new fluorescence strategy was described for ratiometric sensing of formaldehyde (FA) with bifunctional MOF, which acted as a fluorescence reporter as well as biomimetic peroxidase. With the assistance of H2O2, NH2-MIL-101 (Fe) catalyzes the oxidation of non-luminescent substrate o-phenylenediamine (OPD) to produce fluorescent product (oxOPD) with the maximum emission at 570 nm. Besides, intrinsic fluorescence of MOF (λem = 445 nm) was quenched by oxOPD through inner filter effect (IFE). However, FA and OPD reacted to generate Schiff bases, which competitively consumed OPD inhibiting the generation of oxOPD. Under the excitation wavelength of 375 nm, a ratiometric strategy was designed to detect FA with the fluorescence intensity ratio at 445 nm and 570 nm (F445/F570) as readout signal. This strategy exhibited a wide linear range (0.1-50 µM) and low detection limit of 0.03 µM. This method was confirmed for FA detection in food samples. In addition to establishing a new method to detect FA, this work will open new applications of MOF in food safety.

Seed-Morphology-Directed Synthesis of Concave Gold Nanocrystals with Tunable Sizes.

We report the fabrication of concave gold (Au) nanocrystals with a set of morphologies and controlled sizes via seeded growth. Starting with Au seeds with a well-defined morphology and uniform size, cubic and rodlike Au nanocrystals with a noticeable concave feature could be successfully obtained, respectively. We also track the growth process and record the shape evolution process. The effect of several reaction parameters on product morphology, such as capping agent and concentration of Ag+, are systematically investigated. Their optical and electrochemical properties are investigated via UV-vis extinction spectroscopy and cyclic voltammetry, respectively. Compared to spherical counterparts, the current concave Au nanocrystals exhibit a noticeable red shift of the absorbance peak in UV-vis extinction spectra and characterized electrochemical behavior of stepped facets, illustrating the morphological advantage.

Cu3Mo2O9 Nanosheet Array as a High-Efficiency Oxygen Evolution Electrode in Alkaline Solution.

Developing highly active and sustained oxygen evolution reaction (OER) catalysts for energy-saving electrolytic hydrogen generation is highly attractive. In this work, we report the development of a Cu3Mo2O9 nanosheet array on nickel foam (Cu3Mo2O9/NF) as a highly active OER catalyst. Such Cu3Mo2O9/NF shows high catalytic activity in 1.0 M KOH, passing 50 mA cm-2 at an overpotential of 325 mV. It also shows superior long-term durability more than 24 h with a turnover frequency (TOF) of 0.09 mol O2 s-1 at overpotential of 400 mV.

Efficient Hydrogen Evolution Electrocatalysis at Alkaline pH by Interface Engineering of Ni2P-CeO2.

It is of significant importance to develop effective non-noble-metal catalysts for hydrogen evolution electrocatalysis under basic conditions. In this study, we demonstrate the facile construction of a Ni2P-CeO2 interface based on the central point that low-temperature phosphidation of the NiO-CeO2 precursor only converts NiO into Ni2P selectively. The resulting Ni2P-CeO2 nanosheet array on Ti mesh behaves as a durable catalyst for alkaline hydrogen evolution reaction (HER) electrocatalysis, and it can reach 20 mA cm-2 at an overpotential of 84 mV in 1.0 M KOH, outperforming all reported Ni phosphide HER catalysts. Density functional theory calculations reveal that the Ni2P-CeO2 interface can promote water dissociation and optimize hydrogen adsorption free energy.

High-Performance Non-Enzyme Hydrogen Peroxide Detection in Neutral Solution: Using a Nickel Borate Nanoarray as a 3D Electrochemical Sensor.

It is highly attractive to construct natural enzyme-free nanoarray architecture as a 3D catalyst for hydrogen peroxide detection due to its great specific surface area and easy accessibility to target molecules. In this communication, we demonstrate that nickel borate nanoarray supported on carbon cloth (Ni-Bi/CC) behaves as an efficient catalyst electrode for H2 O2 electro-reduction in neutral media. As a non-enzymatic electrochemical H2 O2 sensor, such Ni-Bi/CC shows superior sensing performances with a fast response time (less than 3 s), a low detection limit (0.85 nm, S/N=3), and a high sensitivity (18320 µA mm cm-2 ). Importantly, it also demonstrates favourable reproducibility and long-term stability.

Self-Templating Construction of Hollow Amorphous CoMoS4 Nanotube Array towards Efficient Hydrogen Evolution Electrocatalysis at Neutral pH.

Environmentally friendly electrochemical hydrogen production needs the development of earth-abundant catalyst materials for the hydrogen evolution reaction with high activity and durability at neutral pH. In this work, the self-templating construction of a hollow amorphous CoMoS4 nanotube array on carbon cloth (CoMoS4 NTA/CC) is reported, using hydrothermal treatment of a Co(OH)F nanowire array on CC in (NH4 )2 MoS4 solution. When used as a 3D electrode for hydrogen evolution electrocatalysis, the resulting CoMoS4 NTA/CC demonstrates superior catalytic activity and strong long-term electrochemical durability in 1.0 M phosphate buffer solution (pH=7). It shows small onset overpotential of 21 mV and requires low overpotentials of 104 and 179 mV to drive geometrical current densities of 10 and 50 mA cm-2 , respectively. Density functional theory calculations suggest that CoMoS4 has a more favorable hydrogen adsorption free energy than Co(OH)F.

Facilitating Active Species Generation by Amorphous NiFe-Bi Layer Formation on NiFe-LDH Nanoarray for Efficient Electrocatalytic Oxygen Evolution at Alkaline pH.

Searching for a simple and fast strategy to effectively enhance the oxygen evolution reaction (OER) performance of non-noble-metal electrocatalysts in alkaline media remains a significant challenge. Herein, the OER activity of NiFe-LDH nanoarray on carbon cloth (NiFe-LDH/CC) in alkaline media is shown to be greatly boosted by an amorphous NiFe-Borate (NiFe-Bi ) layer formation on NiFe-layered double hydroxide (NiFe-LDH) surface. Such a NiFe-LDH@NiFe-Bi /CC catalyst electrode only needs an overpotential of 294 mV to drive 50 mA cm-2 in 1.0 m KOH; 116 mV less than that needed by NiFe-LDH/CC. Notably, this electrode also demonstrates strong long-term electrochemical durability. The superior activity is ascribed to the pre-formed amorphous NiFe-Bi layer effectively promoting active species generation on the NiFe-LDH surface. This work opens up exciting new avenues for developing high-performance water-oxidation catalyst materials for application.

Co3 O4 Nanowire Arrays toward Superior Water Oxidation Electrocatalysis in Alkaline Media by Surface Amorphization.

It is highly desirable to develop a simple, fast and straightforward method to boost the alkaline water oxidation of metal oxide catalysts. In this communication, we report our recent finding that the generation of amorphous Co-borate layer on Co3 O4 nanowire arrays supported on Ti mesh (Co3 O4 @Co-Bi NA/TM) leads to significantly boosted OER activity. The as-prepared Co3 O4 @Co-Bi NA/TM demands overpotential of 304 mV to drive a geometrical current density of 20 mA cm-2 in 1.0 M KOH, which is 109 mV less than that for Co3 O4 NA/TM, with its catalytic activity being preserved for at least 20 h. It suggests that the existence of amorphous Co-Bi layer promotes more CoOx (OH)y generation on Co3 O4 surface.

Surface Modification of a NiS2 Nanoarray with Ni(OH)2 toward Superior Water Reduction Electrocatalysis in Alkaline Media.

Interface engineering has been demonstrated to be effective in promoting hydrogen evolution reaction (HER) in an alkaline solution. Herein, we report that the HER activity of a NiS2 nanoarray on a titanium mesh (NiS2/TM) in alkaline media is greatly boosted by the electrodeposition of Ni(OH)2 onto NiS2 [Ni(OH)2-NiS2/TM]. Ni(OH)2-NiS2/TM only needs an overpotential of 90 mV to deliver 10 mA cm-2 in 1.0 M KOH. Density functional theory calculations confirm that Ni(OH)2-NiS2 has a lower water dissociation free energy and a more optimal hydrogen adsorption free energy than NiS2.

WO3 Nanoarray: An Efficient Electrochemical Oxygen Evolution Catalyst Electrode Operating in Alkaline Solution.

It is fascinating to design and synthesize high-efficiency and noble-metal-free alkaline oxygen evolution reaction (OER) electrocatalysts. In this Communication, we describe the one-step hydrothermal synthesis of a WO3 nanoarray directly grown on conductive carbon cloth (WO3/CC) for efficient water oxidation in 1.0 M KOH. As a monolithically integrated array catalyst, WO3/CC exhibits superior OER activity demanding overpotential as low as 280 mV to afford a benchmarking catalytic current density of 10 mA cm-2. It is worth noting that WO3/CC also possesses strong electrochemical durability with 95% Faradaic yields.

Fe2Ni2N nanosheet array: an efficient non-noble-metal electrocatalyst for non-enzymatic glucose sensing.

It is very important to develop enhanced electrochemical sensing platforms for molecular detection and non-noble-metal nanoarray architecture, as electrochemical catalyst electrodes have attracted great attention due to their large specific surface area and easy accessibility to target molecules. In this paper, we demonstrate that an Fe2Ni2N nanosheet array grown on Ti mesh (Fe2Ni2N NS/TM) shows high electrocatalytic activity toward glucose electrooxidation in alkaline medium. As an electrochemical glucose sensor, such an Fe2Ni2N NS/TM catalyst electrode demonstrates superior sensing performance with a short response time of less than 5 s, a wide linear range of 0.05 µM-1.5 mM, a low detection limit of 0.038 µM (S/N = 3), a high sensitivity of 6250 µA mM-1 cm-2, as well as high selectivity and long-term stability.

YWHAG promotes colorectal cancer progression by regulating the CTTN-Wnt/ß-catenin signaling axis.

Colorectal cancer (CRC) ranks as the third most prevalent cancer type globally. Nevertheless, the fundamental mechanisms driving CRC progression remain ambiguous, and the prognosis for the majority of patients diagnosed at an advanced stage is dismal. YWHA/14-3-3 proteins serve as central nodes in several signaling pathways and are closely related to tumorigenesis and progression. However, their exact roles in CRC are still poorly elucidated. In this study, we revealed that YWHAG was the most significantly upregulated member of the YWHA/14-3-3 family in CRC tissues and was associated with a poor prognosis. Subsequent phenotypic experiments showed that YWHAG promoted the proliferation, migration, and invasion of CRC cells. Mechanistically, RNA-seq data showed that multiple signaling pathways, including Wnt and epithelial-mesenchymal transition, were potentially regulated by YWHAG. CTTN was identified as a YWHAG-associated protein, and mediated its tumor-promoting functions by activating the Wnt/ß-catenin signaling in CRC cells. In summary, our data indicate that YWHAG facilitates the proliferation, migration, and invasion of CRC cells by modulating the CTTN-Wnt/ß-catenin signaling pathway, which offers a novel perspective for the treatment of CRC.

Reprogramming tumor-associated macrophages by a dually targeted milk exosome system as a potent monotherapy for cancer.

Tumor-associated macrophages (TAMs) play a key role in inducing an immunosuppressive tumor microenvironment (TME) and cancer immune escape. We previously revealed that PDL1 (a key immune checkpoint) was upregulated in TAMs and induced M2 polarization, highlighting PDL1 in TAMs as a promising cancer therapeutic target. In this study, we developed an engineered milk exosome (mExo) system decorated with M2pep (an M2 macrophage binding peptide) and 7D12 (an anti-EGFR nanobody) (7D12-mExo-M2pep-siPDL1) to specifically deliver siPDL1 into M2 TAMs. A series of in vitro and in vivo assays showed that the dually targeted engineered mExos efficiently delivered siPDL1 into M2 TAMs and repolarized them into M1 macrophages, restoring CD8+ T cell immune activity and remodeling TME. Importantly, systemically administered 7D12-mExo-M2pep-siPDL1 showed efficient single-agent antitumor activity, resulting in nearly 90% tumor growth inhibition in a mouse model of orthotopic epidermal growth factor receptor (EGFR) cancer. Collectively, our study indicates that PDL1 is a promising target for TAM-based cancer immunotherapy, and our engineered mExo-based nanomedicine represents a novel tool for specifically targeting M2 TAMs, distinguishing this novel therapeutic method from other TAM-targeting therapies and highlighting its promising clinical potential.

PoolNet+: Exploring the Potential of Pooling for Salient Object Detection.

We explore the potential of pooling techniques on the task of salient object detection by expanding its role in convolutional neural networks. In general, two pooling-based modules are proposed. A global guidance module (GGM) is first built based on the bottom-up pathway of the U-shape architecture, which aims to guide the location information of the potential salient objects into layers at different feature levels. A feature aggregation module (FAM) is further designed to seamlessly fuse the coarse-level semantic information with the fine-level features in the top-down pathway. We can progressively refine the high-level semantic features with these two modules and obtain detail enriched saliency maps. Experimental results show that our proposed approach can locate the salient objects more accurately with sharpened details and substantially improve the performance compared with the existing state-of-the-art methods. Besides, our approach is fast and can run at a speed of 53 FPS when processing a 300 ×400 image. To make our approach better applied to mobile applications, we take MobileNetV2 as our backbone and re-tailor the structure of our pooling-based modules. Our mobile version model achieves a running speed of 66 FPS yet still performs better than most existing state-of-the-art methods. To verify the generalization ability of the proposed method, we apply it to the edge detection, RGB-D salient object detection, and camouflaged object detection tasks, and our method achieves better results than the corresponding state-of-the-art methods of these three tasks. Code can be found at http://mmcheng.net/poolnet/.

Enhanced detection of ascorbic acid with cascaded fluorescence recovery of a dual-nanoquencher system.

An innovative strategy with target-triggered cascade fluorescence recovery of a dual-nanoquencher system was developed to detect ascorbic acid (AA). Herein, manganese dioxide (MnO2) nanosheets and gold nanoparticles (AuNPs) were used as nanoquenchers simultaneously. Owing to their synergistic effects, the fluorescence of 2,3-diaminophenazine (DAP) was decreased efficiently, thus minimizing the background fluorescence. The introduction of AA triggered the decomposition of MnO2 into Mn2+, which induced the aggregation of AuNPs. Both the decomposed MnO2 and aggregated AuNPs possess weak quenching abilities towards DAP. Such a cascade amplification strategy enhanced the detection sensitivity for AA with a LOD as low as 6.7 nM, which was two orders of magnitude lower than that of MnO2-based fluorescence assay. Furthermore, this amplification strategy was successfully applied to detect AA in food samples.

High expression of CD28 enhanced the anti-cancer effect of siRNA-PD-1 through prompting the immune response of melanoma-bearing mice.

Immune checkpoint blockade is considered to be an effective method of tumor immunotherapy. As one of the main immune checkpoints, blocking PD-1/PD-L1 pathway has been proved to be effective in the treatment of many cancers via activating T cells; however, many patients still do not respond to the blocking PD-1/PD-L1 treatment with satisfying results. Related research demonstrated that the activation of T cells required a co-stimulatory signal generated by the interaction between CD28 and CD80/CD86, whereas in many patients, CD28 on the T cell surface was lost. Thus, in this study, we constructed the co-expression plasmid of CD28-siRNA-PD-1 and explored the anti-tumor mechanism of the co-expression plasmid on mouse model. The results showed that the expression of PD-1 was inhibited and the expression of CD28 was increased significantly in tumor tissues after the mice were treated with the co-expression plasmid. The survival rate of the tumor-bearing mice was recorded every day. PD-1 expression and tumor-infiltrating lymphocytes in cancer tissues were detected by immunofluorescence staining and the ratios of different immune cells in spleens were detected by flow cytometry. We found that treatment with the co-expression plasmid significantly prolonged the survival of melanoma-bearing mice, induced the cell apoptosis, increased the infiltration of T cells in tumor tissues, and altered the ratios of different immune cells in the spleens. These results also laid the foundation for reducing the resistance of PD-1 blockade in the clinic.

A novel polypeptide vaccine and adjuvant formulation of EV71.

Hand foot and mouth disease (HFMD) is an infectious disease mainly caused by Enterovirus 71 (EV 71). However, the effective treatment is limited currently. The aim of this study was to investigate the activity of the vaccine including the EV71 polypeptides mixed with a novel adjuvant containing CpG oligodeoxynucleotides (CpG ODNs). After collecting mouse sera, we determined the antibody concentration in serum by enzyme-linked immunosorbent assays (ELISA). Then, CD19+CD27+ B cells in the spleen were analysed by flow cytometry. The assay revealed that a substantial increase in antibody titers was achieved. This indicates a high level of immunogenicity for peptide vaccine and the good stability of adjuvant, also suggests that the combination of vaccine and adjuvant can stimulate the production of high-level antibodies and CD19+CD27+ B lymphocytes in mice. Furthermore, the antibody could effectively identify EV71 inactivated virus. The results demonstrated that the autonomous construction of EV71 polypeptide vaccine had a good immunogenicity. Moreover, the peptide vaccine injection with a novel adjuvant, which is easy to prepare, could cause a high antibody level of EV71 and shown a good application prospect.