Search

Pancreatic cancer (PC) is featured with low survival rate and poor outcomes. Herein, we found that the expression of caspase-recruitment domain-containing protein 9 (CARD9), predominantly expressed in innate immune cells, was positively related to the prognosis of PC patients. CARD9-deficient PC mice exhibited rapider cancer progression and poorer survival rate. CARD9 knockout decreased dendritic cell (DC) maturation and impaired DC ability to activate T cells in vivo and in vitro. Adoptive DC transfer confirmed that the role of CARD9 deficiency in PC relied on DCs. Creatine was identified as the most significant differential metabolite between WT DCs and CARD9 -/- DCs wherein it played an essential role in maintaining DC maturation and function. CARD9 deficiency led to decreased creatine levels in DCs by inhibiting the transcription of the creatine-specific transporter, solute carrier family 6 member 8 (SLC6A8). Furtherly, CARD9 deletion blocked p65 activation by abolishing the formation of CARD9-BCL10-MALT1 complex, which prevented the binding between p65 and SLC6A8 promoter. These events decreased the creatine transport into DCs, and led to DC immaturity and impairment in antitumor immunity, consequently promoting PC progression., Competing Interests: No potential conflict of interest was reported by the authors., (© 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Cold tumor immune microenvironment (TIME) of pancreatic cancer (PC) with minimal dendritic cell (DC) and T cell infiltration can result in insufficient immunotherapy and chemotherapy. While gemcitabine (GEM) is a first-line chemotherapeutic drug for PC, its efficacy is reduced by immunosuppression and drug resistance. Ginsenoside Rh2 (Rh2) is known to have anti-cancer and immunomodulatory properties. Combining GEM with Rh2 may thus overcome immunosuppression and induce lasting anti-tumor immunity in PC. Here, we showed that after GEM-Rh2 therapy, there was significantly greater tumor infiltration by DCs. Caspase recruitment domain-containing protein 9 (CARD9), a central adaptor protein, was strongly up-regulated DCs with GEM-Rh2 therapy and promoted anti-tumor immune responses by DCs. CARD9 was found to be a critical target for Rh2 to enhance DC function. However, GEM-Rh2 treatment did not achieve the substantial anti-PC efficacy in CARD9 -/- mice as in WT mice. The adoptive transfer of WT DCs to DC-depleted PC mice treated with GEM-Rh2 elicited strong anti-tumor immune responses, although CARD9 -/- DCs were less effective than WT DCs. Our results showed that GEM-Rh2 may reverse cold TIME by enhancing tumor immunogenicity and decreasing the levels of immunosuppressive factors, reactivating DCs via the CARD9-BCL10-MALT1/ NF-κB pathway. Our findings suggest a potentially feasible and safe treatment strategy for PC, with a unique mechanism of action. Thus, Rh2 activation of DCs may remodel the cold TIME and optimize GEM chemotherapy for future therapeutic use., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

In order to demonstrate the effects of isorhamnetin (IH) on the symptoms of type 2 diabetes mellitus (T2DM) and the role of gut microbiota in this process, an T2DM mouse model was established via a high-fat diet and streptozotocin. After 6 weeks of IH intervention and diabetes phenotype monitoring, the mice were dissected. We detected blood indicators and visceral pathology. Contents of the cecum were collected for 16S rRNA sequencing and short chain fatty acid (SCFAs) detection. The results showed that after IH intervention, the body weight of type 2 diabetic mice was gradually stabilized, fasting blood glucose was significantly decreased, and food intake was reduced ( P < 0.05). Isorhamnetin significantly increased the level of SCFAs and decreased the levels of blood lipids and inflammatory factors in mice ( P < 0.05). 16S rRNA sequencing results showed that Lactobacillus were significantly decreased and Bacteroidales S24-7 group&#95;norank were significantly increased ( P < 0.05). Interestingly, gut microbiota was significantly correlated with inflammatory factors, blood lipids, and SCFAs ( P < 0.05). Taken together, our data demonstrated that isorhamnetin could improve the diabetic effects in T2DM mice, which might be mediated by gut microbiota., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Yuan, Zhao, Li, Li, Zhu, Wang, Sun and Xiao.)

Boosting reversible solid-liquid phase transformation from lithium polysulfides to Li 2 S and suppressing the shuttling of lithium polysulfides from the cathode to the lithium anode are critical challenges in lithium-sulfur batteries. Here, sulfiphilic single atomic cobalt implanted in lithiophilic heteroatoms-dopped carbon (SACo@HC) matrix with a CoN 3 S structure for high-performance lithium-sulfur batteries is reported. Density functional theory calculation and in situ experiments demonstrate that the optimal CoN 3 S structure in SACo@HC can effectively improve the adsorption and redox conversion efficiency of lithium polysulfides. Consequently, the S-SACo@HC composite with sulfur loading of 80 wt% delivers a high capacity of 1425.1 mAh g -1 at 0.05 C and outstanding rate performance with 745.9 mAh g -1 at 4 C. Furthermore, a capacity of 680.8 mAh g -1 at 0.5 C with a low electrolyte/sulfur ratio (6 µL mg -1 ) can be achieved even after 300 cycles. With the harsh conditions of lean electrolyte (E/S = 4 µL mg -1 ) and high sulfur loading (5.4 mg cm -2 ), a superior area capacity of 5.8 mAh cm -2 can be obtained. This work contributes to building a profound understanding of the adsorption and interface engineering of lithium polysulfides and provides ideas to tackle the long-standing polysulfide shuttle problem of lithium-sulfur batteries., (© 2022 Wiley-VCH GmbH.)

Organic electrode materials have the typical advantages of flexibility, low cost, abundant resources, and recyclability. However, it is challenging to simultaneously optimize the specific capacity, rate capability, and cycling stability. Radicals are inevitable intermediates that critically determine the redox activity and stability during the electrochemical reaction of organic electrodes. Herein, we select a series of aromatic imides, including pyromellitic diimide (PMDI), 1,4,5,8-naphthalenediimide (NDI), and 3,4,9,10-perylenetetracarboxylicdiimide (PTCDI), which contain different extending π-conjugated aromatic rings, to study the relationship between their electrochemical performance and the size of the aromatic ring. The results show that regulating the aromatic ring size of imide molecules could finely tune the energies of the lowest unoccupied molecular orbital (LUMO), thus optimizing the redox potential. The rate performance of PMDI, NDI, and PTCDI increases with the aromatic ring size, which is consistent with the decrease in the LUMO-HOMO gap of these imide molecules. DFT calculations and experiments reveal that the redox of imide radicals dominates the charge/discharge processes. Also, extending the aromatic rings could more effectively disperse the spin electron density and improve the stability of imide radicals, contributing to the enhanced cycling stability of these imide electrodes. Hence, aromatic ring size regulation is a simple and novel approach to simultaneously enhance the capacity, rate capability, and cycling stability of organic electrodes for high-performance lithium-ion batteries.

Background: Numerous clinical studies have shown that atopic dermatitis (AD) is often associated with mental disorders. This could contribute to the overall burden of atopic dermatitis. However, the underlying mechanism of mental health symptoms in AD has not been fully elucidated. Methods: An AD mouse was induced by 2,4-dinitrofluorobenzene (DNFB), which was repeatedly applied to the back skin of the BALB/C mice to establish an atopic dermatitis mental disorder model. The role of neuroinflammation in the pathogenesis of atopic dermatitis mental disorders was then explored. Results: After the stimulation of DNFB for 35 days, the skin lesions, the HE staining of skin lesions, and the behavioral experiments (including elevated plus maze assay and tail suspension test) suggested that the AD mental disorder mouse model was successfully replicated. The expression of neuroinflammatory factors in the hippocampus was then investigated through Western blotting. The results showed a significant increase in the protein expression of NLRP3, caspase-1, and IL-1β. Conclusion: Mental disorders in AD might be related to the neuroinflammatory response in the hippocampus. An alternative yet essential approach to promoting AD recovery could be through reducing neuroinflammation and improving mental disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer TM declared a shared parent affiliation with the authors to the handling editor at the time of review., (Copyright © 2022 Yuan, Sun, Zhang, Feng, Tian, Liu, Wang, Gao, Tang and Zheng.)

5-Hydroxymethylcytosine (5hmC) modification is a key epigenetic regulator of cellular processes in mammalian cells, and its misregulation may lead to various diseases. Herein, we develop a hydroxymethylation-specific ligation-mediated single quantum dot (QD)-based fluorescence resonance energy transfer (FRET) nanosensor for sensitive quantification of 5hmC modification in cancer cells. We design a Cy5-modified signal probe and a biotinylated capture probe for the recognition of specific 5hmC-containing genes. 5hmC in target DNA can be selectively converted by T4 β-glucosyltransferase to produce a glycosyl-modified 5hmC, which cannot be cleaved by methylation-insensitive restriction enzyme MspI. The glycosylated 5hmC DNA may act as a template to ligate a signal probe and a capture probe, initiating hydroxymethylation-specific ligation to generate large amounts of biotin-/Cy5-modified single-stranded DNAs (ssDNAs). The assembly of biotin-/Cy5-modified ssDNAs onto a single QD through streptavidin-biotin interaction results in FRET and consequently the generation of a Cy5 signal. The nanosensor is very simple without the need for bisulfite treatment, radioactive reagents, and 5hmC-specific antibodies. Owing to excellent specificity and high amplification efficiency of hydroxymethylation-specific ligation and near-zero background of a single QD-based FRET, this nanosensor can quantify 5hmC DNA with a limit of detection of 33.61 aM and a wider linear range of 7 orders of magnitude, and it may discriminate the single-nucleotide difference among 5hmC, 5-methylcytosine, and unmodified cytosine. Moreover, this nanosensor can distinguish as low as a 0.001% 5hmC DNA in complex mixtures, and it can monitor the cellular 5hmC level and discriminate cancer cells from normal cells, holding great potential in biomedical research and clinical diagnostics.

Acute paraquat poisoning is due to the extremely severe toxicity of paraquat. After paraquat enters the human body, it will cause rapid changes in the human body system. Since paraquat poisoning will quickly invade the organs of the whole body, it may cause damage to the functions of multiple organs in the poisoned patient. The liver organ is the most important detoxification site for the human body, so the damage to the liver of the patient is more obvious. This article discovers and observes the structure of paraquat and the dynamic changes of serum cytokines in patients with paraquat poisoning through the clinical phenomenon of paraquat poisoning, and the related changes of human serum cells after the subjects took paraquat and the changes of cell dynamic factors after different doses of paraquat entered the human body were analysed. At the same time, the changes in the immune function of the body of different groups of people were also observed. The experimental results in this article show that according to the intake of paraquat, the severity of poisoning patients will be mild, moderate, severe and outbreak poisoning. Among them, the dose for adults who cannot be treated for prognosis is 10 ml., (© 2022 The Authors. IET Systems Biology published by John Wiley & Sons Ltd on behalf of The Institution of Engineering and Technology.)

Graphene-based analogs and derivatives provide numerous routes to achieve unconventional properties and potential applications. Particularly, two-dimensional (2D) binary materials of group-IV elements are drawing increasing interest. In this work, we proposed the design of three 2D graphene-based materials, namely, XC 6 -enes (X = Ge, Sn, or Pb), based on first-principles calculations. These new materials possess intriguing properties superior to graphene, such as biaxial negative Poisson's ratio (NPR), moderate bandgap, and high carrier mobility. These XC 6 -enes comprise sp 2 carbon and sp 3 X (X = Ge, Sn, Pb) atoms with hexagonal and pentagonal units by doping graphene with X atoms. The stability and plausibility of these 2D materials are verified from formation energies, phonon spectra, ab initio molecular dynamic simulations, and elastic constants. The incorporation of X atoms leads to highly anisotropic mechanical properties along with NPR due to the unique tetrahedral structure and hat-shaped configuration. In the equilibrium state, all the XC 6 -enes are moderate-band-gap semiconductors. The carrier mobilities of the XC 6 -enes were highly anisotropic (∼10 4 cm -2 V -1 s -1 along the [010]-direction). Such outstanding properties make the 2D frameworks promising for application in novel electronic and micromechanical devices.

Catalysts containing isolated single atoms have attracted much interest due to their good catalytic behavior, bridging the gap between homogeneous and heterogeneous catalysts. Here, we report an efficient oxygen reduction reaction (ORR) catalyst that consists of atomically dispersed single copper sites confined by defective mixed-phased TiO 2-x . This synergistic catalyst was produced by introducing Cu 2+ to a metal organic framework (MOF) using the Mannich reaction, occurring between the carbonyl group in Cu(acac) 2 and the amino group on the skeleton of the MOF. The embedding of single copper atoms was confirmed by atomic-resolution high-angle annular dark-field scanning transmission electron microscopy and x-ray absorption fine structure spectroscopy. Electronic structure modulation of the single copper sites coupling with oxygen vacancies was further established by electron paramagnetic resonance spectroscopy and first-principles calculations. Significantly enhanced ORR activity and stability were achieved on this special Cu single site. The promising application of this novel electrocatalyst was demonstrated in a prototype Zn-air battery. This strategy of the stabilization of single-atom active sites by optimization of the atomic and electronic structure on a mixed matrix support sheds light on the development of highly efficient electrocatalysts.

We investigated the optical properties and roles of sp 2 - and sp 3 -hybridized bonds of a hexagonal C/BN family using first-principles calculations. The calculated phonon dispersions confirm the dynamic stability of Hex-(BN) 6 C 12 and Hex-C 12 (BN) 6 . The complex dielectric function evolves from the infrared to the ultraviolet region and has a significant anisotropy for different polarizations. The reflectivity and refractive index spectra show that the sp 2 -hybridized C atoms are more sensitive to the light from infrared to visible region than B-N pairs while the C atoms and B-N pairs have a similar sensitivity to high frequencies. The sharp peaks of the energy-loss spectrum are all concentrated in the 23-30 eV energy region, which can be used to identify these hexagonal structures. The calculated band structures show Hex-C 24 and Hex-(BN) 6 C 12 are metals, but Hex-C 12 (BN) 6 and Hex-(BN) 12 are semiconductors with indirect band gaps of 3.47 and 3.25 eV, respectively. The electronic states near the Fermi level primarily originate from sp 2 -hybridized atoms. In addition, sp 2 -hybridized bonds are the main elements affecting the optical and electronic structure of C/BN materials with sp 2 - and sp 3 -hybridizations. We expect that the results presented will help understand the optical properties of C/BN materials containing sp 2 - and sp 3 -hybridized C atoms and B-N pairs.

A novel visible-light-responding BiVO4-Cu2O-TiO2 ternary heterostructure composite was successfully fabricated via the preparation of BiVO4-TiO2 followed by coupling with Cu2O through facile wet chemistry methods based on the strategy of energy gap engineering. The as-fabricated composite was characterized by X-ray powder diffraction, scanning electron microscopy, transmission electron microscopy, high-resolution transmission electron microscopy, UV-vis diffuse reflectance spectroscopy and X-ray photoelectron spectroscopy. Benefited from the rational design and construction, BiVO4-Cu2O-TiO2 exhibits a significantly enhanced photocatalytic activity for the degradation of rhodamine B (RhB) under the visible-light irradiation as compared with Cu2O and Cu2O-TiO2. Specifically, under the irradiation with an ordinary 9 W energy-saving fluorescent lamp for 8h, the photocatalytic degradation ratio of RhB for 5 wt%BiVO4-40 wt%Cu2O-TiO2 reaches 97.8%. The enhanced photocatalytic activity of BiVO4-Cu2O-TiO2 can be ascribed to the matched band edge positions of BiVO4, Cu2O and TiO2, the heterojunction formations among them as well as the lower charge transfer resistance, favoring the separation of the photo-generated electron-hole pairs. A possible mechanism of the visible-light photocatalytic degradation of RhB is also proposed., (Copyright © 2014 Elsevier Inc. All rights reserved.)