Unveiling cell subpopulations in T1D mouse islets using single-cell RNA sequencing.

Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of beta cells by immune cells. The interactions among cells within the islets may be closely linked to the pathogenesis of T1D. In this study, we used single-cell RNA sequencing (scRNA-Seq) to analyze the cellular heterogeneity within the islets of a T1D mouse model. We established a T1D mouse model induced by streptozotocin and identified cell subpopulations using scRNA-Seq technology. Our results revealed 11 major cell types in the pancreatic islets of T1D mice, with heterogeneity observed in the alpha and beta cell subgroups, which may play a crucial role in the progression of T1D. Flow cytometry further confirmed a mature alpha and beta cell reduction in T1D mice. Overall, our scRNA-Seq analysis provided insights into the cellular heterogeneity of T1D islet tissue and highlighted the potential importance of alpha and beta cells in developing T1D.NEW & NOTEWORTHY In this study, we created a comprehensive single-cell atlas of pancreatic islets in a T1D mouse model using scRNA-Seq and identified 11 major cell types in the islets, highlighting the role of alpha and beta cells in T1D. This study revealed a significant reduction in the maturity alpha and beta cells in T1D mice through flow cytometry. It also demonstrated the heterogeneity of alpha and beta cells, potentially crucial for T1D progression. Overall, our scRNA-Seq analysis provided new insights for understanding and treating T1D by studying cell subtype changes and functions.

Matrilin-2 prevents the TNFα-induced apoptosis of WB-F344 cells via suppressing JNK pathway.

Oval cells, a kind of hepatic progenitor cell quiescent at normal condition, activates to proliferate and differentiate into hepatocytes under severe and long-term liver injury, which usually raises severe inflammation. However, how oval cell survives in the inflammatory milieu interne is still unclear. Tumor necrosis factor α (TNFα), mimicking inflammatory hepatic milieu interne, was used to treat oval cell line, WB-F344, to test the protective function of matrilin-2. In this study, our data suggested that matrilin-2 prevented TNFα-induced apoptosis in WB-F344 cells via inhibiting ASK1/MKK7/JNK pathway. In conclusion, we determined that matrilin-2 plays the key role in maintaining the survival of oval cell and guarantees its proliferation under various injury factors.

Matrilin-2 regulates proliferation, apoptosis and cell cycle during radiation-induced injury in HPAEpiC cell.

Radiation pulmonary injury is related to the accumulation of extracellular matrix proteins in the alveolar interstitial space. Matrilin-2 as a component of extracellular filamentous networks, present higher level in the lung tissue from irradiated mice and irradiated pulmonary epithelial cell line, HPAEpiC cells. Knockdown of endogenous matrilin-2 prevents the apoptosis of HPAEpiC cell induced by the irradiation injury. Consistently, over-expression of matrilin-2 reduced the proliferation and induced apoptosis of HPAEpiC cells. Matrilin-2 promotes the expression of p21 via increasing the transcriptional activity of p53, by which induces the G1 phase arresting in HPAEpiC cells. In summary, matrilin-2, increased by irradiation, reduced the proliferation and induces apoptosis of pulmonary epithelial cells via p53/p21 pathway.

Transition Metal Nitride Coated with Atomic Layers of Pt as a Low-Cost, Highly Stable Electrocatalyst for the Oxygen Reduction Reaction.

The main challenges to the commercial viability of polymer electrolyte membrane fuel cells are (i) the high cost associated with using large amounts of Pt in fuel cell cathodes to compensate for the sluggish kinetics of the oxygen reduction reaction, (ii) catalyst degradation, and (iii) carbon-support corrosion. To address these obstacles, our group has focused on robust, carbon-free transition metal nitride materials with low Pt content that exhibit tunable physical and catalytic properties. Here, we report on the high performance of a novel catalyst with low Pt content, prepared by placing several layers of Pt atoms on nanoparticles of titanium nickel binary nitride. For the ORR, the catalyst exhibited a more than 400% and 200% increase in mass activity and specific activity, respectively, compared with the commercial Pt/C catalyst. It also showed excellent stability/durability, experiencing only a slight performance loss after 10,000 potential cycles, while TEM results showed its structure had remained intact. The catalyst's outstanding performance may have resulted from the ultrahigh dispersion of Pt (several atomic layers coated on the nitride nanoparticles), and the excellent stability/durability may have been due to the good stability of nitride and synergetic effects between ultrathin Pt layer and the robust TiNiN support.

High glucose-induced Matrilin-2 expression in mouse mesangial cells was mediated by transforming growth factor beta 1 (TGF-ß1).

This study aimed at evaluating the effect of high glucose on the expression of extracellular matrix (ECM) protein Matrilin-2 and the mechanism underlying this effect by using a mouse mesangial cell line. Mouse mesangial cells (MMCs) were cultured in media containing normal (5 mM d-glucose) or high concentrations of glucose (30 mM d-glucose). The expression of Matrilin-2 was assessed by either RT-PCR or western blot. Additionally, transforming growth factor beta 1 (TGF-ß1) inhibitors and TGF-ß1 were used to determine whether glucose-regulated Matrilin-2 expression was mediated by the TGF-ß1/Smad3 signaling pathway. Our data demonstrated that Matrilin-2 expression was markedly induced by high glucose and TGF-ß1. High glucose-induced Matrilin-2 expression was inhibited by TGF-ß1/Smad3 inhibitors, indicating that Matrilin-2 was markedly induced by high glucose and this induction was mediated by the TGF-ß1/Smad3 pathway. Taken together, our results showed that high-glucose-induced Matrilin-2 expression that was mediated by the TGF-ß1/Smad3 signaling pathway might play a role in Diabetic nephropathy (DN) pathogenesis and our finding provided a potential diagnostic and/or therapeutic target for DN.

High Expression of Rab-like 3 (Rabl3) is Associated with Poor Survival of Patients with Non-Small Cell Lung Cancer via Repression of MAPK8/9/10-Mediated Autophagy.

BACKGROUND Rab-like 3 (Rabl3) is a member of the Rab subfamily of small GTPases which are involved in controlling proliferation and vesicular trafficking. Recent studies suggest that Rab proteins might play a critical role in regulating cancer cell survival, but the underlying mechanisms remain largely unknown. MATERIAL AND METHODS We performed a bioinformatics analysis to examine the correlation between the expression level of Rabl3 and survival of non-small cell lung cancer (NSCLC) patients in three independent cohorts containing 484 patients. The function of Rabl3 was examined in NSCLC cell line A549 in vitro. Following Rabl3 knockdown, cells were stained with propidium iodine (PI) and Annexin V, followed by flow cytometry analysis (FACS) for cell death and autophagy induction. The activity of the MAPK signaling pathway was assessed by Western blotting of different MAPK phosphorylations, and modulated with different chemical inhibitors. RESULTS High expression of Rabl3 was significantly correlated with poor survival in all three independent NSCLC cohorts. In line with this result, Rabl3 was frequently overexpressed in lung cancer cell lines as compared with normal lung fibroblast cell lines. Knockdown of Rabl3 in lung cancer cells significantly enhanced cell death accompanied with autophagy induction, as evidenced by an increased level of autophagy marker LC3-II. Interestingly, Rabl3 knockdown was associated with enhanced activation of MAPK8/9/10 but not MAPK11/12/13/14. Treatment of MAPK8/9/10-specific inhibitor SP600125, but not MAPK11/12/13/14-specific inhibitor SB203580, largely abolished Rabl3 knockdown-induced LC3-I/LC3-II conversion and autophagic cell death. CONCLUSIONS Together, these results suggest that high expression of Rabl3 might inhibit cell death in NSCLCs via repression of MAPK8/9/10-mediated autophagy.

In vitro antitumor immune response induced by dendritic cells transduced with human livin α recombinant adenovirus.

Transduction with recombinant, replication-defective adenoviral (rAd) vectors encoding a transgene is an efficient method for gene transfer into human dendritic cells (DCs). Livin is a good candidate for cancer immunotherapy since it is overexpressed in most common human cancers, poorly expressed in most normal adult tissues. Two splicing variants of livin, designated livin α and livin ß, have been identified. In this study, we used human livin α recombinant adenovirus (rAd-hlivin α) to transduced DCs. We found that DCs transduced with rAd-hlivin α (rAd-hlivin α DCs) could effectively induce human livin α specific cytotoxic T lymphocytes (CTL) in vitro against various tumor cell lines.

Luminescence of La0.2Y1.8O3 nanostructured scintillators.

For the first time, transparent La0.2Y1.8O3 nanostructured polycrystalline scintillators were fabricated by sintering nanoparticle powders at high temperatures and their scintillation properties are reported. La0.2Y1.8O3 is a host material that has never been investigated as scintillators for radiation detection. Our observations found that La0.2Y1.8O3 has an intense scintillation luminescence, a detection efficiency higher than that of YAG:Ce and a comparable energy resolution to NaI and CsI scintillators. In addition, La0.2Y1.8O3 is stable and has luminescence decay lifetime in the picosecond range which is favorable for radiation detection. The luminescence of La0.2Y1.8O3 has a large Stokes-shift and a large emission bandwidth, and the luminescence is highly temperature dependent. Different from most doped scintillators, the luminescence of La0.2Y1.8O3 is most likely from the self-trapped excitons. The discovery of La0.2Y1.8O3 scintillators opens a new door for the research of new materials for radiation detection.

Preparation of zirconia transparent ceramics by low temperature microwave sintering.

Nanocrystalline yttria-stabilized zirconia (ZrO2-8 mol%Y2O3, 8YSZ) was synthesized by a homogeneous precipitation process using urea as the precipitation agent. Zirconia (ZrO2) transparent ceramics samples have been successfully fabricated by a microwave sintering process at low temperature. The technologies of low-temperature microwave sintering and the relationships of the microstructures and properties of the specified samples have been investigated in detail. We have found out that the low-temperature microwave sintering has its obvious advantages over the other methods in manufacturing zirconia transparent ceramics.

A rare case of primary pulmonary artery myofibroblastic sarcoma--imaging and pathologic features.

Primary myofibroblastic sarcomas of the pulmonary artery are very uncommon, but early detection is critical. Common clinical symptoms include shortness of breath, chest discomfort, and syncope. Patients diagnosed with a pulmonary tumor have a high risk of fatal pulmonary embolism. In this case study, we identified and diagnosed pulmonary artery myofibroblastic sarcoma in a young man by its imaging and pathologic characters. Surgery to excise the tumor was successfully performed and the operation was considered to have improved his prognosis. Postoperative examinations did not show any evidence of residual tumor, recurrence, or metastasis in the lungs or cardiac tissue. Based on the results of this case study, we concluded that the imaging and pathologic features of primary pulmonary artery myofibroblastic sarcoma can assist physicians in making a prompt diagnosis and an immediate surgical and treatment plan to greatly improve prognosis.

Matrilin-2 is proteolytically cleaved by ADAMTS-4 and ADAMTS-5.

Matrilin-2 is a widely distributed, oligomeric extracellular matrix protein that forms a filamentous network by binding to a variety of different extracellular matrix proteins. We found matrilin-2 proteolytic products in transfected cell lines in vitro and in mouse tissues in vivo. Two putative cleavage sites were identified in the unique domain of matrilin-2; the first site was located between D851 and L852 in the middle of the domain and the second, at the boundary with the coiled-coil domain at the C-terminus. Deletion of the entire unique domain eliminated the proteolysis of matrilin-2. While the first cleavage site was present in all matrilin-2 oligomers, the second cleavage site became apparent only in the matrilin-2 hetero-oligomers with matrilin-1 or matrilin-3. Analysis using a variety of extracellular protease inhibitors suggested that this proteolytic activity was derived from a member or several members  of the ADAMTS family. Recombinant human ADAMTS-4 (aggrecanase-1) and ADAMTS-5 (aggrecanase-2), but not ADAMTS-1, cleaved recombinant matrilin-2, thereby yielding matrilin-2 proteolytic peptides at the predicted sizes. These results suggest that ADAMTS-4 and ADAMTS-5 may destabilize the filamentous network in the extracellular matrix by cleaving matrilin-2 in both homo-oligomers and hetero-oligomers.

Zinc-motivated Fe/Fe5C2/Fe1-xS@Fe-N-C active sites grown on N-doped porous carbon toward efficient oxygen reduction reaction in zinc-air batteries.

The development of efficient non-precious metal oxygen reduction reaction catalysts to replace Pt-based catalysts is of great significance to accelerate the commercial application of fuel cells. In this study, a hierarchical porous carbon oxygen reduction reaction catalyst with Fe/Fe5C2/Fe1-xS@Fe-N-C active sites was developed via a simple and efficient solid-phase synthesis method. The introduction of zinc inhibited the growth and agglomeration of the nanoparticles and induced the formation of active nitrogen species and porosity, thus boosting the catalytic activity. The optimal FeZn-N-C-1 catalyst exhibited a high half-wave potential of 0.846 V, which is 24 mV higher than that of the commercial Pt/C, with a 4-e- reaction path under alkaline conditions. When the FeZn-N-C-1 catalyst is employed as a cathode in a zinc-air battery, it achieves a high open circuit voltage of 1.54 V, power density of 143.6 mW cm-2 and specific capacity of 804 mA h g-1.

Metalation of functionalized benzoquinoline-linked COFs for electrocatalytic oxygen reduction and lithium-sulfur batteries.

It is worthwhile to explore and develop multifunctional composites with unique advantages for energy conversion and utilization. Post-synthetic modification (PSM) strategies can endow novel properties to already excellent covalent organic frameworks (COFs). In this study, we prepared a range of COF-based composites via a multi-step PSM strategy. COF-Ph-OH was acquired by demethylation between anhydrous BBr3 and - OMe, and then, M@COF-Ph-OH was further obtained by forming the N - M - O structure. COF-Ph-OH exhibited a 2e--dominated oxygen reduction reaction (ORR) pathway with high H2O2 selectivity, while M@COF-Ph-OH exhibited a 4e--dominated ORR pathway with low H2O2 selectivity, which was due to the introduction of a metal salt with a d electron structure that facilitated the acquisition of electrons and changed the adsorption energy of the reaction intermediate (*OOH). It was proven that the d electron structure was effective at regulating the reaction pathway of the electrocatalytic ORR. Moreover, Co@COF-Ph-OH showed better 4e- ORR properties than Fe@COF-Ph-OH and Ni@COF-Ph-OH. In addition, compared with the other sulfur-impregnated COF-based composites examined in this study, S-Co@COF-Ph-OH had a larger initial capacity, a weaker impedance, and a stronger cycling durability in Li-S batteries, which was attributed to the unique porous structure ensuring high sulfur utilization, the loaded cobalt accelerating LiPS electrostatic adsorption and promoting LiPS catalytic conversion, and the benzoquinoline ring structure being ultra-stable. This work offers not only a rational and feasible strategy for the synthesis of multifunctional COF-based composites, but also promotes their application in electrochemistry.

Multimetallic Single-Atom Catalysts for Bifunctional Oxygen Electrocatalysis.

Multimetallic alloys have demonstrated promising performance for the application of metal-air batteries, while it remains a challenge to design multimetallic single-atom catalysts (MM-SACs). Herein, metal-C3N4 and nitrogen-doped carbon are employed as cornerstones to synthesize MM-SACs by a general two-step method, and the inherent features of atomic dispersion and the strong electronic reciprocity between the multimetallic sites have been verified. The trimetallic FeCoZn-SACs and quatermetallic FeCoCuZn-SACs are both found to deliver superior oxygen evolution reaction and oxygen reduction reaction activity, respectively, as well as outstanding bifunctional durability. Density functional theory calculations elucidate the crucial contribution of Co sites of FeCoCuZn-SACs to the efficient catalysis of both the ORR and the OER. More importantly, Zn-air batteries with FeCoCuZn-SACs as cathodic catalysts exhibit a high power density (252 mW cm-2), high specific capacity (817 mAh gZn-1), and considerable stability (over 225 h) for charging-discharging processes. This work provides a visual perspective for the advantages of MM-SACs toward oxygen electrocatalysis.

Movable type printing method to synthesize high-entropy single-atom catalysts.

The controllable anchoring of multiple isolated metal atoms into a single support exhibits scientific and technological opportunities, while the synthesis of catalysts with multiple single metal atoms remains a challenge and has been rarely reported. Herein, we present a general route for anchoring up to eleven metals as highly dispersed single-atom centers on porous nitride-doped carbon supports with the developed movable type printing method, and label them as high-entropy single-atom catalysts. Various high-entropy single-atom catalysts with tunable multicomponent are successfully synthesized with the same method by adjusting only the printing templates and carbonization parameters. To prove utility, quinary high-entropy single-atom catalysts (FeCoNiCuMn) is investigated as oxygen reduction reaction catalyst with much more positive activity and durability than commercial Pt/C catalyst. This work broadens the family of single-atom catalysts and opens a way to investigate highly efficient single-atom catalysts with multiple compositions.

General Method for Synthesizing Effective and Durable Electrocatalysts Derived from Cellulose for Microbial Fuel Cells.

Microbial fuel cells (MFCs) can be capable of both wastewater treatment and electricity generation, which necessarily depends on the increasing cathodic performances and stability at low cost to realize industrialization. Herein, cellulose, a commercially available and sustainable material, was oxidized as a carbon precursor to produce the oxygen species synergizing the nitrogen-doped carbon (CON-900) catalyst by a facile in situ nitrogen doping method. The incorporation of nitrogen and oxygen with a high content creates more active centers. Meanwhile, the hierarchical porosity of CON-900 contributes to a high specific surface area (652 m2 g-1) and the exposure of accessible active sites. As expected, CON-900 exhibits considerable activity for the oxygen reduction reaction, excellent operating stability, and high poisoning resistance. In addition, the MFC fabricated with CON-900 as a cathode catalyst demonstrates a maximum power density of 1014 ± 23 mW m-2, which is comparable with that of the Pt/C cathode (1062 ± 14 mW m-2). This work offers a facile and versatile strategy for various biomass materials to develop low-cost and high-efficiency carbon-based catalysts for MFCs and beyond.

Progress in the development of heteroatom-doped nickel phosphates for electrocatalytic water splitting.

Hydrogen energy is expected to replace fossil fuels as a mainstream energy source in the future. Currently, hydrogen production via water electrolysis yields high hydrogen purity with easy operation and without producing polluting side products. Presently, platinum group metals and their oxides are the most effective catalysts for water splitting; however, their low abundance and high cost hinder large-scale hydrogen production, especially in alkaline and neutral media. Therefore, the development of high-efficiency, durable, and low-cost electrocatalysts is crucial to improving the overpotential and lowering the electrical energy consumption. As a solution, Ni2P has attracted particular attention, owing to its desirable electrical conductivity, high corrosion resistance, and remarkable catalytic activity for overall water splitting, and thus, is a promising substitute for platinum-group catalysts. However, the catalytic performance and durability of raw Ni2P are still inferior to those of noble metal-based catalysts. Heteroatom doping is a universal strategy for enhancing the performance of Ni2P for water electrolysis over a wide pH range, because the electronic structure and crystal structure of the catalyst can be modulated, and the adsorption energy of the reaction intermediates can be adjusted via doping, thus optimizing the reaction performance. In this review, first, the reaction mechanisms of water electrolysis, including the cathodic hydrogen evolution reaction and anodic oxygen evolution reaction, are briefly introduced. Then, progress into heteroatom-doped nickel phosphide research in recent years is assessed, and a discussion of each representative work is given. Finally, the opportunities and challenges for developing advanced Ni2P based electrocatalysts are proposed and discussed.

Fabrication of (Nd(0.01)La(x)Y(0.99-x))2O3 nanoparticles and transparent ceramics by combustion synthesis.

Y2O3 acts as the matrix material when doped with different content of La2O3 for reducing sintering temperature and refining grains. The (Nd(0.01)La(x)Y(0.99-x))2O3 nanoparticles and transparent ceramics are fabricated by a combustion synthesis. The powder feature is characterized by TEM. The microstructure, mechanical properties and transmittance of the samples are examined by SEM, HV-1000 hardness tester and fluorescence analyzer respectively. The results show that the (Nd(0.01)La(x)Y(0.99-x))2O3 nanoparticles are homogeneous in size and nearly spherical with average diameter in the range of 40-60 nm. There are no other phases except the Y2O3 cubic phase in the (Nd(0.01)La(x)Y(0.99-x))2O3 nanoparticles. The grains of the samples significantly reduce with increasing La2O3 content. The hardness and fracture toughness increase rapidly first and then gradually tend to plateau with increasing La2O3 content. The transmittance of sample also increases gradually with increasing La2O3, the largest transmittance exceeds 77% when the La2O3 content is x = 0.12.

NLRC4 gene silencing-dependent blockade of NOD-like receptor pathway inhibits inflammation, reduces proliferation and increases apoptosis of dendritic cells in mice with septic shock.

Septic shock is one of the most significant health concerns across the world, involving hypo-perfusion and defects in tissue energy. The current study investigates the role of NLR family CARD domain containing protein 4 (NLRC4) in septic shock-induced inflammatory reactions, lung tissue injuries, and dendritic cell (DC) apoptosis. Septic shock mice models were established by modified cecal ligation and puncture and injected with retroviral vector expressing siRNA-NLRC4. DCs were then isolated and transfected with siRNA-NLRC4. The degree of lung tissue injury, cell cycle distribution, cell apoptosis and cell viability of DCs were assessed. NLRC4 was found to be expressed at high levels in mice with septic shock. NLRC4 silencing inhibited the activation of the NOD-like receptor (NLR) pathway as evidenced by the decreased levels of NOD1, NOD2, RIP2, and NF-κB. In addition, NLRC4 silencing reduced the inflammatory reaction as attributed by reduced levels of IL-1ß, TNF-α and IL-6. Suppressed NLRC4 levels inhibited cell viability and promoted cell apoptosis evidenced by inhibited induction of DC surface markers (CD80, CD86, and MHC II), along with alleviated lung tissue injury. In conclusion, NLRC4 silencing ameliorates lung injury and inflammation induced by septic shock by negatively regulating the NLR pathway.

Memantine ameliorates cognitive impairment induced by exposure to chronic hypoxia environment at high altitude by inhibiting excitotoxicity.

AIMS: Memantine is a non-competitive antagonist of glutamatergic NMDA receptor that is mainly used in the treatment of Alzheimer's disease. The excitatory toxicity mediated by glutamate via glutamatergic receptor signals is considered to be one of the mechanisms mediating neuronal injury and cognitive impairment after exposure to a hypoxic environment at a high altitude. Therefore, in this study, we hypothesized that inhibiting glutamate signaling using memantine could alleviate neuronal injury and cognitive impairment in rats exposed to chronic hypoxia. MAIN METHODS: we made animal models in the natural environment of the Qinghai-Tibet Plateau at an altitude of 4300 m, and used animal behavior, morphology, molecular biology and other methods to evaluate the impact of chronic hypoxia exposure on cognitive function and the neuroprotective effect of Memantine. KEY FINDINGS: Our results showed that the expression of NMDA receptors increased, while the expression of AMPA receptors decreased, after 4 weeks of chronic hypoxia exposure. Concomitantly, apoptotic neuronal cell death in the hippocampus and frontal cortex was significantly increased, along with levels of oxidative stress, whereas innate ability to inhibit free radicals decreased. Moreover, after 8 weeks of hypoxia exposure, learning, memory, and space exploration abilities were significantly decreased. Notably, after treatment with memantine, apoptotic neuronal cell death, oxidative stress, and free radical levels decreased, and the cognitive function of the animals improved. SIGNIFICANCE: Present study shows that chronic hypoxia can produce the excitatory toxicity leading to neural injury and cognitive impairment that can be suppressed with memantine treatment by inhibiting excitatory toxicity.