Single-cell analyzing of tumor microenvironment and cell adhesion between early and late-stage lung cancer.

Lung adenocarcinoma (LUAD) is a highly heterogeneous disease that threaten human life with serious incidence and high mortality. High heterogeneity of tumor microenvironment (TME) was reported in multiple studies. However, the factor of controlling the tumor migration progression between eary and late-stage LUAD is still not fully understood. In this study, we conducted a comprehensive analysis of single-cell RNA sequencing (scRNA-seq) data of LUAD obtained from the GEO database. The identification of cell clusters revealed significant expansion of epithelial cells in late-stage patients. Interpretation of the cell-cell communication results between early-stage and late-stage patient samples indicated that early tumor cells may interact with epithelial cells through the TGF-ß pathway to promote tumor progression. The cell cycle analysis demonstrated a significant increase in the number of cells in the G2 and M phases in late-stage lung cancer. Further analysis using Non-negative Matrix Factorization (NMF) revealed early-stage cell-specific gene features involved in cell adhesion-related biological processes. Among these, the Tensin (TNS) gene family, particularly TNS1, showed high expression in epithelial cells and fibroblasts of early-stage samples, specifically associated with cell adhesion. Survival analysis using TCGA database for LUAD demonstrated that patients with high expression of TNS1 exhibited significantly higher overall survival rates compared to those with low expression. Immunofluorescence experiments have demonstrated co-expression of TNS1 with fibroblast and tumor cell markers (α-SMA and EPCAM). Immunohistochemistry experiments further validated the significantly higher expression levels of TNS1 in early-stage LUAD tissues compared to late-stage lung cancer tissues (P<0.05). Pathway experiments have shown that early-stage tumor patients with high expression of TNS1 exhibit stronger phosphorylation levels of Akt and mTOR, indicating a more potent activation of the Akt/mTOR signaling pathway. In conclusion, the results of this study demonstrate that TNS1 is an adhesive molecule in the immune microenvironment of early-stage tumor cells, and it may serve as a novel prognostic marker for lug cancer.

Pseudo-nanostructure and trapped-hole release induce high thermoelectric performance in PbTe.

Thermoelectric materials can realize direct and mutual conversion between electricity and heat. However, developing a strategy to improve high thermoelectric performance is challenging because of strongly entangled electrical and thermal transport properties. We demonstrate a case in which both pseudo-nanostructures of vacancy clusters and dynamic charge-carrier regulation of trapped-hole release have been achieved in p-type lead telluride-based materials, enabling the simultaneous regulations of phonon and charge carrier transports. We realized a peak zT value up to 2.8 at 850 kelvin and an average zT value of 1.65 at 300 to 850 kelvin. We also achieved an energy conversion efficiency of ~15.5% at a temperature difference of 554 kelvin in a segmented module. Our demonstration shows promise for mid-temperature thermoelectrics across a range of different applications.

Design and synthesis of highly selective Janus kinase 3 covalent inhibitors for the treatment of rheumatoid arthritis.

Selective inhibition of Janus kinase 3 (JAK3) is a promising strategy for the treatment of autoimmune diseases. Based on the discovery of a hydrophobic pocket unutilized between the lead compound RB1 and the JAK3 protein, a series of covalent JAK3 inhibitors were prepared by introducing various aromatic fragments to RB1. Among them, J1b (JAK3 IC50 = 7.2 nM, other JAKs IC50 > 1000 nM) stood out because of its low toxicity (MTD > 2 g/kg) and superior anti-inflammatory activity in Institute of Cancer Research mice. Moreover, the acceptable bioavailability (F% = 31.69%) ensured that J1b displayed excellent immune regulation in collagen-induced arthritis mice, whose joints in the high-dose group were almost recovered to a normal state. Given its clear kinase selectivity (Bmx IC50 = 539.9 nM, other Cys909 kinases IC50 > 1000 nM), J1b was nominated as a highly selective JAK3 covalent inhibitor, which could be used to safely treat arthritis and other autoimmune diseases.

Goethite adaptation prompts alterations in antibiotic susceptibility and suppresses development of antibiotic resistance in bacteria.

Understanding the impact of environmental factors on antibiotic sensitivity and the emergence of antibiotic resistance in microorganism is crucial for antibiotics management and environmental risk assessment. Natural materials, like mineral particles, are prevalent in aquatic and terrestrial ecosystems. However, it remains unclear how microorganism adapt to the physical stress of mineral particles and whether this adaptation influences antibiotic sensitivity and the evolution of antibiotic resistance. In this study, the model bacterium Escherichia coli (E. coli) was exposed to the mineral particle goethite for 30 generations. Adaptive morphogenesis, including an increase in the fraction of spherical bacteria, variations in bacterial mobility, a slightly increased cell membrane thickness, and genome-wide changes in the transcriptomic profile, were observed in adapted E. coli samples to counteract the stress. Moreover, the goethite adapted E. coli showed increased susceptibility to antibiotics including amoxicillin and tetracycline, and decreased susceptibility to kanamycin compared to its ancestral counterparts. These alterations in antibiotic susceptibility in the adapted E. coli were not heritable, as evidenced by the gradual recovery of antibiotic tolerance in cells with the cessation of goethite exposure. Transcriptomic data and a series of experiments suggested that these changes may be associated with variations in cell membrane property and iron metabolism. In addition, the evolution of antibiotic resistance in adapted cells occurred at a slower rate compared to their ancestral counterparts. For instance, E. coli adapted to goethite at a concentration of 1 mg/mL did not acquire antibiotic resistance even after 13 generations, probably due to its poor biofilm-formation capacity. Our findings underscore the occurrence of microbial adaptation to goethite, which influenced antibiotic sensitivity and decelerated the development of resistance in microorganisms. This insight contributes to our comprehension of the natural dynamics surrounding the evolution of antibiotic resistance and opens new perspectives for addressing this issue through nanotechnology-based approaches.

Extremely Low Lattice Thermal Conductivity and Significantly Enhanced Near-Room-Temperature Thermoelectric Performance in α-Cu2Se through the Incorporation of Porous Carbon.

In this work, a series of Cu2Se/x wt % porous carbon (PC) (x = 0, 0.2, 0.4, 0.6, 0.8, 1) composite materials were synthesized by ball milling and spark plasma sintering (SPS). The highly ordered porous carbon was synthesized by a hydrothermal method using mesoporous silica (SBA-15) as the template. X-ray diffraction results show that the incorporation of porous carbon induces a phase transition of Cu2Se from the ß phase to the α phase. Meanwhile, the addition of porous carbon reduces the carrier concentration from 2.7 × 1021 to 2.45 × 1020 cm-3 by 1 order of magnitude. The decrease of the carrier concentration leads to the reduction of electrical conductivity and the increase of the Seebeck coefficient, which results in the enhancement of the power factor. On the other hand, the incorporation of porous carbon into Cu2Se increases the porosity of the composites and also introduces more interfaces between the two materials, which is evidenced by positron annihilation lifetime measurements. Both pores and interfaces greatly enhance phonon scattering, leading to extremely low lattice thermal conductivity. In addition, the decrease of electrical conductivity also causes a sufficient reduction in electronic thermal conductivity. Due to the above synergistic effects, the thermoelectric performance of the Cu2Se/PC composite is significantly enhanced with a maximum ZT value of 0.92 at 403 K in the Cu2Se/1 wt % PC composite, which is close to that of the Bi2Te3-based materials. Our work shows that α-Cu2Se has great potential for near-room-temperature thermoelectric materials.

An Ultrathin Composite Polymer Electrolyte Dual-Reinforced by a Polymer of Intrinsic Microporosity (PIM-1) and Poly(tetrafluoroethylene) (PTFE) Porous Membrane.

The performances of solid-state polymer electrolytes are urgently required to be further improved for high energy density lithium metal batteries. Herein, a highly reinforced ultrathin composite polymer electrolyte (PLPP) is successfully fabricated in a large scale by densely filling the well-dispersed mixture of polyethylene oxide (PEO), Li-salt (LiTFSI) and a polymer of intrinsic microporosity (PIM-1) into porous poly(tetrafluoroethylene) (PTFE) matrix. Based on the macro-plus-micro synergistic enhancement of the PTFE with excellent mechanical properties and the soluble PIM-1 with suitable functional groups, the PLPP electrolyte exhibits excellent properties including mechanical stress, thermal stability, lithium-ion transference number, voltage window and ionic conductivity, which are all superior to the typical PEO/LiTFSI electrolytes. As a result, the Li/PLPP/Li symmetric cell can stably cycle for > 2000 h, and the LiFePO4 /PLPP/Li full cell exhibits excellent rate performance (>10 C) and high cycling stability with an initial capacity of 158.8 mAh g-1 and a capacity retention of 78.8% after 300 cycles. In addition, the excellent mechanical properties as well as the wide voltage window reasonably result in the stable operation of full cells with either high-loading cathode up to 28.1 mg cm-2 or high voltage cathode with high energy density.

Sustainable production of Fe-doped MnO2 nanoparticles for accelerated tetracycline antibiotic detoxification.

Manganese dioxide (MnO2) has been recognized as one of the natural systems' most active mineral oxidants. However, when it comes to catalytic oxidation of antibiotic applications, pure MnO2 falls short in delivering satisfactory performance. Hence, a set of Fe3+-doped porous MnO2 (0.02Fe-MnO2, 0.1Fe-MnO2, and 0.14Fe-MnO2) nanoparticles were synthesized here via a convenient and energy-efficient one-step reaction method. A series of experiments revealed that Fe-doping strategy enhances the properties of MnO2 host by suppressing the crystalline structure, increasing the amount of surface oxygen defects, and modifying the Mn3+/Mn4+ ratio. Specifically, the tetracycline (TC) removal efficiency of 0.14Fe-MnO2 reaches 92% without the need for any additional co-oxidant, representing a 20% improvement over pristine MnO2 nanoparticles. Moreover, this process shows a fast dynamic (achieving 70% of TC removal in just 5 min) and demonstrates pH-resistance, maintaining high TC removal efficiency (≥90%) over a wide pH range of 3.0-9.0. Mechanical studies reveal that the degradation of TC can be attributed to the oxidation by reactive oxygen radicals and Mn3+, with 1O2 being the primary radical involved in the reaction, accounting for 55% of TC removal. Importantly, cytotoxicity testing indicates that the biotoxicity of TC toward organisms can be effectively mitigated using 0.14Fe-MnO2 nanomaterial. This study presents a readily applicable candidate for economically and conveniently eliminating of environmental TC pollution, thereby reducing the threat posed by TC pollution to the ecosystem.

Dimensionality reduction induced synergetic optimization of the thermoelectric properties in Bi2Si2X6 (X = Se, Te) monolayers.

Different from three-dimensional bulk compounds, two-dimensional monolayer compounds exhibit much better thermoelectric performance on account of the quantum confinement and interface effect. Here, we present a systematic study on the electronic and thermal transport properties of bulk and monolayer Bi2Si2X6 (X = Se, Te) through theoretical calculations using density functional theory based on first-principles and Boltzmann transport theory. Monolayer Bi2Si2X6 are chemically, mechanically and thermodynamically stable semiconductors with suitable band gaps, and they have lower lattice thermal conductivity (κL) in the a/b direction than their bulk counterparts. The calculated κL of monolayer Bi2Si2Se6 (Bi2Si2Te6) is as low as 0.72 (0.95) W m-1 K-1 at 700 K. Moreover, monolayer Bi2Si2X6 exhibit a higher Seebeck coefficient compared with bulk Bi2Si2X6 owing to the sharper peaks in the electronic density of states (DOS). This results in a significant increase in power factor by dimensionality reduction. Combined with the synergetically suppressed thermal conductivity, the maximum ZT values for monolayer Bi2Si2Se6 and Bi2Si2Te6 are significantly enhanced up to 5.03 and 2.87 with p-type doping at 700 K, which are more than 2 times that of the corresponding bulk compounds. These results demonstrate the superb thermoelectric performance of monolayer Bi2Si2X6 for promising thermoelectric conversion applications.

Balanced High Thermoelectric Performance in n-Type and p-Type CuAgSe Realized through Vacancy Manipulation.

As a liquid-like material, CuAgSe has high carrier mobility and ultralow lattice thermal conductivity. It undergoes an n-p conduction-type transition during ß- to α-phase transition with increasing temperature. Moreover, optimization of the thermoelectric performance of CuAgSe is rather difficult, owing to the two-carrier conduction in this material. In this work, we reported the free tuning of the conduction type and thermoelectric performance of CuAgSe by manipulating the cation vacancies. Positron annihilation measurements reveal that the increase in CuAg content can effectively suppress the cation vacancies and reduce the hole carrier concentration, resulting in n-type conduction at high temperatures. Doping with Zn at the Cu sublattice in the CuAg-excessive CuAgSe can further decrease the number of vacancies, leading to a significant decrease in hole carrier concentration. Furthermore, the reduction of vacancies leads to weakening of carrier scattering. As a result, carrier mobility is also enhanced, thus improving the thermoelectric performance of n-type CuAgSe. On the other hand, high-performance p-type CuAgSe can be achieved by decreasing the CuAg content to introduce more cation vacancies. Ultimately, both n-type and p-type CuAgSe with superb thermoelectric performance are obtained, with a zTmax of 0.84 in Cu1.01Ag1.02Zn0.01Se (n-type) and 1.05 in (CuAg)0.96Se (p-type) at 600 K and average zT of 0.77 and 0.94 between 470 and 630 K for n-type and p-type, respectively.

Vacancy Suppression Induced Synergetic Optimization of Thermoelectric Performance in Sb-Doped GeTe Evidenced by Positron Annihilation Spectroscopy.

Synergetic optimization of the electrical and thermal transport performance of GeTe has been achieved through Sb doping in this work, resulting in a high thermoelectric figure of merit ZT of 2.2 at 723 K. Positron annihilation measurements provided clear evidence that Sb doping in GeTe can effectively suppress the Ge vacancies, and the decrease of vacancy concentration coincides well with the change of hole carrier concentration after Sb doping. The decreased scattering by hole carriers and vacancies causes notable increase in carrier mobility. Despite this, the density of states effective mass is not enhanced by Sb doping, a maximum power factor of 4562 µW m-1 K-2 at 723 K is obtained for Ge0.94Sb0.06Te with an optimized carrier concentration of ∼3.65 × 1020 cm-3. Meanwhile, the electronic thermal conductivity κe is reduced because of the decreased electrical conductivity σ with the increase of the Sb doping amount. In addition, the lattice thermal conductivity κL is also suppressed due to multiple phonon scattering mechanism, such as the large mass and strain fluctuations by the substitution of Sb for Ge atoms, and also the unique microstructure including grain boundary, nano-pore, and dislocation in the samples. In conclusion, a maximum ZT of 2.2 is gained at 723 K, which contributes to preferable TE property for GeTe-based materials.

Ultrasensitive and Rapid Visual Detection of Escherichia coli O157:H7 Based on RAA-CRISPR/Cas12a System.

Escherichia coli (E. coli) O157:H7 is a major foodborne and waterborne pathogen that can threaten human health. Due to its high toxicity at low concentrations, it is crucial to establish a time-saving and highly sensitive in situ detection method. Herein, we developed a rapid, ultrasensitive, and visualized method for detecting E. coli O157:H7 based on a combination of Recombinase-Aided Amplification (RAA) and CRISPR/Cas12a technology. The CRISPR/Cas12a-based system was pre-amplified using the RAA method, which showed high sensitivity and enabled detecting as low as ~1 CFU/mL (fluorescence method) and 1 × 102 CFU/mL (lateral flow assay) of E. coli O157:H7, which was much lower than the detection limit of the traditional real-time PCR technology (103 CFU/mL) and ELISA (104~107 CFU/mL). In addition, we demonstrated that this method still has good applicability in practical samples by simulating the detection in real milk and drinking water samples. Importantly, our RAA-CRISPR/Cas12a detection system could complete the overall process (including extraction, amplification, and detection) within 55 min under optimized conditions, which is faster than most other reported sensors, which take several hours to several days. The signal readout could also be visualized by fluorescence generated with a handheld UV lamp or a naked-eye-detected lateral flow assay depending on the DNA reporters used. Because of the advantages of being fast, having high sensitivity, and not requiring sophisticated equipment, this method has a promising application prospect for in situ detection of trace amounts of pathogens.

Extremely Low Lattice Thermal Conductivity Leading to Superior Thermoelectric Performance in Cu4TiSe4.

Low thermal conductivity is crucial for obtaining a promising thermoelectric (TE) performance in semiconductors. In this work, the TE properties of Cu4TiS4 and Cu4TiSe4 were theoretically investigated by carrying out first-principles calculations and solving Boltzmann transport equations. The calculated results reveal a lower sound velocity in Cu4TiSe4 compared to that in Cu4TiS4, which is due to the weaker chemical bonds in the crystal orbital Hamilton population (COHP) and also the larger atomic mass in Cu4TiSe4. In addition, the strong lattice anharmonicity in Cu4TiSe4 enhances phonon-phonon scattering, which shortens the phonon relaxation time. All of these factors lead to an extremely low lattice thermal conductivity (κL) of 0.11 W m-1 K-1 at room temperature in Cu4TiSe4 compared with that of 0.58 W m-1 K-1 in Cu4TiS4. Owing to the suitable band gaps of Cu4TiS4 and Cu4TiSe4, they also exhibit great electrical transport properties. As a result, the optimal ZT values for p (n)-type Cu4TiSe4 are up to 2.55 (2.88) and 5.04 (5.68) at 300 and 800 K, respectively. For p (n)-type Cu4TiS4, due to its low κL, the ZT can also reach high values over 2 at 800 K. The superior thermoelectric performance in Cu4TiSe4 demonstrates its great potential for applications in thermoelectric conversion.

CEMIP-mediated hyaluronan metabolism facilitates SCLC metastasis by activating TLR2/c-Src/ERK1/2 axis.

Small-cell lung cancer (SCLC) is a highly metastatic and recalcitrant malignancy. Metastasis is the major cause of death in patients with SCLC but its mechanism remains poorly understood. An imbalance of hyaluronan catabolism in the extracellular matrix accelerates malignant progression in solid cancers due to the accumulation of low-molecular-weight HA. We previously found that CEMIP, a novel hyaluronidase, may act as a metastatic trigger in SCLC. In the present study, we found that both CEMIP and HA levels were higher in SCLC tissues than in paracancerous tissues from patient specimens and in vivo orthotopic models. Additionally, high expression of CEMIP was associated with lymphatic metastasis in patients with SCLC, and in vitro results showed that CEMIP expression was elevated in SCLC cells relative to human bronchial epithelial cells. Mechanistically, CEMIP facilitates the breakdown of HA and accumulation of LMW-HA. LMW-HA activates its receptor TLR2, and subsequently recruits c-Src to activate ERK1/2 signalling, thereby promoting F-actin rearrangement as well as migration and invasion of SCLC cells. In addition, the in vivo results verified that depletion of CEMIP attenuated HA levels and the expressions of TLR2, c-Src, and phosphorylation of ERK1/2, as well as liver and brain metastasis in SCLC xenografts. Furthermore, the application of the actin filament inhibitor latrunculin A significantly inhibited the liver and brain metastasis of SCLC in vivo. Collectively, our findings reveal the critical role of CEMIP-mediated HA degradation in SCLC metastasis and suggest its translational potential as an attractive target and a novel strategy for SCLC therapy.

CEMIP promotes small cell lung cancer proliferation by activation of glutamine metabolism via FBXW7/c-Myc-dependent axis.

Small cell lung cancer (SCLC) is the most malignant lung cancer with rapid growth and early metastasis, but still lacks effective targeted therapies to improve the prognosis. Here, we demonstrated that a novel oncogenic protein, cell migration inducing hyaluronic binding protein (CEMIP), was robustly overexpressed in SCLC tissues than that in noncancerous tissues and high expression of CEMIP predicted poor outcomes in clinical specimens and in large sample size cohorts from public databases (GEPIA 2 and CPTAC). Liquid chromatography mass spectrometry (LC-MS) and in vitro/in vivo functional assays indicated that CEMIP contributed to the proliferation by increasing glutamine consumption and their metabolites (glutamate and glutathione) levels in SCLC cells. Moreover, the addition of a GLS1 inhibitor CB-839 dramatically reduced CEMIP-induced SCLC cell proliferation. Mechanistically, beyond as a scaffold protein, CEMIP facilitates glutamine-dependent cell proliferation through inhibiting c-Myc ubiquitination and increasing c-Myc stabilization and nuclear accumulation via hindering the interaction between FBXW7 (a E3 ubiquitin ligase) and its target substrate c-Myc. Taken together, our findings reveal a novel oncogenic role of CEMIP in sustaining SCLC growth via FBXW7/c-Myc-dependent axis, and provide new evidence that inhibition of CEMIP might be a potential therapeutic strategy for the treatment of SCLC.

Novel Microbial Palladium Nanoparticles with a High Photothermal Effect for Antibacterial Applications.

Novel biocompatible palladium nanoparticles (Pd-NPs) have been prepared by microorganisms via Bacillus megaterium Y-4. It was demonstrated that ultrasonication treatment of biologically reduced Pd-NPs impart a much higher absorption in NIR regions and a better photothermal conversion efficiency to the material. The as-prepared material showed excellent biocompatibility and antibacterial activity under NIR irradiation. In less than 10 min, the disinfection efficiency for a low dosage of Pd-NPs (20 mg/L) was 99.99% toward both Staphylococcus aureus and Escherichia coli. The exclusive and even dispersed microbial Pd-NPs display a high efficiency of photothermal conversion under the irradiation of NIR, which endows them with excellent antibacterial activity in a low dosage.

Connexin32 Promotes the Activation of Foxo3a to Ameliorate Diabetic Nephropathy via Inhibiting the Polyubiquitination and Degradation of Sirt1.

Aims: Renal oxidative stress (OSS) is the leading cause of diabetic nephropathy (DN). The silent information regulator 1/forkhead boxo3a (Sirt1/Foxo3a) pathway plays an essential role in regulating the antioxidant enzyme system. In this study, we aimed to investigate the mechanism of connexin32 (Cx32) on the antioxidant enzyme system in DN. Results: In this study, Cx32 overexpression significantly reduced reactive oxygen species generation and effectively inhibited the excessive production of extracellular matrix such as fibronectin (FN) and intercellular adhesion molecule-1 (ICAM-1) in high-glucose (HG)-induced glomerular mesangial cells. In addition, Cx32 overexpression reversed the downregulation of Sirt1, and promoted the nuclear transcription of Foxo3a, subsequently activating the antioxidant enzymes including catalase and manganese superoxide dismutase (MnSOD), however, Cx32 knockdown showed the opposite effects. A further mechanism study showed that Cx32 promoted the autoubiquitination and degradation of Smad ubiquitylation regulatory factor-1 (Smurf1), thereby reducing the ubiquitination of Sirt1 at Lys335 and the degradation of Sirt1. Moreover, the in vivo results showed that adenovirus-mediated Cx32 overexpression activated the Sirt1/Foxo3a pathway, and inhibited OSS in the kidney tissues, eventually improving the renal function and glomerulosclerosis in diabetic mice. Innovation: This study highlighted the antioxidant role of Cx32-Sirt1-Foxo3a axis to alleviate DN, which is a new mechanism of Cx32 alleviating DN. Conclusion: Cx32 alleviated DN via activating the Sirt1/Foxo3a antioxidant pathway. The specific mechanism was that Cx32 upregulated the Sirt1 expression through reducing the ubiquitination of Lys335 of Sirt1 by inhibiting Smurf1. Antioxid. Redox Signal. 39, 241-261.

Polarization-sensitive switchable display through critical coupling between graphene and a quasi-BIC.

Enhanced light-matter interaction of a local field is of prime importance in optics as it can improve the performance of nanophotonic devices. Such enhancement can be achieved by utilizing the optical bound states in the continuum (BICs). In this study, a dielectric metasurface is proposed that could enhance the light-matter interactions in graphene. A symmetry-protected BIC was observed in such a metasurface, which could transform into a quasi-BIC with a high quality (Q-) factor when the in-plane symmetry is broken. As the graphene monolayer was introduced into the system, its absorption was enhanced by the quasi-BIC resonance. By optimizing the graphene Fermi energy and the asymmetry parameter of the metasurface to satisfy the critical-coupling condition, a tunable absorber could be achieved. The absorbing intensity could be efficiently modulated by varying the polarization direction of the incident light, the maximum difference of which was up to 95.4%. Also, further investigation showed that such a feature indicates potential application in digital switches and image displays, which could be switched by incident polarization only, and therefore without dependence on an additional structural change.

KIAA1199 Correlates With Tumor Microenvironment and Immune Infiltration in Lung Adenocarcinoma as a Potential Prognostic Biomarker.

Background: KIAA1199 has been considered a key regulator of carcinogenesis. However, the relationship between KIAA1199 and immune infiltrates, as well as its prognostic value in lung adenocarcinoma (LUAD) remains unclear. Methods: The expression of KIAA1199 and its influence on tumor prognosis were analyzed using a series of databases, comprising TIMER, GEPIA, UALCAN, LCE, Prognoscan and Kaplan-Meier Plotter. Further, immunohistochemistry (IHC), western blot (WB) and receiver operating characteristic (ROC) curve analyses were performed to verify our findings. The cBioPortal was used to investigate the genomic alterations of KIAA1199. Prediction of candidate microRNA (miRNAs) and transcription factor (TF) targeting KIAA1199, as well as GO and KEGG analyses, were performed based on LinkedOmics. TIMER and TISIDB databases were used to explore the relationship between KIAA1199 and tumor immune infiltration. Results: High expression of KIAA1199 was identified in LUAD and Lung squamous cell carcinoma (LUSC) patients. High expression of KIAA1199 indicated a worse prognosis in LUAD patients. The results of IHC and WB analyses showed that the expression level of KIAA1199 in tumor tissues was higher than that in adjacent tissues. GO and KEGG analyses indicated KIAA1199 was mainly involved in extracellular matrix (ECM)-receptor interaction and extracellular matrix structure constituent. KIAA1199 was positively correlated with infiltrating levels of CD4+ T cells, macrophages, neutrophil cells, dendritic cells, and showed positive relationship with immune marker subsets expression of a variety of immunosuppressive cells. Conclusion: High expression of KIAA1199 predicts a poor prognosis of LUAD patients. KIAA1199 might exert its carcinogenic role in the tumor microenvironment via participating in the extracellular matrix formation and regulating the infiltration of immune cells in LUAD. The results indicate that KIAA1199 might be a novel biomarker for evaluating prognosis and immune cell infiltration in LUAD.

Trilobatin alleviates non-alcoholic fatty liver disease in high-fat diet plus streptozotocin-induced diabetic mice by suppressing NLRP3 inflammasome activation.

Diabetes mellitus (DM) is a factor with great risk in the course of non-alcoholic fatty liver disease (NAFLD) due to its high glucotoxicity and lipotoxicity. Trilobatin, a glycosylated dihydrochalcone derived from the leaves of the Chinese sweet tea Lithocarpus polystachyus Rehd, is reported to possess various pharmacological activities. Nevertheless, it is still unclear regarding if trilobatin can alleviate liver injury in diabetic mice with NAFLD and its mechanism. Our aim was to investigative the protective effects of trilobatin against DM with NAFLD and its mechanism of action. A DM mice model was established by high-fat diet (HFD) feeding with streptozocin (STZ) injections, and treated with trilobatin for 10 weeks. The biochemical results showed that trilobatin restored glucose metabolic disorder and liver function in diabetic mice. The histopathological evaluation revealed that trilobatin improved liver injury by alleviating lipid accumulation and liver fibrosis. Mechanistically, trilobatin decreased expression of NLRP3, p65 NF-κB, cleaved-Caspase-1 and N-GSDMD, as well as the release of IL-18 and IL-1ß, leading to a alleviation of inflammation and pyroptosis. Taken together, we determined for the first time found that trilobatin could prevent liver injury in diabetic mice with NAFLD by suppressing NLRP3 inflammasome activation to reduce inflammation and pyroptosis.

Preparation and study of the flame retardant properties of C60/PMMA microspheres.

In this paper, highly flame retardant C60/PMMA composites were prepared using an in situ polymerization method by introducing fullerene (C60) into polymethyl methacrylate (PMMA) to improve its combustion characteristics. The apparent morphologies of PMMA and C60/PMMA microspheres were observed by scanning electron microscopy (SEM), and the structure was characterized by infrared spectroscopy (FT-IR). The thermal stability and flame retardancy were characterized using a synchronous thermal analyzer, a cone calorimeter and an oxygen index tester. The results show that the maximum initial decomposition temperature of C60/PMMA-2 (prepared using C60 with a concentration of 2 mg mL-1) is 234.89 °C, which is about 59.89 °C higher than that of PMMA, and the thermal stability is the best. The limiting oxygen index of the C60/PMMA-2 composite is 21.8, which is 28.2% higher than that of pure PMMA. In addition, the peak heat release rate (PHRR) of C60/PMMA is reduced by 630.4 kW m-2 when compared with pure PMMA, which means that the flame retardant property is improved. Meanwhile, the mechanical properties of the PMMA are also improved by adding C60.