Search

Lysosomal polarity is considered a key indicator of lysosomal function due to its significant impact on membrane fluidity and enzymatic reactions in lysosomes. Monitoring lysosomal polarity can gain insight into the related physiological and pathological processes and develop new diagnostic methods. However, current fluorescent probes with lysosomal polarity response suffer from narrow linear range, photobleaching and complicated preparation. Herein, a ratiometric fluorescent probe (r-bCDs) for intracellular lysosomal polarity imaging is designed and constructed by amide bond assembly of polarity-sensitive red fluorescent carbon dots (rCDs) and referenced blue fluorescent carbon dots (bCDs). r-bCDs show a much wider linear range of polarity response (orientation polarizability Δf from 0.020 to 0.315) than other probes, and the interference of uneven distribution and instrument factors can be effectively eliminated by ratiometric fluorescent sensing. Imaging of intracellular lysosomal polarity with r-bCDs is implemented to observe the polarity variation caused by the change of cell state and the difference between cancer cells and normal cells. This work provides a promising tool for studying the related physiological and pathological processes and developing new diagnostic methods.

Due to the inherent volume expansion effect and low conductivity of silicon monoxide (SiOx, 0

Ternary LiNixCoyMnzO2 oxides with extremely high nickel (Ni) contents (x ≥ 0.9) are promising cathode candidates developed for higher-energy-density lithium-ion batteries, with an aim to relieve mileage anxiety. However, the structural and interfacial instability still restrict their application in electric vehicles. In this work, a novel electrolyte additive 1,2,4-1H-Triazole (HTZ) is introduced to improve the interfacial stability of LiNi0.9Co0.05Mn0.05O2 (NCM90), promoting cycle life both at 30 °C and a harsh condition of 60 °C, as well as rate capability. The NCM90||Li cells with 0.3% HTZ-added electrolyte retain 86.6% of their original capacity after 150 cycles at 1C and 30 °C, well exceeding 74.8% obtained with the baseline electrolyte. It is revealed that the additive HTZ could inhibit the thermal decomposition of LiPF6 salt and suppress the generation of HF acidic species. More importantly, additive HTZ is preferentially oxidized to construct a compact and dense cathode electrolyte interphase (CEI) layer, which is beneficial for stabilizing the electrode/electrolyte interface and suppressing unwanted side reactions.

Ni-rich layered structure materials are appealing cathodes for high-energy-density lithium-ion batteries developed for electric vehicles, drones, power tools, etc. However, poor interfacial stability between a Ni-rich cathode and carbonate electrolyte, especially at high temperatures, and fast capacity fading still hinder their mass market penetration. Here, we investigate cyclopentyl isocyanate (CPI) with a single isocyanate (-NCO) functional group as a bifunctional electrolyte additive for the first time to improve the interfacial stability of Ni-rich cathode LiNi0.83Co0.12Mn0.05O2 (NCM83). With an electrolyte containing 2 wt % CPI, the NCM83 cathode shows capacity retention of up to 92.3% after 200 cycles at 1C and 30 °C, much higher than that with the standard electrolyte (78.6%). It is demonstrated that the -NCO of CPI could largely inhibit the thermal decomposition of LiPF6 salt and scavenge water and hydrogen fluoride (HF) species, improving electrolyte stability. More importantly, the additive CPI could be preferentially oxidized, forming a stabilized and protective cathode electrolyte interphase (CEI) layer on the surface of NCM83, which effectively suppresses the parasitic side reactions and maintains the superior interfacial charge-transfer and lithium-ion diffusion kinetics. Both functions enable a significant improvement in electrochemical performance at both 30 and 60 °C.

In recent years, with the rapid developments of high-technology industries such as information technology and electric vehicles, there are urgent need to develop new generations of lithium-ion batteries with higher energy density, longer cycle life and improved safety. In addition to the development of high specific energy cathode and high specific capacity anode materials, regulating the stability of the electrode/electrolyte interface is critical to achieve and balance various performances of the batteries and finally realize their commercial application widely. However, the traditional carbonate electrolytes not only suffer from severe oxidation decomposition when the charging voltage is higher than 4.3 V (vs. Li/Li+), but also show poor compatibility with high-capacity silicon or silicon-carbon (Si-C) composite anodes and lithium metal anodes. Moreover, the traditional carbonate electrolytes are flammable, which is still a big safety concern to address for lithium ion battery. Therefore, rational design of electrolytes that match the high voltage cathode, high specific capacity Si-C abode or lithium metal anode, and has better safety property and especially under harsh conditions, has become a decisive factor for the rapid developments of high specific energy lithium-ion batteries. The present work reviews different kinds of liquid electrolytes with functional additives and utilization of solid state electrolytes which are explored by our group in the past 15 years. The design strategies and systematic investigations of the electrolytes recipes include: (1) Developing anti-oxidation solvent systems, for example, applications of new high-voltage nitriles or fluorinated solvents for high-voltage cathodes, such as suberonitrile (SUN), fluoroethylene carbonate (FEC) and ethyl-(2,2,2-trifluoroethyl) carbonate (ETFEC); (2) exploiting some novel multifunctional solvents or additives which contain flame retardant groups or can be used as film-forming agents for high-voltage cathodes. For example, some P-containing compounds such as N , N -diallyl-diethoxy phosphoramide (DADEPA), phenoxy cyclophosphazene (PFPN), and ionic liquid such as N-methyl-N-butylpyrrolidinium bis(trifluoromethylsulfonyl)imide (Py14TFSI), etc. In addition, we have also investigated a series of solid electrolytes such as Garnet-type electrolytes, gel polymer or composite polymer electrolyte with inorganic additives, which could greatly reduce the safety risk of batteries. These works include measurements of the activation energy and ion transport mechanism of oxide solid electrolyte with solid NMR techniques, interface modification of sulfide-type solid state battery with ionic liquids, and interface passivation mechanism of PEO-based polymer electrolyte, etc. Finally, some discussions and future perspectives in developing high-voltage and highly-safe liquid electrolyte and flexible solid-state electrolytes for all solid state batteries are presented. Although the commonly used high-voltage electrolytes are mainly composed of lithium salts, anti-oxidation solvents and functional additives such as nitriles, sulfones, fluoro-ethers or fluoro-carbonates, However, the acting mechanisms of those high-voltage electrolytes, especially solvents, salts and additives, are still not clear, especially the composition, structure and evolution of the electrochemical interfaces are lack of quantitative understanding. Therefore, combining theoretical calculation and advanced in-/ex-situ interface characterization techniques, fully understanding the working mechanism of the additives in high-voltage systems and the effective components of interface film, and designing novel functional electrolyte additives are crucial for the development of a new generation of high-specific energy lithium batteries. In addition, applications of flame-retardant solvents or additives to develop flame-retardant liquid-type electrolytes and developing new solid state electrolytes are both important strategies to reduce the potential safety hazards of lithium ion batteries. The future research should focus on how to improve the compatibility between flame-retardant solvents/additives and the cathode/anode interfaces in liquid electrolytes, minimize the negative impact on battery performance (cycle performance, rate performance, etc.), enhance the ionic conductivity and mechanical flexibilities of the solid electrolytes, optimize the electrolyte phase structure/mechanical properties, and regulate the stability of interfaces to ensure the long-term cycling stability of lithium metal anodes and metal oxide cathodes.

α-Terpineol, terpinen-4-ol, and δ-terpineol, isomers of terpineol, are among the compounds that give Cinnamomum longepaniculatum leaf oil its distinguished pleasant smell. The objective of this study was to evaluate the antimicrobial activity of these three isomeric terpineols. The determination of antibacterial activity was based on the minimum inhibition concentration (MIC) and minimum bactericide concentration (MBC). Changes in time-kill curve, alkaline phosphatase (AKP), UV-absorbing material, membrane potential, and scanning electron microscopy (SEM) were measured to elucidate the possible antimicrobial mechanism. α-Terpineol, terpinen-4-ol, and δ-terpineol demonstrated good inhibitory effects against several gram-negative bacteria, particularly Shigella flexneri. MIC and MBC of α-terpineol and terpinen-4-ol were similar (0.766 mg/mL and 1.531 mg/mL, respectively) for S. flexneri, while the MIC and MBC values of δ-terpineol were 0.780 mg/mL and 3.125 mg/mL, respectively. Time-kill curves showed that the antibacterial activities of the tested compounds were in a concentration-dependent manner. Release of nucleic acids and proteins along with a decrease in membrane potential proved that α-terpineol, terpinen-4-ol, and δ-terpineol could increase the membrane permeability of Shigella flexneri. Additionally, the release of AKP suggested that the cell wall was destroyed. SEM analysis further confirmed that S. flexneri cell membranes were damaged by α-terpineol, terpinen-4-ol, and δ-terpineol. Our research suggests that these three isomeric terpineols have the potential of being used as natural antibacterial agents by destroying the cell membrane and wall, resulting in cell death. However, the specific antibacterial activity differences need further investigation.

Polysaccharide derived from natural products has a wide range of sources and mild properties, and exhibit various bioactivities. Ascorbic acid is one of the most important nutrients in fruits and vegetables, as well as their products. Ascorbic acid and polysaccharide coexist in many systems during food production and processing. Many studies have found that ascorbic acid at low concentrations degrades polysaccharide derived from natural products via hydroxyl radical. In this paper, the research progress on ascorbic acid induced polysaccharide degradation is summarized from four aspects: mechanism of action, analytical methods, influencing factors and bioactivity of degradation products. It is expected to provide a theoretical basis for further research.

A new family of dienone musks was discovered by alkylation of different aldehydes with but-3-en-1-yn-1-yllithium and subsequent domino reaction of a Saucy–Marbet transfer vinylation–Claisen rearrangement with an intramolecular Diels–Alder reaction, and concluding Lewis acid catalyzed double-bond isomerization. The newly synthesized dienone structures possess pleasant musk odors displaying fatty, slightly fruity and green facets. Although the dienone musks were predicted in silico to bind to the OR5AN1 receptor based on QM/MM calculations, they were found to be inactive in the in vitro assay. The latter results suggest that the OR5AN1 receptor is not the prime musk receptor but primarily responsible for the animalic character of certain macrocyclic ketones and nitro musks.

A protocol of visible-light-promoted C2 selective arylation of quinoline and pyridine N-oxides, with diaryliodonium tetrafluoroborate as an arylation reagent, using eosin Y as a photocatalyst for the construction of N-heterobiaryls was presented. This methodology provided an efficient way for the synthesis of 2-aryl-substituted quinoline and pyridine N-oxides. This strategy has the following advantages: specific regioselectivity, simple operation, good functional group tolerance, and high to moderate yields under mild conditions.

Toxicological effects of nanoplastics have been demonstrated in a variety of organisms, yet their impacts on bacteria, especially on the antibiotic resistance evolution remain under explored. Herein, we report individual and combined effects of nano-polystyrene (nano-PS) and erythromycin (ERY) on growth and resistance mutations of Escherichia coli. The toxicity of nano-PS was dependent on size and functional modifications, with 30 nm and amino-modified PS (PS-NH2, 200 nm) showing the greatest toxicity. Adsorption of nano-PS onto bacterial surface and the subsequent increase of intracellular ROS or the probable mechanical damage were considered as the primary toxic mechanisms. Furthermore, nano-PS increased the bacterial resistance mutations, which was due to the oxidative damage to DNA and the SOS response. In addition, PS-NH2 presented synergistic effects with ERY while non-modified PS had no impact, although both of them showed adsorption capacity to ERY. This was likely because the positively charged PS-NH2 acted as a carrier of ERY and enhanced the interactions between ERY and the bacteria. Our findings raised the concerns about the risk of nanoplastics in accelerating the bacterial resistance evolution, and highlighted the necessity of including combined effects of nanoplastics and co-contaminants in risk assessment.

Hyperactivation of PARP1 is known to be a major cause of necrotic cell death by depleting NAD+/ATP pools during Ca2+ overload which is associated with many ischemic diseases. However, little is known about how PARP1 hyperactivity is regulated during calcium overload. In this study we show that ATR kinase, well known for its role in DNA damage responses, suppresses ionomycin, glutamate, or quinolinic acid‐induced necrotic death of cells including SH‐SY5Y neuronal cells. We found that the inhibition of necrosis requires the kinase activity of ATR. Specifically, ATR binds to and phosphorylates PARP1 at Ser179 after the ionophore treatments. This site‐specific phosphorylation inactivates PARP1, inhibiting ionophore‐induced necrosis. Strikingly, all of this occurs in the absence of detectable DNA damage and signaling up to 8 hours after ionophore treatment. Furthermore, little AIF was released from mitochondria/cytoplasm for nuclear import, supporting the necrotic type of cell death in the early period of the treatments. Our results reveal a novel ATR‐mediated anti‐necrotic mechanism in the cellular stress response to calcium influx without DNA damage signaling.

In this study, the heat product (90 °C, 10 min) of β-lactoglobulin (β-LG) was analyzed by asymmetric-flow field-flow fractionation (AF4) to observe the effect of heat treatment. The changes in molar mass (M) and molar size induced by heat treatment were characterized by AF4, and changes in molar shape were observed by transmission electron microscopy (TEM). The results showed that β-LG dissociated and aggregated into four fractions with different M values, sizes, and shapes after heat treatment. The vast aggregations with the highest allergenicity (IgE-binding capacity) might enhance the allergenicity of β-LG. However, the number of characterized epitope peptides was decreased due to heat treatment. The above results provide some references for related studies of β-LG and its allergenicity. Further separation and characterization of the high-allergenicity fractions and peptides will help to eliminate allergens in dairy products and reduce the occurrence of allergic reactions.

An atom-economical oxovanadate-catalysed cycloisomerization of hydroxy enynes for the synthesis of bicyclo[4.3.0]non-1(9)-en-2-ones is disclosed, which can be rationalised through a cascade reaction of a dissociative Meyer–Schuster rearrangement to allenyl vanadates, followed by a thermal intramolecular Diels–Alder (IMDA) reaction and hydrolytic regeneration of the catalyst.

Ataxia telangiectasia and Rad3-related protein (ATR) is a serine/threonine-protein kinase of the PI3K family and is well known for its key role in regulating DNA damage responses in the nucleus. In addition to its nuclear functions, ATR also was found to be a substrate of the prolyl isomerase Pin1 in the cytoplasm where Pin1 isomerizes cis ATR at the Ser428-Pro429 motif, leading to formation of trans ATR. Cis ATR is an antiapoptotic protein at mitochondria upon UV damage. Here we report that Pin1’s activity on cis ATR requires the phosphorylation of the S428 residue of ATR and describe the molecular mechanism by which Pin1-mediated ATR isomerization in the cytoplasm is regulated. We identified protein phosphatase 2A (PP2A) as the phosphatase that dephosphorylates Ser428 following DNA damage. The dephosphorylation led to an increased level of the antiapoptotic cis ATR (ATR-H) in the cytoplasm and, thus, its accumulation at mitochondria via binding with tBid. Inhibition or depletion of PP2A promoted the isomerization by Pin1, resulting in a reduction of cis ATR with an increased level of trans ATR. We conclude that PP2A plays an important role in regulating ATR’s anti-apoptotic activity at mitochondria in response to DNA damage. Our results also imply a potential strategy in enhancing cancer therapies via selective moderation of cis ATR levels.

The natural deep eutectic solvent (NADES) is an excellent solvent for insoluble natural products and medicines. Eutectogels formed by gelation of NADESs are interesting materials that deserve attention. In this study, xanthan gum was used as a gelator to gel choline chloride-xylitol with different water contents in virtue of the excellent solubility of choline chloride-xylitol (1:1) to quercetin. We observed that water was critical to the formation of eutectogels. An MTT assay indicated that our eutectogel had excellent biocompatibility as its corresponding hydrogel. According to rheological tests, xanthan gum-based eutectogels had better viscoelastic properties, higher thermal stability, and more defined shear thinning behavior than its corresponding hydrogel. Texture profile analysis showed that eutectogels with less water content had higher hardness and adhesiveness. Meanwhile, Differential scanning calorimeter (DSC) results suggested that the various rheological and texture properties of eutectogels could be attributed to changes in the water state, which was influenced by the hydrogen bonding network of NADES. This biocompatible eutectogel with tunable properties was expected to find applications in novel drug delivery vehicles, which are widely used in the fields of medicine and food.

Peptidyl-prolyl isomerization is an important post-translational modification of protein because proline is the only amino acid that can stably exist as cis and trans, while other amino acids are in the trans conformation in protein backbones. This makes prolyl isomerization a unique mechanism for cells to control many cellular processes. Isomerization is a rate-limiting process that requires a peptidyl-prolyl cis/trans isomerase (PPIase) to overcome the energy barrier between cis and trans isomeric forms. Pin1, a key PPIase in the cell, recognizes a phosphorylated Ser/Thr-Pro motif to catalyze peptidyl-prolyl isomerization in proteins. The significance of the phosphorylation-dependent Pin1 activity was recently highlighted for isomerization of ATR (ataxia telangiectasia- and Rad3-related). ATR, a PIKK protein kinase, plays a crucial role in DNA damage responses (DDR) by phosphorylating hundreds of proteins. ATR can form cis or trans isomers in the cytoplasm depending on Pin1 which isomerizes cis-ATR to trans-ATR. Trans-ATR functions primarily in the nucleus. The cis-ATR, containing an exposed BH3 domain, is anti-apoptotic at mitochondria by binding to tBid, preventing activation of pro-apoptotic Bax. Given the roles of apoptosis in many human diseases, particularly cancer, we propose that cytoplasmic cis-ATR enables cells to evade apoptosis, thus addicting cancer cells to cis-ATR formation for survival. But in normal DDR, a predominance of trans-ATR in the nucleus coordinates with a minimal level of cytoplasmic cis-ATR to promote DNA repair while preventing cell death; however, cells can die when DNA repair fails. Therefore, a delicate balance/equilibrium of the levels of cis- and trans-ATR is required to ensure the cellular homeostasis. In this review, we make a case that this anti-apoptotic role of cis-ATR supports oncogenesis, while Pin1 that drives the formation of trans-ATR suppresses tumor growth. We offer a potential, novel target that can be specifically targeted in cancer cells, without killing normal cells, to significantly reduce the adverse effects usually seen in cancer treatment. We also raise important issues regarding the roles of phosphorylation-dependent Pin1 isomerization of ATR in diseases and propose areas of future studies that would shed more understanding on this important cellular mechanism.

The immune checkpoint molecule, programmed death ligand 1 (PD-L1; B7-H1, CD274), induces T cell apoptosis and tolerance, thus inhibiting the antitumor immunity. PD-L1 expression is increased in many types of cancer, including ovarian cancer (OC), and correlates with poor prognosis. However, the mechanisms that regulate the PD-L1 expression in cancer cells are incompletely understood. The transcriptional regulation of PD-L1 expression is orchestrated by several transcription factors, including NFκB. The human PD-L1 promoter contains five NFκB-binding sites. Interferon-γ (IFNγ) stimulation of OC cells induces p65, and particularly K314/315 acetylated p65 recruitment to all five NFκB-binding sites in PD-L1 promoter, resulting in increased PD-L1 expression. In this chapter, we describe a protocol that uses chromatin immunoprecipitation (ChIP) to analyze the transcriptional regulation of PD-L1 by measuring recruitment of NFκB p65 and K314/315 acetylated p65 to PD-L1 promoter in human OC cells.

Expression of programmed death ligand-1 (PD-L1, CD274) on cancer cells is regulated by interferon-γ (IFNγ) signaling as well as by epigenetic mechanisms. By binding to PD-1 on cytotoxic T cells, PD-L1 inhibits T cell-mediated antitumor responses, resulting in immune escape. This chapter describes analysis of the surface PD-L1 expression in ovarian cancer (OC) cells using flow cytometry (FC). Our data demonstrate that the surface PD-L1 expression in OC cells is induced by IFNγ as well as by the class I histone deacetylase (HDAC) inhibition by romidepsin, suggesting that class I HDAC inhibition might provide a useful strategy to modulate the PD-L1 levels on OC cells.

Expression of the immune checkpoint programmed death ligand 1 (PD-L1, CD274) is increased in many types of cancer, including ovarian cancer (OC), but the mechanisms that regulate the PD-L1 expression are not fully understood. In addition to binding to PD-1 on T cells, thus inhibiting T cell-mediated antitumor responses, PD-L1 has also tumor-intrinsic effects that include increased cancer cell survival and proliferation, and that might be in part mediated by the intracellular PD-L1. In this chapter, we describe a protocol for the analysis of the intracellular PD-L1 protein levels in OC cells by immunoblotting. Our results show that interferon-γ (IFNγ) induces the intracellular levels of PD-L1 and the proto-oncogene Bcl3 in OC cells. However, the PD-L1 expression is significantly decreased in OC cells stably transfected with Bcl3 shRNA, demonstrating that the IFNγ-induced PD-L1 expression in OC cells is mediated by Bcl3. These data identify the IFNγ-Bcl3-PD-L1 axis as a novel therapeutic target in OC, and suggest that targeting Bcl3 may provide a novel strategy to regulate the PD-L1 expression, and especially the tumor-intrinsic PD-L1 effects mediated by the intracellular PD-L1 in OC cells.

A highly fluorinated additive, pentafluoropyridine (PFP), is used here to enhance the interfacial stability of the Ni-rich LiNi0.9Co0.05Mn0.05O2 (NCM90) cathode at a cut-off voltage of 4.3 V vs. Li/Li+ at 30 °C. The capacity retention of the NCM90||Li cell is obviously improved from 72.3% to 80.3% after 200 cycles at 1C (1C = 180 mA g-1) when 0.2% PFP is introduced into the baseline electrolyte (1 mol L-1 LiPF6 in ethylene carbonate/diethyl carbonate). The improvement in electrochemical performance could be attributed to the formation of a compact and uniform cathode electrolyte interphase (CEI) layer enriched with F-containing polypyridine moieties and LiF species on the NCM90 particles. This CEI prevents side reactions between the electrode and electrolyte and hinders the corrosion of the cathode caused by HF attack. In addition, the formation of internal particle cracks is somewhat suppressed by the robust CEI, thus prohibiting the irreversible phase transformation and better maintaining the superior lithium-ion diffusion kinetics.

Great efforts have been made to develop facile and efficient methods to prepare carbonaceous nanostructures with long-wavelength emission. Herein, we report a low-temperature aqueous strategy to synthesize red-emissive carbon polymer dots (R-CPDs) through the regulation of oxidative polymerization of p-phenylenediamine at 80 °C. The morphology, chemical composition and photophysical properties of the R-CPDs are characterized and analyzed in detail, thereby elucidating their photoluminescence origins from the surface state and crosslink enhanced emission effect. The resulting R-CPDs possess unique features including high pH-sensitivity within pH 4–6 and a wide-range tunable solvent-color effect (λem 528–600 nm). Moreover, the R-CPDs show high stability in physiological media with high salinity, and good resistance to photobleaching. In addition to their favorable biocompatibility, the R-CPDs are applied for monitoring the pH fluctuation in HeLa cells. This study not only provides a unique red emissive carbonaceous nanomaterial for cellular imaging and multicolor applications, but also presents a novel perspective for the construction of long-wavelength emission carbon-based nanomaterials by simple and controllable strategies.

A stabilized cathode electrolyte interphase (CEI) formed on the cathode electrode by virtue of effective electrolyte additives is crucial for prolonging the lifespan of lithium-ion battery adopting high energy density Ni-rich cathode materials. Here, we report a novel multifunctional additive trimethylsilyl 2-(fluorosulfonyl)difluoroacetate (TMSFS) for LiNi0.9Co0.05Mn0.05O2 (NCM90). By adding 0.5% TMSFS, the NCM90 electrode shows an enhanced capacity retention of 85.1% at 1C up to 200 cycles, superior over that of 73.1% for baseline electrolyte. The improvement on cycling performance can be also achieved at harsh testing conditions (e.g., 60 °C and even a high voltage of 4.4 V), along with fast electrode kinetics in the presence of TMSFS. It's demonstrated that TMSFS additive could scavenge the undesired H2O, PF5 and HF species in electrolyte, alleviating the subsequent damages to both cathode-electrolyte interface and NCM90 cathode structure. More importantly, a compact, inorganics-enriched CEI layer formed in TMSFS-added electrolyte is further revealed, rationalizing the impressive improvement in electrochemical performance. Furthremore, we also prove the effectiveness of TMSFS additive for graphite||NCM90 full cells.

Interferon-γ (IFNγ) is a pleiotropic cytokine that has a crucial role in immune response and tumor immunity. Because of its anti-tumor effects, IFNγ has been used in cancer treatment. However, IFNγ also has tumor-promoting functions that are less well understood. Here, we show that IFNγ induces expression of the pro-inflammatory and pro-angiogenic chemokine interleukin-8 (IL-8, CXCL8) in ovarian cancer (OC) cells. The IFNγ-induced IL-8 expression is dependent on JAK1, STAT1, and p65 NFκB, and is associated with an increased occupancy of K314/315 acetylated p65 NFκB and Ser-727 phosphorylated STAT1 at the IL-8 promoter. Neutralization of IL-8 using anti-IL-8 antibody reduces IFNγ-induced migration of OC cells, and their invasion ability in 3D spheroids. Together, these findings identify IL-8 as a novel target induced by IFNγ/JAK1/STAT1/p65 NFκB signaling, and indicate that the IFNγ-induced IL-8 contributes to IFNγ pro-tumorigenic effects in ovarian cancer cells.

The water-extracted polysaccharide from Portulaca oleracea L. mainly consisted of two pectic polysaccharides designated as POWP-H and POWP-L. The POWP-L was rich in linear homogalacturonan with GalA content of 77.6%, while POWP-H might be a rhamnogalacturonan I (RG-I) pectin composed of Rha (15.7%), Ara (31.7%), Gal (42.5%) and GalA (10.1%). The structure of POWP-H was elucidated by partial degradation, methylation analysis combined with GC-MS method and NMR spectroscopy. It had a weight-average molecular weight of 1.2 × 106 g/mol and high degree of branch of 0.57. The presence of abundant arabinogalactan-II and certain galactan side chains in POWP-H was verified by the T-Araf (17.4%), 1,3,6-Galp (11.8%), 1,3-Galp (8.1%), T-Galp (13.4%) and 1,4-Galp (14.3%). The evidence for the RG-I backbone of POWP-H was demonstrated by the structure analysis of its degraded product POWP-H-H, which had the backbone of →4)-α-GalpA-(1 → 2)-α-Rhap-(1 → 4)-α-GalpA-(1 → 2,4)-α-Rhap-(1→ substituted by short side chain of β-Galp-(1 → 4)-β-Galp-(1→ at O-4 position of →2,4)-α-Rhap-(1 → . Moreover, the POWP-H-H was mainly O-acetylated at O-3 position of α-Rhap with 24.8% acetylation degree. In conclusion, POWP-H was mainly the highly branched and acetylated RG-I pectin with relative short RG-I backbone and abundant arabinogalactan II and certain galactan side chains. Besides, it adopted a flexible chain conformation in 0.1 M NaNO3 solution.

β-Glucans are widely found in plants and microorganisms, which has a variety of functional activities. During production and application, interactions with other components have a great influence on the structure and functional properties of β-glucan. In this paper, interactions (including non-covalent interaction and free-radical reaction) between natural product derived β-glucan and ascorbic acid, polyphenols, bile acids/salts, metal ion or other compounds were summarized. Besides, the mechanism and influence factors of interactions between β-glucan and small-molecule compounds, and their effects on the functional properties of β-glucan were detailed. This review aims to develop an understanding and practical suggestions on interactions between β-glucan and small-molecule compounds, which is expected to provide a useful reference for processing and application.

In this paper, the polystyrene–silica hybrid particles were prepared by mechanochemical method. The surface activity index of the hybrid particle was prepared by mechanochemical method, and the contact angle is 128.8°, which indicates that it has the very good hydrophobicity. We can observe that the surface of the modified SiO2 coated with a layer of polystyrene under the transmission electron microscopy. In infrared, we found that there are Si–C bonds on the surface of the modified SiO2, which indicates that styrene monomer is successfully grafted to the surface of silica in the form of polystyrene whose maximum viscosity average degree of polymerization is 158 under mechanical force. The grafting rate was 4.28% measured by thermogravimetric analysis.

Anthropogenic activities have significantly changed the stoichiometry and concentrations of nutrients in coastal waters. Silicon (Si) has become a potential limiting nutrient due to disproportionate nitrogen, phosphorus, and silicate inputs into these areas. The disrupted nutrient ratios can cause changes to metal sensitivity and accumulation in marine diatoms, an important group of eukaryotic phytoplankton that requires silicon for growth. In this study, we examined the effects of Si availability on the metal sensitivity in the diatom P. tricornutum. We found that Si starvation dramatically compromised its cadmium, copper, and lead tolerances. Interestingly, multiple lines of evidence indicated that Si-enriched cells had higher metal adsorption and influx rates than Si-starved cells. Yet Si-enriched cells also had a greater ability to respond to and counteract metal toxicity via elevated expression of membrane and vacuolar metal transporters and greater antioxidant activities which scavenge reactive oxygen species created by metal stress.

To elucidate the inhibitory effects of different herbicides on soil nitrification, eight widely used herbicides, i.e., acetochlor, atrazine, dicamba, isoproturon, paraquat, puma, tribenuron-methyl, and 2,4-dichlorophenoxyacetic acid butyl ester (2,4-Dbe), which represent different chemical taxonomy were selected. Our results indicated that herbicide 2,4-Dbe displayed the best inhibitory effect on nitrification, followed by puma and tribenuron-methyl, whereas the remaining five herbicides exhibited less effect when 10 mg of active ingredient (A.I.) of every herbicide per kg of soil was applied in vegetable-planting soil. The inhibition appeared when 5–100 mg of A.I. 2,4-Dbe was employed, which was enhanced with an increment in its dose in both vegetable-planting and fluvo-aquic soils. However, the inhibitory effect of 10 mg of A. I. 2,4-Dbe exhibited obvious differences in these two types of soils, where the duration of inhibition was shorter as it only continued about a week in fluvo-aquic and calcic cambisols soils with strong nitrification activity but poorer effect as compared to 10 mg of dicyandiamide (DCD). In contrast, the duration of inhibition exceeded 2 months in dryland red and shajiang black soils with a weak nitrification activity which was equivalent to DCD. In addition, comparing with five nitrification inhibitors, 10 mg of 2,4-Dbe had better inhibition than the substituted pyrimidine (AM) and sulfocarbamide (SU), but was equivalent to DCD, nitrapirin, and 3,4-dimethylpyrazole phosphate (DMPP) at their recommended application rates in dryland red soil. These obtained data clearly indicated that 2,4-Dbe could play a stronger role as a nitrification inhibitor in soils.

Endogenous formaldehyde (FA) exists in many living cells and in inhomogeneous distribution in organelles. In particular, lysosomes play significant roles in FA generation and the biofunction of living cells. Herein, we developed a new ratiometric fluorescent nanoprobe, based on naphthalimide derivative (ND)-functionalized carbon dots (CDs), for monitoring endogenous FA in lysosomes. The fluorescence intensity (F535) of green-emitting ND at 535 nm serves as the response signal and the fluorescence intensity (F414) of blue-emitting CDs at 414 nm acts as the reference signal. The fluorescence intensity ratio (F535/F414) of the CD-ND probe is linearly correlated with FA concentration within the range of 1-40 μM in aqueous solution, and the detection limit (3σ/slope) is estimated to be 0.34 μM. As for practical application, this nanoprobe is utilized for the ratiometric fluorescence imaging of FA in live cells. Remarkably, this nanoprobe can specifically target and stain the lysosomes and detect exogenous and endogenous FA in HeLa cells. The new FA probe shows a superior lysosomal targeting ability with a Pearson's coefficient of 0.93, which is attributed to the macromolecular size and basic amine group functionalized surface of CD-ND.

Retinoblastoma is a childhood retinal tumor that develops from cone photoreceptor precursors in response to inactivating RB1 mutations and loss of functional RB protein. The cone precursor's response to RB loss involves cell type-specific signaling circuitry that helps to drive tumorigenesis. One component of the cone precursor circuitry, the thyroid hormone receptor β2 (TRβ2), enables the aberrant proliferation of diverse RB-deficient cells in part by opposing the down-regulation of S-phase kinase-associated protein 2 (SKP2) by the more widely expressed and tumor-suppressive TRβ1. However, it is unclear how TRβ2 opposes TRβ1 to enable SKP2 expression and cell proliferation. Here, we show that in human retinoblastoma cells TRβ2 mRNA encodes two TRβ2 protein isoforms: a predominantly cytoplasmic 54-kDa protein (TRβ2-54) corresponding to the well-characterized full-length murine Trβ2 and an N-terminally truncated and exclusively cytoplasmic 46-kDa protein (TRβ2-46) that starts at Met-79. Whereas TRβ2 knockdown decreased SKP2 expression and impaired retinoblastoma cell cycle progression, re-expression of TRβ2-46 but not TRβ2-54 stabilized SKP2 and restored proliferation to an extent similar to that of ectopic SKP2 restoration. We conclude that TRβ2-46 is an oncogenic thyroid hormone receptor isoform that promotes SKP2 expression and SKP2-dependent retinoblastoma cell proliferation.

The silver-deposited silicon (Si/Ag) is a successful strategy to enhance the conductivity of Si anode material. However, Ag nanoparticles can be separated from the Si due to the huge volume variation, which causes the deterioration of cycling performance. In this research, we propose a facile method of synthesizing Si/Ag particles with alloyed interface (Si/Ag2Si/Ag) by rapid thermal process to enhance the mechanical contact between Si and Ag. The reversible capacity of Si/Ag2Si/Ag still remains 1138 mAh g−1 over 100 cycles at 0.5 C (1 C = 4.2 A g−1), which is 267 mAh g−1 higher than of Si/Ag. Besides, Si/Ag2Si/Ag holds the reversible capacity of 849 mAh g−1 at 2 C.

A series of silicon-containing derivatives of linear alicyclic musks comprising sila-Rosamusk (3b), sila-Romandolide (5b), sila-Applelide (11b), and the corresponding dehydro derivatives was synthesized from sila-analogs of Artemone and Herbac, respectively, by means of sodium borohydride reduction and subsequent esterification with the corresponding acid chlorides in the presence of triethylamine. The olfactory properties of the new sila-odorants 3b–13b are reported in comparison with their carba-analogs 3a–13a, and quantitative threshold data allowed the generation of an improved musk olfactophore model featuring a correlation of 80.5 % with a null-cost distance of 244. This olfactophore model shows that it is likely that linear and macrocyclic musks address the same odorant receptors, and it should facilitate the design of new musks.

The radiative deexcitation processes of excitons and charge-transfer states exist simultaneously in the emitting material PFOPV. In this work, polymer light-emitting devices based on PFOPV were fabricated, the two kinds of microscopic processes were investigated via magnetic field effects (MFEs) on electroluminescence (magneto-electroluminescence, MEL) and current (magnetoconductance, MC). At room temperature, the MEL of balanced device presented negative effects, compared with the positive MEL values of the unbalanced device; at low temperatures, the sign of MEL turned from negative to positive with the increasing injection current in the balanced deice. However, under all driving voltages, the sign of MC was always negative. These dependences of MFEs on temperature and driving voltage can be attributed to the competition between the two different emission processes in devices. Analysis shows that MFEs differences of the two emission processes are caused by the combined effects of intersystem crossing and reverse intersystem crossing induced by hyperfine interaction. This study reveals that charge-transfer states are important in improving the luminous efficiency of fluorescent organic light-emitting devices.

A novel synthetic approach to (±)- Z -recifeiolide 6, a 12-membered-ring lactone which can be selectively isomerized into ( E )-recifeiolide, a natural antibiotic product isolated from fungus ( Cephalosporium recifei ) is reported. The synthesis is accomplished in five steps starting from readily available cyclooctanone and acetaldehyde based on the Lewis acid-catalyzed TMS-directed oxy-2-oxonia-Cope rearrangement. The work represents a novel strategy to assemble related macrolides.

The proto-oncogene Bcl3 induces survival and proliferation in cancer cells; however, its function and regulation in ovarian cancer (OC) remain unknown. Here, we show that Bcl3 expression is increased in human OC tissues. Surprisingly, however, we found that in addition to promoting survival, proliferation, and migration of OC cells, Bcl3 promotes both constitutive and interferon-γ (IFN)-induced expression of the immune checkpoint molecule PD-L1. The Bcl3 expression in OC cells is further increased by IFN, resulting in increased PD-L1 transcription. The mechanism consists of an IFN-induced, Bcl3- and p300-dependent PD-L1 promoter occupancy by Lys-314/315 acetylated p65 NF-κB. Blocking PD-L1 by neutralizing antibody reduces proliferation of OC cells overexpressing Bcl3, suggesting that the pro-proliferative effect of Bcl3 in OC cells is partly mediated by PD-L1. Together, this work identifies PD-L1 as a novel target of Bcl3, and links Bcl3 to IFNγ signaling and PD-L1-mediated immune escape.

Lactic acid has been used as a bio-based green solvent to study the ultrasound-assisted scale-up synthesis. We report here, for the first time, on the novel and scalable process for synthesis of pyrrole derivatives in lactic acid solvent under ultrasonic radiation. Eighteen pyrrole derivatives have been synthesized in lactic acid solvent under ultrasonic radiation and characterized by (1)H NMR, IR, ESI MS. The results show, under ultrasonic radiation, lactic acid solvent can overcome the scale-up challenges and exhibited many advantages, such as bio-based origin, shorter reaction time, lower volatility, higher yields, and ease of isolating the products.

In the presence of a Lewis acid, trimethylsilyl-substituted β,γ-unsaturated ketones and aldehydes (imines) undergo nucleophilic addition to produce zwitterionic intermediates, followed by oxy-2-oxonia(azonia)-Cope rearrangements to give homoallylic esters (amides). In the case of TMS-containing 2-vinylcycloalkanones, the process results in ring-enlargement, providing 10- to 16-membered lactones. This protocol was applied to the total synthesis of (R)-phoracantholide I.

The construction and application of a new type of composite material are achieved more and more attention. However, expected Sb2Se3/attapulgite composites aim to use the low price, and high adsorption of attapulgite in assembling Sb2Se3 is quite difficult to be acquired by a facile and benign environmental hydrothermal method. In this manuscript, we developed a new way for preparation of an emerging composite by means of Sb2O3 as a media linking Sb2Se3 and attapulgite together, and finally won an emerging composite Sb2Se3/Sb2O3@attapulgite, which presented an excellent catalytic properties for catalytic hydrogenation of p-nitrophenol. It was noted that the Sb2Se3/Sb2O3@attapulgite composites exhibited a high conversion rate for the hydrogenation of p-nitrophenol that was up to 90.7% within 15 min, which was far more than the 61.5% of Sb2Se3 sample. The excellent catalytic performance was attributed to the highly dispersion Sb2Se3 microbelts and Sb2Se3@Sb2O3@attapulgite rods, which would improve the adsorption of the reactant species and facility electronic transfer process of the catalytic hydrogenation of p-nitrophenol.

The sensitivity of Xeroderma pigmentosa (XP) patients to sunlight has spurred the discovery and genetic and biochemical analysis of the eight XP gene products (XPA-XPG plus XPV) responsible for this condition. These studies also have served to elucidate the nucleotide excision repair (NER) process, especially the critical role played by the XPA protein. More recent studies have shown that NER also involves numerous other proteins normally employed in DNA metabolism and cell cycle regulation. Central among these is ataxia telangiectasia and Rad3-related (ATR), a protein kinase involved in intracellular signaling in response to DNA damage, especially replicative and transcription stresses. This review summarizes recent findings on the interplay between ATR as a DNA damage signaling kinase and as a novel ligand for intrinsic cell death proteins to delay damage-induced apoptosis, and on ATR’s regulation of XPA and the NER process for repair of UV-induced DNA adducts. ATR’s regulatory role in the cytosolic-to-nuclear translocation of XPA will be discussed. In addition, recent findings elucidating a non-NER role for XPA in DNA metabolism and genome stabilization at ds-ssDNA junctions, as exemplified in prematurely aging progeroid cells, also will be reviewed.

Silicon compounds 1b–3b are sila-analogues of the galbanum odorants α-galbanone (1a), α-spirogalbanone (2a), and nor-α-galbanone (3a), respectively. Sila-α-galbanone (1b), sila-α-spirogalbanone (2b), and sila-nor-α-galbanone (3b) were synthesized in multistep syntheses in isomerically pure form, starting from Me2SiCl2, (CH2=CH)2SiCl2, and Me2(CH2=CH)SiCl, respectively. Hydroformylation of vinylsilanes, followed by either ring-closing aldol condensation or ring-closing alkene metathesis, were the key steps in these syntheses. The C/Si pairs 1a/1b, 2a/2b, and 3a/3b were studied for their olfactory properties. All compounds possess green-fruity galbanum-type odors with pineapple aspects and thus are olfactorily related. However, sila-analogues 1b–3b were found to be weaker than the corresponding parent carbon compounds 1a–3a. This effect is most pronounced for the C/Si pair 2a/2b as indicated by the odor thresholds of 0.023 ng L–1 air (2a) and 3.8 ng L–1 air (2b). However, due to their higher molecular mass, the silicon compounds are less volatile and thus more substantive in functional applications. In contrast to the stable 5-silacyclohex-1-enes 1b and 2b, the 4-silacyclopent-1-ene 3b shows a limited chemical stability. For compound 3a an extremely low odor threshold of 0.0087 ng L–1 air was measured, and the silicon analogue 3b with an odor threshold of 0.085 ng L–1 air is the sila-odorant with the lowest odor threshold measured so far.