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Background/Aims: Anti-phospholipase A2 receptor (PLA2R) autoantibody is the main biomarker of idiopathic membranous nephropathy (IMN). We aimed to find a new cutoff value of anti-PLA2R for patients with IMN and to explore the relevance between this antibody and baseline clinical parameters.Methods: A total of 670 subjects including 374 IMN cases and 296 non-IMN controls were included between January 2017 and January 2020. All clinical parameters were collected at the time of renal biopsy. The levels of anti-PLA2R were detected by a commercial enzyme-linked immunosorbent assay (ELISA) kit. The optimal cutoff value was calculated by a receiver operating characteristic curve and compared in diagnostic efficiency.Results: The optimal cutoff value of anti-PLA2R for IMN was 7.45 RU/mL with the highest Youden index, and the corresponding sensitivity, specificity, positive predictive value and negative predictive value were 80.75%, 97.97%, 98.05% and 80.11%, respectively. Anti-PLA2R levels in IMN patients demonstrated a significant positive correlation with serum creatinine and 24-hour urinary protein, while they showed a negative correlation with serum albumin and estimated glomerular filtration rate.Conclusions: The recommended cutoff value of anti-PLA2R is 7.45 RU/mL using ELISA detection for distinguishing IMN from non-IMN nephropathy. The level of anti-PLA2R is related to baseline renal function in IMN. This new threshold can improve the diagnostic efficiency and facilitate early diagnosis of IMN.

All-inorganic zero-dimensional (0D) metal halides are composed of isolated metal halide polyhedrons bridged by monovalent alkali metal ions. The unique structure gives rise to molecule-like electronic configuration and consequently highly attractive optical properties. In comparison with their three-dimensional (3D) counterparts, the 0D metal halides exhibit characteristic features such as broadband emission and long-term stability. In addition, 0D metal halides can be constructed from a diverse range of metal ions and permit high-level impurity doping, thereby offering great structural designability and spectral tunability. This Review surveys recent advances in 0D metal halides, including crystal preparation, luminescence modulation, and emerging applications.

Microorganisms including Bacillus can produce signal molecules such as surfactin, resulting in the variation of membrane potential to trigger quorum sensing such as biofilm formation and sporulation in response to the environment stresses. However, biosynthesis of surfactin requires multiple resources such as huge enzyme complex, amino acids, fatty acids, and energy. Insufficient resources in the natural soil environment restrain biosynthesis of surfactin. When surfactin is inadequate, cations in soil might serve as substitutes to regulate quorum sensing. Our results showed that both surfactin and cations could lead to the variation of membrane potential, thus providing signals to trigger the quorum sensing such as growth, biofilm formation, and sporulation in Bacillus amyloliquefaciens. Neither KinC nor Abh was essential for surfactin or cations to trigger quorum sensing. The cation signaling pathway is only partially dependent on Spo0A, but the surfactin signaling pathway is fully dependent on this global regulator. Compared to surfactin, cations are less effective in promoting biofilm formation, but more effective to trigger sporulation in B. amyloliquefaciens. This study reveals a pathway through which cations regulate the quorum sensing in B. amyloliquefaciens in the case of insufficient surfactin in environment.

This paper reports a fresh and robust strategy to develop polyurethane/polysiloxane pressure-sensitive adhesives (PSAs) with excellent properties by replacing part of C5 petroleum resin with modified lignin. A unique aspect of this work is the use of renewable lignin to obtain modified monomers. The phenolic hydroxyl group of lignin is increased by 21.4% after demethylation, which will help to introduce 6-bromo-1-hexene into the lignin structure through Williamson method. The L3 lignin and C5 petroleum resin are mixed with polyurethane/polysiloxane prepolymer, and furthermore a series of PSAs are obtained under ultraviolet light. It turns out that L3 lignin can not only replace part of C5 petroleum resin, but also obtain attractive and controllable features. Especially when the mass ratio of C5 petroleum resin to L3 lignin is 6:4, compared with pure C5 petroleum resin, the 180° peel strength and the shear strength of PU46 are increased by 24.1% and 91.5% respectively. Additionally, the shear strength on the wood substrate is increased by 320.6%. This study provides an effective method for the preparation of high value-added lignin PSA, and expands the application fields of PSA.

We previously reported the inhibitory effects of microRNA-26a (miR-26a) on the conversion of pyruvate to acetyl coenzyme A in glucose metabolism by directly targeting pyruvate dehydrogenase protein X component in colorectal cancer (CRC) cells (Chen B et al., BMC Cancer 2014). Here, using microRNA in situ hybridization, we confirmed that miR-26a levels were elevated in 77 human CRC tissue samples and further investigated the key miR-26a-mediated metabolic regulation elements and signaling pathways in CRC cells through quantitative proteomic dissection combined with cancer cell biology and biochemical loss-of-function analysis. We found that AKT transcription signaling was a target pathway via miR-26a-mediated deacetylation modification of Ras-responsive element-binding protein 1 (RREB1) at the Lys-60 residue. miR-26a improved the deacetylation level of RREB1, thus contributing to RREB1 binding to the AKT1 promoter to activate AKT transcription and its related signaling pathway in glycolysis. Moreover, miR-26a promoted CRC tumorigenesis in CRC cells and subcutaneous xenograft mice. Thus, miR-26a is a key regulator of CRC tumorigenesis that mediates the deacetylation modification of RREB1 to enhance AKT1 transcription and downstream target gene expression in glycolysis for CRC growth.

Targeting P-glycoprotein (ABCB1 or P-gp) has been recognized as a promising strategy to overcome multidrug resistance. Here, we reported our medicinal chemistry efforts that led to the discovery of the triazolo[1,5-a]pyrimidine derivative WS-898 as a highly effective ABCB1 inhibitor capable of reversing paclitaxel (PTX) resistance in drug-resistant SW620/Ad300, KB-C2, and HEK293/ABCB1 cells (IC50 = 5.0, 3.67, and 3.68 nM, respectively), more potent than verapamil and zosuquidar. WS-898 inhibited the efflux function of ABCB1, thus leading to decreased efflux and increased intracellular PTX concentration in SW620/Ad300 cells. The cellular thermal shift assay indicated direct engagement of WS-898 to ABCB1. Furthermore, WS-898 stimulated the ATPase activity of ABCB1 but had minimal effects on cytochrome P450 3A4 (CYP3A4). Importantly, WS-898 increased PTX sensitization in vivo without obvious toxicity. The results suggest that WS-898 is a highly effective triazolo[1,5-a]pyrimidine-based ABCB1 inhibitor and shows promise in reversing ABCB1-mediated PTX resistance.

Metal halide perovskites are highly attractive for lighting applications, but the multiexcitonic emission processes in these crystals are largely unexplored. This study presents an investigation of Sb3+-doped Cs2ZrCl6 perovskite crystals that display double luminescence due to the intrinsic host self-trapped excitons (denoted as host STEs) and dopant-induced extrinsic self-trapped excitons (denoted as dopant STEs), respectively. Steady-state and transient-state spectroscopy reveal that the host and dopant STEs can be independently charged at specific energies. Density functional theory calculations confirm that the multiexcitonic emission stems from minimal interactions between the host and dopant STEs in the zero-dimensional crystal lattice. By selective excitation of different STEs through precise control of excitation wavelength, we further demonstrate dynamic color tuning in the Cs2ZrCl6:Sb3+ crystals. The color kinetic feature offers exciting opportunities for constructing multicolor light-emitting devices and encrypting multilevel optical codes.

Lithium-sulfur (Li–S) batteries hold great expectations as next-generation advanced capacity storage devices due to their higher theoretical energy density and low cost. Even so, polysulfide shuttles, insulation, and volume expansion of sulfur impede its commercial progress. To suppress these problems, we used electrospinning and self-templating to construct C/Co9S8 hybrid polyhedra-modified carbon nanofibers (denoted as C/Co9S8–C@S fibers) as sulfur hosts. The quasi-metallic polar Co9S8 strongly bonds and locks polysulfides, and the hollow polyhedra provide sulfur storage space. Moreover, the overall nanofiber forms an interconnected conductive network to assist the transmission of Li+/e− and restrain the escape of the sulfur phase to a certain extent. Compared with C/Co9S8 polyhedra and carbon nanofibers, the C/Co9S8–C@S fiber delivers excellent adsorption characteristics for polysulfides. As a Li–S battery cathode, the C/Co9S8–C@S fiber (sulfur content: 87.20 wt%) exhibits an initial specific capacity of 1013.7 mAh g−1 at 0.1 C, displaying a stable capacity of 694.9 mAh g−1 after 150 cycles. Additionally, it shows a high specific capacity of 894.7 mAh g−1 at 1C with a capacity decay of ~0.116% per cycle over 500 cycles.

To study the influence of pipe length on premixed gas explosion characteristics in a contraction pipe. A Large Eddy Simulation (LES) and Zimont combustion model was used to simulate the propane/air...

The lithium-ion battery is subject to the limited theoretical specific capacity of electrode materials, which is difficult to achieve capacity breakthrough. However, the theoretical specific capaci...

Polymers present typically low thermal conductivity (TC) and potential fire hazards and thus restricted its application in electronics. Here, graphene oxide (GO) was employed to replace the traditional synthetic polymers. Then, the vacuum-assisted self-assembly technique was developed to prepare multifunctional flexible hybrid film based on synergistic effect of functionalized GO (PGO) and boron nitride nanosheets (BNNS). Results show that a “nacre structure” can be observed and a superior interface between matrix and fillers was constructed. Thus, the films possess high in-plane TC of 30.44 W m−1 K−1, as well as excellent flexibility. The high TC is ascribed to constructing of the hydrogen bonding between BNNS and PGO to form a well-designed BNNS–PGO interface. Another contribution is that the dispersion of BNNS was enhanced and formed continuous TC paths. Furthermore, as-prepared hybrid films possess excellent flame retardancy and the total heat release rate and peak heat release were dropped by 75.4% and 72%, respectively, compared with original GO. Fire experiment shows that the alarm lamp and alarm buzzer connected with the hybrid film will send out the alerts within 2 s to people for taking emergency actions. This nanocomposite presents great potential applications in next-generation intelligent electronic equipment.

Benzene-1,3,5-triyl tribenzoate (TBB), both 3,5-bis(benzoyloxy)benzoate-terminated poly (aryl ether ketone) oligomers (BPAPK and TMPK), containing active ester (Ph−O−(C=O)− structure), were prepared and served as curing agents for dicyclopentadiene novoalc epoxy (DCPD). The curing kinetics and properties of three epoxy thermosets were systematically investigated. The model reaction of TBB and glycidyl phenyl ether was designed to understand the curing mechanism of oxirane ring with active ester. TMPK/DCPD displays the lowest reaction activation energy, which is the result of the combined influence of free volume and diffusion. In addition, TMPK/DCPD has the highest Tg value (218°C), which enhances 34.6% and 42.5% compared with BPAPK/DCPD and TBB/DCPD, respectively. Meanwhile, TMPK/DCPD also shows superior dielectric and water resistance properties due to no secondary alcohol generated after curing and hydrophobic tetramethyl-substituted biphenyl structure. Herein, TMPK/DCPD as high-performance epoxy thermosets has potential applications in electronic packaging fields.

Inwardly rectifying potassium (Kir) channels make it easier for K+ to enter into a cell and subsequently regulate cellular biological functions. Kir5.1 (encoded by KCNJ16) alone can form a homotetramer and can form heterotetramers with Kir4.1 (encoded by KCNJ10) or Kir4.2 (encoded by KCNJ15). In most cases, homomeric Kir5.1 is non-functional, while heteromeric Kir5.1 on the cell membrane contributes to the inward flow of K+ ions, which can be regulated by intracellular pH and a variety of signaling mechanisms. In the form of a heterotetramer, Kir5.1 regulates Kir4.1/4.2 activity and is involved in the maintenance of nephron function. Actually, homomeric Kir5.1 may also play a very important role in diseases, including in the ventilatory response to hypoxia and hypercapnia, hearing impairment, cardiovascular disease and cancer. With an increase in the number of studies into the roles of Kir channels, researchers are paying more attention to the pathophysiological functions of Kir5.1. This minireview provides an overview regarding these Kir5.1 roles.

Design and development of intelligent fire warning materials with rapid response capabilities has always been an urgent need for the safety of many flammable materials in their applications. Herein...

Although multivalent glycosidase inhibitors have shown enhanced glycosidase inhibition activities, further applications and research directions need to be developed in the future. In this paper, two positional isomeric perylene bisimide derivatives (PBI-4DNJ-1 and PBI-4DNJ-2) with 1-deoxynojirimycin conjugated were synthesized. Furthermore, PBI-4DNJ-1 and PBI-4DNJ-2 showed positional isomeric effects on the optical properties, self-assembly behaviors, glycosidase inhibition activities, and hypoglycemic effects. Importantly, PBI-4DNJ-1 exhibited potent hypoglycemic effects in mice with 41.33 ± 2.84 and 37.45 ± 3.94% decreases in blood glucose at 15 and 30 min, respectively. The molecular docking results showed that the active fragment of PBI-4DNJ-1 has the highest binding energy (9.649 kcal/mol) and the highest total hydrogen bond energy (62.83 kJ/mol), which were related to the positional isomeric effect on the hypoglycemic effect in mice. This work introduced a new means to develop antihyperglycemic agents in the field of multivalent glycomimetics.

Coal and coal gangue spontaneous combustion (CGSC) occurs globally, causing significant environmental pollution. However, its emissions are poorly quantified and are overlooked in global or regional air pollutant emission inventories in previous studies, resulting in the underestimation of its impacts on climate, environment, and public health. This study quantified the emissions of various air pollutants originating from CGSC in Wuhai, a city in China, investigated emission characteristics, and estimated the contribution of CGSC emissions to fine particulate matter (PM2.5) air pollution and related health impacts on a regional scale. The results revealed that the CGSC-related PM2.5 emissions were approximately 4643 t a-1 (95% confidence interval (95% CI): 721; 10447), accounting for 26.3% of the total PM2.5 emissions. Alkanes, alkenes, and aromatics accounted for 69.4, 17.9, and 2.9%, respectively, of the total emissions of volatile organic compounds (VOCs). Due to CGSC emissions, the ambient PM2.5 concentration in Wuhai increased by 5.7 μg m-3 on average, while the nitrate concentration decreased. The number of premature deaths caused by exposure to ambient PM2.5 associated with CGSC reached 381 (95% CI: 290; 452) in Wuhai and surrounding cities in 2017. Urgent control strategies and engineering techniques are needed to mitigate CGSC to protect public health.

Lithium-sulfur(Li–S)batteries have received extensive attention due to the high theoretical energy density. However, tremendous works have been made to improve the three major problems of Li–S batteries. Namely, electrical insulation of sulfur, shuttle effect of polysulfide, and volume expansion of sulfur. However, there are still huge challenges to solve these problems and improve capacity. Here, we propose a strategy to prepare a double-shelled structure S@V2O5 spheres @GO composite.The polar hollow V2O5 sphere can realize the chemical adsorption of polysulfides and graphene oxide facilitates good electronic conductivity, thereby improving rate capability and cycling performance. The cycle capacity of S@V2O5 spheres @GO composite remains 895.7 mAh/g at 0.1C after 100 cycles and low capacity decay of 0.015% after 200 cycles at 1C rate, attributed to the double-shelled structure of the S@V2O5 spheres @ GO, the resulting electrode exhibits better performance. Offering a potential candidate for practical application of Li–S batteries in the future.

A base-promoted unprecedented strategy for the regioselective and chemoselective divergent synthesis of highly functionalized aposafranones and their N-oxides has been developed from the [3 + 3] annulation of enaminones with o-fluoronitrobenzenenes. This novel synthetic strategy offers an alternative method for the construction of aposafranones and their N-oxides are meaningful in the fields of both biology and organic synthesis. The established protocol explores the annulation scope of enaminones, and it expands the application of nitro-based cyclization.

[Image: see text] Triple-negative breast cancer (TNBC) has limited treatment options and the worst prognosis among all types of breast cancer. We describe two prodrugs, namely, CWB-20145 (1) and its methyl analogue FAN-NM-CH(3) (2) that reduced the size of TNBC-derived tumors. The DNA cross-linking of nitrogen mustard prodrugs 1 and 2 was superior to that of chlorambucil and melphalan once activated in the presence of H(2)O(2). The cellular toxicity of 1 and 2 was demonstrated in seven human cancer cell lines. The TNBC cell line MDA-MB-468 was particularly sensitive toward 1 and 2. Compound 2 was 10 times more cytotoxic than chlorambucil and 16 times more active than melphalan. An evaluation of the gene expression demonstrated an upregulation of the tumor suppressor genes p53 and p21 supporting a transcriptional mechanism of a reduced tumor growth. Pharmacokinetic studies with 1 showed a rapid conversion of the prodrug. The introduction of a methyl group generated 2 with an increased half-life. An in vivo toxicity study in mice demonstrated that both prodrugs were less toxic than chlorambucil. Compounds 1 and 2 reduced tumor growth with an inhibition rate of more than 90% in athymic nude mice xenografted with MDA-MB-468 cells. Together, the in vivo investigations demonstrated that treatment with 1 and 2 suppressed tumor growth without affecting normal tissues in mice. These phenylboronic acid nitrogen mustard prodrugs represent promising drug candidates for the treatment of TNBC. However, the mechanisms underlying their superior in vivo activity and selectivity as well as the correlation between H(2)O(2) level and in vivo efficacy are not yet fully understood.

Background While the influence of meteorology on carbon monoxide (CO) poisoning has been reported, few data are available on the association between air pollutants and the prediction of CO poisoning. Our objective is to explore meteorological and pollutant patterns associated with CO poisoning and to establish a predictive model. Results CO poisoning was found to be significantly associated with meteorological and pollutant patterns: low temperatures, low wind speeds, low air concentrations of sulfur dioxide (SO2) and ozone (O38h), and high daily temperature changes and ambient CO (r absolute value range: 0.079 to 0.232, all P values 2 + 0.0008 *O38h; j = 1, 2, 3, 4; a1 = -4.12, a2 = -2.93, a3 = -1.98, a4 = -0.92.” The proposed prediction model based on combined factors showed better predictive capacity than a model using only meteorological factors as a predictor. Conclusion Low temperatures, wind speed, and SO2 and high daily temperature changes, O38h, and CO are related to CO poisoning. Using both meteorological and pollutant factors as predictors could help facilitate the prevention of CO poisoning.

Aberrant expression of circular RNAs (circRNAs) is involved in cancer progression through interaction with RNA-binding proteins (RBPs). Herein, we screened circRNA expression of A549 cells in circBase and the crosslinking immunoprecipitation (CLIP) data of human antigen R (HuR), an extensively studied RBP, and identified a circRNA, circ-defective in cullin neddylation 1 domain containing 4 (circDCUN1D4), originating from the DCUN1D4 gene transcript. circDCUN1D4 is downregulated in tumor samples under the mediation of DExH-box helicase 9 (DHX9), which inhibits the formation of circRNA by binding inverted repeat Alus (IRAlus) in flanking sequences. circDCUN1D4 depletion promoted invasion in vitro and metastasis in vivo. Importantly, the interaction between circDCUN1D4 and HuR increased the transportation of HuR to the cytoplasm. circDCUN1D4 acts as a scaffold to facilitate the interaction between the HuR protein and thioredoxin-interacting protein (TXNIP) mRNA, which enhances the stability of the TXNIP mRNA. Additionally, circDCUN1D4 directly interacts with TXNIP mRNA through base complementation, indicating the formation of the circDCUN1D4/HuR/TXNIP RNA-protein ternary complex. Furthermore, circDCUN1D4 suppressed metastasis and glycolysis of lung cancer cells in a TXNIP-dependent manner. Clinically, the downregulated expression of circDCUN1D4 was more prevalent in lymph node metastatic tissues and served as an independent risk factor for the overall survival of lung adenocarcinoma (LUAD) patients. These findings demonstrated that a novel circRNA, circDCUN1D4, is involved in the metastasis and glycolysis of LUAD., Graphical Abstract, Liang et al. reported that circular RNA, circDCUN1D4, could act as the tumor suppressor in lung adenocarcinoma by interacting with HuR and increasing HuR cytoplasmic retention to maintain the stability of TXNIP mRNA, which suppressed metastasis and glycolysis.

A palladium-catalyzed asymmetric tandem C-C bond activation/Cacchi reaction between cyclobutanones and o-ethynylanilines was reported. The transient chiral σ-alkylpalladium species generated via enantioselective C(sp3)-C(sp2) bond activation of cyclobutanones promotes cyclization of o-ethynylanilines, leading to one-carbon-tethered chiral indanone-substituted indoles. Two C-C bonds and one C-N bond are created with concomitant formation of an all-carbon quaternary stereocenter. Furthermore, a chiral C2-aryl axis can be created in 2,3-disubstituted indole moiety, leading to indanone-substituted indoles with both central and axial stereogenic elements.

Hydrogen production via alkaline water electrolysis is of significant interest. However, the additional water dissociation step makes the Volmer step a relatively more sluggish kinetics and consequently leads to a slower reaction rate than that in acidic solution. Herein, we demonstrate an effective strategy that Co(OH)2 can promote the Volmer process by accelerating water dissociation and enhance the electrocatalytic performance of CoP toward alkaline hydrogen evolution reaction. The Co(OH)2 nanoplates are electrochemically induced in-situ generated to form a nanotree-like structure with porous CoP nanowires, endowing the hybrid electrocatalyst with superior charge transportation, more exposed active sites, and enhanced reaction kinetics. This strategy may be extended to other phosphides and chalcogenides and provide insight into the design and fabrication of efficient alkaline HER catalysts.

Lithium-sulfur battery is investigated as the most promising next-generation energy storage devices owing to its high energy density and environmental friendliness. However, it is a challenge to solve the electrical insulation of sulfur and the dissolution of intermediates in the electrolyte for the lithium-sulfur battery. To solve these issues, we report a novel Co9S8@S/GO hybrid, as host for the sulfur cathode. The graphene oxide and polar hollow Co9S8 nanotube can capture polysulfides in both physical and chemical adsorption. The Co9S8@S/GO composite exhibits a discharge capacity of 1022 mAh/g after 100 cycles at 0.1C and an ultralow fade rate of 0.027% per cycle at 1C with a high sulfur content of 89.22 wt%. The obtained Co9S8@S/GO electrode exhibits better electrochemical performance.

A palladium-catalyzed carbonylative C–C bond activation reaction of cyclobutanones proceeding by C–C bond cleavage, ring-opening, and amino- or alkoxycarbonylation is reported here. Two C–C bonds and one C–O or C–N bond are created to afford a variety of indanones bearing ester or amide groups under gas-free conditions by using phenyl formate and benzene-1,3,5-triyl triformate (TFBen) as convenient CO surrogates.

Currently, coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 has posed an enormous threat to public health worldwide. An andrographolide sulfonates preparation, named Xiyanping injection in Chinese, which was prepared from the aqueous extract of Andrographis paniculata (Burm. F.) Nees, showed favorable therapeutic effectiveness on COVID-19, suggesting A. paniculata could contain powerful therapeutic ingredients against COVID-19. In this study, to search for the potential drug candidates for COVID-19 in the herb, 68 potential target proteins and 24 active ingredients from A. paniculata were screened out using TCMSP, STP, Genecards and TTD databases firstly. A. paniculata-Compound-Target network constructed by cytoscape software showed that the protein targets PTGS2, EGFR, MAPK14, etc. had a high network relevance value. GO and KEGG enrichment analysis indicated that the 24 compounds in A. paniculata might exert their therapeutic effects by the biological processes, cellular response to biotic stimulus, response to lipopolysaccharide, response to molecule of bacterial origin, etc. And AGE-RAGE signaling pathway in diabetic complications (hsa04933), Kaposi sarcoma-associated herpesvirus infection (hsa05167), Human cytomegalovirus infection (hsa05163), etc. were predicted as the most significant effect pathways. Andrographidine C (MOL008223) and andrographolide (MOL008232) were found with strong binding affinity to the target active sites of the potential targets by molecular docking. Ultimately, the application of molecular dynamics simulations demonstrated that andrographidine C could bind well to the ACE2 and PIK3CG proteins. This research identified novel molecules against COVID-19 for developing natural medicines from A. paniculate and also provides a possible explanation for the molecular mechanisms of Xiyanping Injection against COVID-19.

A label-free, rapid, and highly sensitive colorimetric assay for the detection of glutathione (GSH) was developed. o-Phenylenediamine (OPD) can be selectively oxidized by Au3+ in phosphate buffer to produce light yellow 2,3-diaminophenazine. After the addition of GSH, the autocatalytic redox reaction between OPD and Au3+ can be effectively inhibited, resulting in a significant decrease in chroma and absorbance intensity. Reduced absorbance intensity can be used for the quantification of GSH. In addition, this method can achieve the discriminative detection of biothiols, such as cysteine and homocysteine. Based on these findings, a simple colorimetric assay was developed for the detection of GSH in the range of 1 nM to 1 mM with a low detection limit of 0.08 nM. More importantly, this procedure is simple, and the whole assay can be accomplished quickly within 15 min. Additionally, the proposed method was successfully used for the determination of GSH in biological fluids, such as serum samples.

Nanotechnology has emerged as an ideal approach for achieving the efficient chemo agent delivery. However, the potential toxicity and unclear internal metabolism of most nano-carriers was still a major obstacle for the clinical application. Herein, a novel “core‒shell” co-assembly carrier-free nanosystem was constructed based on natural sources of ursolic acid (UA) and polyphenol (EGCG) with the EpCAM-aptamer modification for hepatocellular carcinoma (HCC) synergistic treatment. As the nature products derived from food-plant, UA and EGCG had good anticancer activities and low toxicity. With the simple and “green” method, the nanodrugs had the advantages of good stability, pH-responsive and strong penetration of tumor tissues, which was expected to increase tumor cellular uptake, long circulation and effectively avoid the potential defects of traditional carriers. The nanocomplex exhibited the low cytotoxicity in the normal cells in vitro, good biosafety of organic tissues and efficient tumor accumulation in vivo. Importantly, UA combined with EGCG showed the immunotherapy by activating the innate immunity and acquired immunity resulting in significant synergistic therapeutic effect. The research could provide new ideas for the research and development of self-assembly delivery system in the future, and offer effective intervention strategies for clinical HCC treatment., Graphical abstract A carrier-free nanosystem was constructed based on natural sources of ursolic acid and polyphenol (EGCG) with the EpCAM-aptamer modification for hepatocellular carcinoma (HCC) treatment. The dual-drugs self-assembly nanosystem induced synergistic and efficient therapeutic effect by activating the innate and acquired immunity.Image 1

Intracerebral hemorrhage (ICH) is one of the most common refractory diseases. Long non-coding RNAs (lncRNAs) play crucial roles in ICH. This study was designed to investigate the role of lncRNA H19 in ICH and the underlying molecular mechanisms involved. Real-time quantitative polymerase chain reaction (RT-qPCR) was performed to determine mRNA expression. Cell viability was analyzed using Cell Counting Kit 8 (CCK8). PI staining Flow cytometry and TdT-mediated biotinylated nick end-labeling (TUNEL) assays were performed to determine ferroptosis in brain microvascular endothelial cells (BMVECs). Targeting relationships were predicted using Starbase and TargetScan and verified by RNA pull-down and luciferase reporter gene assays. Western blotting was performed to assess protein expression. LncRNA H19 is highly expressed in ICH model cells. Over-expression of H19 suppressed cell viability and promoted ferroptosis of BMVECs. miR-106b-5p is predicted to be a target of H19. The expression of miR-106b-5p was lower in oxygen and glucose deprivation hemin-treated (OGD/H-treated) cells. Over-expression of miR-106b-5p reversed the effects of H19 on cell viability and ferroptosis in BMVECs. Furthermore, acyl-CoA synthetase long-chain family member 4 (ACSL4) was verified to be a target gene of miR-106b-5p and was highly expressed in OGD/H-treated cells. Upregulation of ACSL4 inhibited the effects of miR-106b-5p and induced BMVEC dysfunction. In conclusion, lncRNA H19 was overexpressed in ICH. Knockdown of H19 promoted cell proliferation and suppressed BMVECs ferroptosis by regulating the miR-106b-5p/ACSL4 axis. Therefore, H19 knockdown may be a promising therapeutic strategy for ICH., Graphical abstract

Cerebral ischemia is an extremely complex disease that can be caused by a variety of factors. Cerebral ischemia can cause great harm to human body. Sevoflurane is a volatile anesthetic that is frequently used in clinic, and has a lot of advantages, such as quick induction of general anesthesia, quick anesthesia recovery, no respiratory tract irritation, muscle relaxation, and small cycle effect. The mechanism of sevoflurane preconditioning or post-treatment induction is poorly understood. The purpose of this study was to illustrate the mechanism underlying sevoflurane-induced protection in cerebral ischemia–reperfusion injury and also provide theoretical guidance for future research.