Baicalin enhances the chemotherapy sensitivity of oxaliplatin-resistant gastric cancer cells by activating p53-mediated ferroptosis.

Gastric cancer is one of the most common malignant tumors, and chemotherapy is the main treatment for advanced gastric cancer. However, chemotherapy resistance leads to treatment failure and poor prognosis in patients with gastric cancer. Multidrug resistance (MDR) is a major challenge that needs to be overcome in chemotherapy. According to recent research, ferroptosis activation is crucial for tumor therapeutic strategies. In this work, we explored the solution to chemoresistance in gastric cancer by investigating the effects of the Chinese medicine monomer baicalin on ferroptosis. Baicalin with different concentrations was used to treat the parent HGC27 and drug-resistant HGC27/L cells of gastric cancer. Cell viability was measured by CCK8, and synergistic effects of baicalin combined with oxaliplatin were evaluated using Synergy Finder software. The effects of baicalin on organelles and cell morphology were investigated using projective electron microscopy. Iron concentration, MDA production and GSH inhibition rate were measured by colorimetry. ROS accumulation was detected by flow cytometry. The ferroptosis-related genes (IREB2, TfR, GPX4, FTH1), P53, and SLC7A11 were analysed by Western blot, and the expression differences of the above proteins between pretreatment and pretreatment of different concentrations of baicalin, were assayed in both parental HGC27 cells and Oxaliplatin-resistant HGC27/L cells. Mechanically, Baicalin disrupted iron homeostasis and inhibits antioxidant defense, resulting in iron accumulation, lipid peroxide aggregation, and specifically targeted and activated ferroptosis by upregulating the expression of tumor suppressor gene p53, thereby activating the SLC7A11/GPX4/ROS pathway mediated by it. Baicalin activates ferroptosis through multiple pathways and targets, thereby inhibiting the viability of oxaliplatin-resistant gastric cancer HGC27/L cells and enhancing the sensitivity to oxaliplatin chemotherapy.

The 'Candidatus Phytoplasma ziziphi' effectors SJP1/2 negatively control leaf size by stabilizing the transcription factor ZjTCP2 in jujube.

Phytoplasmas manipulate host plant development to benefit insect vector colonization and their own invasion. However, the virulence factors and mechanisms underlying small-leaf formation caused by jujube witches' broom (JWB) phytoplasmas remain largely unknown. Here, effectors SJP1 and SJP2 from JWB phytoplasmas were identified to induce small-leaf formation in jujube (Ziziphus jujuba). In vivo interaction and expression assays showed that SJP1 and SJP2 interacted with and stabilized the transcription factor ZjTCP2. Overexpression of SJP1 and SJP2 in jujube induced ZjTCP2 accumulation. In addition, the abundance of miRNA319f_1 was significantly reduced in leaves of SJP1 and SJP2 transgenic jujube plants and showed the opposite pattern to the expression of its target, ZjTCP2, which was consistent with the pattern in diseased leaves. Overexpression of ZjTCP2 in Arabidopsis promoted ectopic leaves arising from the adaxial side of cotyledons and reduced leaf size. Constitutive expression of the miRNA319f_1 precursor in the 35S::ZjTCP2 background reduced the abundance of ZjTCP2 mRNA and reversed the cotyledon and leaf defects in Arabidopsis. Therefore, these observations suggest that effectors SJP1 and SJP2 induced small-leaf formation, at least partly, by interacting with and activating ZjTCP2 expression both at the transcriptional and the protein level, providing new insights into small-leaf formation caused by phytoplasmas in woody plants.

Identification of molecular markers for predicting the severity of heart failure after AMI: An Olink precision proteomic study.

BACKGROUND: Acute myocardial infarction (AMI) still has a high incidence of varying degrees of heart failure (HF). The aim of this study is to identify new molecular markers for predicting the severity of HF after AMI. METHODS: We analyzed demographic indicators, past medical history, clinical indicators, major adverse cardiac events (MACEs) and molecular markers in patients with different Killip classifications after AMI. Olink proteomics was used to explore new molecular markers for predicting different severity of HF after AMI. RESULTS: Neutrophil count was the independent risk factors for in-hospital MACEs. Nineteen differentially expressed proteins (DEPs) increased significantly with increasing Killip classification. Five DEPs were also found to have an AUC (95 % CI) value greater than 0.8: GDF-15, NT-pro BNP, TNF-R2, TNF-R1 and TFF3. CONCLUSIONS: Neutrophil count, GDF-15, TNF-R2, TNF-R1 and TFF3 were closely related to the Killip classification of HF after AMI, which suggests that the inflammatory response plays an important role in the severity of HF after AMI and that regulating inflammation might become a new target for controlling HF.

Jujube witches' broom phytoplasmas inhibit ZjBRC1-mediated abscisic acid metabolism to induce shoot proliferation.

Jujube witches' broom (JWB) phytoplasmas parasitize the sieve tubes of diseased phloem and cause an excessive proliferation of axillary shoots from dormant lateral buds to favour their transmission. In previous research, two JWB effectors, SJP1 and SJP2, were identified to induce lateral bud outgrowth by disrupting ZjBRC1-mediated auxin flux. However, the pathogenesis of JWB disease remains largely unknown. Here, tissue-specific transcriptional reprogramming was examined to gain insight into the genetic mechanisms acting inside jujube lateral buds under JWB phytoplasma infection. JWB phytoplasmas modulated a series of plant signalling networks involved in lateral bud development and defence, including auxin, abscisic acid (ABA), ethylene, jasmonic acid, and salicylic acid. JWB-induced bud outgrowth was accompanied by downregulation of ABA synthesis within lateral buds. ABA application rescued the bushy appearances of transgenic Arabidopsis overexpressing SJP1 and SJP2 in Col-0 and ZjBRC1 in the brc1-2 mutant. Furthermore, the expression of ZjBRC1 and ABA-related genes ZjHB40 and ZjNCED3 was negatively correlated with lateral main bud outgrowth in decapitated healthy jujube. Molecular evidence showed that ZjBRC1 interacted with ZjBRC2 via its N-terminus to activate ZjHB40 and ZjNCED3 expression and ABA accumulation in transgenic jujube calli. In addition, ZjBRC1 widely regulated differentially expressed genes related to ABA homeostasis and ABA signalling, especially by binding to and suppressing ABA receptors. Therefore, these results suggest that JWB phytoplasmas hijack the ZjBRC1-mediated ABA pathways to stimulate lateral bud outgrowth and expansion, providing a strategy to engineer plants resistant to JWB phytoplasma disease and regulate woody plant architecture to promote crop yield and quality.

A rigidity-flexibility balance strategy enabling highly photoluminescent two-dimensional covalent organic framework nanosheets.

The fluorescence quenching phenomenon commonly found in two-dimensional COFs is due to either the strong interlayer π-π stacking or the non-radiative decay caused by intramolecular rotation. Here, we report a rigidity-flexibility balance strategy for constructing highly photoluminescent 2D COF nanosheets via the integration of rigid fluorescent molecular nodes with flexible non-planar building blocks. The prepared COF nanosheets, termed TPE-DBC-COF, achieve extremely high PLQY in common organic solvents, especially in tetrahydrofuran (43.5%). Besides, the prepared TPE-DBC-COF exhibits excellent sensitivity and selectivity to tetracycline hydrochloride and high cycling stability, so it can be used as a high-efficiency fluorescent sensor for the detection of tetracycline hydrochloride down to the ppm level.

Towards biomass production and wastewater treatment by enhancing the microalgae-based nutrients recovery from liquid digestate in an innovative photobioreactor integrated with dialysis bag.

Microalgae-based nutrients recovery from liquid anaerobic digestate of swine manure has been a hotspot in recent decades. Nevertheless, in consideration of the high NH4+-N content and poor light penetrability exhibited by the original liquid digestate, uneconomical pretreatment on liquid digestate including centrifugation and dilution are indispensable before microalgae cells inoculation. Herein, aiming at eliminating the energy-intensive and freshwater-consuming pretreatment on liquid digestate and enhancing microalgae growth, the dialysis bag which permits nutrients transferring across its wall surface whereas retains almost all matters characterized by impeding light transmission within the raw liquid digestate was integrated into a column photobioreactor (DB-PBR). Consequently, light availability of microalgae cells in DB-PBR was elevated remarkably and thus contributed to a 357.58% improvement on microalgae biomass concentration in DB-PBR than the conventional PBR under 80 µmol m-2 s-1. Likewise, superior nutrients removal efficiencies from liquid digestate were obtained in DB-PBR (NH4+-N: 74.84%, TP: 63.75%) over the conventional PBR (NH4+-N: 30.27%, TP: 16.86%). Furthermore, higher microalgae biomass concentration (1.87 g L-1) and nutrients removal efficiencies (NH4+-N: 95.12%, TP: 76.87%) were achieved in the DB-PBR by increasing the light intensity to 140 µmol m-2 s-1. More importantly, the DB-PBR may provide a simple and greener solution to purify other kinds of wastewater.

Research on recognition and classification of pulse signal features based on EPNCC.

To rapidly obtain the complete characterization information of pulse signals and to verify the sensitivity and validity of pulse signals in the clinical diagnosis of related diseases. In this paper, an improved PNCC method is proposed as a supplementary feature to enable the complete characterization of pulse signals. In this paper, the wavelet scattering method is used to extract time-domain features from impulse signals, and EEMD-based improved PNCC (EPNCC) is used to extract frequency-domain features. The time-frequency features are mixed into a convolutional neural network for final classification and recognition. The data for this study were obtained from the MIT-BIH-mimic database, which was used to verify the effectiveness of the proposed method. The experimental analysis of three types of clinical symptom pulse signals showed an accuracy of 98.3% for pulse classification and recognition. The method is effective in complete pulse characterization and improves pulse classification accuracy under the processing of the three clinical pulse signals used in the paper.

High-Fat Diet Rapidly Modifies Trafficking, Phenotype, and Function of Plasmacytoid Dendritic Cells in Adipose Tissue.

Plasmacytoid dendritic cells (pDCs) display an increased abundance in visceral adipose tissue (VAT) of humans with obesity. In the current study, we set out to decipher the molecular mechanisms of their recruitment to VAT and the functional relevance of this process. We observed increased pDC numbers in murine blood, liver, spleen, and VAT after feeding a high-fat diet (HFD) for 3 wk when compared with a standard diet. pDCs were enriched in fat-associated lymphoid clusters representing highly specific lymphoid regions within VAT. HFD led to an enlargement of fat-associated lymphoid clusters with an increased density and migratory speed of pDCs as shown by intravital multiphoton microscopy. For their recruitment into VAT, pDCs employed P-selectin with E-selectin and L-selectin being only critical in response to HFD, indicating that the molecular cues underlying pDC trafficking were dependent on the nutritional state. Subsequent recruitment steps required α4ß1 and α4ß7 integrins and engagement of CCR7. Application of fingolimod (FTY720) abrogated egress of pDCs from VAT, indicating the involvement of sphingosine-1-phosphate in this process. Furthermore, HFD altered pDC functions by promoting their activation and type 1 IFN expression. Blocking pDC infiltration into VAT prevented weight gain and improved glucose tolerance during HFD. In summary, a HFD fundamentally alters pDC biology by promoting their trafficking, retention, and activation in VAT, which in turn seems to regulate metabolism.

Constructing a Solar Evaporator with Salt-Collecting Paper by Stacking Hydrophilic Sponges for Freshwater Production and Salt Collection.

Solar water evaporation is universally considered as an effective method to alleviate the freshwater shortage worldwide. A series of three-dimensional, salt-resistant evaporators have been brought out to improve the evaporation performance. However, little attention was paid to the collection of salt from seawater and high salinity brine. In this work, a carbon black polyvinyl alcohol (PVA) sponge was prepared to harvest light using a physical adsorption method to load carbon black on the PVA sponge. The experimental results showed that optimal light absorption (97.8%) and evaporation rate (1.60 kg m-2 h-1) were achieved when the carbon black PVA sponge was produced at a carbon black concentration of 1 g L-1. Moreover, we stacked PVA sponges beneath the carbon black PVA sponge to construct a non-photothermal evaporation area. It was seen that the evaporator with an eight-layer PVA sponge had an excellent evaporation rate as high as 2.35 kg m-2 h-1. In addition, the salt-collecting paper, all-black printed by a laser printer, was inserted between the stacked PVA sponges for salt collection, and the eight-layer PVA sponge evaporator with the salt-collecting paper at the fourth floor was tested in a 2 h desalination experiment. The outcome indicated that a square meter of this evaporator can produce about 7.03 L of freshwater and 206 g of salt per day from 10 wt % NaCl solution. As a result, the solar evaporator developed in this work is capable of collecting salt and maintaining a high evaporation rate, which is of great competence in the fields of freshwater production and salt collection.

Temporal stability and maintenance mechanisms of alpine meadow communities under clipping and fertilization.

Negative effects of long-term overgrazing have been seriously, grasslands temporal stability is an important ecological concern we need to research. Here, we performed a 12-year-long (2007-2018) two-factor controlled experiment on Kobresia humilis meadow on the Tibetan Plateau. The manipulations included three clipping levels (no clipping, NC; moderate clipping, MC; heavy clipping, HC) and two fertilization levels (no fertilization, NF; fertilization, F). Our results revealed that the two clipping manipulations significantly increased the temporal stability of alpine meadow communities, whose significant increase was more pronounced under the MC than HC treatment. Species asynchrony had a significant positive correlation with species abundance along with compound community gradient. Moreover, asynchrony effects, portfolio effects, and facilitation interactions were all present in the communities under the six types of experimental treatment combinations. Additionally, a selection effect was detected in the compound communities, demonstrating characteristics that are common to different mechanisms. There were no significant differences in the effects of these mechanisms on community temporal stability between the NC-NF and MC-NF interactive communities. The portfolio effects predominated when clipping intensity was moderate under both fertilization and nonfertilization conditions. By contrast, in the compound communities, the selection effect predominated. In summary, we conclude that in meadow communities that undergo clipping and fertilization disturbances, facilitation interactions and weak interactions make a greater contribution toward maintaining their temporal stability.

Deuterated Covalent Organic Frameworks with Significantly Enhanced Luminescence.

Luminescent covalent organic frameworks (COFs) find promising applications in chemical sensing, photocatalysis, and optoelectronic devices, however, the majority of COFs are non or weakly emissive owing to the aggregation-caused quenching (ACQ) or the molecular thermal motion-based energy dissipation. Here, we report a previously unperceived approach to improve luminescence performance of COFs by introducing isotope effect, which is achieved through substitution of hydrogen from high-frequency oscillators X-H (X=O, N, C) by heavier isotope deuterium. Combining the "bottom-up" and in situ deuteration methods generates the first deuterated COF, which exhibits an impressively 19-fold enhancement in quantum yield over that of the non-deuterated counterpart. These results are interpreted by theoretical calculations as the consequence of slower C/N-D and OD⋅⋅⋅O vibrations that impede the nonradiative deactivation process. The proposed strategy is proved applicable to many other types of emissive COFs.

The study of citrus-derived flavonoids as effective bitter taste inhibitors.

BACKGROUND: The pericarp of citrus in rutaceae is rich in flavonoids that may possess diverse biological activities. Some citrus flavonoids have been used as natural bitterness inhibitors; however, many citrus flavonoid analogues that possess merit taste amelioration functions have not been reported with respect to utilization in food industry. RESULTS: The effects of 12 citrus flavonoids on the inhibition of the bitter taste of naringin, quinine hydrochloride and stevioside were evaluated both by a sensory panel and electronic tongue analysis. Among the flavonoid compounds evaluated, both neohesperidin dihydrochalcone (NHDC) and neodiosmin were identified to show an excellent bitterness inhibition effect on all three bitterness vehicles tested. The results of the electronic tongue evaluation also showed that the addition of neodiosmin, NHDC or hesperidin dihydrochalcone-7-o-glucoside (HDC-7-G) was able to reduce significantly the bitterness response value of quinine hydrochloride, which is consistent with the sensory panel evaluation. Structure-activity relationship analysis found that the 7-linked neohesperidosyloxy group in the A-ring of the citrus flavonoid skeleton has the best bitterness inhibition effect. In addition, a ternary mixture of NHDC, neodiosmin and naringin, and neodiosmin/ß-cyclodextrin was formulated and it demonstrated, for the first time in the flavor improvement of citrus fruit wine, an enhancement of sweetness and a reduction of bitter taste. CONCLUSION: Twelve citrus flavonoids were found to inhibit the bitter taste of naringin, quinine hydrochloride and stevioside. With respect to the structure-activity relationship analysis, it was found that the 7-linked neohesperidosyloxy group in the A-ring of the citrus flavonoid skeleton possessed the best bitterness inhibition effect. © 2021 Society of Chemical Industry.

TRIM32 promotes inflammatory responses in rheumatoid arthritis fibroblast-like synoviocytes.

Rheumatoid arthritis (RA) is a worldwide autoimmune disease. The study of its aetiology and mechanism has always been a focus topic in medicine. This research was designed to investigate the effect of E3 ubiquitin ligase tripartite motif protein 32 (TRIM32) in rheumatoid arthritis (RA). We found in fibroblast-like synoviocytes (FLS) of RA patients, the expression of TRIM32 was significantly increased compared with its expression in osteoarthritis (OA) patients FLS. A widely used pro-inflammatory stimuli tumour necrosis factor-alpha (TNF-α) was found to promote TRIM32 expression in a time-dependent manner. Furthermore, we observed that overexpression of TRIM32 aggravated the production of pro-inflammatory cytokines in FLS, silencing of TRIM32 showed the consistent results. In addition, TRIM32 was found to activate nuclear factor κB (NF-κB) signalling pathway, and TRIM32 could interact with TNF receptor-associated factor 2 (TRAF2) to promote the K63-linked polyubiquitination of TRAF2 in RA-FLS. In conclusion, we suggested that TRIM32 as a positive regulator of inflammatory responses in RA-FLS.

Enhanced CO2 biofixation and protein production by microalgae biofilm attached on modified surface of nickel foam.

In this work, a photobioreactor with microalgae biofilm was proposed to enhance CO2 biofixation and protein production using nickel foam with the modified surface as the carrier for immobilizing microalgae cells. The results demonstrated that, compared with microalgae suspension, microalgae biofilm lowered mass transfer resistance and promoted mass transfer efficiency of CO2 from the bubbles into the immobilized microalgae cells, enhancing CO2 biofixation and protein production. Moreover, parametric studies on the performance of the photobioreactor with microalgae biofilm were also conducted. The results showed that the photobioreactor with microalgae biofilm yielded a good performance with the CO2 biofixation rate of 4465.6 µmol m-3 s-1, the protein concentration of effluent liquid of 0.892 g L-1, and the protein synthesis rate of 43.11 g m-3 h-1. This work will be conducive to the optimization design of microalgae culture system for improving the performance of the photobioreactor.

Characterization of herb residue and high ash-containing paper sludge blends from fixed bed pyrolysis.

High ash-containing paper sludge which is rich in various metal oxides is employed in herb residue pyrolysis to enhance the yield of fuel gas and reduce tar yield in a drop tube fixed bed reactor. Effects of heat treatment temperature and blending ratio of paper sludge on the yields and composition of pyrolysis products (gas, tar and char) were investigated. Results indicate that paper sludge shows a significantly catalytic effect during the pyrolysis processes of herb residue, accelerating the pyrolysis reactions. The catalytic effect resulted in an increase in gas yield but a decrease in tar yield. The catalytic effect degree is affected by the paper sludge proportions, and the strongest catalytic effect of paper sludge is noted at its blending ratio of 50%. At temperature lower than 900 °C, the catalytic effect of paper sludge in the pyrolysis of herb residue promotes the formation of H2 and CO2, inhibits the formation of CH4, but shows slight influence on the formations of CO, while the formation of the four gas components was all promoted at 900 °C. SEM results of residue char show that ash particles from paper sludge adhere to the surface of the herb residue char after pyrolysis, which may promote the pyrolysis process of herb residue for more gas releasing. FT-IR results indicate that most functional groups disappear after pyrolysis. The addition of paper sludge promotes deoxidisation and aromatization reactions of hetero atoms tars, forming heavier polycyclic aromatic hydrocarbons and leading to tar yield decrease.