Fraxetin pretreatment alleviates cisplatin-induced kidney injury by antagonizing autophagy and apoptosis via mTORC1 activation.

Cisplatin-induced kidney injury (CKI) is a common complication of chemotherapy. Fraxetin, derived from Fraxinus bungeana A. DC. bark, has antioxidant, anti-inflammatory, and anti-fibrotic effects. This study aims to investigate fraxetin's effects on CKI and its underlying mechanism in vivo and in vitro. Tubular epithelial cells (TECs) and mice were exposed to cisplatin with and without fraxetin preconditioning assess fraxetin's role in CKI. TECs autophagy was observed using transmission electron microscopy. Apoptosis levels in animal tissues were measured using TUNEL staining. The protective mechanism of fraxetin was explored through pharmacological and genetic regulation of mTORC1. Molecular docking was used to identify potential binding sites between fraxetin and mTORC1. The results indicated that fraxetin pretreatment reduced cisplatin-induced kidney injury in a time- and concentration-dependent way. Fraxetin also decreased autophagy in TECs, as observed through electron microscopy. Tissue staining confirmed that fraxetin pretreatment significantly reduced cisplatin-induced apoptosis. Inhibition of mTORC1 using rapamycin or siRNA reversed the protective effects of fraxetin on apoptosis and autophagy in cisplatin-treated TECs, while activation of mTORC1 enhanced fraxetin's protective effect. Molecular docking analysis revealed that fraxetin can bind to HEAT-repeats binding site on mTORC1 protein. In  summary, fraxetin pretreatment alleviates CKI by antagonizing autophagy and apoptosis via mTORC1 activation. This provides evidence for the potential therapeutic application of fraxetin in CKI.

Smad4 regulates TGF-ß1-mediated hedgehog activation to promote epithelial-to-mesenchymal transition in pancreatic cancer cells by suppressing Gli1 activity.

Pancreatic cancer (PC) is an aggressive and metastatic gastrointestinal tumor with a poor prognosis. Persistent activation of the TGF-ß/Smad signaling induces PC cell (PCC) invasion and infiltration via epithelial-to-mesenchymal transition (EMT). Hedgehog signaling is a crucial pathway for the development of PC via the transcription factors Gli1/2/3. This study aimed to investigate the underlying molecular mechanisms of action of hedgehog activation in TGF-ß1-triggered EMT in PCCs (PANC-1 and BxPc-3). In addition, overexpression and shRNA techniques were used to evaluate the role of Smad4 in TGF-ß1-treated PCCs. Our data showed that TGF-ß1 promoted PCC invasion and infiltration via Smad2/3-dependent EMT. Hedgehog-Gli signaling axis in PCCs was activated upon TGF-ß1 stimulation. Inhibition of hedgehog with cyclopamine effectively antagonized TGF-ß1-induced EMT, thereby suggesting that the hedgehog signaling may act as a downstream cascade signaling of TGF-ß1. As a key protein that assists the nuclear translocation of Smad2/3, Smad4 was highly expressed in PANC-1 cells, but not in BxPc-3 cells. Conversely, Gli1 expression was low in PANC-1 cells, but high in BxPc-3 cells. Furthermore, knockdown of Smad4 in PANC-1 cells by shRNA inhibited TGF-ß1-mediated EMT and collagen deposition. Overexpression of Smad4 did not affect TGF-ß1-mediated EMT due to the lack of significant increase in nuclear expression of Smad4. Importantly, Gli1 activity was upregulated by Smad4 knockdown in PANC-1 cells and downregulated by Smad4 overexpression in BxPc-3 cells, indicating that Gli1 may be a negative target protein downstream of Smad4. Thus, Smad4 regulates TGF-ß1-mediated hedgehog activation to promote EMT in PCCs by suppressing Gli1 activity.

Lower Limb Joint Torque Prediction Using Long Short-Term Memory Network and Gaussian Process Regression.

The accurate prediction of joint torque is required in various applications. Some traditional methods, such as the inverse dynamics model and the electromyography (EMG)-driven neuromusculoskeletal (NMS) model, depend on ground reaction force (GRF) measurements and involve complex optimization solution processes, respectively. Recently, machine learning methods have been popularly used to predict joint torque with surface electromyography (sEMG) signals and kinematic information as inputs. This study aims to predict lower limb joint torque in the sagittal plane during walking, using a long short-term memory (LSTM) model and Gaussian process regression (GPR) model, respectively, with seven characteristics extracted from the sEMG signals of five muscles and three joint angles as inputs. The majority of the normalized root mean squared error (NRMSE) values in both models are below 15%, most Pearson correlation coefficient (R) values exceed 0.85, and most decisive factor (R2) values surpass 0.75. These results indicate that the joint prediction of torque is feasible using machine learning methods with sEMG signals and joint angles as inputs.

The sequence effect: Character position processing in Chinese words.

Numerous studies indicate that letter position processing is important for word recognition; also, the position processing of external letters (especially the initial letter) is better than that of inner letters in the Roman script. Similarly, the position processing of characters is critical in Chinese word recognition. However, the position processing pattern of characters within Chinese words is still understudied. Therefore, using a single-presentation lexical decision task with 79 university students in China, we conducted two experiments with three- and four-character words to explore this issue. The results revealed clear character position processing with transposed pseudowords. Crucially, we identified a sequence effect in Chinese character position processing within words, directly supporting the hypothesis that character-based processing occurs with Chinese words. We also discussed other possibilities in Chinese character position processing.

Inhibition of STAT3Y705 phosphorylation by Stattic suppresses proliferation and induces mitochondrial-dependent apoptosis in pancreatic cancer cells.

Patients with pancreatic cancer (PC) show dismal prognosis and high mortality. The development of PC is associated with the overactivation of STAT3. Here, we have determined that the non-peptide small molecule Stattic inhibits PC development by targeting STAT3. In vitro, Stattic treatment time- and dose-dependently inhibited proliferation of pancreatic cancer cells (PCCs) by reducing c-Myc expression and enhancing p53 activity. Consequently, p-Rb, cyclin D1, Chk1, and p21 (cell cycle proteins) were downregulated, and PCCs were arrested at the G1 phase, which was also confirmed by decreased Ki67 expression and unaltered PCNA expression. In addition, Stattic-induced mitochondrial-dependent apoptosis by elevating cleaved caspase-3, and Bax, cytochrome C levels, while reducing expression of Bcl-2, which may be regulated by reduced survivin expression. Further studies showed that Stattic exerts its anti-tumor effect via inhibition of STAT3Y705 phosphorylation and nuclear localization in PCCs. In a nude mouse tumorigenesis model, Stattic inhibited PC growth by antagonizing STAT3Y705 phosphorylation. Interleukin-6 used as a molecule agonist to activate STAT3, as well as overexpression of STAT3, could partially reverse Stattic-mediated anti-proliferation and pro-apoptotic effects of PCCs. Thus, these findings indicate that inhibition of STAT3Y705 phosphorylation by Stattic suppresses PCC proliferation and promotes mitochondrial-mediated apoptosis.

The Imbalance in Th17 and Treg Cells in Polycystic Ovarian Syndrome Patients with Autoimmune Thyroiditis.

The ratio of T helper (Th) 17 and T regulatory (Treg) cells in patients with polycystic ovary syndrome complicated with autoimmune thyroiditis (PCOS-AIT) remains unreported. The study aimed to determine the Th17/Treg cell paradigm in PCOS-AIT patients. In peripheral blood mononuclear cells from PCOS patients and controls, the percentages of Th17 and Treg cells were measured by flow cytometry, the mRNA levels of a Th17-related transcription factor (ROR-γt) and a Treg-specific transcription factor (Foxp3) were determined by qRT-PCR, and the levels of Th17-related cytokines and Treg-related cytokines were measured by ELISA. Additionally, to examine the effect of testosterone on the Th17/Treg cell balance in vitro, cultured PCOS-AIT CD4+ T cells were treated with 10 µM testosterone for 24 h, and the Th17/Treg cell proportions and expression of Th17/Treg cell-associated transcription factors and cytokines were analyzed by flow cytometry, qRT-PCR, and ELISA. The Th17 cell percentage, Th17/Treg cell ratio, and expression of Th17-related ROR-γt and IL-17 were significantly higher in peripheral blood mononuclear cells from PCOS-AIT patients than in those from controls. In CD4+ T cells derived from PCOS-AIT patients, testosterone significantly decreased the Th17 cell percentage, Th17/Treg ratio, mRNA level of ROR-γt, and production of Th17-related cytokines and increased the Treg cell percentage, mRNA level of Foxp3, and secretion of Treg-related cytokines. The Th17/Treg cell imbalance favoring proinflammatory Th17 cells is involved in the pathogenesis of PCOS-AIT. Targeting the Th17/Treg cell axis may have therapeutic potential in the treatment of PCOS-AIT.

Eye-movement control during learning and scanning of Landolt-C stimuli: Exposure frequency effects and spacing effects in a visual search task.

We examined whether typical frequency effects observed in normal reading would also occur in a target search task using non-linguistic Landolt-C stimuli. In an initial learning session, we simulated development of frequency effects by controlling exposures participants received of Landolt-C clusters during learning. In a subsequent scanning session, we manipulated the cluster demarcation form of linear strings of Landolt-C clusters (i.e., spaced vs. unspaced vs. shaded unspaced). Participants were required to scan and search for pre-learnt target clusters that were embedded in longer Landolt-C strings. During learning, frequency effects were successfully simulated such that targets with more exposures received shorter fixation time than those with fewer exposures. Participants were unable to successfully detect the pre-learnt targets when they were embedded in the strings during scanning. No evidence of frequency effects was observed in the scanning session. In contrast, eye-movement control was significantly influenced by cluster demarcation form, with increased difficulty for unspaced strings, less for shaded strings, and least for spaced strings. Furthermore, typical landing position distributions that occur in reading of spaced languages also occurred during scanning of spaced Landolt-C strings but not for the shaded or the unspaced strings. In conclusion, exposure frequency effects were successfully simulated during learning but did not carry over to target search during scanning of Landolt-C strings. Possible reasons why frequency effects did not occur in the scanning session are discussed.

Eye-movement control during learning and scanning of English pseudoword stimuli: Exposure frequency effects and spacing effects in a visual search task.

Wang et al. (Attention, Perception, and Psychophysics, in press, 2021) reported a Landolt-C learning and scanning experiment. In a learning session, they simulated exposure frequency effects successfully by training participants to learn target Landolt-C clusters with different exposures. The rate of learning high-frequency (HF) targets were greater than that of learning low-frequency (LF) targets. In a subsequent scanning session, participants were required to scan text-like Landolt-C strings to detect whether any pre-learnt target was embedded in the strings. The Landolt-C strings were displayed under different spacing formats (i.e., spaced format, unspaced format, and unspaced shaded format). However, the simulated exposure frequency effect did not occur in the scanning session. Wang et al. argued one straightforward reason for this might be because participants failed to maintain the memory of pre-learnt target to the scanning session. In the current study, we employed the same learning and scanning paradigm to investigate whether exposure frequency would occur in a target search task by using easier learning materials - pseudoword stimuli. The learning of pseudoword stimuli was much more successful than Landolt-C stimuli. Interestingly, however, we found a very different rate of learning effect such that the rate of learning LF targets was greater than HF targets. To our surprise, we did not find any influence of exposure frequency on eye movements during scanning even when participants were able to identify pre-learnt pseudowords in strings. Learning rate effect, exposure frequency effects, and saccadic targeting during the scanning of strings under different spacing formats are discussed in this paper.

Simultaneous purifying of Hg0, SO2, and NOx from flue gas by Fe3+/H2O2: the performance and purifying mechanism.

Hg0, SO2, and NOx result in heavily global environmental pollution and serious health hazards. Up to now, how to efficiently remove mercury with SO2 and NOx from flue gas is still a tough task. In this study, series of high oxidizing Fenton systems were employed to purify the pollutants. The experimental results showed that Fe3+/H2O2 was more suitable to purify Hg0 than Fe2+/H2O2 and Cu2+/H2O2. The optimal condition includes Fe3+ concentration of 0.008 mol/L, Hg0 inlet concentration of 40 µg/m3, solution temperature of 50 °C, pH of 3, H2O2 concentration of 0.7 mol/L, and O2 percentage of 6%. When SO2 and NOx were taken into account under the optimal condition, Hg0 removal efficiency could be enhanced to 91.11% while the removal efficiency of both NOx and SO2 was slightly declined, which was consistent to the analysis of purifying mechanism. The removal efficiency of Hg0 was stimulated by accelerating the conversion of Fe2+ to Fe3+, which resulted from the existence of SO2 and NOx. The results of this study suggested that simultaneously purifying Hg0, SO2, and NOx from flue gas is feasible.

Purification of Hg0 from flue gas by wet oxidation method and its mechanism: a review.

The vast majority of Hg2+ can be removed while elemental mercury (Hg0) can hardly be removed due to its characteristic of high volatility and insolubility in water. Till now, how to oxidize Hg0 to Hg2+ is the key for the purification of Hg0, especially when there are others pollutants, such as HCl, SO2, and NOx. In this review, the method and mechanism of Hg0 purification from flue gas by H2O2, KMnO4, NaClO2, and O3 are reviewed comprehensively. It is concluded that the oxidation of Hg0 mainly depends on the electronic supply efficiency from the solution. The Fenton reagent, composed of H2O2 and metal cations, is superior to O3 and the solution of KMnO4 and NaClO2. Moreover, HCl, SO2, and NOx in the flue gas can influence the oxidation and purification mechanism of Hg0. It is found that HCl in flue gas had obvious auxo-action on the oxidation of mercury, and SO2 and NOx have different effects on the oxidation of Hg0 with the change of compositions and concentration of pollutants in the flue gas. In general, SO2 and NOx can slightly promote the oxidation of Hg0 due to the synergistic effect.

[Screening, resistance and growth-promoting effect of endophytic bacteria with ACC deaminase activity isolated from soybean nodules].

Objective: We screened endophytic bacteria containing ACC (1-aminocyclopropane-1-carboxylate) deaminase from soybean nodules, and evaluated salt-alkaline resistance, phylogenetic status and the growthpromoting of representative strain. Methods: The features of strains producing ACC deaminase were determined by using the ACC as a sole nitrogen source, adopting standard curve method, colorimetric method, solid medium screening method, bacterial morphology, physio-biochemical characteristics, similarity analysis of 16S rRNA gene, inoculation tests. Results: Eight endophytic bacteria containing ACC deaminase were screened from soybean nodules collected from 36 points of 13 cities (regions)in Henan province. Enzymaticactivity of DD132 was the highest (15.712 U/mg). Screened strain tolerated to medium of 4%-6% NaCl concentration. Among of them, DD165 and DD132 could tolerate 9% NaCl concentration. Five bacteria growing well under pH 11, showing that these strains had stronger alkali resistance. Eight strains containing ACC deaminase activity were affiliated to four genera: Bacillus, Enterobacter, Stenotrophomonas and Pantoea. Inoculation test showed that DD132 had a significant growthpromoting effect on wheat seedlings. Conclusions: Endophytic bacteria containing high ACC deaminase activity from soybean nodules have stronger salt-alkaline resistance. DD132 has obvious growth-promoting effect on wheat seedlings.

Seven novel coordination polymers constructed by rigid 4-(4-carboxyphenyl)-terpyridine ligands: synthesis, structural diversity, luminescence and magnetic properties.

Seven coordination polymers, namely [Mn(4-cptpy)2]n (1), [Co(4-cptpy)2]n (2), [Mn3(4-cptpy)6(H2O)]n·2nH2O (3), [Co(4-cptpy)(HCOO)(H2O)]n·nDMF (4), [Zn2(4-Hcptpy)2Cl4]n·2nC2H5OH·nH2O (5), [Co4(3-cptpy)4(HCOO)4(H2O)2]n (6), and [Mn(3-cptpy)2]n (7) (4-Hcptpy = 4-(4-carboxyphenyl)-4,2':6',4''-terpyridine; 3-Hcptpy = 4-(4-carboxyphenyl)-3,2':6',3''-terpyridine), have been synthesized under hydro(solvo)thermal conditions and structurally characterized. A general solvothermal method is proposed for preparing carboxylate complexes in DMF solution without any basic additive. 1 and 2 possess isostructural 3D metal-organic frameworks containing nanosized cavities. 3 is a beautiful 2D coordination polymer assembled by flower-like Mn3(4-cptpy)6(H2O) subunits. 4 and 6 both display 2D polymeric networks constructed from 4/3-cptpy(-) ligands, in which the formate ligands originate from the hydrolysis of DMF. 5 is a 1D 2(1) helical chain polymer. 7 shows a 2D network with a (3.6) two-nodal kgd topology. 4/3-Hcptpy ligands display seven types of coordination modes. The zinc complex 5 emits strong violet luminescence. 1 and 2 are both thermally stable below 440 °C and exhibit antiferromagnetic interactions.