Glycyrrhizae radix et rhizoma processing ameliorates adverse reactions of polygalae radix in zebra fish and rabbit models.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygala tenuifilia Willd (Polygalaceae), a traditional Chinese medicine, has been used for a long time to treat various illnesses with serious adverse reactions. Glycyrrhizae radix et rhizoma processing is generally used to reduce the adverse reactions. AIM OF THE STUDY: The aim of this study was to validate the irritation caused by raw Polygalaceae (RPA), to investigate whether processed Polygalaceae (PGA) was less irritating, and to screen and validate irritant properties of virgaureagenin G (polygala acid, PA), 3,6'-disinapoylsucrose (DSS), Tenuifolia (TEN) and polygalaxanthone III (POL), which had pharmacologically active in Polygalaceae. Zebrafish model, Draize test and High-Performance Liquid Chromatography (HPLC) were utilized to achieve the aim. MATERIALS AND METHODS: Scanning Electron Microscopy (SEM) and optical microscope were used to determine the presence of calcium oxalate needle crystal in RPA and PGA. Zebrafish egg spinning changes and zebrafish embryo behavior were used for irritation validation, irritation comparison and irritant screening. For additional evidence, the Draize test, HE staining of rabbit eyes and ELISA kit were used. Finally, changes in the composition of RPA and PGA were investigated using HPLC. RESULTS: SEM and optical microscopy revealed no calcium oxalate needle crystals in Polygalaceae. RPA, PGA, PA and DSS were able to accelerate the spinning of zebrafish eggs and the movement of embryos, while TEN and POL were not. RPA, PGA, DSS and PA may cause rabbit eyes to become hyperemic and swollen, resulting in damage to the iris, cornea and conjunctiva and increased levels of interleukin-6 (IL-6) and interleukin-10 (IL-10). Comparatively, the effects caused by PGA were less severe than those caused by RPA. In addition, compared to RPA, PGA had lower levels of DSS and PA. CONCLUSIONS: RPA, PGA, DSS, and PA were irritating. However, processing and curing could reduce the irritation by reducing the levels of DSS and PA. DSS and PA could be two potential irritants of Polygalaceae.

Myricetin induces M2 macrophage polarization to alleviate renal tubulointerstitial fibrosis in diabetic nephropathy via PI3K/Akt pathway.

BACKGROUND: Development of end-stage renal disease is predominantly attributed to diabetic nephropathy (DN). Previous studies have indicated that myricetin possesses the potential to mitigate the pathological alterations observed in renal tissue. Nevertheless, the precise molecular mechanism through which myricetin influences the progression of DN remains uncertain. AIM: To investigate the effects of myricetin on DN and explore its potential therapeutic mechanism. METHODS: Db/db mice were administered myricetin intragastrically on a daily basis at doses of 50 mg/kg or 100 mg/kg for a duration of 12 wk. Subsequently, blood and urine indexes were assessed, along with examination of renal tissue pathology. Kidney morphology and fibrosis were evaluated using various staining techniques including hematoxylin and eosin, periodic acid-Schiff, Masson's trichrome, and Sirius-red. Additionally, high-glucose culturing was conducted on the RAW 264.7 cell line, treated with 25 mM myricetin or co-administered with the PI3K/Akt inhibitor LY294002 for a period of 24 h. In both in vivo and in vitro settings, quantification of inflammation factor levels was conducted using western blotting, real-time qPCR and ELISA. RESULTS: In db/db mice, administration of myricetin led to a mitigating effect on DN-induced renal dysfunction and fibrosis. Notably, we observed a significant reduction in expressions of the kidney injury markers kidney injury molecule-1 and neutrophil gelatinase associated lipocalin, along with a decrease in expressions of inflammatory cytokine-related factors. Furthermore, myricetin treatment effectively inhibited the up-regulation of tumor necrosis factor-alpha, interleukin-6, and interluekin-1ß induced by high glucose in RAW 264.7 cells. Additionally, myricetin modulated the M1-type polarization of the RAW 264.7 cells. Molecular docking and bioinformatic analyses revealed Akt as the target of myricetin. The protective effect of myricetin was nullified upon blocking the polarization of RAW 264.7 via inhibition of PI3K/Akt activation using LY294002. CONCLUSION: This study demonstrated that myricetin effectively mitigates kidney injury in DN mice through the regulation of macrophage polarization via the PI3K/Akt signaling pathway.

Effect of Early Electroacupuncture Combined with Enhanced Recovery after Surgery (ERAS) on Pain Perception and Dysfunction in Patients after Total Knee Arthroplasty (TKA).

Objective: A retrospective case-control study was performed to observe the effect and clinical significance of early electroacupuncture combined with enhanced recovery after surgery (ERAS) on pain perception and dysfunction after total knee arthroplasty (TKA). Methods: About 100 patients who diagnosed with TKA from February 2019 to April 2021 were enrolled in our hospital. The patients were arbitrarily assigned into control group and study group. The former group was cured with electroacupuncture in the early stage, and the latter group was intervened on the basis of early electroacupuncture combined with the concept of ERAS. The curative effect, the time of getting out of bed for the first time after operation, the time of postoperative rehabilitation, postoperative rehabilitation cost, pain score and knee joint function score, range of motion (ROM) of knee joint, low shear of whole blood viscosity, plasma viscosity, fibrinogen level, and postoperative complications were compared. Results: There exhibited no statistical difference in clinical data. In terms of the treatment effects, there were 27 cases of markedly effective, 22 cases of effective, and 1 case of ineffective in the study group, and the total effective rate was 98.00%; in the control group, 15 cases were markedly effective, 28 cases were effective, and 13 cases were ineffective, and the total effective rate was 86.00%. Compared to the control group, the total effective rate of the study group was higher (P < 0.05). And the first time to get out of bed and the postoperative rehabilitation time in the study group were lower. Compared to the control group (10113.42 ± 524.83) yuan, the postoperative rehabilitation cost in the study group (12401.71 ± 530.77) yuan was higher. In terms of the scores of VAS and HSS, there exhibited no remarkable difference before treatment (P > 0.05). After treatment, the VAS score lessened and the HSS score augmented the study group VAS score (1.76 ± 0.28); the score in the control group was lower compared to the control group (3.45 ± 0.36), and HSS scoring (83.48 ± 11.23) points higher compared to the control group (65.82 ± 10.44) points (P < 0.05). The ROM of knee joint augmented successively at the 1st, 2nd, 4th, and 8th week after treatment comparison between groups, the ROM of the knee joint in the study group at the 1st, 2nd, 4th, and 8th week was (49.47 ± 3.60)°, (64.38 ± 5.32)°, (86.93 ± 6.72)°, and (104.20 ± 9.11)°, is higher compared to the control group (46.53 ± 3.41)°, (61.52 ± 5.20)°, (78.42 ± 6.45)°, and (98.77 ± 8.67)° (P < 0.05). One day after operation, there exhibited no remarkable difference in whole blood viscosity low shear, plasma viscosity, and fibrinogen level (P > 0.05). However, there exhibited no remarkable difference in plasma viscosity and fibrinogen level at 1 day and 7 days after operation (P > 0.05). Seven days after operation, the whole blood viscosity, plasma viscosity, and fibrinogen in the study group were lower (P < 0.05). The probability of postoperative complications was compared. In the study group, there were 2 cases of limb swelling and pain, 1 case of joint stiffness, and no swelling and pain complicated with deep venous thrombosis, and the total incidence was 6.00%. In the control group, there were 5 cases of limb swelling and pain, 3 cases of joint stiffness, and 3 cases of swelling and pain complicated with deep venous thrombosis, with a total incidence of 22.00%. The incidence of adverse reactions in the study group was lower (χ 2 = 5.317 P < 0.05). Conclusion: Early electroacupuncture combined with ERAS is of positive significance to the patients after TKA, which can reduce the pain, enhance the function of the knee joint, and promote the ROM of the knee joint, and can effectively shorten the first time out of bed and postoperative rehabilitation time and reduce whole blood viscosity low shear, plasma viscosity, and fibrinogen level, but the overall rehabilitation cost is high, and clinical application should be combined with the actual situation of patients.

A novel bee-friendly peptidomimetic insecticide: Synthesis, aphicidal activity and 3D-QSAR study of insect kinin analogs at Phe2 modification.

BACKGROUND: As one of the most abundant and destructive pests in agriculture, aphids cause significant damage to crops due to their sap-taking and as virus vectors. Chemical insecticides are the most effective method to control aphids, but they bring insecticide resistance problems and harm nontarget organisms, especially bees, therefore the search for novel eco-friendly aphid control agents with low bee toxicity is urgent. Insect kinins are a class of small neuropeptides that control important functions in insects. In our previous study, we found insect kinin analog IV-3 has good aphicidal activity and the location of the aromatic ring on the side chain of Phe2 is the key to the formation of the ß-turn resulting in the biological activity of insect kinin analogs. However, there are few studies on insect kinin Phe2 substitution and modification, and its structure-activity relationship is still unclear. RESULTS: In this project, 44 insect kinin analogs with the Phe2 modification, replacing it with different natural or unnatural amino acids, were designed and synthesized based on the lead IV-3 to explore the role of the Phe2 residues. Bioassays with soybean aphids of Aphis glycines indicated that nine analogs have better aphicidal activity than the lead IV-3. In particular, compound L25 exhibits excellent aphicidal activity (LC50  = 0.0047 mmol L-1 ) and has low toxicity to bees. Furthermore, a reliable three-dimensional quantitative structure-activity relationship (3D-QSAR) was established to produce a helpful clue that introducing hydrophobic groups away from the backbone chain is beneficial to improve aphicidal activity. CONCLUSION: The residue Phe2 of insect kinin analogs is the key position and has a significant impact on the activity. L25 has a high toxicity for aphids, while a low toxicity to bees, and therefore can be considered as a lead compound to develop new biosafe aphid control agents. Finally, we provide a useful 3D-QSAR model as theoretical guidance for further structural optimization. © 2022 Society of Chemical Industry.

Comprehensive analysis of lumbar disc degeneration and autophagy-related candidate genes, pathways, and targeting drugs.

BACKGROUND: Lumbar disc degeneration (LDD) is an essential pathological mechanism related to low back pain. Current research on spinal surgery focused on the sophisticated mechanisms involved in LDD, and autophagy was regarded as an essential factor in the pathogenesis. OBJECTIVES: Our research aimed to apply a bioinformatics approach to select some candidate genes and signaling pathways in relationship with autophagy and LDD and to figure out potential agents targeting autophagy- and LDD-related genes. MATERIALS AND METHODS: Text mining was used to find autophagy- and LDD-related genes. The DAVID program was applied in Gene Ontology and pathway analysis after selecting these genes. Several important gene modules were obtained by establishing a network of protein-protein interaction and a functional enrichment analysis. Finally, the selected genes were searched in the drug database to find the agents that target LDD- and autophagy-related genes. RESULTS: There were 72 genes related to "autophagy" and "LDD." Three significant gene modules (22 genes) were selected by using gene enrichment analysis, which represented 4 signaling pathways targeted by 32 kinds of drugs approved by the Food and Drug Administration (FDA). The interactions between drugs and the genes were also identified. CONCLUSION: To conclude, a method was proposed in our research to find candidate genes, pathways, and drugs which were involved in autophagy and LDD. We discovered 22 genes, 4 pathways, and 32 potential agents, which provided a theoretical basis and new direction for clinical and basic research on LDD.

Quercetin Antagonizes Glucose Fluctuation Induced Renal Injury by Inhibiting Aerobic Glycolysis via HIF-1α/miR-210/ISCU/FeS Pathway.

Background and Objective: Glucose fluctuation (GF) has been reported to induce renal injury and diabetic nephropathy (DN). However, the mechanism still remains ambiguous. Mitochondrial energy metabolism, especially aerobic glycolysis, has been a hotspot of DN research for decades. The activation of HIF-1α/miR210/ISCU/FeS axis has provided a new explanation for aerobic glycolysis. Our previous studies indicated quercetin as a potential therapeutic drug for DN. This study aims to evaluate levels of aerobic glycolysis and repressive effect of quercetin via HIF-1α/miR210/ISCU/FeS axis in a cell model of GF. Methods: The mouse glomerular mesangial cells (MCs) were exposed in high or oscillating glucose with or without quercetin treatment. Cell viability was measured by CCK8 assay. Aerobic glycolysis flux was evaluated by lactate acid, pH activity of PFK. Apoptosis level was confirmed by Annexin V-APC/7-AAD double staining and activity of caspase-3. TNF-α and IL-1ß were used to evaluate inflammation levels. Results: GF deteriorated inflammation damage and apoptosis injury in MCs, while quercetin could alleviate this GF-triggered cytotoxicity. GF intensified aerobic glycolysis in MCs and quercetin could inhibit this intensification in a dose-dependent manner. Quercetin prevented activities of two FeS-dependent metabolic enzymes, aconitase, and complex I, under GF injury in MCs. The mRNA expression and protein contents of HIF-1α were increased after GF exposure, and these could be alleviated by quercetin treatment. Knockdown of ISCU by siRNA and Up-regulating of miR-210 by mimic could weaken the effects of quercetin that maintained protein levels of ISCU1/2, improved cell viability, relieved inflammation injury, decreased apoptosis, and reduced aerobic glycolysis switch in MCs. Conclusion: Quercetin antagonizes GF-induced renal injury by suppressing aerobic glycolysis via HIF-1α/miR-210/ISCU/FeS pathway in MCs cell model. Our findings contribute to a new insight into understanding the mechanism of GF-induced renal injury and protective effects of quercetin.

Highly efficient radiative recombination in intrinsically zero-dimensional perovskite micro-crystals prepared by thermally-assisted solution-phase synthesis.

Zero-dimensional (0D) quantum confinement can be achieved in perovskite materials by the confinement of electron and hole states to single PbX6 4- perovskite octahedra. In this work, 0D perovskite (Cs4PbBr6) micro-crystals were prepared by a simple thermally-assisted solution method and thoroughly characterized. The micro-crystals show a high level of crystallinity and a high photoluminescence quantum yield of 45%. The radiative recombination coefficient of the 0D perovskite micro-crystals, 1.5 × 10-8 s-1 cm3, is two orders of magnitude higher than that of typical three-dimensional perovskite and is likely a strong contributing factor to the high emission efficiency of 0D perovskite materials. Temperature dependent luminescence measurements provide insight into the role of thermally-activated trap states. Spatially resolved measurements on single 0D perovskite micro-crystals reveal uniform photoluminescence intensity and emission decay behaviour suggesting the solution-based fabrication method yields a high-quality and homogenous single-crystal material. Such uniform emission reflects the intrinsic 0D nature of the material, which may be beneficial to device applications.

MicroRNA­379­5p suppresses renal fibrosis by regulating the LIN28/let­7 axis in diabetic nephropathy.

MicroRNAs (miRNAs or miRs) play an important role in pathological processes in diabetic nephropathy (DN). This study aimed to explore whether miR­379­5p is associated with renal fibrosis in DN and to elucidate the underlying mechanisms. In vitro experiments indicated that miR­379­5p expression was downregulated by high glucose (HG) treatment in mouse mesangial cells (MMCs). Transfection with miR­379­5p mimics suppressed the proliferation and the accumulation of extracellular matrix (ECM) components, which were promoted by HG treatment. LIN28B was proven to be a direct target of miR­379­5p by luciferase report assay. In addition, the loss of expression of LIN28B, as well as the decrease in cell proliferation and in the accumulation of ECM components, which were induced by the knockdown of LIN28B, were attenuated in the MMCs following transfection with miR­379­5p inhibitors. Furthermore, type 2 diabetic db/db mice were used to examine the efficiency of miR­379­5p agomir in the alleviation of renal fibrosis. Consistent with the results of the in vitro experiments, miR­379­5p agomir suppressed mesangial cell proliferation and the accumulation of ECM components by regulating the LIN28B/let­7 pathway. Taken together, the findings of this study suggest that miR­379­5p is highly involved in renal fibrosis in DN, and that it may be a potential effective therapeutic target for DN.

An Obvious Improvement in the Performance of Ternary Organic Solar Cells with "Guest" Donor Present at the "Host" Donor/Acceptor Interface.

A small-molecule material, 7,7-(4,4-bis(2-ethylhexyl)-4H-silolo[3,2-b:4,5-b']dithiophene-2,6-diyl)bis(6-fluoro-4-(5'-hexyl-[2,2'-bithiophen]-5-yl)benzo-[c] [1,2,5]thiadiazole) (p-DTS(FBTTH2)2), was used to modify the morphology and electron-transport properties of the polymer blend of poly(3-hexythiophene) (P3HT) and [6,6]-phenyl-C71-butyric acid methyl ester (PC71BM) bulk heterojunctions. As a result, a 24% increase in the power-conversion efficiency (PCE) of the p-DTS(FBTTH2)2:P3HT:PC71BM ternary organic solar cells (OSCs) is obtained. The improvement in the performance of OSCs is attributed to the constructive energy cascade path in the ternary system that benefits an efficient Förster resonance energy/charge transfer process between P3HT and p-DTS(FBTTH2)2, thereby improving photocurrent generation. It is shown that p-DTS(FBTTH2)2 molecules engage themselves at the P3HT/PC71BM interface. A combination of absorption enhancement, efficient energy transfer process, and ordered nanomorphology in the ternary system favors exciton dissociation and charge transportation in the polymer bulk heterojunction. The finding of this work reveals that distribution of the appropriate "guest" donor at the "host" donor/acceptor interface is an effective approach for attaining high-performance OSCs.

Effects of Processing Solvent on the Photophysics and Nanomorphology of Poly(3-butyl-thiophene) Nanowires:PCBM Blends.

We report the effect of the processing solvent on the nanoscale morphology and photophysical dynamics of poly(3-butyl-thiophene) nanowires (P3BT-nw). P3BT-nw assembled in ortho-dichlorobenzene (ODCB) show higher crystallization and a longer conjugation length with increased exciton delocalization compared with those assembled in chlorobenzene (CB). It is proposed that this solvent effect is associated with the higher ordered structures formed from ODCB solution state. Charge-transfer dynamics and phase separation for P3BT-nw:PCBM blends were investigated by ultrafast fluorescence techniques. The more efficient fluorescence quenching observed in P3BT-nw:PCBM blend films processed from ODCB suggests that there is intimate contact between P3BT-nw and PCBM that facilitates charge transfer. The superior performance of organic photovoltaic devices based on P3BT-nw:PCBM bulk heterojunctions processed using ODCB is attributed to the higher crystallization of P3BT-nw, optimized phase separation, and more efficient charge transfer from P3BT-nw to PCBM.

Purified dispersions of graphene in a nonpolar solvent via solvothermal reduction of graphene oxide.

It is demonstrated that oxidative debris can be separated and largely removed during the surfactant assisted phase transfer of graphene oxide from a water/ethanol mixture to dichlorobenzene. The new procedure described provides a facile method to obtain monolayer dispersed graphene sheets in a nonpolar solvent via solvothermal reduction of graphene oxide accompanied by an effective purification process.