The mechanism and experimental verification of Ixeris sonchifolia promoting apoptosis of hepatocellular carcinoma based on network pharmacology: Ixeris sonchifolia Induces Hepatocellular Carcinoma Apoptosis via the PI3K/AKT Pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Ixeris sonchifolia alias Kudiezi, it was named Ixeris sonchifolia (Bunge) Hance, a synonym for Crepidiastrum sonchifolium (Bunge) Pak & Kawano in the https://www.iplant.cn/. And it was first published in J. Linn. Soc., Bot. 13: 108 (1873), which was named Ixeris sonchifolia (Maxim.) Hance in the MPNS (http://mpns.kew.org). As a widely distributed medicinal and edible wild plant, it possesses unique bitter-cold characteristics and constituents with various pharmacological activities. Its main antitumor substances, same as artemisinin and paclitaxel, are classified as terpenoids and have become research foci in recent years. However, its specific biological activity and role in antitumor treatment remain largely unclear. AIM OF THE STUDY: This study aimed to elucidate the molecular targets and potential mechanisms of hepatocellular carcinoma apoptosis induced by Ixeris sonchifolia. MATERIALS AND METHODS: We used network pharmacology methods to analyze and screen the active ingredients and possible underlying mechanisms of Ixeris sonchifolia in treating liver cancer and employed integrative time- and dose-dependent toxicity, transcriptomics, and molecular biology approaches to comprehensively verify the function of Ixeris sonchifolia extract (IsE) in human hepatoblastoma cell (HepG2) apoptosis and its potential mechanism. RESULTS: A total of 169 common targets were screened by network pharmacology, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that IsE inhibited HepG2 cell activity in a time- and dose-dependent manner. Western blot analysis confirmed that IsE promoted HepG2 cell apoptosis by inhibiting the PI3K/AKT signaling pathway and that the PI3K/AKT inhibitor LY294002 also substantially enhanced IsE-induced apoptosis. The PI3K/AKT signaling pathway exhibited significant differences compared to that in the control group. CONCLUSION: Combining network pharmacology with experimental verification, IsE inhibited mitochondrial function and the PI3K/AKT pathway while inducing hepatoma cell apoptosis. IsE may have promising potential for liver cancer treatment and chemoprevention.

Elevating Lithium-Sulfur Battery Durability through Samarium Oxide/Ketjen Black Modified Separator.

Lithium-sulfur batteries have garnered significant attention as a promising next-generation battery technology due to their potential for high energy density. However, their practical application is hampered by slow reaction kinetics and the shuttle effect of lithium polysulfide intermediates. In this context, the authors introduce a pioneering solution in the form of a novel porous carbon nanostructure modified with samarium oxide, denoted as Sm2O3/KB. The material has a highly polar surface, allowing lithium polysulfide to be chemisorbed efficiently. The unsaturated sites provided by the oxygen vacancies of Sm2O3 promote Li2S nucleation, lowering the reaction energy barrier and accelerating Li2S dissolution. The porous structure of Ketjen Black provides a highly conductive channel for electron transport and effectively traps polysulfides. Meanwhile, the batteries with Sm2O3/KB/PP spacers exhibited remarkable electrochemical performances, including a low-capacity decay rate of only 0.046 % for 1000 cycles at 2 C and an excellent multiplicative performance of 624 mAh g-1 at 3 C. This work opens up a new avenue for the potential use of rare-earth-based materials in lithium-sulfur batteries.

Ferroelectric Nanorods as a Polymer Interface Additive for High-Performance Garnet-Based Solid-State Batteries.

Sandwiching polymer interlayers between the electrode and solid electrolyte is considered promising in solving the interfacial issues arising from solid-solid contact in garnet-based solid-state batteries, but drawbacks including low ionic conductivity, inferior Li+ transference number, and unsatisfying mechanical property of the polymer hindered the practical application of such strategy. To solve the mentioned shortcomings of the polymer interlayer simultaneously, we introduce the ferroelectric material, BaTi2O5 (BT) nanorods, into the polymer matrix in this work. By taking full advantage of the plasticization effect and intrinsic spontaneous polarization of the introduced ferroelectric, the polymer's ionic conductivity and Li+ transference number have been significantly enhanced. The built-in electric field BT introduced also benefits the modulation of CEI components formed on the cathode particles, further enhancing the battery performance by decreasing cathode degradation. Besides, the BT nanorods' particular high aspect ratio also helps increase the mechanical property of the obtained polymer film, making it more resistant to lithium dendrite growth across the interface. Benefitting from the merits mentioned above, the assembled lithium symmetric cells using garnet SE with the BT-modified polymer interlayer exhibit stable cycling performance (no short circuit after 1000 h under RT) with low polarization voltage. The full battery employing LiFePO4 as a cathode also presents superior capacity retentions (94.6% after 200 cycles at 0.1 C and 93.4% after 400 cycles at 0.2 C). This work highlights the importance of ferroelectric materials with specific morphology in enhancing the electrochemical performance of polymer-based electrolytes, promoting the practical application of solid-state batteries.

Regulated Li2 S Deposition toward Rapid Kinetics Li-S Batteries by a Separator Modified by CeO2 -Decorated Porous Carbon Nanostructure.

Although the high-energy-density lithium sulfur (Li-S) battery has been considered one of the most promising next-generation energy storage technology, the practical applications have been plagued by the sluggish reaction kinetics and the shuttle effect of lithium polysulfides intermediates. Here, to address the above issues, the authors report a novel separator modified by CeO2 -decorated porous carbon nanostructure (CeO2 /KB/PP). Benefiting from the strong polar surface and large specific surface area, (CeO2 -doped Ketjen Black) delivers efficient chemical adsorption toward lithium polysulfides. Moreover, rich oxygen vacancies of CeO2 provide abundant active sites to expedite lithium polysulfides conversion and regulate deposition and nucleation of Li2 S. Taking advantage of these merits, the battery with the CeO2 /KB/PP separator exhibits remarkable electrochemical performance, including low-capacity decay of only 0.06% per cycle over 1000 cycles at 2 C and superior rate capability of 627 mAh g-1 at 3 C. Even with a high sulfur loading of 6.6 mg cm-2 , the battery can achieve a high areal capacity of 3.6 mAh cm-2 after 100 cycles. This work provides a new application of rare-earth-based materials to facilitate Li-S batteries.

A novel battery separator coated by a europium oxide/carbon nanocomposite enhances the performance of lithium sulfur batteries.

Lithium sulfur (Li-S) batteries represent one of the most promising future power batteries due to their remarkable advantages of low cost and ultrahigh theoretical energy density. However, the commercial applications of Li-S batteries have long been plagued by the shuttling effect of polysulfides and sluggish redox kinetics of these species. Herein, we designed a novel battery separator coated by a europium oxide-doped porous Ketjen Black (Eu2O3/KB) and tested its performance for the Li-S batteries for the first time. Experimental results and theoretical calculations reveal that the improved electrochemical performance can be attributed to the presence of Eu2O3. The strong binding effect between Eu2O3 and polysulfides is demonstrated in two aspects: (1) there exist strong interactions between Eu2O3 as a Lewis acid and polysulfides of strong Lewis basicity; (2) Eu2O3 with oxygen-vacancy defects provides active sites for catalyzing polysulfide conversion and polysulfide trapping. Thus, a Li-S battery with the Eu2O3/KB modified separator delivers highly stable cycling performance and excellent rate capability, with the capacity decay ratio of merely 0.05% per cycle under 1 C rate during 500 cycles, and high specific capacity of 563 mAh g-1 at 3 C rate. This work offers a meaningful exploration of the application of rare earth oxides for the modification of the separator towards high performance Li-S batteries.

Rational design of Co4N nanoparticle loaded porous carbon as a sulfur matrix for advanced lithium-sulfur batteries.

Lithium-sulfur (Li-S) batteries have a high specific capacity of 1675 mAh g-1 and are considered to be a promising next-generation energy storage system. A sulfur host for loading Co4N nanoparticles into porous carbon has been designed as the cathode for high-performance Li-S batteries. The porous carbon successfully confines sulfur and Co4N in the pores, and the synergistic effect of physical and chemical adsorption can effectively inhibit the dissolution and diffusion of polysulfides. Besides, the Co4N nanoparticles can also catalyze the redox reaction kinetics. At a current density of 0.5 C, S@KJ-Co4N cathodes deliver a high specific discharge capacity of 958.3 mAh g-1 and retain at 784.0 mAh g-1 after 200 cycles, corresponding to a decay rate of 0.09% per cycle. It is believed that this work can provide a promising strategy for the design of many energy storage systems.

In Situ Seed-Mediated Growth of Polymer-Grafted Gold Nanoparticles.

We report a facile yet general in situ seed-mediated method for the synthesis of polymer-grafted gold nanoparticles with narrow size distributions (<10%), accurately tunable sizes, and excellent colloidal stability. This method can be extended to a broad range of types and molecular weights of polymer ligands. Nanoparticles with different shapes can also be prepared by using preformed shaped nanoparticles directly as the seeds.

Kidney Injury Molecule-1 Level is Associated with the Severity of Renal Interstitial Injury and Prognosis in Adult Henoch-Schönlein Purpura Nephritis.

BACKGROUND AND AIMS: Kidney injury molecule-1 (KIM-1) was identified the most highly upregulated protein in chronic kidney diseases and prolonged KIM-1 expression may be maladaptive. The present study was aimed to investigate urinary, renal and plasma KIM-1 levels and to analyze association between KIM-1 levels with clinical and pathological indexes in adult Henoch-Schönlein purpura (HSP) patients. METHODS: Twenty healthy individuals, 20 HSP patients without nephritis and 35 HSP patients with nephritis were recruited. Urinary and plasma KIM-1 levels were determined by ELISA and Luminex, respectively. Renal KIM-1 expression was evaluated by immunohistochemistry. RESULTS: HSP patients with nephritis were characterized as elevated levels of urinary, renal and plasma KIM-1. Those with more severe tubular injury of renal biopsy tissues presented significantly higher urinary and renal KIM-1 levels compared to control and patients without nephritis. Urinary and renal levels of KIM-1 were positively correlated with blood urea nitrogen and proteinuria, while they were negatively correlated with eGFR at both baseline and after two years follow-up. Moreover, plasma KIM-1 levels were associated with blood urea nitrogen and proteinuria as well. Further univariate correlation analysis indicated urinary and renal KIM-1 levels were positively correlated with interstitial inflammation index and tubulointerstitial chronicity index. Only urinary KIM-1 levels were associated with interstitial inflammation index, tubulointerstitial chronicity index and extracapillary glomerular activity index, after logistic regression analysis. The area under the curve (AUC) for urinary KIM-1/Cr predicting progression of renal damage was significantly greater than the AUC for proteinuria. CONCLUSIONS: This finding suggests that measurement of urinary and renal KIM-1 level may be helpful to evaluate severity of renal pathological damage and prognosis in adult HSP patients with nephritis.

Chiral Plasmonic Nanochains via the Self-Assembly of Gold Nanorods and Helical Glutathione Oligomers Facilitated by Cetyltrimethylammonium Bromide Micelles.

Gold nanorods are excellent anisotropic building blocks for plasmonic chiral nanostructures. The near-infrared plasmonic band of nanorods makes them highly desirable for biomedical applications such as chiral bioimaging and sensing, in which a strong circular dichroism (CD) signal is required. Chiral assemblies of gold nanorods induced by self-associating peptides are especially attractive for this purpose as they exhibit plasmonic-enhanced chiroptical activity. Here, we showed that the presence of cetyltrimethylammonium bromide (CTAB) micelles in a gold nanorod solution promoted the self-association of l-/d-glutathione (GSH) and significantly enhanced the chirality of the resulting plasmonic nanochains. Chiroptical signals for the ensemble in the presence of CTAB micelles were 20 times greater than those obtained below the critical micelle concentration of CTAB. The strong optical activity was attributed to the formation of helical GSH oligomers in the hydrophobic core of the CTAB micelles. The helical GSH oligomers led the nanorods to assemble in a chiral, end-to-end crossed fashion. The CD signal intensities were also proportional to the fraction of nanorods in the nanochains. In addition, finite-difference time-domain simulations agreed well with the experimental extinction and CD spectra. Our work demonstrated a substantial effect from the CTAB micelles on gold nanoparticle assemblies induced by biomolecules and showed the importance of size matching between the inorganic nanobuilding blocks and the chiral molecular templates (i.e., the GSH oligomers in the present case) in order to attain strong chiroptical activities.

Endoscope-guided interstitial intensity-modulated brachytherapy and intracavitary brachytherapy as boost radiation for primary early T stage nasopharyngeal carcinoma.

BACKGROUND: Intracavitary brachytherapy (ICBT) is usually applied as boost radiotherapy for superficial residual of nasopharyngeal carcinoma (NPC) after primary extern-beam radiptherapy (ERT). Here, we evaluated the outcome of endoscope-guided interstitial intensity-modulated brachytherapy (IMBT) boost radiation for deep-seated residual NPC. METHODOLOGY/PRINCIPAL FINDINGS: Two hundred and thirteen patients with residual NPC who were salvaged with brachytherapy boost radiation during 2005-2009 were analyzed retrospectively. Among these patients, 171 patients had superficial residual NPC (≤1 cm below the nasopharyngeal epithelium) were treated with ICBT boost radiation, and interstitial IMBT boost radiation was delivered to 42 patients with deep-seated residual NPC (>1 cm below the nasopharyngeal epithelium). We found that IMBT boost subgroup had a higher ratio of T2b (81.0% VS 34.5%, P<0.001) and stage II (90.5% VS 61.4%, P = 0.001) than that of ICBT boost subgroup. The dosage of external-beam radiotherapy in the nasopharyngeal (63.0±3.8 VS 62.6±4.3 Gray (Gy), P = 0.67) and regional lymph nodes (55.8±5.0 VS 57.5±5.7 Gy, P = 0.11) was comparable in both groups. For brachytherapy, IMBT subgroup had a lower boost radiation dosage than ICBT subgroup (11.0±2.9 VS 14.8±3.2 Gy, P<0.01). Though the IMBT group had deeper residual tumors and received lower boost radiation dosages, both subgroups had the similar 5-year actuarial overall survival rate (IMBT VS ICBT group: 96.8% VS 93.6%, P = 0.87), progression-free survival rate (92.4% VS 86.5%, P = 0.41) and distant metastasis-free survival rate (94.9% VS 92.7%, P = 0.64). Moreover, IMBT boost radiation subgroup had a similar local (97.4% VS 94.4%, P = 0.57) and regional (95.0% VS 97.2%, P = 0.34) control to ICBT subgroup. The acute and late toxicities rates were comparable between the both subgroups. CONCLUSIONS/SIGNIFICANCE: IMBT boost radiation may be a promising therapeutic selection for deep-seated residual NPC.

Blimp-1 siRNA inhibits B cell differentiation and prevents the development of lupus in mice.

Cumulative evidence suggest that B-lymphocytes play a role in the development of systemic lupus erythematosus (SLE). Thus, the therapeutic approach targeting specific B cells provides a promising way to treat SLE. Blimp-1 (B lymphocyte induced maturation protein), a transcriptional factor, controls the terminal differentiation of mature B cells to plasma cells. To explore the potential of Blimp-1 in the SLE development, we constructed the adenovirus encoding Blimp-1 siRNA, and injected it into BWF1 lupus mice. The results demonstrated that Blimp-1 siRNA decreased the Blimp-1 expression of B cells by regulating XBP-1 (X Box binding protein-1), BCMA (B-cell maturation antigen) expression through c-myc pathway. In addition, Blimp-1 siRNA eliminated anti-dsDNA antibody-producing plsma cells, reduced serum anti-dsDNA antibody levels and impeded the development of lupus. Therefore, our data provide the insight into the mechanism of Blimp-1 in SLE development and might represent a promising therapeutic strategy for autoantibody-mediated diseases.

Dose-volume parameters and clinical outcome of CT-guided free-hand high-dose-rate interstitial brachytherapy for cervical cancer.

Currently, image-based 3-dimentional (3D) planning brachytherapy allows for a better assessment of gross tumor volume (GTV) and the definition and delineation of target volume in cervix cancer. In this study, we investigated the feasibility of our novel computed tomography (CT)-guided free-hand high-dose-rate interstitial brachytherapy (HDRISBT) technique for cervical cancer by evaluating the dosimetry and preliminary clinical outcome of this approach. Dose-volume histogram (DVH) parameters were analyzed according to the Gynecological GEC-ESTRO Working Group recommendations for image-based 3D treatment in cervical cancer. Twenty cervical cancer patients who underwent CT-guided free-hand HDRISBT between March 2009 and June 2010 were studied. With a median of 5 (range, 4-7) implanted needles for each patient, the median dose of brachytherapy alone delivered to 90% of the target volume (D90) was 45 (range, 33-54) Gyα/ß10 for high-risk clinical target volume (HR-CTV) and 30 (range, 20-36) Gyα/ß10 for intermediate-risk clinical target volume (IR-CTV). The percentage of the CTV covered by the prescribed dose (V100) of HR-CTV with brachytherapy alone was 81.9%-99.2% (median, 96.7%). With an additional dose of external beam radiotherapy (EBRT), the median D90 was 94 (range, 83-104) Gyα/ß10 for HR-CTV and 77 (range, 70-87) Gyα/ß10 for IR-CTV; the median dose delivered to 100% of the target volume (D100) was 75 (range, 66-84) Gyα/ß10 for HR-CTV and 65 (range, 57-73) Gyα/ß10 for IR-CTV. The minimum dose to the most irradiated 2 cc volume (D2cc) was 73-96 (median, 83) Gyα/ß3 for the bladder, 64-98 (median, 73) Gyα/ß3 for the rectum, and 52-69 (median, 61) Gyα/ß3 for the sigmoid colon. After a median follow-up of 15 months (range, 3-24 months), two patients experienced local failure, and 1 showed internal iliac nodal metastasis. Despite the relatively small number of needles used, CT-guided HDRISBT for cervical cancer showed favorable DVH parameters and clinical outcome.

[Application of interstitial brachytherapy via parapharynx involvement transnasal approach to enhance dose in radiotherapy for nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: Although intracavitary irradiation (ICI) is usually applied to enhance dose in radiotherapy for early stage nasopharyngeal carcinoma (NPC), its use in parapharyngeal enhancing dose is limited because of dislocation and poor repetition of conventional catheterization. This study was to evaluate the application of a new technique, interstitial brachytherapy via parapharynx involvement transnasal approach, to enhance dose in radiotherapy for NPC. METHODS: Twenty-three naive and recurrent NPC patients with tumor residue of more than 1 cm under nasopharyngeal mucosa or restricted tumor residue in the parapharyngeal space received interstitial brachytherapy between Sep. 2005 and Aug. 2006 via parapharynx involvement transnasal approach under the guidance of sinus endoscopy. The 3-dimensional (3D) planning system was used to delineate target volume, optimize dose distribution, and perform interstitial brachytherapy after CT scan. The depths of catheters under mucosa on the moment of inserting and pulling out were measured. The efficacy and complications were assessed. RESULTS: All catheters were intubated into tumors successfully; the veracity of catheter location was 100%. The submucosa depths of catheters were (9.59+/-2.72) mm when inserted and (9.43+/-2.30) mm when pulled out, without significant difference (t = 0.23,P > 0.05); the shift length was (0.75+/-0.75) mm. The patients were followed up from 3 to 15 months (median, 6 months), and no one dropt out. Three cases of irradiation-associated turbinate adhesion occurred and were cured after lysis; no infection, serious bleeding, palatal perforation, nasopharyngeal necrosis, and other serious complications occurred. All tumors disappeared in 3 months after treatment. No local recurrence and distant metastasis occurred. CONCLUSIONS: The nasopharyngeal and parapharyngeal catheterization with sinus endoscopy guidance is accurate, steady, safe, and feasible. Interstitial brachytherapy is effective for tumor residue in the nasopharynx or parapharyngeal space of NPC patients after radiotherapy without serious complications.